Exposome in ischaemic heart disease: beyond traditional risk factors.

Ischaemic heart disease represents the leading cause of morbidity and mortality, typically induced by the detrimental effects of risk factors on the cardiovascular system. Although preventive interventions tackling conventional risk factors have helped to reduce the incidence of ischaemic heart disease, it remains a major cause of death worldwide. Thus, attention is now shifting to non-traditional risk factors in the built, natural, and social environments that collectively contribute substantially to the disease burden and perpetuate residual risk. Of importance, these complex factors interact non-linearly and in unpredictable ways to often enhance the detrimental effects attributable to a single or collection of these factors. For this reason, a new paradigm called the 'exposome' has recently been introduced by epidemiologists in order to define the totality of exposure to these new risk factors. The purpose of this review is to outline how these emerging risk factors may interact and contribute to the occurrence of ischaemic heart disease, with a particular attention on the impact of long-term exposure to different environmental pollutants, socioeconomic and psychological factors, along with infectious diseases such as influenza and COVID-19. Moreover, potential mitigation strategies for both individuals and communities will be discussed.

Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.

Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.

An update on the mechanisms of Takotsubo syndrome: "At the end an acute coronary syndrome".

Takotsubo syndrome (TTS) is an acute reversible form of myocardial dysfunction, often preceded by a physical or emotional stressful event, that acts as a trigger. Despite, recent advances in the comprehension of the mechanisms leading to TTS, its pathophysiology is far from being completely understood. However, several studies seem to suggest that an acute coronary microvascular dysfunction may represent a crucial pathogenic mechanism involved in TTS occurrence. In this article, we aim to review the complex pathophysiology of TTS and the possible different mechanisms underlying this clinical condition, focusing on the role of coronary microvascular dysfunction and the remaining knowledge's gaps in the field.

Sodium-glucose cotransporter 2 inhibitors and the cancer patient: from diabetes to cardioprotection and beyond.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new drug class initially designed and approved for treatment of diabetes mellitus, have been shown to exert pleiotropic metabolic and direct cardioprotective and nephroprotective effects that extend beyond their glucose-lowering action. These properties prompted their use in two frequently intertwined conditions, heart failure and chronic kidney disease. Their unique mechanism of action makes SGLT2i an attractive option also to lower the rate of cardiac events and improve overall survival of oncological patients with preexisting cardiovascular risk and/or candidate to receive cardiotoxic therapies. This review will cover biological foundations and clinical evidence for SGLT2i modulating myocardial function and metabolism, with a focus on their possible use as cardioprotective agents in the cardio-oncology settings. Furthermore, we will explore recently emerged SGLT2i effects on hematopoiesis and immune system, carrying the potential of attenuating tumor growth and chemotherapy-induced cytopenias.

Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes.

OBJECTIVE: We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve in patients with type 2 diabetes (T2D) with stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular disease is inflammation of epicardial adipose tissue (EAT). Since the latter is often increased in type 2 diabetes patients, it could play a role in coronary microvascular dysfunction. It is also well known that SGLT-2i modify adipose tissue metabolism. We aimed to investigate the effects of the SGLT-2i dapagliflozin on metabolism and visceral and subcutaneous adipose tissue thickness in T2D patients with stable coronary artery disease and to verify whether these changes could explain observed changes in myocardial flow. METHODS: We performed a single-center, prospective, randomized, double-blind, controlled clinical trial with 14 T2D patients randomized 1:1 to SGLT-2i dapagliflozin (10 mg daily) or placebo. The thickness of visceral (epicardial, mediastinal, perirenal) and subcutaneous adipose tissue and glucose uptake were assessed at baseline and 4 weeks after treatment initiation by 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp. RESULTS: The two groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, BMI, renal and heart function). Dapagliflozin treatment significantly reduced EAT thickness by 19% (p = 0.03). There was a significant 21.6% reduction in EAT glucose uptake during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p = 0.014). There were no significant effects on adipose tissue thickness/metabolism in the other depots explored. CONCLUSIONS: SGLT-2 inhibition selectively reduces EAT thickness and EAT glucose uptake in T2D patients, suggesting a reduction of EAT inflammation. This could explain the observed increase in myocardial flow reserve, providing new insights into SGLT-2i cardiovascular benefits.

Left Ventricular-Arterial Coupling and Vascular Function in Childhood Cancer Survivors Exposed to Anthracycline Chemotherapy.

