The Influence of High-Dose Parenteral Vitamin C on the Incidence and Severity of Postoperative Pulmonary Complications in Cardiac Surgery with Extracorporeal Circulation: A Randomized Controlled Trial.

Cardiac surgery (CS) with extracorporeal circulation (ECC), induces intense oxidative stress (OS) and systemic inflammatory response (SIR), which may seriously affect postoperative lung function. We aimed to test if high parenteral (200 mg/kg/24 h) daily doses of Vitamin C (VitC), given within 48 h after the beginning of the operation, may reduce the incidence and severity of postoperative pulmonary complications (PPCs) in CS patients. This single-center, prospective, randomized, single-blinded, interventional trial included 150 patients, assigned to control Group A (n = 75) and interventional Group B (n = 75). Group B intraoperatively received one-fourth (i.e., 50 mg/kg) of the planned daily Vit C dose, divided into three equal parts and diluted in 10 mL of normal saline, while Group A received an equal volume of normal saline at the same time frames (i.e., the induction of anesthesia, aortic cross-clamp release, and sternal closure). After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 50 mg/kg, 30 min i.v. infusion of VitC in 50 mL of normal saline, every 6 h, for the next 48 h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 h, for the next 48 h. Modified Kroenke's score was used to determine the incidence and severity of PPCs. The overall incidence of PPCs was 36.7% and was significantly lower in Group B (13.3% vs. 60.0%, p < 0.001). The PPCs severity score was also significantly lower in Group B (1 vs. 3, p < 0.001). In addition, patients from Group B had significantly less damaged lungs, better postoperative renal function, shorter ICU stays, fewer ICU re-admissions, and lower hospital mortality. No VitC-related adverse effects were recorded. High parenteral daily VitC doses given within 48 h after the beginning of CS are safe and effective in reducing the incidence and severity of PPCs. A multicenter RCT is needed to confirm these results.

Acquired von Willebrand syndrome and post-operative drainage: a comparison of patients with aortic stenosis versus coronary artery disease.

OBJECTIVE: Degenerative aortic stenosis and coronary artery disease are considered to be the most prevalent cardiovascular diseases in industrialized countries. This study aims to determine the change over time in von Willebrand factor antigen, von Willebrand factor activity, and factor VIII and where there is a correlation with total post-operative drainage. METHODS: The single-center retrospective study included 203 consecutive patients (64.5% male), undergoing coronary artery bypass surgery between March 1, 2019 and June 30, 2020 at the University Clinical Center of Serbia in the Clinic for Cardiac Surgery in Belgrade, Serbia. All patients 18 years or older who presented with isolated, hemodynamically significant aortic stenosis were included. The control group consisted of patients who presented with only coronary artery disease. RESULTS: Between patients with only coronary artery disease and patients with coronary artery diseases and aortic stenosis, there was a statistically significant difference between pre-op and 1-month post-op fibrinogen, factor VIII, von Willebrand factor antigen, and von Willebrand factor (p < 0.001), post-op drainage, with overall lower drainage in coronary artery disease patients, and consistent increase in von Willebrand factor antigen, von Willebrand factor activity, and Factor VIII post-operatively in patients with coronary artery diseases and aortic stenosis. CONCLUSION: This study has shown that there is a correlation between von Willebrand factor antigen, von Willebrand factor activity and total drainage to the level of statistical significance in aortic stenosis patients and in the overall study population.

Update on Myocarditis: From Etiology and Clinical Picture to Modern Diagnostics and Methods of Treatment.

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic methods. The multitude of different etiological factors, the diversity of the clinical picture, and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated with diseases that in their natural course can lead to myocardial involvement, as well as the iatrogenic cause of myocarditis, which is due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, such as changes in ECG and echocardiography readings, has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive and is the gold standard for diagnosis and clinical follow-up of these patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening cases with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support, and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high.

Cardiac tamponade.

Cardiac tamponade is a medical emergency caused by the progressive accumulation of pericardial fluid (effusion), blood, pus or air in the pericardium, compressing the heart chambers and leading to haemodynamic compromise, circulatory shock, cardiac arrest and death. Pericardial diseases of any aetiology as well as complications of interventional and surgical procedures or chest trauma can cause cardiac tamponade. Tamponade can be precipitated in patients with pericardial effusion by dehydration or exposure to certain medications, particularly vasodilators or intravenous diuretics. Key clinical findings in patients with cardiac tamponade are hypotension, increased jugular venous pressure and distant heart sounds (Beck triad). Dyspnoea can progress to orthopnoea (with no rales on lung auscultation) accompanied by weakness, fatigue, tachycardia and oliguria. In tamponade caused by acute pericarditis, the patient can experience fever and typical chest pain increasing on inspiration and radiating to the trapezius ridge. Generally, cardiac tamponade is a clinical diagnosis that can be confirmed using various imaging modalities, principally echocardiography. Cardiac tamponade is preferably resolved by echocardiography-guided pericardiocentesis. In patients who have recently undergone cardiac surgery and in those with neoplastic infiltration, effusive-constrictive pericarditis, or loculated effusions, fluoroscopic guidance can increase the feasibility and safety of the procedure. Surgical management is indicated in patients with aortic dissection, chest trauma, bleeding or purulent infection that cannot be controlled percutaneously. After pericardiocentesis or pericardiotomy, NSAIDs and colchicine can be considered to prevent recurrence and effusive-constrictive pericarditis.

