Background: Heart failure with preserved ejection fraction (HFpEF) represents a significant portion of heart failure cases, but diagnosis is challenging due to its diverse presentation and the limitations of traditional echocardiographic parameters. Left atrial (LA) strain provides valuable insights into LA function and is increasingly used to evaluate cardiac function, including left ventricular (LV) diastolic function. LA strain, particularly reservoir strain, is considered a reliable indicator of LV diastolic function and can be used to grade diastolic function and estimate LV filling pressure. Unlike traditional LA measurements, LA strain offers detailed insights into LA function, conduit, and booster-pump phases, making it crucial for evaluating both structural and functional cardiac performance, especially in HFpEF. HFpEF diagnosis currently relies on a combination of echocardiographic parameters, clinical symptoms, and natriuretic peptide levels, encompassing various pathophysiological entities and complicating standardized management. Precise characterization of cardiac pathologies in HFpEF patients is essential. This review assesses global longitudinal strain (GLS) and left atrial strain (LAS) as echocardiographic biomarkers for diagnosing and characterizing HFpEF. Strain imaging, particularly speckle tracking echocardiography, offers a refined assessment of myocardial deformation, providing detailed insights into left heart function beyond traditional measures. Normal ranges for GLS and LAS are discussed, acknowledging demographic and technical influences. Clinical studies confirm the prognostic value of GLS and LAS in HFpEF, especially for predicting cardiovascular outcomes and distinguishing HFpEF from other dyspnea causes. However, variability in strain measurements and false-negative risks necessitate cautious clinical interpretation. The HFA-PEFF scoring system includes these biomarkers but does not fully cover the HFpEF pathology spectrum. Combining GLS and LAS shows promise in defining HFpEF phenogroups, potentially guiding individualized treatments. Global longitudinal strain (GLS) and left atrial strain (LAS) are central to non-invasive HFpEF diagnosis and stratification, with potential for more tailored therapies. Integration of these biomarkers into standard diagnostic practice requires an organized approach, and future guidelines should recommend their combined use for comprehensive HFpEF assessment.

Background: SGLT2 inhibitors are key therapies in heart failure (HF), but their combined multidomain effects have not been analyzed together. Methods: We conducted a PROSPERO-registered (CRD420251235850) systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing SGLT2i (dapagliflozin, empagliflozin, canagliflozin, sotagliflozin) with placebo in adults with HF, regardless of ejection fraction or diabetes status. We searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, and Web of Science through 1 February 2025. Outcomes were grouped into four domains: (1) clinical events, (2) symptoms/health status (Kansas City Cardiomyopathy Questionnaire, KCCQ), (3) functional capacity (6 min walk distance, peak VO₂), and (4) cardiac remodeling/energetics (cardiac MRI, 31P-MRS). We used random-effects models with Hartung–Knapp adjustment and assessed heterogeneity by I² and prediction intervals. Results: Eleven RCTs with 23,812 patients (HFrEF, HFmrEF, HFpEF, and acute or recently decompensated HF) were included. SGLT2i lowered the risk of cardiovascular death or first HF hospitalization by 23% (HR 0.77, 95% CI 0.72–0.82; p < 0.0001; I² = 28%; prediction interval 0.68–0.87), with similar effects across ejection fraction, diabetes status, and presentation type. All-cause and cardiovascular mortality dropped by 12% (HR 0.88, 95% CI 0.81–0.96) and 14% (HR 0.86, 95% CI 0.78–0.95), respectively. SGLT2i improved KCCQ—Clinical Summary Score by 4.6 points (95% CI 3.4–5.8; p < 0.0001) and increased the odds of a ≥5-point improvement (OR 1.49, 95% CI 1.32–1.68; NNT = 12). Six-minute walk distance increased by 21.8 m (95% CI 9.4–34.2; p = 0.001), and mechanistic trials showed significant reverse remodeling (ΔLVEDV −19.8 mL, ΔLVEF +6.1%; both p < 0.001). No improvement was observed in myocardial PCr/ATP ratio. Safety was favorable, with no excess ketoacidosis or severe hypoglycemia. Conclusions: This multidomain synthesis demonstrates that SGLT2 inhibitors provide consistent, robust reductions in mortality and hospitalizations, while also delivering early, clinically meaningful improvements across multiple patient-centered domains. These results establish SGLT2i as a foundational component of contemporary HF management.

Background/Objectives: Heart failure remains a complex syndrome with high morbidity and mortality, highlighting the urgent need for alternative treatments that address underlying bioenergetic impairments. CoQ10, which plays a crucial role in mitochondrial ATP production, has shown promising results in small studies, although larger trials are needed to confirm its efficacy. Results: This randomized controlled trial investigated the effects of coenzyme Q10 (CoQ10) supplementation on cardiac function and quality of life in heart failure patients. A total of 120 patients were randomly assigned to receive either CoQ10 (2 × 60 mg daily) or a placebo for six months. Baseline characteristics were similar between groups. The primary outcomes were changes in global longitudinal strain (GLS) and left ventricular ejection fractions (LVEFs), while secondary outcomes included improvements in functional capacity and quality of life. At the 6-month endpoint, the CoQ10 group showed significant improvements in GLS (−11.7% to −14.9%, p < 0.001), NT-proBNP levels (815.6 vs. 1378.5 pg/mL, p = 0.012), blood pressure, and 6 min walk test distance (349.3 vs. 267.0 m, p = 0.008) compared to the placebo group. LVEFs improved slightly in the CoQ10 group (38.9% to 40.6%, p = 0.170) but remained unchanged in the placebo group. Conclusions: These findings suggest that CoQ10 supplementation may improve cardiac function, reduce cardiac stress, and enhance functional capacity and quality of life in heart failure patients. Further research is needed to optimize dosage and identify the subgroups that may benefit most from CoQ10 therapy.

