Background: Functional assessment of myocardial bridging (MB) remains clinically challenging because of the dynamic nature of the extravascular coronary compression with a certain degree of intraluminal coronary reduction. The aim of our study was to assess performance and diagnostic value of diastolic‐fractional flow reserve (d‐FFR) during dobutamine provocation versus conventional‐FFR during adenosine provocation with exercise‐induced myocardial ischemia as reference. Methods and Results: This prospective study includes 60 symptomatic patients (45 men, mean age 57±9 years) with MB on the left anterior descending artery and systolic compression ≥50% diameter stenosis. Patients were evaluated by exercise stress‐echocardiography test, and both conventional‐FFR and d‐FFR in the distal segment of left anterior descending artery during intravenous infusion of adenosine (140 μg/kg per minute) and dobutamine (10–50 μg/kg per minute), separately. Exercise–stress‐echocardiography test was positive for myocardial ischemia in 19/60 patients (32%). Conventional‐FFR during adenosine and peak dobutamine had similar values (0.84±0.04 versus 0.84±0.06, P =0.852), but d‐FFR during peak dobutamine was significantly lower than d‐FFR during adenosine (0.76±0.08 versus 0.79±0.08, P =0.018). Diastolic‐FFR during peak dobutamine was significantly lower in the exercise‐stress‐echocardiography test –positive group compared with the exercise‐ stress‐echocardiography test –negative group (0.70±0.07 versus 0.79±0.06, P <0.001), but not during adenosine (0.79±0.07 versus 0.78±0.09, P =0.613). Among physiological indices, d‐FFR during peak dobutamine was the only independent predictor of functionally significant MB (odds ratio, 0.870; 95% CI, 0.767–0.986, P =0.03). Receiver‐operating characteristics curve analysis identifies the optimal d‐FFR during peak dobutamine cut‐off ≤0.76 (area under curve, 0.927; 95% CI, 0.833–1.000; P <0.001) with a sensitivity, specificity, and positive and negative predictive value of 95%, 95%, 90%, and 98%, respectively, for identifying MB associated with stress‐induced ischemia. Conclusions: Diastolic‐FFR, but not conventional‐FFR, during inotropic stimulation with high‐dose dobutamine, in comparison to vasodilatation with adenosine, provides more reliable functional significance of MB in relation to stress‐induced myocardial ischemia.

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.

Background: Microvascular dysfunction might be a major determinant of clinical deterioration and outcome in patients with hypertrophic cardiomyopathy (HCM). However, long‐term prognostic value of transthoracic Doppler echocardiography (TDE) coronary flow velocity reserve (CFVR) on clinical outcome is uncertain in HCM patients. Therefore, the aim of our study was to assess long‐term prognostic value of CFVR on clinical outcome in HCM population. Methods and Results: We prospectively included 150 HCM patients (82 women; mean age 48±15 years). Patients’ clinical characteristics, echocardiographic and CFVR findings (both for left anterior descending [LAD] and posterior descending artery [PD]), were assessed in all patients. The primary outcome was a composite of: HCM related death, heart failure requiring hospitalization, sustained ventricular tachycardia and ischemic stroke. Patients were stratified into 2 subgroups depending on CFVR LAD value: Group 1 (CFVR LAD>2, [n=87]) and Group 2 (CFVR LAD≤2, [n=63]). During a median follow‐up of 88 months, 41/150 (27.3%) patients had adverse cardiac events. In Group 1, there were 8/87 (9.2%), whereas in Group 2 there were 33/63 (52.4%, P <0.001 vs. Group 1) adverse cardiac events. By Kaplan‐Meier analysis, patients with preserved CFVR LAD had significantly higher cumulative event‐free survival rate compared to patients with impaired CFVR LAD (96.4% and 90.9% versus 66.9% and 40.0%, at 5 and 8 years, respectively: log‐rank 37.2, P <0.001). Multivariable analysis identified only CFVR LAD≤2 as an independent predictor for adverse cardiac outcome (HR 6.54; 95% CI 2.83–16.30, P <0.001), while CFVR PD was not significantly associated with outcome. Conclusions: In patients with HCM, impaired CFVR LAD (≤2) is a strong, independent predictor of adverse cardiac outcome. When the aim of testing is HCM risk stratification and CFVR LAD data are available, the evaluation of CFVR PD is redundant.

Coronary atherosclerosis in patients with diabetes mellitus is the most significant pathophysiological mechanism responsible for ischemic heart disease. Atherosclerosis in diabetes is premature, more diffuse, and more progressive, and it affects more coronary blood vessels compared to non-diabetics. Atherosclerosis begins with endothelial dysfunction, continues with the formation of fatty streaks in the intima of coronary arteries, and ends with the appearance of an atherosclerotic plaque that expands centrifugally and remodels the coronary artery. If the atherosclerotic plaque is injured, a thrombus forms at the site of the damage, which can lead to vessel occlusion and potentially fatal consequences. Diabetes mellitus and atherosclerosis are connected through several pathological pathways. Among the most significant factors that lead to atherosclerosis in diabetics are hyperglycemia, insulin resistance, oxidative stress, dyslipidemia, and chronic inflammation. Chronic inflammation is currently considered one of the most important factors in the development of atherosclerosis. However, to date, no adequate anti-inflammatory therapeutic measures have been found to prevent the progression of the atherosclerotic process, and they remain a subject of ongoing research. In this review, we summarize the most significant pathophysiological mechanisms that link atherosclerosis and diabetes mellitus.