Heart failure (HF) is a complex clinical syndrome with a huge social burden in terms of cost, morbidity, and mortality. Brain natriuretic peptide (BNP) appears to be the gold standard in supporting the daily clinical management of patients with HF. Novel biomarkers may supplement BNP to improve the understanding of this complex disease process and, possibly, to personalize care for the different phenotypes, in order to ameliorate prognosis. In this review, we will examine some of the most promising novel biomarkers in HF. Inflammation plays a pivotal role in the genesis and progression of HF and, therefore, several candidate molecules have been investigated in recent years for diagnosis, prognosis, and therapy monitoring. Noncoding RNAs are attractive as biomarkers and their potential clinical applications may be feasible in the era of personalized medicine. Given the complex pathophysiology of HF, it is reasonable to expect that the future of biomarkers lies in the application of precision medicine, through wider testing panels and “omics” technologies, to further improve HF care delivery.

Coronary microvascular dysfunction (CMD) is related to a broad variety of clinical scenarios in which cardiac microvasculature is morphologically and functionally affected, and it is associated with impaired responses to vasoactive stimuli. Although the prevalence of CMD involves about half of all patients with chronic coronary syndromes and more than 20% of those with acute coronary syndrome, the diagnosis of CMD is often missed, leading to the underestimation of its clinical importance. The established and validated techniques for the measurement of coronary microvascular function are invasive and expensive. An ideal method to assess endothelial dysfunction should be accurate, non-invasive, cost-effective and accessible. There are varieties of biomarkers available, potentially involved in microvascular disease, but none have been extensively validated in this heterogeneous clinical population. The investigation of potential biomarkers linked to microvascular dysfunction might improve the assessment of the diagnosis, risk stratification, disease progression and therapy response. This review article offers an update about traditional and novel potential biomarkers linked to CMD.

BACKGROUND: The FORZA trial (FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty) prospectively compared the use of fractional flow reserve (FFR) or optical coherence tomography (OCT) for treatment decisions and percutaneous coronary intervention (PCI) optimization in patients with angiographically intermediate coronary lesions. Murray law-based quantitative-flow-ratio (μQFR) is a novel noninvasive method for the computation of FFR. In the present study, we evaluated the clinical impact of μQFR, FFR, or OCT guidance in FORZA trial lesions at 3-year follow-up. METHODS: μQFR was assessed at baseline and, in the case of a decision to intervene, after (FFR- or OCT-guided) PCI. The baseline μQFR was considered the final μQFR for deferred lesions, and post-PCI μQFR value was taken as final for stented lesions. The primary end point was target vessel failure ([TVF]; cardiac death, target-vessel-related myocardial infarction, and target-vessel-revascularization) at a 3-year follow-up. RESULTS: A total of 419 vessels (199 OCT-guided and 220 FFR-guided) were included in the FORZA trial. μQFR was evaluated in 256 deferred lesions and 159 treated lesions (98 OCT-guided PCI and 61 FFR-guided PCI). In treated lesions, post-PCI μQFR was higher in OCT-group compared with FFR-group (median, 0.93 versus 0.91; P =0.023), and the post-PCI μQFR improvement was greater in FFR-group (0.14 versus 0.08; P <0.0001). At 3-year follow-up, OCT- and FFR-guided treatment decisions resulted in comparable TVF rate (6.7% versus 7.9%; P =0.617). Final μQFR was the only predictor of TVF. μQFR ≤0.89 was associated with 3× increase in TVF (11.6% versus 3.7%; P =0.004). PCI was a predictor of higher final μQFR (odds ratio, 0.22 [95% CI, 0.14–0.34]; P <0.001). CONCLUSIONS: In vessels with angiographically intermediate coronary lesions, OCT-guided PCI resulted in comparable clinical outcomes as FFR-guided PCI. μQFR estimated at the end of diagnostic or interventional procedure predicted 3-year TVF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01824030.

Atherosclerotic plaque healing is a dynamic process developing after plaque rupture or erosion, which aims to prevent lasting occlusive thrombus formation and to promote plaque repair. We hypothesized that diabetes mellitus, one of the major conventional cardiovascular risk factors, may influence the healing capacity after plaque destabilization. In this single-centre observational cohort study, patients with acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) who underwent optical coherence tomography (OCT) imaging at Fondazione Policlinico A. Gemelli–IRCCS, Rome, were included. Patients were divided into two groups (i.e. diabetes vs. no diabetes), and stratified based on diabetes medications (i.e. insulin, vs. oral antidiabetic drugs). OCT analysis of non-culprit coronary segments was performed. 105 patients were included (44 diabetes, 61 no diabetes). Prevalence of HCPs was not significantly different between patients with and without diabetes (3.6% vs. 3.8%, P = 0.854). However, patients with diabetes on insulin showed a lower prevalence of HCPs both at patient-based (7.1% vs. 26.4%, P = 0.116) and at segment-based analysis (1.2% vs. 4.2%, P = 0.020). When comparing HbA1c levels based on the presence or absence of healed plaque at the non-culprit lesions, patients with healed plaque showed significantly lower levels of HbA1c compared to patients without healed plaques (43.5 ± 12.1% vs. 61.2 ± 10.4%, P < 0.001). At segment-based analysis, normal vessel structure, pathological intimal thickening (PIT), and spotty calcifications were significantly less prevalent in diabetic patients (2.1% vs. 5.1%, P = 0.001; 7.2% vs. 9.5%, P = 0.05; 9.9% vs. 13.6%, P = 0.02, respectively), whereas neovascularization was significantly higher (19.2% vs. 15.6%, P = 0.035). Patients with diabetes have a distinct coronary non-culprit plaque phenotype. Healing capacity may be impaired in patients with advanced diabetes on insulin therapy and in those with a suboptimal control of the disease. Further prospective, larger scale studies are warranted to confirm these findings.