Background and Objectives: Type 2 diabetes mellitus (T2DM) is associated with subclinical cardiovascular changes, such as increased arterial stiffness and myocardial dysfunction. Vitamin D deficiency has been recognized as a potential contributing factor to vascular disease; however, its impact on early cardiac changes associated with T2DM remains poorly understood. Our aim was to evaluate the association between serum levels of 25-hydroxyvitamin D3 [25(OH)D3], arterial stiffness, and left ventricular global longitudinal strain (LV GLS) in patients with T2DM who do not have a clinically evident cardiovascular disease. Material and methods: This cross-sectional study evaluated the carotid intima–media thickness (IMT), aortic pulse wave velocity (PWVao), LV GLS, and serum 25(OH)D3 levels in patients diagnosed with T2DM (n = 65) compared to healthy control subjects (n = 55). Independent predictors of arterial stiffness were identified by a multivariate logistic regression analysis. Results: Patients with T2DM showed a significant increase in IMT and PWVao, a reduction in LV GLS, and low levels of 25(OH)D3 compared to subjects in the control group (all p < 0.05). Both vitamin D deficiency and T2DM were found to be independently associated with an increased arterial stiffness, with odds ratios of 2.4 and 4.8, respectively. A significant inverse relationship was identified between 25(OH)D3 levels and markers of arterial stiffness, as well as LV GLS, suggesting a possible association between the vitamin D status and the early onset of cardiovascular dysfunction. Conclusions: Patients with T2DM show early signs of heart and blood vessel problems, even with an ejection fraction that remains within normal limits. There is a significant correlation between vitamin D deficiency and increased arterial stiffness, along with impaired LV GLS, indicating its possible involvement in cardiovascular complications associated with diabetes. These findings support the utility of integrating vascular, myocardial, and vitamin D assessments in early cardiovascular risk stratification for T2DM patients.

Most studies analyzing data from patients who experienced at least one episode of acute COVID-19 infection have attributed the cascade of immediate and late complications to disruption of the inflammatory system and neutrophil activity in particular. Among the various functions of neutrophils is the release of pro-inflammatory mediators, including interleukin-6 (IL-6). Oxidative stress induced by pro-inflammatory mediators secreted by neutrophils leads to vascular endothelial dysfunction. Neutrophil counts and the neutrophil-to-lymphocyte ratio (NLR) are directly associated with COVID-19 patient survival, with higher values correlating with increased mortality. To assess endothelial dysfunction secondary to COVID-19 infection, we conducted a retrospective study involving two patient cohorts, each comprising 99 participants: one group with a history of COVID-19 infection and another without. The study aimed to demonstrate the presence of endothelial dysfunction in patients with moderate COVID-19 infection using flow-mediated dilatation (FMD) of the brachial artery and to evaluate its correlation with key inflammatory markers (erythrocyte sedimentation rate—ESR, fibrinogen, NLR, IL-6). FMD values were significantly reduced (p < 0.0001) in post-COVID-19 patients compared to those without prior infection. ESR (p < 0.0001), fibrinogen (p < 0.0001), C-reactive protein (CRP) (p < 0.0001), leukocyte count (p < 0.0001), and granulocyte count (p < 0.0001) were inversely correlated with FMD values. Among post-COVID-19 patients, all analyzed parameters demonstrated a statistically significant impact on FMD, with ESR showing the strongest effect, accounting for nearly 63% of the dependency. ANOVA testing confirmed an inverse association between NLR quartiles and FMD, as well as between IL-6 levels and FMD. In conclusion, this study highlights the presence of endothelial dysfunction in post-COVID-19 patients, as assessed by FMD, and demonstrates statistically significant inverse correlations between FMD values, IL-6 levels, and the neutrophil-to-lymphocyte ratio.

Background and Objectives: Heart failure frequently coexists with CKD, compounding prognosis via cardio-renal interplay. Sodium glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardiovascular and renal benefits in randomized trials, but data remain limited in real-world lower-resource settings. Materials and Methods: We conducted a retrospective single-center cohort study at a tertiary university hospital in western Romania, including adults with chronic HF and LVEF ≤ 45%, monitored between 2021–2024. Patients were stratified based on receipt of SGLT2 inhibitors. The primary endpoint was a composite of cardiovascular death, HF hospitalization, or ≥40% sustained decline in eGFR/initiation of KRT. Annual eGFR slope was analyzed to assess renal trajectory. Results: Among 240 patients, treatment with SGLT2 inhibitors was associated with a lower risk of the composite cardio-vasculo-renal endpoint compared with no treatment (adjusted HR 0.70, 95% CI 0.50–0.98). The reduction was primarily driven by fewer heart failure hospitalizations. Decline in kidney function was slower among SGLT2 inhibitor-treated patients in longitudinal mixed-effects analyses. Conclusions: In this retrospective cohort, SGLT2 inhibitor use was associated with fewer cardio-renal events and a slower decline in kidney function. Given the observational design and residual confounding risk, these findings should be considered hypothesis-generating but provide implementation-relevant signals supporting further prospective evaluation.