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Gerasimos Filippatos

Publications and source records attributed to Gerasimos Filippatos.

At least 19 recordsLinked to original sources
PubMed2026

Proteomic patterns according to ejection fraction: an EMPEROR-programme analysis.

AIMS: Left ventricular ejection fraction (LVEF) has been incorporated as an inclusion criterion in HF trials. Patient's characteristics, event risk, and treatment response vary according to LVEF. A better understanding of the biological processes across LVEF is warranted. To study proteomic biomarker expression across LVEF using data from the EMPEROR-Programme. METHODS: Two thousand two hundred and fifty-four patients who had proteomic measurements available using 1134 proteins overlapping between the Explore 1536 and 3072 Olink® platforms were included. Main analyses were performed within the EMPEROR-Preserved dataset due to differences in entry criteria between EMPEROR-Preserved and EMPEROR-Reduced with higher entry N-terminal pro B-type natriuretic peptide (NT-proBNP) levels that varied by LVEF cut-offs in the latter. Protein concentrations were compared using ordinal logistic regression across LVEF categories: 41%-49%, 50%-59%, and ≥60%. The resulting β-coefficient indicates the change in the log-odds for the outcome of being in a lower LVEF category for every NPX unit in log2 scale. Analyses were adjusted for covariates and a false-discovery-rate (FDR) correction was applied. RESULTS: A total of 297 proteins exhibited a trend of expression across LVEF categories in EMPEROR-Preserved after adjustment for potential confounders and correction for test multiplicity. Of these, the top 10 proteins were: NT-pro BNP (β = 0.18, 95% CI 0.09-0.27), Wnt inhibitory factor-1 (β = 0.40, 95% CI 0.19-0.61), sialomucin core protein 24 (β = 0.48, 95% CI 0.22-0.74), phospholipid transfer protein (β = 0.38, 95% CI 0.17-0.59), natriuretic peptides B (β = 0.13, 95% CI 0.06-0.20), intercellular adhesion molecule 5 (β = 0.31, 95% CI 0.14-0.49), neural cell adhesion molecule 2 (β = 0.45, 95% CI 0.19-0.70), neural cell adhesion molecule L1-like protein (β = 0.45, 95% CI 0.19-0.71), interactor protein for cytohesin exchange factors 1 (β = 0.12, 95% CI 0.05-0.19), and 3-ketoacyl-CoA thiolase, peroxisomal (β = 0.17, 95% CI 0.07-0.26). The correlation between these proteins and LVEF was generally weak (Rho ≤0.2). CONCLUSIONS: Within EMPEROR-Preserved, the top differentially expressed circulating proteins suggest that pathways related to natriuretic peptides, cell-adhesion, and clonal haematopoiesis are overexpressed at mildly-reduced ejection fraction, but none of the proteins passed the 5%FDR cut-off, and the correlation between circulating proteins and LVEF was weak. These findings suggest that circulating proteins may not be a good discriminant of ejection fraction.

Humans↗
PubMed2026

Efficacy and Safety of the Kidney Function-Based Finerenone Dosing Strategy Used in FINEARTS-HF.

