Initially developed as glucose-lowering drugs, sodium-glucose co-transporter type 2 inhibitors (SGLT2i) have demonstrated to be effective agents for the risk reduction of cardiovascular (CV) events in patients with type 2 diabetes mellitus (T2DM). Subsequently, data has emerged showing a significant CV benefit in patients treated with SGLT2i regardless of diabetes status. Renal protection has been initially evaluated in CV randomized trials only as secondary endpoints; nonetheless, the positive results gained have rapidly led to the evaluation of nephroprotection as primary outcome in the CREDENCE trial. Different renal and vascular mechanisms can account for the CV and renal benefits enlightened in recent literature. As clinical guidelines rapidly evolve and the role of SGLT2i appears to become pivotal for CV, T2DM, and kidney disease management, in this review, we analyze the renal effects of SGLT2, the benefits derived from its inhibition, and how this may result in the multiple CV and renal benefits evidenced in recent clinical trials.

A great deal of evidence has revealed an important link between gut microbiota and the heart. In particular, the gut microbiota plays a key role in the onset of cardiovascular (CV) disease, including heart failure (HF). In HF, splanchnic hypoperfusion causes intestinal ischemia resulting in the translocation of bacteria and their metabolites into the blood circulation. Among these metabolites, the most important is Trimethylamine N-Oxide (TMAO), which is responsible, through various mechanisms, for pathological processes in different organs and tissues. In this review, we summarise the complex interaction between gut microbiota and CV disease, particularly with respect to HF, and the possible strategies for influencing its composition and function. Finally, we highlight the potential role of TMAO as a novel prognostic marker and a new therapeutic target for HF.

Aims The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan reduces mortality and hospitalizations in patients with heart failure and reduced ejection fraction (HFrEF). Favourable effects on haemodynamic and functional parameters have been observed in patients with HFrEF undergoing ARNI therapy, using standard transthoracic echocardiography. Global longitudinal strain (GLS) assessment uses a semi‐automatic procedure to provide a reliable and repeatable method that improves the detection of early changes of contractile function. We aimed to assess the effects of ARNI on GLS and myocardial mechanics in patients with HFrEF. Methods and results Thirty patients with New York Heart Association class II–III HFrEF were treated with ARNI and monitored using standard echocardiographic examination and GLS measurements at baseline, 3 months, and 6 months. ARNI therapy resulted in a significant reduction of ventricular volumes and a significant increase in left ventricular ejection fraction at 6 months but not 3 months by standard transthoracic echocardiography (left ventricular ejection fraction from 28 ± 8% at baseline to 34 ± 12% at 6 months, P < 0.001). Non‐significant differences in the size of the left atrium, right ventricular function, and pulmonary pressures were found at 6 months. By using GLS, there was a progressive improvement of all strain parameters by 3 months. The improvement showed a progressive trend over time and maintained significance at 6 months: GLS 4ch −7.2 ± 4.8% at baseline vs. −7.5 ± 3.9% at 3 months (P = 0.025) and − 9.2 ± 5.2% at 6 months (P = 0.0001); AVG GLS −6.9 ± 4.3 at baseline vs. −7.9 ± 4.2 at 3 months (P = 0.04) and − 8.8 ± 4.4 at 6 months (P = 0.035); GLS endo 8.2 ± 4.8 at baseline vs. −9.0 ± 4.8 at 3 months (P = 0.05) and − 10.1 ± 5.1 at 6 months (P = 0.001). Conclusions Sacubitril/valsartan induces an early benefit on left ventricular remodelling, which is captured by myocardial strain and not by standard echocardiography. Strain method represents a practical tool to assess early and minimal variations of left ventricular systolic function.

Aims: Accurate risk stratification for patients with non-dilated left ventricular cardiomyopathy (NDLVC) remains challenging due to lack of dedicated clinical trials. This post hoc analysis aims to delineate the arrhythmic risk and assess the incremental value of cardiac magnetic resonance (CMR) imaging in the CarDiac magnEtic Resonance for prophylactic Implantable-cardioVerter defibrillAtor ThErapy (DERIVATE) study cohort meeting the NDLVC diagnostic criteria. Methods and results: Patients with NDLVC from the DERIVATE registry were identified in the absence of left ventricular (LV) dilatation and in the presence of non-ischaemic LV scarring (‘fibrotic NDLVC’) or isolated LV systolic dysfunction (LV ejection fraction < 50%) without fibrosis (‘hypokinetic NDLVC’). The primary endpoint was all-cause mortality. Major adverse arrhythmic cardiac events (MAACE) were the secondary endpoint and included sudden cardiac death (SCD) and aborted SCD. One hundred and ninety-seven NDLVC patients were identified from the cohort of the DERIVATE study (mean age: 59 ± 14 years; male: 135). Over a median follow-up of 2.7 years, 15 (8%) patients died and 8 (4%) experienced MAACE. Patients with ‘hypokinetic’ NDLVC had significantly lower rates of MAACE than non-ischaemic dilated cardiomyopathy (NIDCM) (P = 0.001), while patients with ‘fibrotic’ NDLVC had same rate of both primary (P = 0.48) and secondary endpoints (P = 0.616) compared with NIDCM patients. Multivariable analysis identified late gadolinium enhancement (LGE) with midwall distribution as an independent predictor of MAACE in NDLVC patients (hazard ratio 6.7, 95% confidence interval: 1.33–33.67; P = 0.021). Conclusion: NDLVC patients exhibit a heterogeneous risk profile for arrhythmic events. The presence of midwall LGE, similarly to NIDCM, is a significant predictor of MAACE, highlighting the importance of CMR imaging for risk stratification.

Far from being historically considered a primary healthcare problem, tricuspid regurgitation (TR) has recently gained much attention from the scientific community. In fact, in the last years, robust evidence has emerged regarding the epidemiological impact of TR, whose prevalence seems to be similar to that of other valvulopathies, such as aortic stenosis, with an estimated up to 4% of people >75 years affected by at least moderate TR in the United States, and up to 23% among patients suffering from heart failure with reduced ejection fraction. This recurrent coexistence of left ventricular systolic dysfunction (LVSD) and TR is not surprising, considered the multiple etiologies of tricuspid valve disease. TR can complicate heart failure mostly as a functional disease, because of pulmonary hypertension (PH), subsequent to elevated left ventricular end-diastolic pressure, leading to right ventricular dilatation, and valve tethering. Moreover, the so-called “functional isolated” TR can occur, in the absence of PH, as a result of right atrial dilatation associated with atrial fibrillation, a common finding in patients with LVSD. Finally, TR can result as a iatrogenic consequence of transvalvular lead insertion, another frequent scenario in this cohort of patients. Nonetheless, despite the significant coincidence of these two conditions, their mutual relation, and the independent prognostic role of TR is still a matter of debate. Whether significant TR is just a marker for advanced left-heart disease, or a crucial potential therapeutical target, remains unclear. Aim of the authors in this review is to present an update concerning the epidemiological features and the clinical burden of TR in the context of LVSD, its prognostic value, and the potential benefit for early tricuspid intervention in patients affected by contemporary TR and LVSD.