Giulia Renda

Background: The hemoglobin-to-red cell distribution width ratio (HRR) is a composite hematologic biomarker that integrates oxygen-carrying capacity and inflammation-related erythrocyte variability. Its prognostic value in idiopathic pulmonary fibrosis (IPF), and its relationship with right ventricular (RV) function, have not been established. Methods: We conducted a single-center retrospective study of 198 patients with IPF. A total of 165 patients with baseline hemoglobin, red cell distribution width (RDW) and date of diagnosis available constituted the analytical cohort. An HRR cutoff (≤0.86) was derived by time-dependent Receiver Operating Characteristic (ROC) curve analysis at 5 years. All-cause mortality from diagnosis was assessed by Kaplan–Meier and Cox regression, with bootstrap internal validation. Associations between hematologic markers and TAPSE (Tricuspid Annular Plane Systolic Excursion), PAPs (pulmonary arterial systolic pressure) and TAPSE/PASP were examined by linear and logistic regression, followed by joint stratification of HRR and RV–PA coupling. Results: Over a median follow-up of 70.3 months, 57 patients (34.5%) died. Low HRR was associated with higher mortality (72.7% vs. 15.5%; adjusted HR 3.07, 95% CI 1.68–5.63; optimism-corrected HR 2.37) and improved a clinical model beyond RDW (likelihood-ratio p = 0.012). HRR was not associated with TAPSE, PAPs, TAPSE/PASP or RV–PA uncoupling. In exploratory joint stratification, mortality rose from 11.7% with both markers preserved to 100% with both abnormal (age-adjusted HR 6.47, 95% CI 2.64–15.86). At 5 years, HRR and RDW showed similar discrimination (time-dependent AUC 0.70 and 0.71), higher than TAPSE/PASP (0.61). Conclusions: HRR is a simple, inexpensive and independent predictor of mortality in IPF that is unrelated to RV–PA coupling. The two markers provide complementary prognostic information, and their combination identifies a subgroup at very high risk. These findings require external validation.

Preeclampsia (PE) is associated with enhanced platelet activation, with thromboxane A₂ playing a key pathogenic role. Urinary 11-dehydro-thromboxane B₂ (TXM) reflects in vivo platelet activation. Although low-dose aspirin (ASA) is recommended for PE prevention in high-risk pregnancies, variable thromboxane suppression may lead to persistent platelet activation. This study aimed at identifying platelet-derived predictors of PE in high-risk women receiving ASA and assessing biomarkers improving risk stratification. This observational study included 25 high-risk pregnant women on ASA and 12 with physiological pregnancies. Clinical evaluation and blood/urine sampling were performed at baseline (T0), and at 21 (T4) and 27 (T5) weeks. Urinary TXM and percentage inhibition (<75% = reduced inhibition) were assessed. Platelet biomarkers included thrombopoietin (TPO), glycocalicin (GC), P-selectin, and CD40L. Late-onset PE occurred in 6/25 (24%) high-risk women and in none of the controls. TXM levels were higher in high-risk versus physiological pregnancies (p=0.009), especially at T4-T5 (p<0.0001). Women developing PE had higher TXM at T4 (adjusted p=0.014) and lower TXM inhibition (51% vs 81%; p=0.020). Reduced inhibition (<75%) was associated with increased PE risk (44.4% vs 14.3%; OR 4.8). TPO showed a different longitudinal pattern according to PE occurrence (time-by-outcome interaction p=0.036). Glycocalicin showed higher estimated values at baseline in women who developed PE (p=0.048), but the time-specific contrast was attenuated after Holm adjustment (adjusted p=0.19). Incomplete thromboxane suppression during ASA therapy is associated with PE. TXM, together with opposite trends of TPO and GC, identifies a profile consistent with altered platelet homeostasis and possible changes in platelet turnover, potentially enhancing risk prediction in high-risk pregnancies.