BACKGROUND: Given that mineralocorticoid receptor antagonists have the potential to impair renal function and induce hyperkalemia, close monitoring of estimated glomerular filtration rate (eGFR) and serum potassium levels is essential to ensure the safe administration of this therapy. OBJECTIVES: In this prespecified analysis, the authors evaluated the efficacy and safety of the kidney function-based finerenone dosing strategy used in the FINEARTS-HF trial. METHODS: In FINEARTS-HF, patients with an eGFR of 25 to 60&#x2009;mL/min/1.73&#x2009;m2 at baseline were stratified at randomization to the low-dose group and started on 10&#x2009;mg of finerenone once daily (titrated to a maximum 20&#x2009;mg/d) or matching placebo, whereas those with an eGFR >60&#x2009;mL/min/1.73&#x2009;m2 at baseline were stratified to the high-dose group and started on 20&#x2009;mg of finerenone once daily (titrated to a maximum 40&#x2009;mg/d) or matching placebo. The primary outcome was the composite of total (first and recurrent) heart failure events and cardiovascular death. RESULTS: Among 5,986 (99.8%) analyzable patients, 3,159 were assigned to the higher eGFR/high-dose stratum and 2,827 to the lower eGFR/low-dose stratum group. The mean &#xb1; SD achieved dose was 32.3&#x2009;&#xb1;&#x2009;9.1&#x2009;mg (finerenone) and 34.4&#x2009;&#xb1;&#x2009;7.8&#x2009;mg (placebo) in the higher eGFR/high-dose stratum, and 15.6&#x2009;&#xb1;&#x2009;4.3&#x2009;mg (finerenone) and 16.7&#x2009;&#xb1;&#x2009;4.0 mg (placebo) in the lower eGFR/low-dose stratum. The effect of finerenone on the primary outcome was consistent across the 2 dosing strata (higher eGFR/high-dose stratum: rate ratio: 0.77 [95% CI: 0.63-0.94] vs lower eGFR/low-dose stratum: rate ratio: 0.87 [95% CI: 0.74-1.03]; P for interaction = 0.34). Consistent benefits were observed for the components of the primary outcome and all-cause death. Safety was also consistent between dosing strata, except for hypokalemia, where the reduction in the odds of hypokalemia with finerenone compared to placebo was greater in the higher eGFR/high-dose stratum (P-interaction < 0.01). CONCLUSIONS: In FINEARTS-HF, an eGFR-based dosing strategy allowed effective and safe use of finerenone in patients with heart failure with mildly reduced ejection fraction/ heart failure with preserved ejection fraction with a baseline eGFR as low as 25&#x2009;mL/min/1.73&#x2009;m2. We recommend that clinicians implement the trial-validated dosing strategy and incorporate appropriate uptitration to the target dose to ensure optimal therapeutic outcomes. (FINEARTS-HF [Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40%; NCT04435626).

Aged↗
PubMed2025

Finerenone and Atrial Fibrillation in Heart Failure: A Secondary Analysis of the FINEARTS-HF Randomized Clinical Trial.

IMPORTANCE: Heart failure (HF) with mildly reduced or preserved ejection fraction and atrial fibrillation (AF) are closely intertwined. OBJECTIVE: To examine the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist finerenone in patients with HF with mildly reduced or preserved ejection fraction according to the absence or presence of AF and the type of AF (paroxysmal vs persistent or permanent). DESIGN, SETTING, AND PARTICIPANTS: Prespecified analyses were conducted in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) randomized clinical trial. The trial was conducted across 653 sites in 37 countries. Participants were adults aged 40 years and older with symptomatic HF and left ventricular ejection fraction of 40% or greater, randomized between September 2020 and January 2023. Data analysis was conducted from September 1 to October 1, 2024. INTERVENTION: Finerenone (titrated to 20 mg or 40 mg) or placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of total HF events and cardiovascular death. New-onset AF or atrial flutter (AFL) was a prespecified exploratory outcome. RESULTS: Among 5984 patients (mean [SD] age, 72.0 [9.6] years; 2724 [45.5%] female) with known AF status at baseline, 1384 (23.1%) had paroxysmal AF and 1886 (31.5%) had persistent or permanent AF. Patients with both types of AF were older and had worse HF status compared with those without AF (2714 patients [45.4%]). Both types of AF were associated with a higher unadjusted risk of the primary outcome compared with no AF (event rate per 100 person-years of follow-up, 20.3 [95% CI, 17.9-23.1] with paroxysmal AF, 19.8 [95% CI, 17.8-22.0] with persistent or permanent AF, and 11.9 [95% CI, 10.7-13.3] with no AF; rate ratio [RR], 1.62 [95% CI, 1.37-1.92] with paroxysmal AF and 1.66 [95% CI, 1.43-1.93] with persistent or permanent AF vs no AF); however, the associations were attenuated after adjustment for known prognostic variables. The benefit of finerenone on the primary outcome (overall RR, 0.84 [95% CI, 0.74-0.95]) was not modified by baseline AF status (RR, 0.80 [95% CI, 0.65-0.98] with no AF, 0.83 [95% CI, 0.65-1.06] with paroxysmal AF, and 0.85 [95% CI, 0.69-1.05] with persistent or permanent AF; P for interaction&#x2009;=&#x2009;.94). New-onset AF or AFL occurred in 6.5% of patients and was associated with a higher subsequent adjusted risk of the primary outcome (rate ratio, 3.65 [95% CI, 2.57-5.18]; P&#x2009;<&#x2009;.001). The subdistribution hazard ratio for new-onset AF or AFL among those receiving finerenone vs placebo was 0.77 (95% CI, 0.57-1.04; P&#x2009;=&#x2009;.09). CONCLUSIONS AND RELEVANCE: The efficacy of finerenone was consistent regardless of AF status. New-onset AF was associated with a substantially higher risk of subsequent outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

