Livio D’Angelo

Hypertension remains the leading modifiable cause of cardiovascular death, yet fewer than one in four treated adults achieves guideline-recommended blood pressure targets. Catheter-based renal denervation interrupts efferent and afferent renal sympathetic signalling and lowers blood pressure continuously and independently of medication adherence. After a decade of controversy following the neutral SYMPLICITY HTN-3 trial, a coherent body of second-generation sham-controlled randomised evidence, generated with radiofrequency, endovascular ultrasound, and perivascular alcohol platforms, has established a reproducible, modest, and durable antihypertensive effect with a favourable safety profile. Between 2024 and 2026, the field crossed three thresholds simultaneously: guideline endorsement on both sides of the Atlantic, including the first United States recommendation in the 2025 AHA/ACC guideline; a national coverage determination with coverage with evidence development; and the maturation of randomised and real-world follow-up to three years in cohorts exceeding 3000 patients. This state-of-the-art review synthesises the contemporary evidence base; quantifies the expected treatment effect and its heterogeneity; appraises safety across renal and vascular domains; examines emerging data in chronic kidney disease, diabetes, heart failure, and atrial fibrillation; and details the practical requirements for delivering renal denervation responsibly. We conclude by defining the research agenda that must now be addressed: the identification of responders, the development of an intraprocedural endpoint, a direct comparison with newly approved pharmacotherapy, and evidence of cardiovascular event reduction.

Background: Peripheral endovascular intervention is the preferred revascularization strategy for patients with chronic lower-limb ischemia. Although generally safe, peri-procedural mechanical complications may occur and are influenced by both lesion complexity and procedural strategy. Data identifying determinants of such complications in routine clinical practice remain limited. Methods: We performed a retrospective single-center analysis of consecutive patients undergoing peripheral endovascular intervention for chronic lower-limb ischemia between 2010 and 2023. The primary endpoint was the occurrence of peri-procedural mechanical complications, defined as mechanical adverse events occurring during or immediately following the index intervention and directly related to catheter manipulation, device deployment, or vascular access. Lesion- and procedure-related predictors were evaluated using multivariable logistic regression analysis. Results: A total of 283 index procedures were included. Peri-procedural mechanical complications occurred in 9 procedures (3.2%), with arterial dissection being the most frequent event (2.1%). No cases of peri-procedural bleeding, distal embolization, or emergent surgical conversion were observed. In multivariable analysis, chronic total occlusion (adjusted odds ratio [aOR] 1.89, 95% confidence interval [CI] 1.14–3.11; p = 0.014), moderate-to-severe arterial calcification (aOR 1.74, 95% CI 1.03–2.93; p = 0.039), introducer sheath size ≥7 French (aOR 2.08, 95% CI 1.21–3.57; p = 0.007), and ≥3 vascular access attempts (aOR 1.67, 95% CI 1.00–2.81; p = 0.048) were associated with increased risk of peri-procedural mechanical complications in adjusted analyses. Conclusions: In this real-world institutional registry, peri-procedural mechanical complications during peripheral endovascular intervention were uncommon. Lesion complexity and procedural factors, rather than access route or device type, were the primary determinants of mechanical risk. These findings highlight the importance of careful lesion assessment and procedural planning to optimize peri-procedural safety in routine practice.