Stress echocardiography (SE) has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease (CAD). We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities. In a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs (initially from Italy, Brazil, Hungary, and Serbia) will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease (such as hypertrophic cardiomyopathy). We expect to recruit about 10,000 patients over a 5-year period (2016-2020), with sample sizes ranging from 5,000 for coronary flow velocity/ left ventricular elastance/ B-lines in CAD to around 250 for hypertrophic cardiomyopathy or repaired Tetralogy of Fallot. This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios. The study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, sharing common criteria of indication, execution, reporting and image storage of SE to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities. The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls.

Insulin resistance (IR) assessed by the Homeostatic Model Assessment (HOMA) index in the acute phase of myocardial infarction in non-diabetic patients was recently established as an independent predictor of intrahospital mortality. In this study we postulated that acute IR is a dynamic phenomenon associated with the development of myocardial and microvascular injury and larger final infarct size in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI).

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021–2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Nicorandil, as a selective potassium channel opener, has dual action including coronary and peripheral vasodilatation and cardioprotective effect through ischemic preconditioning. Considering those characteristics, nicorandil was suggested to reduce the degree of microvascular dysfunction. Thirty-two patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI) were included in the study. Index of microvascular resistance (IMR) was measured in all patients immediatelly after pPCI before the after administration of Nicorandil. ST segment resolution was monitored before intervention and 60 min after terminating the procedure. Echocardiographic evaluation of myocardial function and transthoracic Doppler derived Coronary flow reserve (CFR) of infarct related artery (IRA) was performed during hospitalization and 3 months later. IMR was significantly lower after administration of Nicorandil (9.9 ± 3.7 vs. 14.1 ± 5.1, p < 0.001). There was significant difference in ST segment elevation before and after primary PCI with administration of Nicorandil (6.9 ± 3.7 mm vs. 1.6 ± 1.6 mm, p < 0.001). Transthoracic Doppler CFR measurement improved after 3 months (2.69 ± 0.38 vs. 2.92 ± 0.54, p = 0.021), as well as WMSI (1.14 ± 0.17 vs. 1.07 ± 0.09, p = 0.004). Intracoronary Nicorandil administration after primary PCI significantly decreases IMR, resulting in improved CFR and ventricular function in patients with STEMI undergoing primary PCI.

The aim of the study was to evaluate the relation between fractional flow reserve (FFR) and simultaneously evaluated coronary flow reserve by thermodilution (CFRthermo), with the improvement of left ventricular (LV) function in patients with previous myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). Study population consisted of 46 patients (mean age 53 ± 7 years; 36 male) with previous MI and significant coronary stenosis undergoing PCI of infarct-related coronary artery. In all patients, we evaluated FFR and CFRthermo by single pressure/thermo wire during maximal hyperaemia before and immediately after PCI. We performed echocardiographic assessment of LV ejection fraction before and 6 months after PCI. Dobutamine stress echocardiography test was also performed before PCI. LV functional improvement was observed in 33/46 (72%) of patients. In patients with LV functional recovery in comparison with patients with no recovery, there was a significant difference in FFR before PCI (0.56 ± 0.14 vs. 0.70 ± 0.07, P < 0.001), improvement of FFR (0.35 ± 0.14 vs. 0.21 ± 0.07, P < 0.001), improvement of CFRthermo (1.3 ± 0.6 vs. 0.5 ± 0.3, P < 0.001), and CFRthermo after PCI (2.6 ± 0.7 vs. 2.0 ± 0.4, P < 0.001). When only parameters evaluated before PCI were taken into account, FFR before angioplasty (P = 0.001) and dobutamine-assessed viability (P = 0.006) were the most significant multivariate predictors of myocardial recovery. When all significant univariate parameters were evaluated, the most significant independent predictors for improvement in myocardial function were the improvement of CFRthermo during angioplasty (P < 0.001) and FFR before angioplasty (P = 0.002). Simultaneous evaluation of FFR and CFRthermo provide significant complementary data on the improvement in myocardial function in patients with previous MI. However, the evaluation of FFR before angioplasty identifies viable myocardium that may recover following revascularization and may be used as an alternative to non-invasive testing.

Myocardial ischemia represents a state of reduced coronary perfusion with oxygenated blood, insufficient to meet the metabolic demands of the myocardium. Both acute and chronic ischemia trigger a cascade of cellular events that lead to disturbances in ionic balance, mitochondrial function and energy metabolism. During ischemia, cardiomyocytes (CMs) shift from aerobic to anaerobic metabolism, resulting in adenosine triphosphate (ATP) depletion, loss of ionic homeostasis and calcium (Ca²⁺) overload that activate proteases, phospholipases and membrane damage. Reperfusion restores oxygen supply and prevents irreversible necrosis but paradoxically initiates additional injury in marginally viable myocardium. The reoxygenation phase induces excessive production of reactive oxygen species (ROS), endothelial dysfunction and a strong inflammatory response mediated by neutrophils, platelets and cytokines. Mitochondrial dysfunction and opening of the mitochondrial permeability transition pore (mPTP) further amplify oxidative stress and inflammation and trigger apoptosis and necroptosis. Understanding these intertwined cellular and molecular mechanisms remains essential for identifying novel therapeutic targets aimed at reducing reperfusion injury and improving myocardial recovery after ischemic events.