Dilemmas in the Choice of Adequate Therapeutic Treatment in Patients with Acute Pulmonary Embolism-From Modern Recommendations to Clinical Application.

Pulmonary thromboembolism is a very common cardiovascular disease, with a high mortality rate. Despite the clear guidelines, this disease still represents a great challenge both in diagnosis and treatment. The heterogeneous clinical picture, often without pathognomonic signs and symptoms, represents a huge differential diagnostic problem even for experienced doctors. The decisions surrounding this therapeutic regimen also represent a major dilemma in the group of patients who are hemodynamically stable at initial presentation and have signs of right ventricular (RV) dysfunction proven by echocardiography and positive biomarker values (pulmonary embolism of intermediate-high risk). Studies have shown conflicting results about the benefit of using fibrinolytic therapy in this group of patients until hemodynamic decompensation, due to the risk of major bleeding. The latest recommendations give preference to new oral anticoagulants (NOACs) compared to vitamin K antagonists (VKA), except for certain categories of patients (patients with antiphospholipid syndrome, mechanical valves, pregnancy). When using oral anticoagulant therapy, special attention should be paid to drug-drug interactions, which can lead to many complications, even to the death of the patient. Special population groups such as pregnant women, obese patients, patients with antiphospholipid syndrome and the incidence of cancer represent a great therapeutic challenge in the application of anticoagulant therapy. In these patients, not only must the effectiveness of the drugs be taken into account, but great attention must be paid to their safety and possible side effects, which is why a multidisciplinary approach is emphasized in order to provide the best therapeutic option.

Prevention of sudden death in heart failure with reduced ejection fraction: do we still need an implantable cardioverter-defibrillator for primary prevention?

Sudden death is a devastating complication of heart failure (HF). Current guidelines recommend an implantable cardioverter-defibrillator (ICD) for prevention of sudden death in patients with HF and reduced ejection fraction (HFrEF) specifically those with a left ventricular ejection fraction ≤35% after at least 3 months of optimized HF treatment. The benefit of ICD in patients with symptomatic HFrEF caused by coronary artery disease has been well documented; however, the evidence for a benefit of prophylactic ICD implantation in patients with HFrEF of non-ischaemic aetiology is less strong. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers (BB), and mineralocorticoid receptor antagonists (MRA) block the deleterious actions of angiotensin II, norepinephrine, and aldosterone, respectively. Neprilysin inhibition potentiates the actions of endogenous natriuretic peptides that mitigate adverse ventricular remodelling. BB, MRA, angiotensin receptor-neprilysin inhibitor (ARNI) have a favourable effect on reduction of sudden cardiac death in HFrEF. Recent data suggest a beneficial effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in reducing serious ventricular arrhythmias and sudden cardiac death in patients with HFrEF. So, in the current era of new drugs for HFrEF and with the optimal use of disease-modifying therapies (BB, MRA, ARNI and SGLT2i), we might need to reconsider the need and timing for use of ICD as primary prevention of sudden death, especially in HF of non-ischaemic aetiology.

Heart Failure Association, Heart Failure Society of America, and Japanese Heart Failure Society Position Statement on Endomyocardial Biopsy.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumors. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples has significantly improved the diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (1) an overview of the practical approach to EMB, (2) an update on indications for EMB, (3) a revised plan for heart transplant rejection surveillance, (4) the impact of multimodality imaging on EMB, and (5) the current clinical practice in the worldwide use of EMB.

Heart Failure Association of the ESC, Heart Failure Society of America and Japanese Heart Failure Society Position statement on endomyocardial biopsy.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples have significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (i) an overview of the practical approach to EMB, (ii) an update on indications for EMB, (iii) a revised plan for HTx rejection surveillance, (iv) the impact of multimodality imaging on EMB, and (v) the current clinical practice in the worldwide use of EMB.

Positron emission tomography in clinically suspected myocarditis - STREAM study design.

