Mallardo M, Filardi PP, Micheletto C
… +19 more, Montano N, Spampinato A, Volterrani M, Zito GB, Agosti S, Avogadri E, Basile C, Gabriele M, Marra AM, Mattioli AV, Micanti A, Nodari S, Oliviero U, Paolillo S, Ratti G, Ruvolo A, Salzano A, Sorrentino R, Cittadini A
Eur J Intern Med
· 2026 May · PMID 42069489
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Heart failure (HF) remains one of the most prevalent and burdensome chronic conditions worldwide, with rising incidence and poor prognosis despite major therapeutic advances. Effective management requires a comprehensive...Heart failure (HF) remains one of the most prevalent and burdensome chronic conditions worldwide, with rising incidence and poor prognosis despite major therapeutic advances. Effective management requires a comprehensive, multidisciplinary approach that ensures diagnostic accuracy, therapeutic optimization, and continuity of care from hospital to community settings. This consensus document outlines an integrated model for HF care in Italy, developed to improve patient outcomes and resource efficiency. HF should be diagnosed and phenotyped through clinical evaluation, electrocardiography, echocardiography, biomarkers, and, when indicated, advanced imaging. Guideline-directed medical therapy, including sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, β-blockers, and mineralocorticoid receptor antagonists, remains the cornerstone of treatment across the ejection-fraction spectrum. Device therapy, cardiac rehabilitation, and iron supplementation complement pharmacological management. Telemedicine and remote monitoring enable early detection of clinical deterioration and strengthen hospital-community integration, while multidisciplinary HF clinics coordinate pharmacological care, rehabilitation, and patient education. Structured training of healthcare professionals and caregivers, along with therapeutic education programs, enhances adherence, empowers patients, and promotes self-management. Community-based associations further support cardiovascular prevention through educational and screening initiatives. The integration of hospital, community, and digital health resources, combined with continuous professional training and patient empowerment, represents a sustainable and effective model to improve survival, reduce hospitalizations, and enhance quality of life for patients with HF.
The recently introduced cardiovascular-kidney-metabolic (CKM) syndrome captures the close interplay between metabolic risk factors, chronic kidney disease, and cardiovascular disease, but insufficiently reflects the impo...The recently introduced cardiovascular-kidney-metabolic (CKM) syndrome captures the close interplay between metabolic risk factors, chronic kidney disease, and cardiovascular disease, but insufficiently reflects the important additional role of the liver. Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver disease worldwide, is strongly associated with cardiovascular events, kidney disease progression, and all-cause mortality, yet remains frequently under-recognized in routine clinical practice. We propose the concept of a cardiovascular-kidney-liver-metabolic syndrome (CKLMS) and present a multidisciplinary, primary care-centered framework for its assessment and management. Based on expert consensus and current evidence, the framework integrates cardiovascular, renal, hepatic, and metabolic risk stratification using accessible, validated tools feasible in primary care, including blood pressure and lipid profiling, assessment of kidney function and albuminuria, non-invasive liver fibrosis testing, and systematic screening for diabetes and obesity. Management emphasizes early lifestyle intervention, use of pharmacological therapies with multi-organ benefit, and clearly defined referral pathways to specialist care. Primary care professionals are positioned as coordinators of longitudinal, patient-centered, multidisciplinary management. Early, integrated identification and treatment of CKLMS in primary care represents a pragmatic and effective strategy to prevent disease progression, reduce cardiovascular and kidney events, and improve long-term outcomes.
Karagiannidis AG, Baroutidou A, Theodorakopoulou M
… +8 more, Karkamani E, Manti S, Afkou Z, Vagdatli E, Faitatzidou D, Giamalis P, Papadopoulos C, Sarafidis P
BACKGROUND: In CKD, hypertension is often accompanied by sodium sensitivity. Uromodulin promotes sodium sensitivity by activating tubular sodium transporters (NKCC2, NCC). In the general population, individuals with high...BACKGROUND: In CKD, hypertension is often accompanied by sodium sensitivity. Uromodulin promotes sodium sensitivity by activating tubular sodium transporters (NKCC2, NCC). In the general population, individuals with higher urine uromodulin have a positive association between 24-h urine sodium and 24-h BP, whereas those with lower uromodulin show a negative association between these parameters. Whether similar patterns occur in CKD remains unclear. This study evaluated the effect of urine uromodulin on the relationship between 24-h urine sodium excretion and 24-h BP in CKD patients. METHODS: 130 patients with CKD G1-G5 on stable antihypertensive treatment underwent 24-h ambulatory BP monitoring and 24-h urine collections. Patients were divided into two groups using the median 24-h urine uromodulin. Associations between 24-h urine sodium excretion and 24-h BP were examined applying multivariable linear regression models. RESULTS: Mean age was 62.6 ± 14.9 years and mean eGFR 49.0 ± 25.1mL/min/1.73m². 24-h SBP, DBP and urine sodium excretion did not differ across CKD stages, whereas urine uromodulin decreased significantly with advancing CKD (p < 0.001). In the multivariable linear regression models of the overall population, neither 24-h urine sodium nor urine uromodulin alone predicted 24-h SBP/DBP. However, in stratified models, higher 24-h urine sodium was associated with higher 24-h SBP (β=0.051, 95%CI:0.018-0.087, p = 0.005) and DBP (β=0.041, 95%CI:0.018-0.068, p = 0.002) only in the high-uromodulin group. In contrast, in the low-uromodulin group, no significant associations were observed. The β-coefficients for urine sodium differed significantly between uromodulin groups for both 24-h SBP and DBP models (p = 0.025 and p = 0.004 respectively). CONCLUSIONS: In CKD, urine uromodulin modifies the association between dietary sodium intake and ambulatory BP. Patients with higher urine uromodulin show a positive association between 24-h sodium excretion and BP, whereas this finding is absent in those with lower uromodulin. These findings support urine uromodulin as a useful biomarker of sodium sensitivity in CKD. CLINICAL TRIAL REGISTRATION NUMBER: NCT06363097 (ClinicalTrial.gov).