Humans↗
PubMed2006

Effects of levosimendan on right ventricular function in patients with advanced heart failure.

Right ventricular (RV) dysfunction frequently complicates advanced left ventricular heart failure and contributes to an unfavorable prognosis. Levosimendan is a novel inodilator that beneficially affects hemodynamics and left ventricular systolic and diastolic function in patients with advanced heart failure. However, its effects on RV function have not yet been properly assessed in these patients. In this randomized trial, the impact of levosimendan or placebo on various echocardiographic parameters of RV systolic and diastolic function was investigated in 54 patients with advanced heart failure due to left ventricular systolic dysfunction. Tissue Doppler imaging maximal systolic tricuspid annular velocity (S wave) increased significantly only in the levosimendan group (8.2 +/- 3.2 vs 9.0 +/- 3.0 cm/s, p <0.03). Tissue Doppler imaging RV early diastolic velocity (E wave) and the ratio of early to late diastolic velocities (E/A) also increased significantly after levosimendan administration (p <0.01 and p <0.05, respectively). Systolic pulmonary arterial pressure decreased significantly (54 +/- 11 vs 43 +/- 11 mm Hg, p <0.01) in the levosimendan-treated patients. Levosimendan beneficially modulated neurohormonal and inflammatory status by decreasing B-type natriuretic peptide levels (p <0.05) and by altering the ratio of interleukin-6 to interleukin-10 in favor of the latter (p <0.05). In conclusion, levosimendan could offer further therapeutic advantages in patients with advanced heart failure by improving systolic and diastolic RV function.

Blood Pressure↗
PubMed2006

The second Euro Heart Survey on acute coronary syndromes: Characteristics, treatment, and outcome of patients with ACS in Europe and the Mediterranean Basin in 2004.

AIMS: Our study aimed to examine the management of acute coronary syndromes (ACS) in Europe and the Mediterranean basin, and to compare adherence to guidelines with that reported in the first Euro Heart Survey on ACS (EHS-ACS-I), 4 years earlier. METHODS AND RESULTS: In a prospective survey conducted in 2004 (EHS-ACS-II), data describing the characteristics, treatment, and outcome of 6385 patients diagnosed with ACS in 190 medical centres in 32 countries were collected. ACS with ST-elevation was the initial diagnosis in 47% of patients, no ST-elevation in 48%, and undetermined electrocardiographic pattern in 5% of patients. Comparison of data collected in 2000 and 2004 showed similar baseline characteristics, but greater use of recommended medications and coronary interventions in EHS-ACS-II. Among patients with ST-elevation, the use of primary reperfusion increased slightly (from 56 to 64%), with a significant shift from fibrinolytic therapy to primary percutaneous coronary intervention (PPCI). The use of PPCI rose from 37 to 59% among those undergoing primary reperfusion therapy. Analysis of data in 34 centres that participated in both surveys showed even greater improvement with respect to the use of recommended medical therapy, interventions, and outcome. CONCLUSION: Data from EHS-ACS-II suggest an increase in adherence to guidelines for treatment of ACS in comparison with EHS-ACS-I.

