Myocardial ischemia in chronic coronary syndromes extends far beyond the presence of obstructive epicardial coronary stenoses. Advanced cardiovascular imaging has emerged as a cornerstone for the identification of the diverse anatomic and functional mechanisms underlying myocardial ischemia, including atherosclerotic coronary artery disease, vasospastic angina, myocardial bridging, and coronary microvascular dysfunction. Coronary computed tomography angiography, cardiac magnetic resonance, and PET provide complementary insights. This article reviews the diagnostic performance, characteristic imaging findings, and contemporary clinical applications of these modalities, highlighting their role in refining phenotypic characterization and enabling a more precise and individualized approach to patients with chronic coronary syndromes.

Structural coronary microvascular dysfunction (CMD) is an important endotype of ischemia with nonobstructive coronary arteries (INOCA) and is characterized by adverse arteriolar remodeling and capillary rarefaction. These alterations impair coronary vasodilator capacity and increase microcirculatory resistance, all of which contribute to impaired myocardial perfusion. In this article, we aim to review the anatomic and pathophysiological basis of structural CMD, its clinical presentation and prognostic relevance, and the role of invasive physiologic indices in its identification. We also highlight new considerations about dynamic aspects of structural CMD laying the groundwork for emerging therapeutic strategies and future research directions.

Epicardial coronary disease includes dynamic disorders capable of causing myocardial ischaemia without fixed obstructive stenosis. Vasospastic angina (VSA) and myocardial bridging (MB) are paradigmatic entities characterized by transient luminal narrowing and reversible flow impairment. Although traditionally viewed as distinct, they frequently overlap, sharing mechanisms such as endothelial dysfunction, smooth muscle hyperreactivity, altered shear stress, and autonomic imbalance. VSA results from episodic coronary constriction, whereas MB involves systolic compression of an intramyocardial segment with possible diastolic flow limitation. The aim of this article is to provide a mechanistic appraisal of these conditions and their clinical implications within chronic coronary syndromes.

Persistent low-grade inflammation, oxidative stress, cellular senescence, and disturbance of cellular homeostasis are all connected with ageing and can lead to the development of age-related diseases. Ferroptosis, an iron-dependent type of controlled cell death, has been linked to these processes more and more. It may represent a key connection between inflammation, oxidative damage, and tissue failure as people age. With a focus on neurodegenerative, cardiovascular, metabolic, pulmonary, and musculoskeletal problems, this study explores the new idea of a ferroptosis-inflammaging axis and its role in age-associated degenerative disorders. The review addresses the data supporting ferroptosis as a potential therapeutic target and summarises the current understanding on the relationship between ferroptosis and the main biological processes linked to ageing. Natural products are given particular attention as possible ferroptosis modulators, emphasizing their therapeutic significance and the growing data from experimental models. Additionally included are the translational difficulties related to ferroptosis-targeted therapies, such as the lack of clinical validation, the development of biomarkers, pharmacokinetic issues, and disease-specific treatment approaches. All things considered, comprehending the ferroptosis-inflammaging axis may offer a foundation for discovering cutting-edge therapeutic strategies to delay tissue dysfunction and enhance healthy ageing.

Mitochondria and their biomacromolecular complexes-such as the electron transport chain (ETC), mitochondrial permeability transition pore (mPTP), and protein quality control systems-play pivotal roles in aging and age-related diseases. This review integrates recent insights into how structural and functional disruptions of these complexes drive cellular senescence and systemic decline. We outline the architecture of mitochondrial assemblies (e.g., oxidative phosphorylation (OXPHOS) complexes, mtDNA-protein interactions) essential for energy production and organelle stability. Age-related alterations in stoichiometry, conformational states (e.g., mPTP opening), and post-translational modifications (e.g., SIRT3-mediated acetylation) compromise mitochondrial integrity, fueling metabolic dysfunction and chronic inflammation ("inflammaging"). Therapeutic strategies include small-molecule stabilizers of ETC supercomplexes, peptide-based mPTP inhibitors, and CRISPR-mediated correction of mtDNA-protein mismatches. Tissue-specific models (e.g., Complex I in skin aging, Bcl-2 protein imbalance in ovarian aging) exemplify the clinical relevance. We also categorize nine age-associated diseases-neurodegenerative, cardiovascular, and cancer types-based on their dependence on distinct mitochondrial complexes, such as ATP synthase in cancer resistance and the TIM/TOM import machinery in Alzheimer's disease. By linking structural findings (e.g., cryo-EM studies) with therapeutic innovation, this review offers a framework for targeting mitochondrial complexes to mitigate aging and its related pathologies.