We critically appraise a large prospective cohort study on left atrial enlargement and 1-year cerebrovascular events in patients without atrial fibrillation. While the study provides valuable short-term prognostic eviden...We critically appraise a large prospective cohort study on left atrial enlargement and 1-year cerebrovascular events in patients without atrial fibrillation. While the study provides valuable short-term prognostic evidence, we highlight four key considerations: the overlooked impact of cardiovascular-kidney-metabolic interaction, cautious interpretation of sex-specific findings due to lacking formal interaction tests, potential indication bias in antiplatelet protection claims, and the value of additional atrial cardiomyopathy markers beyond left atrial volume index. Addressing these aspects would enhance risk stratification and translational applicability.
BACKGROUND: Cardiac allograft vasculopathy (CAV) affects >50% of patients following heart transplantation (HTX) within ten years and is one of the main reasons for late graft failure. The study aimed to investigate the i...BACKGROUND: Cardiac allograft vasculopathy (CAV) affects >50% of patients following heart transplantation (HTX) within ten years and is one of the main reasons for late graft failure. The study aimed to investigate the interventional and prognostic outcomes of HTX recipients undergoing percutaneous coronary intervention (PCI) for different indications. METHODS: HTX recipients who underwent PCI from January 2011 until June 2023 were included retrospectively at one institution. Procedural and prognostic outcomes of these patients were evaluated comparing patients undergoing PCI for acute coronary syndrome (ACS) or elective PCI. The primary endpoint all-cause mortality at 3 years, secondary endpoint was the risk of major adverse cardiac and cerebrovascular events (MACCE). RESULTS: One hundred fifty-nine HTX recipients undergoing PCI were included, 80% of them underwent elective PCI and 20% ACS-PCI. Dyslipidemia was more frequently observed in the elective PCI group, whereas a history of myocardial infarction was more prevalent among patients undergoing PCI for ACS. No significant difference was observed regarding the rates of technical (85.04% elective PCI vs. 87.50% ACS-PCI, p = 1.000) and procedural success (85.04% elective PCI vs. 84.38% ACS-PCI, p = 1.000). ACS-PCI was associated with an increased risk of all-cause mortality at 3 years compared to patients undergoing elective PCI after multivariable adjustment (hazard ratio (HR)=2.011, 95% confidence interval (CI) 1.049 -3.856, p = 0.035) in HTX recipients - primarily driven by higher rates of in-hospital all-cause mortality. In contrast, the rates of MACCE at 3 years were comparable between the two groups. CONCLUSION: In HTX recipients undergoing PCI, long-term all-cause mortality at 3 years was significantly increased in patients undergoing ACS-PCI, which was mainly attributed to higher rates of in-hospital mortality.
BACKGROUND: The current therapy for resistant hypertension is often limited by hyperkalemia, renal decline, and a failure to prevent compensatory increases in circulating aldosterone. The aldosterone synthase inhibitors...BACKGROUND: The current therapy for resistant hypertension is often limited by hyperkalemia, renal decline, and a failure to prevent compensatory increases in circulating aldosterone. The aldosterone synthase inhibitors (ASIs) address these limitations by directly suppressing aldosterone biosynthesis sparing other steroid pathways. AIM: To evaluate the safety and efficacy of ASIs in resistant hypertension. METHODS: Databases searched through March 2026 to find relevant studies, following PRISMA guidelines. Data analysis was performed using R-Software. Primary outcome analyzed was reduction in systolic and diastolic blood pressures. RESULTS: A total of 8 RCTs were analyzed which showed that Aldosterone Synthase Inhibitors (ASI) significantly reduced systolic blood pressure (MD:8.0; 95% CI:10.53, -5.47, p < 0.01) and diastolic blood pressure (MD:3.44; 95% CI:5.03, -1.86, p < 0.01) and with double the likelihood of achieving target SBP < 130 mmHg (RR: 2.26; 95% CI: 1.73, 2.95, p = 0.002). ASI were associated with significant risk of any adverse events (RR: 1.23; 95% CI: 1.08, 1.41, p = 0.02), hyponatremia (RR: 2.04; 95% CI: 1.10, 3.80, p = 0.024), hypotension (RR: 2.47; 95% CI: 1.14,5.33, p = 0.02), and notably seven-fold increase risk of hyperkalemia (RR: 7.18; 95% CI: 3.20, 16.12, p < 0.001). Despite these risks, there was no statistically significant increase in serious adverse events (RR: 1.26; 95% CI: 0.68, 2.34, p = 0.47) and drug discontinuation rate (RR: 1.84; 95% CI: 0.41, 8.12, p = 0.28) with ASIs compared to placebo. Mechanistically, ASI was associated with a significant reduction in aldosterone (SMD:1.12; 95% CI:1.25, -1.0; p < 0.01), reduction in eGFR (MD:6.48; 95% CI:9.02, -3.94, p < 0.01) and an increase in plasma renin activity (SMD: 0.53; 95% CI: 0.37, 0.68, p < 0.01) associated with significant increase in serum potassium level(MD:0.47; 95% CI:0.34, 0.61; p < 0.01). CONCLUSION: Aldosterone synthase inhibitors (ASI) provide clinically meaningful reductions in systolic and diastolic blood pressure in uncontrolled or resistant hypertension, doubling the likelihood of achieving target blood pressure levels, with treatable safety concerns which is evidenced by non-significant trend in serious adverse events and drug discontinuation rate.
