Lipoprotein(a) (Lp(a)) is increasingly recognized as a genetically determined and clinically relevant contributor to residual cardiovascular risk. Through pro-atherogenic, pro-inflammatory, pro-thrombotic, and pro-calcific mechanisms, Lp(a) appears to play a significant role in both coronary artery disease and aortic valve disease. In patients undergoing percutaneous coronary intervention, elevated Lp(a) has been associated with worse long-term outcomes, including recurrent ischemic events, repeat revascularization, and in-stent restenosis, even in the setting of controlled low-density lipoprotein cholesterol. In parallel, experimental, genetic, and clinical data support a role for Lp(a) in the initiation and progression of calcific aortic stenosis, while its prognostic significance after transcatheter aortic valve interventions remains less clearly defined. Current guidelines now recognize Lp(a) as a relevant risk-enhancing factor, and emerging targeted therapies are achieving substantial reductions in circulating levels. Overall, Lp(a) should be regarded as both a meaningful biomarker and a promising therapeutic target, although ongoing outcome trials are needed to determine whether selective Lp(a) lowering translates into clinical benefit across interventional cardiovascular settings. The aim of this narrative review is to provide a single, comprehensive account of lipoprotein(a) [Lp(a)] in interventional cardiology, following this lipoprotein from its biology and pathophysiology through to its clinical impact and to the therapies that are now reaching the clinic, with a specific focus on the two most frequent catheter-based procedures in which it may carry prognostic weight: percutaneous coronary intervention (PCI) and transcatheter aortic valve implantation (TAVI). PCI and TAVI are deliberately addressed within the same review since they share a common upstream biology: Lp(a) contributes both to the atherosclerotic process that underlies coronary disease and to the calcific process that underlies aortic valve disease, and the corresponding patient populations overlap considerably in everyday interventional practice. Covering them together offers the interventional cardiologist a single, practical reference on how a patient with elevated Lp(a) may be approached in both scenarios.

Elevated plasma lipoprotein(a) [Lp(a)] levels represent a predominantly genetically determined risk factor for atherosclerotic cardiovascular disease and calcific aortic valve disease (CAVD). Mechanistically, Lp(a) transports oxidized phospholipids, lysophosphatidylcholine, and autotaxin, components capable of promoting inflammation, oxidative stress, and valvular fibrocalcific remodeling. This review synthesizes the molecular, cellular, and clinical evidence linking Lp(a) to CAVD progression. Retention of Lp(a) and other apolipoprotein B-containing lipoproteins in the valvular matrix promotes endothelial activation, recruitment of cells of the monocytic lineage, and the release of proinflammatory mediators. Oxidized phospholipids and the autotaxin-lysophosphatidic acid axis activate redox-dependent pathways and promote the transition of valvular interstitial cells toward myofibroblastic and/or osteogenic phenotypes. These processes converge in alterations in cholesterol metabolism, the release of procalcifying extracellular vesicles, and hydroxyapatite nucleation. Genetic and imaging evidence supports an association between elevated Lp(a), microcalcifying activity, and accelerated hemodynamic progression. Although anti-Lp(a) therapies substantially reduce plasma Lp(a) concentrations, their effect on valvular outcomes has not yet been demonstrated.

The clinical trials in low risk patients have clearly demonstrated clinical outcomes of transcatheter aortic-valve replacement (TAVR) comparable to those of surgical aortic-valve replacement (SAVR) in patients with severe aortic stenosis (AS). However, data are lacking on the appropriate treatment selection for patients with severe AS and low surgical risk in Japanese routine clinical practice. Among 3369 patients enrolled in the CURRENT AS Registry-2 between April 2018 and December 2020, the current study population include 826 patients with low Society of Thoracic Surgeons (STS) score and not on hemodialysis who actually underwent TAVR (439 patients) or SAVR (387 patients). After propensity score matching, there remained 162 patients in each group. The primary outcome was a composite of all-cause death, disabling stroke, or heart failure hospitalization. The cumulative 3-year incidence of the primary outcome was not significantly different between the TAVR and SAVR groups (19.5% and 17.4%, P = 0.82). Even after adjusting for age and institution, there was no excess risk of TAVR relative to SAVR for the primary outcome (adjusted HR: 1.05, 95% CI: 0.50-2.20, P = 0.91). In low-risk patients with severe AS, TAVR compared to SAVR was associated with comparable clinical outcomes for a composite of all-cause death, disabling stroke and heart failure hospitalization.

