The sGCa Vericiguat Exhibit Cardioprotective and Anti-Sarcopenic Effects through NLRP-3 Pathways: Potential Benefits for Anthracycline-Treated Cancer Patients.

Anthracycline-induced cardiomyopathies and sarcopenia are frequently seen in cancer patients, affecting their overall survival and quality of life; therefore, new cardioprotective and anti-sarcopenic strategies are needed. Vericiguat is a new oral guanylate cyclase activator that reduces heart failure hospitalizations or cardiovascular death. This study highlighted the potential cardioprotective and anti-sarcopenic properties of vericiguat during anthracycline therapy. Human cardiomyocytes and primary skeletal muscle cells were exposed to doxorubicin (DOXO) with or without a pre-treatment with vericiguat. Mitochondrial cell viability, LDH, and Cytochrome C release were performed to study cytoprotective properties. Intracellular Ca++ content, TUNEL assay, cGMP, NLRP-3, Myd-88, and cytokine intracellular levels were quantified through colorimetric and selective ELISA methods. Vericiguat exerts significant cytoprotective and anti-apoptotic effects during exposure to doxorubicin. A drastic increase in cGMP expression and reduction in NLRP-3, MyD-88 levels were also seen in Vericiguat-DOXO groups vs. DOXO groups (p < 0.001) in both cardiomyocytes and human muscle cells. GCa vericiguat reduces cytokines and chemokines involved in heart failure and sarcopenia. The findings that emerged from this study could provide the rationale for further preclinical and clinical investigations aimed at reducing anthracycline cardiotoxicity and sarcopenia in cancer patients.

Use of cangrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Study design and interim analysis of the ARCANGELO study.

BACKGROUND: The itAlian pRospective Study on CANGrELOr (ARCANGELO) was aimed to assess the safety of using cangrelor during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) in the daily practice. HYPOTHESIS: The safety of cangrelor after the transition to oral P2Y12 inhibitors was evaluated as the incidence of bleeding outcomes in the 30 days following PCI according to postauthorization safety study guidelines. METHODS: Adults with ACS who were treated with cangrelor in one of the 28 centers involved in the study. Patients who consented to participate were followed in the 30 days following their PCI. Bleedings (Bleeding Academic Research Consortium [BARC] classification), major adverse cardiac events (MACEs), and adverse events were recorded. The interim results at two-thirds of the enrollment period are presented. RESULTS: A total of 17 bleedings were observed in the 320 patients who completed the study at this stage. All bleedings were classified as BARC Type 1-2, except for one case of Type 3a (vessel puncture site hematoma). Four patients experienced MACEs (2 acute myocardial infarctions, 1 sudden cardiac death, 1 noncardiovascular death due to respiratory distress, and multiorgan failure). None of the bleedings was rated as related to cangrelor. CONCLUSIONS: The interim results of the ARCANGELO study provide a preliminary confirmation that the use of cangrelor on patients with ACS undergoing PCI is not associated with severe bleedings.

The Pharmacological Approach to Oncologic Patients with Acute Coronary Syndrome.

Among acute coronary syndrome (ACS) patients, 15% have concomitant cancer, especially in the first 6 months after their diagnosis, as well as in advanced metastatic stages. Lung, gastric, and pancreatic cancers are the most frequent malignancies associated with ACS. Chemotherapy and radiotherapy exert prothrombotic, vasospastic, and proinflammatory actions. The management of cancer patients with ACS is quite challenging: percutaneous revascularization is often underused, and antiplatelet and anticoagulant pharmacological therapy should be individually tailored to the thrombotic risk and to the bleeding complications. Sometimes oncological patients also show different degrees of thrombocytopenia, which further complicates the pharmacological strategies. The aim of this review is to summarize the current evidence regarding the treatment of ACS in cancer patients and to suggest the optimal management and therapy to reduce the risk of adverse coronary events after ACS in this high-risk population.

Safety and feasibility of balloon aortic valvuloplasty in non-TAVI centers: The "BAV for life" experience.