Acute Disease↗
PubMed2006

Depression in coronary artery disease: novel pathophysiologic mechanisms and therapeutic implications.

Depression is a common comorbid condition in patients with coronary artery disease and a well-documented risk factor for recurrent cardiac events and mortality. The exact mechanisms underlying the interplay between depression and ischemic heart disease remain poorly understood and the same is true for the most effective depression treatment for cardiac patients. This review summarizes current knowledge regarding the prognostic role of depression in patients with coronary artery disease, the pathophysiologic pathways involved, and the effects of antidepressant therapy on cardiovascular disease outcomes. With recent evidence suggesting that selective serotonin reuptake inhibitors may improve survival after myocardial infarction in patients with depression, diagnosis and treatment of this co-morbidity may be essential for the clinical management of coronary artery disease.

Antidepressive Agents↗
PubMed2006

Congestion in acute heart failure syndromes: an essential target of evaluation and treatment.

Patients with acute heart failure syndromes (AHFS) typically present with signs and symptoms of systemic and pulmonary congestion at admission. However, elevated left ventricular (LV) filling pressures (hemodynamic congestion) may be present days or weeks before systemic and pulmonary congestion develop, resulting in hospital admission. This "hemodynamic congestion," with or without clinical congestion, may have deleterious effects including subendocardial ischemia, alterations in LV geometry resulting in secondary mitral insufficiency, and impaired cardiac venous drainage from coronary veins resulting in diastolic dysfunction. It is possible that these hemodynamic abnormalities in addition to neurohormonal activation may contribute to LV remodeling and heart failure progression. Approximately 50% of patients admitted for AHFS are discharged with persistent symptoms and/or minimal or no weight loss in spite of the fact that the main reason for admission was clinical congestion. Accordingly, the assessment and management of pulmonary and systemic congestion in these patients require reevaluation.

Acute Disease↗
PubMed2006

Prognosis and therapy approaches of cardiac cachexia.

PURPOSE OF REVIEW: This review focuses on the prognostic implications and therapeutic approaches in cardiac cachexia - a syndrome that has been recognized for a long time, although it has only received increased attention lately. RECENT FINDINGS: Cardiac cachexia is a common and serious complication of chronic heart failure and associated with very poor prognosis, yet is often recognized by the clinicians only at late stage. Approximately 15% of heart failure patients will develop cardiac cachexia, defined by a 6% non-edematous, non-voluntary weight loss over a period of 6 months. Several studies have demonstrated that cardiac cachexia is a multi-factorial disease, which involves increased neurohormonal activity and immune abnormalities, resulting in hormonal and metabolic catabolic/anabolic imbalance of the body, leading to the loss of fat and lean mass and ultimately death. So far, there are no standardized therapies available for this disease. SUMMARY: Cardiac cachexia in heart failure patients is under-recognized and there is currently no causal therapy available. Several interesting treatment options exist, however, which have emerged recently, including appetite stimulants, hormones and 'classical' drugs, such as beta-blockers and ACE inhibitors.

Cachexia↗
PubMed2006

Hematopoietic colony stimulating factors in cardiovascular and pulmonary remodeling: promoters or inhibitors?

Hemopoietic colony stimulating factors (HCSFs) are naturally occurred substances that are released in response to infection or inflammation and regulate the proliferation and differentiation of hemopoietic progenitor cells. Some representative members of this peptide family induce atherogenesis through the mediation of monocyte-endothelial cell adhesive interaction and promotion of angiogenesis within the atherosclerotic plaques. HCSFs, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), also promote post-infarction cardiac remodeling though the enhanced activation and infiltration of monocytes into injured myocardial tissue and through altered equilibrium of collagen deposition/degradation. On the other hand, exogenous administration of granulocyte colony-stimulating factor (G-CSF) or eythropoietin (EPO) in patients with chronic ischemic disease or recent myocardial infarction have lead to beneficial arteriogenesis or myocardial cell regeneration, thus preventing adverse cardiac remodeling. While GM-CSF may hold therapeutic potential as an inhibitor of lung fibrogenesis, G-CSF appears to promote fibrosis in the lungs. The pathophysiological role of HCSFs also depends on the timing of their action on cardiovascular remodeling, as well as on the target progenitor hematopoietic cell. This article summarizes current knowledge about the clinical and therapeutic implications of these factors in chronic artery disease, post-infarction cardiac remodeling, chronic heart failure and in pulmonary fibrosis.