Background: Idiopathic pulmonary fibrosis (IPF) is frequently complicated by pulmonary vascular involvement and right ventricular (RV) dysfunction, both of which adversely affect prognosis. The relationship between impaired gas exchange and echocardiographic indices of RV function, particularly the TAPSE/PAPs (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) ratio as a marker of RV–pulmonary arterial (RV–PA) coupling, has not been fully characterized. Methods: We retrospectively evaluated 198 consecutive patients with IPF assessed at a single tertiary referral center between 2020 and 2026; 188 with complete pulmonary function testing were included in the main analyses. The primary exposure was gas exchange, measured by single-breath DLCO% (diffusing capacity of the lung for carbon monoxide) and stratified into four categories (Normal ≥ 80%, n = 21; Mild 60–79%, n = 56; Moderate 40–59%, n = 70; Severe < 40%, n = 41). The main outcome measures were echocardiographic indices of RV function—TAPSE, systolic pulmonary artery pressure (PAPs), and the TAPSE/PAPs ratio. Associations were assessed using Pearson’s correlation, one-way ANOVA, and multivariable linear regression adjusted for age, sex, and smoking status, with the Mild group as the reference for categorical analyses. Results: Lower DLCO values were independently associated with higher PAPs (adjusted β = −0.24 mmHg per 1% DLCO, p = 0.004) and with a lower TAPSE/PAPs ratio (adjusted β = +0.005 per 1% DLCO, p = 0.040). Compared with the Mild reference group, patients with Severe DLCO reduction had markedly higher PAPs (+14.6 mmHg, p = 0.002) and a lower TAPSE/PAPs ratio (−0.37, p = 0.002), with attenuated findings in the Moderate category; the small Normal group did not differ significantly from the Mild one. TAPSE alone showed only a weak, non-significant trend (r = 0.195, p = 0.083). Conclusions: In patients with IPF, lower DLCO was independently associated with higher pulmonary artery pressure and, to a lesser extent, with reduced RV–PA coupling (a lower TAPSE/PAPs ratio), whereas RV longitudinal systolic function (TAPSE) appeared preserved. Among pulmonary function parameters, DLCO showed the strongest association with PAPs. In this exploratory, cross-sectional analysis, combined evaluation of DLCO and the TAPSE/PAPs ratio may help characterize right heart involvement in IPF; its value for pulmonary hypertension (PH) screening requires prospective confirmation.

Aims: Non-ischaemic left ventricular (LV) scar is increasingly recognized in athletes with preserved left ventricular ejection fraction (LVEF) and may represent a substrate for malignant ventricular arrhythmias. The role of electrophysiological study (EPS) with programmed ventricular stimulation (PVS) for risk stratification in this population remains unclear. This study aimed to evaluate the prognostic value of inducibility at EPS in symptomatic athletes with non-ischaemic LV scar and preserved LVEF. Methods and results: We prospectively enrolled 72 consecutive athletes (mean age 48.9 ± 13.1 years; 66.7% male) with documented non-ischaemic LV scar, preserved LVEF (≥50%), and arrhythmic symptoms (tachycardic palpitations, syncope/presyncope, and/or exercise-related ventricular arrhythmias) undergoing EPS. Inducibility was defined as sustained ventricular arrhythmias during PVS. The primary endpoint was the occurrence of major arrhythmic events (MAE), including sudden cardiac death, sustained ventricular tachycardia/ventricular fibrillation, or appropriate implantable cardioverter-defibrillator therapy. Twenty-three athletes (31.9%) were inducible (EPS+), while 49 (68.1%) were non-inducible (EPS−). Baseline characteristics were largely comparable between groups, although QRS duration was longer in inducible athletes (104.6 ± 15.2 ms vs. 95.5 ± 14.3 ms; P = 0.019). Twenty-three inducible athletes underwent ICD implantation (18 transvenous and 5 subcutaneous devices), whereas 16 non-inducible athletes received an implantable loop recorder. During a median follow-up of 42 months, 11 major arrhythmic events occurred. Nine events occurred among inducible athletes and consisted of sustained ventricular arrhythmias (monomorphic VT, polymorphic VT, or ventricular fibrillation) successfully terminated by appropriate ICD therapy, whereas two major arrhythmic events occurred among non-inducible athletes and required successful resuscitation followed by ICD implantation. No arrhythmic deaths occurred during follow-up. Event-free survival at 50 months was 40.6% in inducible athletes and 95.9% in non-inducible athletes (log-rank P < 0.001). Conclusion: In symptomatic athletes with non-ischaemic LV scar and preserved LVEF, inducibility at EPS identifies a subgroup at higher risk of MAE, whereas non-inducibility is associated with a low event rate. EPS may represent a useful adjunctive tool for arrhythmic risk stratification in athletes, particularly in those without conventional high-risk features.