Background: Cardiovascular (CV) diseases are a cause of increased long-term morbidity and mortality in childhood cancer survivors (CCSs) treated with anthracyclines. These drugs may affect not only the heart, but also the vascular system. Left ventricular-arterial coupling (LVAC) represents a reliable parameter of altered ventricular and vascular performance, with validated prognostic value and never investigated in this setting. Aim of this study was to assess, in CCSs and matched controls, LVAC changes, performed with different echocardiographic modalities, and their relationship with endothelial function. Methods: Twenty survivors treated with anthracyclines for childhood malignancies and a matched control group of 20 healthy subjects were enrolled. Arterial elastance (Ea), end-systolic elastance (Ees), Ea/Ees ratio, as well as three-dimensional (3D) LVAC (assessed by measurement of End Systolic Volume [ESV]/Stroke Volume [SV] ratio) were performed at rest. Endothelial function was evaluated by measurement of flow-mediated dilatation (FMD) of the brachial artery. Results: 3D SV and 3D ESV/SV ratio resulted respectively significantly lower and higher in CCSs than in controls, while Ea, Ees and Ea/Ees ratio were not different among groups. A positive correlation between 3D ESV/SV ratio and cumulative anthracycline doses, as well as with time after drug exposure were also found. Mean FMD was similar in CCSs and controls (8.45 ± 1.79 versus 9.41 ± 3.41, p = 0.34). Conclusions: In conclusion, conventional LVAC parameters were not shown to be significantly different between CCSs and controls; however, 3D SV and LVAC were significantly impaired in our population. In these patients, endothelial function was comparable to controls. Larger validation studies are therefore needed.

Bleeding Complications in Patients Undergoing Percutaneous Coronary Intervention.

Percutaneous coronary intervention (PCI) is considered a relatively safe procedure associated with low rates of complications, but is inevitably associated with short and mid-to-long term increased bleeding risk. Besides the short term risk associated with the arterial access to perform PCI, enhanced bleeding risk persists for several months, given the need for antithrombotic therapy to prevent procedure-related thrombotic complications as well as ischemic recurrences. Bleeding is a powerful harbinger of adverse outcomes. This awareness has fuelled intense research on bleeding reduction strategies, including new PCI devices and techniques as well as new medications and antithrombotic regimens. We here review the mechanisms and prevalence of bleeding in PCI patients, discuss the available evidence from a practical point of view, and explore future perspectives on how to treat and prevent bleeding complications in these patients.

PCI Deferral Based on Fractional Flow Reserve or Optical Coherence Tomography: Two-Year Results of the Forza Trial.

Backgroud: The "FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty" (FORZA) trial showed that in patients with angiographically intermediate coronary lesions (AICLs), optical coherence tomography (OCT) guidance of percutaneous coronary intervention (PCI) reduced the occurrence of the composite endpoint of major adverse cardiac events (MACE) or significant angina at 13 months, while fractional flow reserve (FFR) guidance was associated with a higher rate of medical management and with lower costs. Safety of PCI deferral when FFR > 0.80 is known, while data on clinical outcomes using an OCT guidance are lacking. We assessed the safety of PCI deferral based on OCT findings. Methods: This is a subgroups analysis of the FORZA Trial focusing on the clinical outcome of patients in whom PCI was originally deferred. In details, patients with AICLs were randomized to FFR or OCT imaging. In the FFR arm, PCI was deferred if FFR was > 0.80 while in the OCT arm in the absence of any of the following conditions: area stenosis > 75%, or 50% to 75% with minimum lumen area < 2.5 mm 2 or plaque rupture. Angina status (evaluated using the Seattle Angina Questionnaire, SAQ), MACE (death, myocardial infarction, target vessel revascularization) and rate of patients treated with optimal medical therapy alone were assessed at 24 months. Results: From a total of 350 patients with 446 AICLs enrolled in the trial (176 randomized to FFR and 174 to OCT), based on the predefined FFR and OCT criteria, PCI was deferred in 119 patients (67.6%) in the FFR arm, and in 82 patients (47.1%) in the OCT arm. At 24-months follow-up, significant residual angina (defined as a value < 90 on the angina frequency scale) was observed in 6 patients (5.0%) in the FFR arm, and in 6 patients (7.3%) in the OCT arm (p = 0.55). Rate of MACE was 10.9% in the FFR arm and 6.1% in the OCT arm (p = 0.32). The number of patients managed by optimal medical therapy alone was still significantly higher using FFR than OCT guidance also at 24 months (60.2% vs 44.2%, p = 0.0038). Conclusions: PCI-deferral based on OCT (using the FORZA trial criteria) is safe and associated with numerically less events at 24-months follow up. FFR guidance is still associated with a higher number of patients managed by optimal medical therapy alone.