Ricerc@Sapienza

The innovation of the research can be summarized in four points:
- 1. The RV has long been overlooked by studies regarding cardiac diseases and defined "the forgotten chamber" because considered poorly influential in the clinical manifestations and in the prognosis.
In recent years, a large number of studies have demonstrated how the RV may play a crucial role in the pathogenesis, symptomatology and mortality of patients with heart failure (Kang et al, Am J Physiol Heart Circ Physiol, 2019) compared to LV.
Studies on the RV involvement in DCMs are rare, in terms of both diagnosis and prognosis, as well as it is unknown the potential rule as target of therapy.
Among the few available data, it has clearly emerged that the RV is subject to abundant remodeling in diabetic patients (Whitaker et al, Am. J Med, 2018), even in young people with DMT1 assessed by echocardiography (Karamitsos et al., Int J Cardiol 2007).
The pathophysiology of RV injury certainly shares mechanisms with that of the LV, but we also expect important differences, considering the peculiar tissue composition and the special biomechanical characteristics, linked to the connection with a low pressure regimen.
The RV involvement in DCM has likely been underestimated, and RV role on disease progression to symptomatic stage, clinical deterioration and determination of irreversible myocardial injury is largely unknown.
Conversely, when the RV has been the subject of specific investigations, a direct impact of RV deterioration or involvement to prognosis and clinical manifestation was found. The development of new software equipped with tissue tracking technique now enables a highly sophisticated analysis of global and segmental myocardial contractility on the routinely acquired cineRM sequences, that combine a accurate and precise geometric deformation and displacement of myocardial wall.
Early identification RV involvement in DCM subjects could allow intervention at early stage of dysfunction to prevent the development of more severe complications or evolution to heart failure, with a potential benefit in clinical outcome, reduction of morbidity and mortality.
2. Although the individual's gender is among the most important modulators of cardiovascular risk and response to treatment, the integration of gender in research and clinical decision-making is yet overlooked. In the era of precision medicine, reporting on gender-related variables in clinical trials has become necessary in order to understand how they interact and influence cardiovascular health.
There are many prominent sex differences in diabetes-related cardiac disease. Women generally develop coronary artery disease and myocardial infarction later than men. However, DCM is more prevalent in women as emerged by the few studies available investigating gender differences.
DCM promotes fibrosis and an hypertrophy and it is known how the gender influences the regulation of collagen also occur during the development of hypertrophy. These gender differences in regulation of collagen likely contribute to the altered remodelling in males vs. females following hypertrophy. In addition, also gender differences in contractile proteins have also been reported and may play a role in differences of ventricular remodeling, as defined as the complex of morphology, functional and dimensional features of both ventricles.
3.Morphological (parietal thickness, ventricular shape and volumes) and functional (systolic contraction and diastolic relaxation) myocardial findings have long been evaluated separately from the underlying tissue transformations. Therefore, their associations have only been hypothesized in most of cases or investigated by indirect markers as circulating factors. The CMR has the great power to offer a comprehensive, non invasive and contemporary evaluation of all these aspects and may be highlight their correlations, especially regarding the study of the right ventricle.
4. The unit of personnel that will be recruited with the research grant could also offer a further valuable insight on the effect of diabetes in the geometric remodeling of the RV, identifying patterns of ventricular morphology and shape deformation that could reveal a RV involvement in a subclinical stage.
This would have multiple advantages, such as finding a rapid, reliable and reproducible tool to identify early markers of RV involvement predictive of subsequent functional deterioration and symptomatic evolution of DCM.
Moreover, deep learning techniques applied to a small study population could identify signs of myocardial fibrosis by the simple and fast computerized processing of morphological and functional images, such as cineMRs, which do not require the use of contrast media and would greatly reduce acquisition and analysis time of CMR exams, which currently represent one of the factors that most reduce patient compliance, keeps the cost of the exam high due to long machine and staff occupation times.