Coronary-subclavian steal syndrome (CSSS) is an uncommon but clinically important entity that may occur after coronary artery bypass grafting (CABG) with internal mammary artery conduits. Hemodynamically significant proximal left subclavian artery (LSA) stenosis can alter distal branch vessel flow and, in patients with prior left internal mammary artery (LIMA)-based CABG, may raise concern for coronary-subclavian steal physiology. Concurrent vertebral artery flow reversal may further predispose to cerebrovascular insufficiency. We report a case of a 75-year-old male with an extensive cardiovascular history, including prior CABG, transcatheter aortic valve replacement (TAVR), thoracic endovascular aortic repair (TEVAR), and a cardiac implantable electronic device, who presented with dizziness and was found to have severe proximal left subclavian artery stenosis. Computed tomography angiography demonstrated severe (~90%) proximal LSA stenosis, while duplex ultrasonography revealed alternating vertebral artery flow consistent with evolving steal physiology. Invasive hemodynamic assessment confirmed a significant trans-stenotic gradient (>25 mmHg). Given the patient's prior LIMA-based CABG, severe proximal LSA stenosis raised concern for possible coronary-subclavian steal physiology, although direct angiographic confirmation of retrograde LIMA flow was not available. The patient underwent a hybrid endovascular approach utilizing intravascular ultrasound (IVUS)-guided lesion assessment and optimization, drug-coated balloon (DCB) angioplasty, and precise deployment of a balloon-expandable covered stent (GORE VIABAHN VBX; Flagstaff, AZ: W. L. Gore & Associates). The procedure restored antegrade subclavian flow, normalized the trans-stenotic pressure gradient, and preserved the vertebral artery origin. This case demonstrates the technical feasibility of a multimodality endovascular approach for severe proximal LSA stenosis with evolving vertebrobasilar steal physiology in a high-risk post-CABG patient. Integration of IVUS guidance, DCB therapy, and covered stent technology may assist procedural optimization in carefully selected patients, although further studies are required to define the long-term role of this strategy in supra-aortic trunk disease.

This case presents a 67-year-old man with familial hypertrophic cardiomyopathy, severe heart failure (LVEF 31%, NYHA III), and significant interatrial conduction delay. After ruling out cardiac resynchronization therapy due to unsuitable ventricular activation characteristics, a dual-chamber implantable cardioverter-defibrillator was implanted, using Bachmann bundle pacing for the atrial lead to optimize interatrial synchrony. BBP successfully corrected the IACD, evidenced by P-wave shortening and normalization. This led to remarkable clinical improvements within 1 month: LVEF increased from 31% to 49%, and NYHA class improved from III to II. Echocardiography confirmed enhanced left atrial-left ventricular coupling. This case demonstrates BBP combined with ICD as a novel and effective strategy for HCM patients with IACD, offering both sudden cardiac death protection and substantial hemodynamic and functional benefits by optimizing atrial activation and atrioventricular synchrony.

Calcific aortic valve stenosis (AS) is the most prevalent valvular heart disease in high-income countries, affecting 9.4 million persons globally. While surgical and transcatheter aortic valve replacement have transformed outcomes, they address end-stage disease rather than the underlying pathobiology. The development of pharmacological therapies to slow or halt AS progression would represent a paradigm shift in disease management. Recent advances have substantially expanded our understanding of AS pathogenesis. Large-scale genome-wide association studies have identified over 260 risk loci, with the LPA locus confirming lipoprotein(a) as the most robustly validated genetic risk factor. Single-cell transcriptomics have revealed unexpected cellular heterogeneity and novel mechanisms including macrophage-to-mesenchymal transition. Emerging insights into metabolic reprogramming, epigenetic regulation, innate immunity and clonal hematopoiesis have identified multiple therapeutic targets. Despite these pathophysiological advances, no pharmacological therapy has yet demonstrated efficacy in adequately powered randomized trials. Statin therapy and skeletal bone metabolism-targeted agents have proven ineffective previously and multiple mechanistically diverse approaches are now under investigation. The most promising developments center on lipoprotein(a) reduction with antisense oligonucleotides, with the first dedicated AS trial ongoing. Additional strategies include PCSK9 inhibition, supplementation of omega-3 fatty acids, treatment with colchicine, soluble guanylate cyclase activation with ataciguat, and DPP-4 inhibition. Success in any of these trials would represent the first disease-modifying therapy for AS, with potential to delay valve replacement, preserve myocardial function, and improve outcomes for millions of patients worldwide.