Individual cardiometabolic diseases are associated with psychiatric conditions and suicide. However, the association between the recently proposed Cardiovascular-Kidney-Metabolic (CKM) syndrome framework and suicide-related mortality remains unevaluated.

We analyzed data from 4,601,001 participants in the Korean National Health Insurance Service database, categorizing CKM health into Stages 0-4. The association between CKM stages and suicide-related mortality was evaluated using multivariable Cox regression with sequential adjustment for clinicodemographic variables, comorbidity, and claims-based psychiatric diagnoses, and using Fine-Gray subdistribution hazard models treating non-suicide death as a competing event.

During a median follow-up of 10.11 years, 12,034 suicidal death events occurred. After adjustment, advanced CKM stages were associated with an increased risk of suicidal death (stage 3: adjusted HR 1.328, 95% CI 1.217-1.449; stage 4: adjusted HR 1.319, 95% CI 1.220-1.426), and the association persisted after further adjustment for other psychiatric disorders. Estimates were attenuated but remained significant in Fine-Gray models accounting for the competing risk of non-suicide death (stage 3: subdistribution HR 1.199, 95% CI 1.098-1.310; stage 4: 1.246, 95% CI 1.150-1.349). Exploratory subgroup analyses indicated that the association was most pronounced in younger adults aged 20-39 and in individuals without a claims-based diagnosis of depression.

Advanced CKM syndrome is associated with increased suicide-related mortality. Mental health surveillance within the clinical management of CKM dysfunction may serve as a potential preventive strategy. Future studies are needed to evaluate the utility of CKM-based risk stratification in suicidal death prevention.

In patients with nonischemic cardiomyopathy (NICM) undergoing cardiac resynchronization therapy (CRT), there are no clear recommendations on selecting CRT with defibrillator (CRT-D) vs pacemaker (CRT-P). Patients with high probability of response to CRT and low arrhythmic risk may be ideal candidates to CRT-P.

The objectives of the study was to evaluate if the absence of late gadolinium enhancement (LGE) is associated with CRT response and ventricular arrhythmia (VA) in NICM treated with CRT.

A systematic review and meta-analysis was conducted. Search of PubMed, Web of Science, and Scopus identified observational studies of NICM patients who underwent cardiac magnetic resonance before CRT implantation. Studies assessing echocardiographic response to CRT or VA stratified by LGE status were included. The VA endpoint comprised sustained ventricular tachycardia, appropriate implantable cardioverter-defibrillator therapy, resuscitated cardiac arrest, and sudden death.

Ten studies were included: 9 (n = 831) for CRT response and 6 (745 patients) for arrhythmic risk. CRT response was significantly higher in patients without LGE than in patients with LGE (78.7% vs 50.7%; P < 0.001). The cumulative incidence of VA was extremely low in LGE cases, significantly lower than that of LGE+ ones (0.8% vs 21.1%, P < 0.001). The absence of LGE was strongly associated with higher CRT response (OR: 3.52; 95% CI: 2.54-4.88; P < 0.001) and much lower arrhythmic risk (OR: 0.06; 95% CI: 0.02-0.15; P < 0.001).