OBJECTIVES: To evaluate the safety and the feasibility of balloon aortic valvuloplasty (BAV) procedure made by trained operators in centers not performing transcatheter aortic valve implantation (TAVI). BACKGROUND: BAV is a valuable therapeutic tool for patients with symptomatic severe aortic valve stenosis (AS) at prohibitive risk for TAVI or surgery. METHODS: Consecutive high-risk AS patients underwent BAV in five non-TAVI centers, where BAV operators had completed a 6-month training period in high-volume TAVI centers (Group A). All clinical, echocardiographic, and procedural data were prospectively collected and compared with data of patients treated in TAVI center (Group B). RESULTS: Between June 2016 and June 2017, 55 patients (83.9 ± 7.0 years) were enrolled: 25 in Group A and 30 in Group B. After BAV, a substantial reduction of the peak-to-peak aortic valve gradient was obtained in both groups (-35.3 ± 15.2 vs -28.8 ± 13.9 mmHg, P =0.25). No major bleeding or vascular complications occurred. In-hospital death was observed in three patients of Group A and two patients of Group B (P =0.493). The mean follow-up time was 303 ± 188 days; no patients were lost. The 1-year survival free from overall death (Group A 75.8% vs Group B 68.8%; P =0.682) and heart failure rehospitalization (Group A 73.0% vs Group B 66.8%; P =0.687) was similar in the two groups. At multivariable analysis, low left ventricular (LV) ejection fraction (HR: 0.943; P = 0.011) and cardiogenic shock (HR: 5.128; P = 0.002) at admission were independent predictors of mortality. CONCLUSIONS: BAV is a safe and effective procedure that can be performed by trained operators in centers not performing TAVI.

[ANMCO position paper on sacubitril/valsartan in the management of patients with heart failure]. / Position paper ANMCO sull'utilizzo della terapia con sacubitril/valsartan nel paziente con scompenso cardiaco.

Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is the first medication to demonstrate a mortality benefit in patients with chronic heart failure and reduced ejection fraction (HFrEF) since the early 2000s. Sacubitril/valsartan simultaneously suppresses renin-angiotensin-aldosterone system activation through blockade of angiotensin II type 1 receptors and enhances the activity of vasoactive peptides including natriuretic peptides, through inhibition of neprilysin, the enzyme responsible for their degradation. In the landmark PARADIGM-HF trial, patients with HFrEF treated with sacubitril/valsartan had a 20% reduction in the primary composite endpoint of cardiovascular death or heart failure hospitalization, a 20% lower risk of cardiovascular death, a 21% to 20% lower risk of a first heart failure hospitalization, and a 16% to 20% lower risk of death from any cause, compared with subjects allocated to enalapril (all p<0.001).Following the trial, new international guidelines endorsed sacubitril/valsartan as a class I recommendation for the management of patients with HFrEF who remain symptomatic despite optimal medical management. In Italy, sacubitril/valsartan is reimbursed by the National Health Service since March 2017 within criteria set by the Italian Medicines Agency subject to patient inclusion in a dedicated monitoring registry. Although numerous post-hoc analyses of the original trial suggested that the benefits of this innovative medication may extend across a variety of subgroups, many questions do not yet have an evidence-based answer.In this position paper, we discuss the current role of sacubitril/valsartan in the management of chronic HFrEF, treatment eligibility and the modulating role of patients' characteristics. Moreover, we address concerns elicited by the PARADIGM-HF study and shortcomings of this novel drug, to clarify the place of this new therapy in the context of global care of heart failure in Italy. Our aim is to provide clinical cardiologists with a concise and practical guidance on when and how to use sacubitril/valsartan, to assist clinicians in closing the gap between scientific innovation and real-world experience.

Mitral Prolapse: An Old Mysterious Entity - The Incremental Role of Multimodality Imaging in Sports Eligibility.

Mitral valve prolapse is generally a benign condition characterized by fibromyxomatous changes of the mitral leaflet with displacement into the left atrium and late-systolic regurgitation. Although it is an old clinical entity, it still arouses perplexity in diagnosis and clinical management. Complications, such as mitral regurgitation (MR), atrial fibrillation, congestive heart failure, endocarditis, ventricular arrhythmias, and sudden cardiac death (SCD), have been reported. A large proportion of the overall causes of SCD in young competitive athletes is explained by mitral valve prolapse. Recent studies have shown the fibrosis of the papillary muscles and inferobasal left ventricular wall in mitral valve prolapse, suggesting a possible origin of ventricular fatal arrhythmias. Athletes with mitral valve prolapse and MR should undergo annual evaluations including physical examination, echocardiogram, and exercise stress testing to evaluate the cardiovascular risks of competitive sports and obtain the eligibility. In this setting, multimodality imaging techniques - echocardiography, cardiac magnetic resonance, and cardiac computed tomography - should provide a broad spectrum of information, from diagnosis to clinical management of the major clinical profiles of the disease.