AIM: Myocarditis is an inflammatory disease associated with increased glucose uptake. The hypothesis of this study assumes that 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) may improve specificity and sensitivity in the diagnosis of myocarditis and referral for endomyocardial biopsy (EMB), adding additional information for post-discharge risk stratification. The aim of the study is to assess the diagnostic and prognostic feasibility of FDG-PET/CT in comparison to cardiac magnetic resonance (CMR) (alone or in combination) in patients with clinically suspected myocarditis undergoing EMB. METHODS: Fifty hospitalized patients with clinically suspected myocarditis who meet the inclusion/exclusion criteria will be enrolled in a prospective, observational, multicentre, cohort study (NCT04085718). The primary endpoint is the sensitivity and specificity of FDG-PET/CT imaging in the diagnosis of myocarditis. The main secondary endpoints include correlation of FDG-PET/CT imaging with CMR, echocardiography, and EMB results. The patients will undergo the following evaluations: clinical examination, blood tests (including biomarkers of fibrosis and anti-heart autoantibodies (AHA)), ECG, 24 h Holter ECG, echocardiography, CMR, as well as resting single photon emission computed tomography (SPECT) to assess possible myocardial perfusion defects, cardiac FDG-PET/CT and right ventricular EMB. After 6-months a follow-up visit will be performed (including 24 h Holter ECG, echocardiography and CMR). Investigators evaluating individual studies (CMR, SPECT, FDG-PET/CT and EMB) are to be blinded to the other tests' results. CONCLUSION: We believe that FDG-PET/CT alone or in combination with CMR may be a useful tool for improving diagnostic accuracy in patients with clinically suspected myocarditis.

Design of the SILICOFCM study: Effect of sacubitril/valsartan vs lifestyle intervention on functional capacity in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease with a broad spectrum of disease severity. HCM ranges from a benign course to a progressive disorder characterized by angina, heart failure, malignant arrhythmia, syncope, or sudden cardiac death. So far, no medical treatment has reliably shown to halt or reverse progression of HCM or to alleviate its symptoms. While the angiotensin receptor neprilysin inhibitor sacubitril/valsartan has shown to reduce mortality and hospitalization in heart failure with reduced ejection fraction, data on its effect on HCM are sparse. HYPOTHESIS: A 4-month pharmacological (sacubitril/valsartan) or lifestyle intervention will significantly improve exercise tolerance (ie, peak oxygen consumption) in patients with nonobstructive HCM compared to the optimal standard therapy (control group). METHODS: SILICOFCM is a prospective, multicenter, open-label, randomized, controlled, three-arm clinical trial (NCT03832660) that will recruit 240 adult patients with a confirmed diagnosis of nonobstructive HCM. Eligible patients are randomized to sacubitril/valsartan, lifestyle intervention (physical activity and dietary supplementation with inorganic nitrate), or optimal standard therapy alone (control group). The primary endpoint is the change in functional capacity (ie, peak oxygen consumption). Secondary endpoints include: (a) Change in cardiac structure and function as assessed by transthoracic echocardiography and cardiac magnetic resonance (MRI imaging), (b) change in biomarkers (ie, CK, CKMB, and NT-proBNP), (c) physical activity, and (d) quality of life. RESULTS: Until December 2019, a total of 41 patients were recruited into the ongoing SILICOFCM study and were allocated to the study groups and the control group. There was no significant difference in key baseline characteristics between the three groups. CONCLUSION: The SILICOFCM study will provide novel evidence about the effect of sacubitril/valsartan or lifestyle intervention on functional capacity, clinical phenotype, injury and stretch activation markers, physical activity, and quality of life in patients with nonobstructive HCM.

Heart failure in cardiomyopathies: a position paper from the Heart Failure Association of the European Society of Cardiology.

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and ∼10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies.

Treatments targeting inotropy.

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.

Streptococcus Gallolyticus endocarditis in patient with liver cirrhosis: a case report.

Streptococcus gallolyticus (S. gallolyticus) bacteremia is commonly associated with endocarditis and diseases of gastrointestinal tract, especially with colorectal carcinoma. On the other side, it is rarely connected to liver disease, especially alcoholic liver disease. A 44-old patient with a history of one month fever, pre-existing heart murmur and previous alcohol abuse, was treated in Clinic for Infectious and tropical diseases, Clinical Centre of Serbia (CCS), Belgrade. The diagnose of infective endocarditis (IE) of the aortic valve caused by S. gallolyticus has been established. Despite the conducted antibiotic treatment based on antibiogram, pericardial effusion with paracardial aortic abscess was diagnosed on the 9th day of treatment. Pericardiocentesis was done and 800 mL of haemorrhagic fluid was evacuated in the Clinic for Cardiology, CCS. Unfortunately, 20th day of hospitalization the patient died. Clinical autopsy confirmed endocarditis, liver cirrhosis and chronic pericarditis. Prognosis of the outcome of treatment of patient with endocarditis caused S. gallolyticus and liver cirrhosis is not optimistic. Therefore, significant attention should be given to patients with liver cirrhosis and febrile of unknown origin.

Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology.

This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co-morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short-term mechanical circulatory support devices for immediate management of cardiogenic shock and long-term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co-morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence-based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population.

Percutaneous Therapy in Pericardial Diseases.

Interventional procedures for pericardial diseases include pericardiocentesis, drainage of pericardial effusion, intrapericardial therapy, and percutaneous balloon pericardiotomy or percutaneous pericardiostomy. Echocardiographic and fluoroscopic guidance have greatly increased safety and feasibility. Several devices for pericardiocentesis have been tested (PerDucer, PeriAttacher, visual puncture systems, Grasper, Scissors, and Reverse slitter), mainly to facilitate access to the pericardium in the absence of effusion for epicardial ablations or left atrial appendage ligation. In selected patients with pericardial effusions that cannot be managed medically or with prolonged drainage, various medications can be applied intrapericardially to prevent further recurrences or induce sclerosis of the pericardial space.

Management and Outcome of Periprocedural Cardiac Perforation and Tamponade with Radiofrequency Catheter Ablation of Cardiac Arrhythmias: A Single Medium-Volume Center Experience.

INTRODUCTION: Cardiac tamponade (CT) is a life-threatening complication of radiofrequency ablation (RFA). The course and outcome of CT in low-to-medium volume electrophysiology centers are underreported. METHODS: We analyzed the incidence, management and outcomes of CT in 1500 consecutive RFAs performed in our center during 2011-2016. RESULTS: Of 1500 RFAs performed in 1352 patients (age 55 years, interquartile range: 41-63), 569 were left-sided procedures (n = 406 with transseptal access). Conventional RFA or irrigated RFA was performed in 40.9% and 59.1% of procedures, respectively. Ablation was performed mostly for atrioventricular nodal reentrant tachycardia (25.4%), atrial fibrillation (AF; 18.5%), atrial flutter (18.4%), accessory pathway (16.5%) or idiopathic ventricular arrhythmia (VA; 12.3%), and rarely for structural VA (2.1%). CT occurred in 12 procedures (0.8%): 10 AF ablations, 1 idiopathic VA and 1 typical atrial flutter ablation. Factors significantly associated with CT were older age, pre-procedural oral anticoagulation, left-sided procedures, transseptal access, AF ablation, irrigated RFA and longer fluoroscopy time (on univariate analysis), and AF ablation (on multivariable analysis). The perforation site was located in the left atrium (n = 7), right atrium (n = 3), or in the left ventricle or coronary sinus (n = 1 each). Upon pericardiocentesis, two patients underwent urgent cardiac surgery because of continued bleeding. There was no fatal outcome. During the follow-up of 19 ± 14 months, eight patients were arrhythmia free. CONCLUSION: Incidence of RFA-related CT in our medium-volume center was low and significantly associated with AF ablation. The outcome of CT was mostly favorable after pericardiocentesis, but readily accessible cardiothoracic surgery back-up should be mandatory in RFA centers.

Diabetes mellitus and coronary microvascular function in asymptomatic patients with severe aortic stenosis and nonobstructed coronary arteries.

BACKGROUND AND AIM: Coronary flow reserve is impaired in asymptomatic patients with aortic stenosis and has a prognostic value. We investigated whether the type II diabetes mellitus additionally impairs microvascular circulation assessed by coronary flow reserve in patients with asymptomatic severe aortic stenosis, normal left ventricular ejection fraction and nonobstructed coronary arteries. METHODS: A total of 128 patients, mean age of 66.35 ± 10.51 (58.6% males), with severe aortic stenosis and normal left ventricular ejection fraction were enrolled in this study. Patients with diabetes mellitus, those who were treated for diabetes mellitus or had documentation confirming the diagnosis of diabetes mellitus, were considered. All patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis >50% in diameter), standard transthoracic Doppler-echocardiographic study and adenosine stress transthoracic echocardiography for coronary flow reserve measurement. RESULTS: Diabetes mellitus was present in 26 patients (20.31%). There was no significant difference in aortic stenosis severity between diabetic and non-diabetic patients [aortic valve area (0.81 ± 0.18 vs 0.85 ± 0.15 cm(2)) and Vmax (4.20 ± 0.57 vs 4.21 ± 0.48 m/s)]. Mean coronary flow reserve in diabetic patients was 1.98 ± 0.48, while mean coronary flow reserve in non-diabetic patients was 2.64 ± 0.54 (p < 0.01). Diabetes mellitus was independent predictor of coronary flow reserve [B = -0.636, 95% confidence interval (-0.916 to -0.368), p < 0.001]. CONCLUSION: Diabetes mellitus additionally impairs coronary microvascular function in asymptomatic patients with severe aortic stenosis and nonobstructed coronary arteries.