Michele Alfieri

Background/Objectives: Excessive trabeculation of the left ventricle, previously known as left ventricular non-compaction (LVNC), is a rare phenotypic trait whose mechanisms and pathogenesis still remain conflictual. Its presentations may range from heart failure to embolism and, most importantly, ventricular arrhythmias (VAs). This study aims to find novel predictive factors for the occurrence of potentially fatal VAs in patients with left ventricular hypertrabeculation. Methods: All consecutive patients meeting the echocardiographic (Chin, Jenny or Stöllberger) and/or MRI criteria (Petersen) for hypertrabeculation were prospectively enrolled from October 2009 to December 2023. The primary outcome was a composite of sudden cardiac death, sustained ventricular tachycardias (sVTs), ventricular fibrillation (VF) or appropriate implantable cardioverter defibrillator (ICD) interventions. The secondary outcome was a composite of cardiovascular death and cardiovascular hospitalizations. Results: Overall, 64 patients (41 males, mean age 46 ± 19 years old) were enrolled and followed for a median time of 2.2 years. Six patients (9.4%) experienced a composite outcome at eight years, three with previous sVTs and three with previous non-sustained VTs (nsVTs). The strongest predictor of the primary endpoint was the anamnesis of nsVTs and sVTs before LVNC diagnosis. In addition, nsVTs and sVTs were significantly associated with the secondary outcome. Conclusions: Hypertrabeculation of the left ventricle is a complex and poorly understood condition whose status of cardiomyopathy is currently challenged. In our population, patients with a trabecular pattern experienced a high incidence of VAs, cardiovascular death and hospitalizations. VAs before LVNC diagnosis were predictive of the outcome independently from systolic function.

Background: Resynchronization therapy has become a cornerstone in patients with heart failure (HF). Recent advancements in this field have led to the development of the so-called “left bundle branch area pacing” (LBBAP), a form of pacing where a single ventricular catheter directly addresses the left bundle for a more physiological stimulation. The current literature provides encouraging evidence regarding this topic, but there is still limited data for the older population, particularly those aged ≥75 years. This review aims to clarify how LBBAP has been explored in this cohort and if its application could be safe and effective even in the most advanced stages of life. Methods: A search of articles from PubMed was conducted. Patients were considered older if above 75 years of age. Data regarding Italian statistics were obtained from national registries. Results: The current literature supports the safety and effectiveness of LBBAP in older patients across different indications, with outcomes comparable to those reported in younger patients and a suggested cost-effectiveness. Conversely, data regarding patients affected by cardiac amyloidosis are still inconclusive. Conclusions: LBBAP represents a valuable resource for patients of all ages, but frailty is a major issue in the older population that needs to be addressed. The potential integration of this technology with defibrillator capabilities will enable an even more extensive application in the near future.

Sarcopenia, characterized by the progressive loss of skeletal muscle mass, strength, and function, represents a growing public health challenge in aging populations. Emerging mechanistic evidence suggests that ketogenic diets (KDs) and elevated circulating β-hydroxybutyrate (βOHB) levels may offer selective and context-dependent nutritional strategies to support muscle health during aging. This review summarizes current evidence on the effects of ketogenic diets and ketone body metabolism on muscle mass and function, with a focus on underlying molecular mechanisms and clinical relevance in older adults. βOHB acts not only as an alternative energy substrate but also as a signaling molecule, notably through histone deacetylase inhibition and modulation of inflammatory pathways. Nutritional ketosis in humans typically results in circulating βOHB concentrations of approximately 0.5–3.0 mM, which may be sufficient to engage some of these signaling pathways, although the extent of these effects in human tissues remains incompletely defined. Preclinical studies indicate that long-term ketogenic diets preserve muscle mass, strength, and mitochondrial function in aging models. Limited clinical evidence, largely derived from populations with sarcopenic obesity or metabolic comorbidities, suggests that protein-adequate ketogenic diets, when implemented as an adjunct to physical exercise, may help preserve fat-free mass and improve functional outcomes, while exogenous ketones show potential to augment post-exercise anabolic signaling. Overall, the integration of mechanistic and preliminary clinical data provides a supplementary and exploratory framework suggesting that ketogenic diets may represent a promising adjunctive strategy for sarcopenia prevention, although well-designed long-term randomized controlled trials are required to define their efficacy, safety, and optimal clinical application.

Left ventricular hypertrabeculation is one of the most debated conditions in modern cardiology. Many studies have tried to characterise this disease by addressing the various clinical risks and diagnostic tools, but its very nosological existence is currently being challenged. The latest ESC guidelines on cardiomyopathies state that it should be addressed as a morphologic trait rather than an intrinsic disease of the cardiac muscle. Despite the huge number of diagnostic criteria and possible phenocopies, no specific consensus identifies a specific flowchart regarding the management of patients with suspected hypertrabeculation. This review aims to provide a clinical approach for patients with a phenotypical appearance of excessive trabeculation.