Animals↗
PubMed2006

Selective serotonin re-uptake inhibitors for the treatment of depression in coronary artery disease and chronic heart failure: evidence for pleiotropic effects.

Depression is a common co-morbidity in patients with cardiovascular diseases such as chronic coronary artery disease, acute coronary syndromes, post by-pass surgery and chronic heart failure. There is a significant body of evidence suggesting that the presence of depression is independently associated with a decline in health status and an increase in the risk of hospitalization and death for patients with coronary artery disease or congestive heart failure. Novel treatment modalities such as selective serotonin re-uptake inhibitors (SSRIs) may improve depressive symptoms and prognosis of post-myocardial infarction and heart failure patients interacting with the common pathophysiologic mechanisms of depression and cardiovascular disease. This review summarizes current experimental and clinical evidence regarding the pleiotropic effects of SSRIs on platelet functions, immune and neurohormonal activation, and cardiac rhythm disturbances in patients with cardiovascular disease. These bio-modulatory properties of SSRIs may be translated into improvement of patient clinical outcomes beyond their anti-depressant action.

Blood Platelets↗
PubMed2005

Implementation of reperfusion therapy in acute myocardial infarction. A policy statement from the European Society of Cardiology.

Reperfusion therapy in ST-segment elevation myocardial infarction (STEMI) is the most important component of treatment, as it strongly influences short- and long-term patient outcome. The main objective of healthcare providers should be to achieve at least 75% of reperfusion therapy applied to patients suffering from STEMI in a timely manner, and preferably within the first 3 h after onset of symptoms. Establishing networks of reperfusion at regional and national level, implying close collaboration between all the actors involved in reperfusion therapy, namely hospitals, departments of cardiology, PCI centres, emergency medical systems (EMS), (para)medically staffed ambulances, private cardiologists, primary care physicians, etc., is a key issue. All forms of reperfusion, depending on local facilities, need to be available to patients. Protocols must be written and agreed for the strategy of reperfusion to be applied within a network. Early diagnosis of STEMI is essential and is best achieved by rapid ECG recording and interpretation at first medical contact, wherever this contact takes place (hospital or ambulance). Tele-transmission of ECG for immediate interpretation by experienced cardiologists is an alternative. Primary PCI is the preferred reperfusion option if it can be performed by experienced staff within 90 min after first medical contact. Thrombolytic treatment, administered if possible in the pre-hospital setting, is a valid option if PCI cannot be performed in a timely manner, particularly within the first 3 h following onset of symptoms. Thrombolysis is not the end of the reperfusion therapy. Rescue PCI must be performed in the case of thrombolysis failure. Next-day PCI after successful thrombolysis has been proven efficacious. Quality control is important for monitoring the efficacy of networks of reperfusion. All elements that influence time to reperfusion must be taken into account, particularly transfer delays, in-hospital delays, and door-to-balloon or door-to-needle times. The rate of reperfusion achieved must also be taken into consideration. Professional organizations such as the European Society of Cardiology (ESC) have the responsibility to impart this message to the cardiology community, and inform politicians and health authorities about the best possible strategy to achieve reperfusion therapy.

Angioplasty, Balloon, Coronary↗
PubMed2005

Pathophysiologic targets in the early phase of acute heart failure syndromes.