Cardiac involvement in systemic sclerosis (SSc) is mechanistically heterogeneous, driven by concurrently operative processes spanning right ventricular dysfunction, pulmonary microvascular remodeling, and mitochondrial damage. The existing literature rarely synthesizes these domains simultaneously, leaving substantive gaps in mechanistic understanding and the clinical management of SSc cardiac disease. An integrative review of original primary research was conducted using PubMed, Scopus, and Web of Science. Search terms combined “systemic sclerosis,” “right ventricular dysfunction,” “echocardiographic strain,” “pulmonary microvascular disease,” “nailfold capillaroscopy,” “mitochondrial dysfunction,” “oxidative stress,” and “cardiac biomarkers.” Eligible articles were required to report original empirical findings in SSc or SSc-related pulmonary arterial hypertension populations, encompassing echocardiographic, microvascular, molecular, or biomarker outcomes. Right ventricular function is compromised across multiple echocardiographic dimensions—from an elevated myocardial performance index and impaired ventriculoarterial coupling to prognostically significant speckle-tracking strain abnormalities—independent of overt pulmonary hypertension. Pulmonary microvascular disease, quantified by nailfold capillaroscopy and flow-mediated dilation, correlates directly with cardiac magnetic resonance tissue characterization in SSc-related pulmonary arterial hypertension. Mitochondrial dysfunction involving respiratory chain impairment, abnormal fusion dynamics, and altered mitochondrial DNA (mtDNA)copy number is demonstrable across dermal fibroblasts, monocytes, and immune cell populations. Circulating cardiac biomarkers complement echocardiographic findings and predict cardiopulmonary mortality. The integrative framework linking right ventricular remodeling, peripheral vasculopathy, and mitochondrial injury offers substantially richer insight into SSc cardiac pathophysiology than any single-domain perspective can provide, with direct implications for early detection and therapeutic targeting.

Cardiac contractility modulation (CCM) is an implantable device-based therapy that delivers biphasic, non-excitatory electrical signals to the ventricular myocardium during the absolute refractory period. By enhancing contractile performance without inducing depolarization or altering ventricular activation, CCM acts as bioelectronic myocardial conditioning. Current evidence supports its use in selected patients with symptomatic heart failure, reduced or mildly reduced left ventricular ejection fraction, narrow QRS duration, persistent symptoms despite guideline-directed medical therapy, and no indication for cardiac resynchronization therapy. In this population, CCM improves functional status and quality of life, whereas evidence for reductions in mortality or recurrent heart failure hospitalization remains less definitive. Whether CCM also reduces arrhythmic burden remains uncertain. Candidates for CCM frequently exhibit atrial and ventricular remodeling, neurohormonal activation, implantable cardioverter-defibrillators, and vulnerability to atrial fibrillation, ventricular arrhythmias, and device therapies. Mechanistically, CCM may render the failing myocardium less arrhythmogenic through coordinated effects on calcium handling, electromechanical remodeling, fibrosis-related substrate, contractile efficiency, and heart-failure stability. However, pivotal trials were not designed to assess arrhythmic endpoints, leaving the relationship between CCM and arrhythmic burden insufficiently characterized. This review summarizes CCM evidence, mechanistic rationale, available arrhythmic signals, device-related considerations, and future research priorities for prospective studies in this evolving field.

The 2025 European Society of Cardiology (ESC) Guidelines on cardiovascular disease in pregnancy introduce a life-course approach to cardiovascular prevention, extending risk assessment and management from preconception through the postpartum period. Beyond the management of established cardiovascular disease, the guidelines emphasize the importance of identifying modifiable risk factors and pregnancy-related complications as early markers of future cardiovascular risk. This narrative mini-review provides a prevention-oriented interpretation of the 2025 ESC Guidelines, focusing on their implications for hypertension prevention and long-term cardiovascular health in women. Pregnancy is increasingly recognized as a biological stress test capable of unmasking latent cardiometabolic and vascular vulnerability, while adverse pregnancy outcomes, including preeclampsia, gestational hypertension, gestational diabetes, fetal growth restriction, and preterm delivery, represent important predictors of future hypertension and cardiovascular disease. Particular emphasis is placed on preconception cardiovascular assessment, lifestyle optimization, obesity management, and the cardiovascular implications of assisted reproductive technologies. The Pregnancy Heart Team is discussed as a multidisciplinary model for integrating cardiovascular and obstetric care across the reproductive continuum. In addition, we propose a practical life-course prevention framework incorporating structured postpartum surveillance, blood pressure monitoring, cardiometabolic screening, and long-term follow-up after adverse pregnancy outcomes. By translating contemporary ESC recommendations into a clinically applicable prevention strategy, this review highlights pregnancy as a unique opportunity for early cardiovascular risk identification and implementation of sex-specific preventive interventions aimed at reducing the future burden of hypertension and cardiovascular disease in women.