INTRODUCTION: Cardiovascular (CV) risk assessment and early detection of subclinical cardiac involvement in rheumatoid arthritis (RA) patients enable timely intervention and improve prognosis. OBJECTIVES: This study eval...INTRODUCTION: Cardiovascular (CV) risk assessment and early detection of subclinical cardiac involvement in rheumatoid arthritis (RA) patients enable timely intervention and improve prognosis. OBJECTIVES: This study evaluated associations of serum levels of fatty acid binding protein 4 (FABP4) and resistin with both echocardiographic parameters of left ventricular diastolic dysfunction (LVDD) and CV risk quantified using four validated scores (ERS-RA, QRISK3, modified SCORE2, LIFE-CVD2) in a cohort of RA patients. Additionally, we sought to identify the most informative LVDD parameter for CV risk stratification. MATERIALS AND METHODS: Fifty-one RA patients (46 females, 5 males; mean age 48.8± 8.2 years; median disease duration of 12 years) were enrolled. Serum FABP4 and resistin levels were analysed for associations with CV risk scores using univariable and multivariable linear regression, while relationships with LVDD parameters were assessed via univariable regression analyses. RESULTS: FABP4 demonstrated a positive association with ERS-RA risk score in both univariable (β = 0.09, p = 0.01) and multivariable (β = 0.08, p = 0.007) models. FABP4 was negatively associated with E/A ratio (β = -0.005, p = 0.04), and positively with left atrial volume index (β = -0.09, p = 0.04). Among LVDD parameters, lateral e' velocity showed the strongest associations with all CV risk scores, exhibiting the lowest p-values. CONCLUSIONS: FABP4 is significantly associated with increased RA-specific CV risk (ERS-RA) and abnormal echocardiographic parameters of LVDD. Lateral e' velocity represents the most informative echocardiographic LVDD parameter associated with CV risk.
BACKGROUND: Cocaine adulterated with levamisole has been implicated as a trigger of Cocaine-Levamisole-Associated Autoimmune Syndrome (CLAAS), frequently mimicking granulomatosis with polyangiitis (GPA). OBJECTIVES: To c...BACKGROUND: Cocaine adulterated with levamisole has been implicated as a trigger of Cocaine-Levamisole-Associated Autoimmune Syndrome (CLAAS), frequently mimicking granulomatosis with polyangiitis (GPA). OBJECTIVES: To characterize the clinical, serologic, and histopathologic features of CLAAS and compare them with GPA. METHODS: Retrospective analysis of 194 patients diagnosed with ANCA-associated vasculitis between 2000-2024 at a referral center in Northern Spain. Classification followed the 2022 ACR/EULAR criteria. ANCA serologies were assessed by chemiluminescence. Ten patients (5.15%) were identified as having CLAAS via self-report or urine toxicology. A comparative analysis with GPA (n=64) and a structured literature review (2015-2025) were conducted. RESULTS: CLAAS cases had a mean age of 49.9±10.4 years and a female predominance (70%). Otolaryngologic (ENT) manifestations were prominent, frequently accompanied by septal perforation and midline destructive lesions. Articular symptoms occurred in 40%, and renal involvement in 20%, including one biopsy-proven crescentic glomerulonephritis. All were ANCA-positive, predominantly PR3+ (80%), and 30% showed anti-neutrophil elastase antibodies. ENT biopsies showed inflammatory but non-vasculitic changes; these findings were supportive but not pathognomonic for CLAAS. Treatments included corticosteroids, methotrexate, and rituximab, with remission strongly associated with cocaine abstinence. Compared with GPA, CLAAS cases showed more extensive ENT and cutaneous involvement, higher rates of dual ANCA positivity, and elastase reactivity. CONCLUSIONS: CLAAS is a distinct clinicopathologic entity that overlaps with GPA but differs in histopathology, therapeutic response, and prognosis. Accurate diagnosis requires integrating toxicologic testing and recognizing substance-use patterns.