In NICM patients undergoing CRT, the absence of LGE is strongly associated with greater echocardiographic response and very low arrhythmic risk. In this subgroup the incremental benefit of CRT with defibrillator over CRT-P may be limited.

Obstructive sleep apnea (OSA) is closely linked with cardiovascular disease (CVD), but different cardiovascular phenotypes may influence ECG-derived RR interval dynamics differently. Previous work has shown that scale-dependent detrended fluctuation analysis (sDFA) can detect OSA across broad CVD status, but it remains unclear whether this relationship differs between CVD subtypes.

Overnight polysomnography recordings from the Sleep Heart Health Study were analyzed in participants with a history of myocardial infarction (MI), congestive heart failure (CHF), or angina pectoris (ANG). Participants with more than one of these conditions were excluded. OSA was analyzed as a binary outcome using an apnea-hypopnea index threshold of 5 events/h. Propensity score matching was performed within each subgroup using age and body mass index. ECG-derived RR interval dynamics were analyzed using cHRV metrics and second-order sDFA, with discrimination assessed using ROC-AUC.

The matched subgroups consisted of 112 participants with MI, 18 with CHF, and 54 with ANG. sDFA achieved higher ROC-AUC values than cHRV metrics in all subgroups. The highest sDFA ROC-AUC was observed in ANG (0.79), compared with 0.66 in MI and 0.69 in CHF. MI and ANG showed broadly similar scale-dependent profiles, whereas CHF appeared distinct; however, the CHF analysis was substantially underpowered.

ECG-derived sDFA features showed subtype-dependent behavior for OSA discrimination, with the strongest performance observed in ANG. These exploratory findings suggest that cardiovascular phenotype may influence OSA-related RR interval dynamics. Binary OSA grouping may mask severity-related differences, while exclusion of participants with multiple cardiovascular conditions limits clinical applicability.

Spontaneous intracranial hypotension (SIH) is most commonly caused by spinal CSF leaks, with ventral dural defects frequently requiring surgical repair when conservative measures fail. Endoscopic transforaminal approaches have emerged as minimally invasive alternatives to traditional open techniques, but the physiological consequences of continuous irrigation in the presence of a dural defect remain poorly understood. The authors report the case of a 36-year-old woman with recurrent SIH due to a persistent ventral T11-12 CSF leak despite prior laminectomy, revision repair, and multiple targeted interventions. She underwent transforaminal endoscopic discectomy and ventral dural repair. During the procedure, under continuous gravity-assisted irrigation, she developed sudden, severe, and reproducible hypertension with her systolic blood pressure reaching 275 mm Hg, refractory to anesthetic deepening and multiple antihypertensive agents. Irrigation cessation resulted in immediate hemodynamic normalization, while irrigation reintroduction led to recurrence of the hypertensive response. The procedure was completed after minimizing irrigation, and the patient stabilized postoperatively without further hemodynamic instability. The authors propose that this phenomenon reflects direct transmission of irrigation-induced epidural pressure into the intrathecal space through the persistent dural defect, resulting in acute intracranial pressure elevation and sympathetic activation. In contrast to standard endoscopic cases, chronic CSF leak states may create a compartmentalized and fibrotic epidural environment with reduced compliance and impaired outflow, predisposing the epidural space/operative field to rapid pressure accumulation even under low-pressure irrigation systems. This case highlights a previously underrecognized mechanism of intraoperative hemodynamic instability during endoscopic spine surgery and underscores the importance of considering altered pressure dynamics in patients with CSF leaks. Surgeons should maintain a high index of suspicion for irrigation-related complications in this population and consider strategies to minimize inflow pressure, optimize outflow, and promptly interrupt irrigation in the setting of unexplained physiological changes. These findings have important implications for surgical planning, intraoperative management, and the safe expansion of endoscopic techniques in CSF leak repair.

Hypertension worsens osteoarthritis and could be a therapeutic target in patients with both conditions.