An episode of acute heart failure syndromes (AHFS) can be defined as a rapid or gradual onset of signs and symptoms of heart failure (HF) in hospital admission and can arise from a variety of pathophysiologic mechanisms. This article reviews our current understanding of the pathophysiology of AHFS in order to identify potential therapeutic targets. Most patients with AHFS present with either normal systolic blood pressure or elevated blood pressure. Patients who present with elevated systolic blood pressure usually have pulmonary congestion and a relatively preserved left ventricular ejection fraction (LVEF), and have symptoms that typically develop abruptly, these patients often are elderly women. Patients with normal systolic blood pressure presenting with systemic congestion and reduced LVEF are usually younger, with a history of chronic HF, and have symptoms that develop gradually over days or weeks. Accordingly, most episodes of AHFS can be classified as either "vascular" failure or "cardiac" failure. In addition to the abnormal hemodynamics (increase in pulmonary capillary wedge pressure and/or decrease in cardiac output) that characterize patients with AHFS, myocardial injury--which may be related to a decrease in coronary perfusion and/or further activation of neurohormones and renal dysfunction (ie, the cardiorenal syndrome)--probably contributes to short-term and post-discharge cardiac events. Patients with AHFS also have significant cardiac and non-cardiac underlying conditions that contribute to the pathogenesis of AHFS, including coronary artery disease (ischemia, hibernating myocardium, and endothelial dysfunction), hypertension, atrial fibrillation, and type 2 diabetes mellitus. The goals of therapy for AHFS should be not only to improve symptoms and hemodynamics, but also to preserve or improve renal function and prevent myocardial damage.

Acute Disease↗
PubMed2005

Effects of levosimendan on markers of left ventricular diastolic function and neurohormonal activation in patients with advanced heart failure.

In this randomized, placebo-controlled study, it was found that a 24-hour levosimendan infusion improves echocardiographic markers of abnormal left ventricular diastolic function (transmitral flow patterns and mitral annulus velocities, as assessed by transthoracic pulse-wave Doppler and tissue Doppler imaging, respectively) and reduces substances of excessive neurohormonal activation (plasma B-type natriuretic peptide and interleukin-6) in patients with advanced heart failure. Moreover, levosimendan-treated patients had fewer events and longer progression-free survival during a 5-month follow-up compared with those who received placebo. Thus, levosimendan seems to be effective in improving left ventricular diastolic function and reducing neurohormonal activation in patients with severe heart failure.

Aged↗
PubMed2005

Impaired systolic dysfunction of left ventricular longitudinal fibers: a sign of early hypertensive cardiomyopathy.

BACKGROUND: Atrioventricular plane displacement (AVPD) study by M-mode echocardiography can supply useful clinical information about left ventricular (LV) long-axis function. HYPOTHESIS: We assessed the hypothesis that AVPD estimation could be used to detect early hypertensive cardiomyopathy. METHODS: The study population included 81 hypertensive patients with normal LV ejection fraction and fractional shortening, and 50 age- and gender-matched healthy controls. By utilizing M-mode and apical views, the following parameters were estimated: early mitral flow peak velocity (E) and deceleration time (DT), peak velocity of late mitral flow (A), A/E ratio, isovolumic relaxation time (IVRT), total AVPD, AVPD motion during atrial systole (At), systolic AVPD (total AVPD-At), and At/total AVPD ratio. RESULTS: Of 81 hypertensive patients, 16 (19.7%) had a normal (Group 1) and 65 (80.3%) an impaired LV relaxation filling pattern (Group 2). Mean total AVPD-At was significantly lower in Group 2 than in Group 1 (7.1 +/- 2 vs. 10.3 +/- 3 mm, p<0.001) and in Group 1 compared with healthy subjects (10.3 +/- 3 vs. 13.1 +/- 1 mm, p<0.001). Mean At and At/total AVPD were significantly higher in Group 2 than in Group 1 (46.9 +/- 8.6 vs. 37.7 +/- 8.7%, p<0.001), but not in Group 1 compared with healthy subjects (37.7 +/- 8.7 vs. 36 +/- 6%, p>0.05). CONCLUSIONS: Hypertensive patients without overt systolic dysfunction demonstrate LV long-axis systolic dysfunction, while long-axis diastolic dysfunction always coexists with abnormal diastolic filling patterns. This suggests that long-axis systolic dysfunction precedes diastolic dysfunction at the same axis in hypertensive patients.

Adult↗