Consensus Document of the Italian Association of Hospital Cardiologists (ANMCO), Italian Society of Cardiology (SIC), Italian Association of Interventional Cardiology (SICI-GISE) and Italian Society of Cardiac Surgery (SICCH): clinical approach to pharmacologic pre-treatment for patients undergoing myocardial revascularization procedures.

The wide availability of effective drugs in reducing cardiovascular events together with the use of myocardial revascularization has greatly improved the prognosis of patients with coronary artery disease. The combination of antithrombotic drugs to be administered before the knowledge of the coronary anatomy and before the consequent therapeutic strategies, can allow to anticipate optimal treatment, but can also expose the patients at risk of bleeding that, especially in acute coronary syndromes, can significantly weigh on their prognosis, even more than the expected theoretical benefit. In non ST-elevation acute coronary syndromes patients in particular, we propose a 'selective pre-treatment' with P2Y12 inhibitors, based on the ischaemic risk, on the bleeding risk and on the time scheduled for the execution of coronary angiography. Much of the problems concerning this issue would be resolved by an early access to coronary angiography, particularly for patients at higher ischaemic and bleeding risk.

ANMCO Position Paper: the use of non-vitamin K dependent new oral anticoagulant(s) in pulmonary embolism therapy and prevention.

The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including (i) their mechanism of action, pharmacodynamics, and pharmacokinetics; (ii) the use in the acute phase with the 'double drug single dose' approach or with 'single drug double dose'; (iii) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; (iv) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance > 30 mL/min), the elderly (>75 years); (v) they propose a possible laboratory clinical pathway for follow-up; and (vi) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications. The authors conclude that the use of NOACs both in the acute phase and in the extended phase is equally effective to conventional therapy and associated with fewer major bleeding events, which make their use in patients at higher risk of recurrences safer.

[ANMCO position paper: Use of new oral anticoagulants for the treatment and prevention of pulmonary thromboembolism]. / Position paper ANMCO: Uso dei nuovi anticoagulanti orali nella terapia e nella prevenzione della tromboembolia polmonare.

The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including 1) their mechanism of action, pharmacodynamics and pharmacokinetics; 2) the use in the acute phase with the "double drug single dose" approach or with "single drug double dose"; 3) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; 4) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance >30 ml/min), the elderly (>75 years); 5) they propose a possible laboratory clinical pathway for follow-up; 6) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications. The authors conclude that the use of NOACs both in the acute phase and in the extended phase is equally effective to conventional therapy and associated with fewer major bleeding events, which make their use in patients at higher risk of recurrences safer.

[ANMCO statement on prevention of thromboembolism in atrial fibrillation and role of the new oral anticoagulants]. / Documento ANMCO su prevenzione del tromboembolismo nella fibrillazione atriale e ruolo dei nuovi anticoagulanti orali.

The introduction in the therapeutic armamentarium of three new oral anticoagulants for the prevention of thromboembolism in atrial fibrillation (AF) has stimulated the development of this position paper from the Italian Association of Hospital Cardiologists (ANMCO). First, the pathophysiology of arterial thromboembolism in AF is reviewed, describing the mechanisms of action of the new oral anticoagulants, their pharmacology and pharmacokinetics, and highlighting differences and similarities observed in preclinical studies and trials. Stratification of thromboembolic and bleeding risk is made using different risk scores; a comprehensive analysis of the various international guidelines should emphasize convergences or divergences. An in-depth examination of the limitations of current therapeutic strategies for the prevention of stroke in non-valvular AF provides insight into the difficulty in maintaining adequate adherence to therapy with warfarin and a constant and effective anticoagulation, without wide fluctuations in prothrombin time international normalized ratio (INR) values. Clinical trials of new oral anticoagulants for AF are discussed in detail in the present document, with a focus on similarities and differences, efficacy and safety data, and the net clinical benefit of each new oral anticoagulant. Results obtained in elderly patients, or in patients with renal, liver and ischemic heart disease or previous stroke are reported separately, as well as those regarding combination therapy with antiplatelet agents. Finally, this document provides indications, practical applications and cost-effectiveness analysis of each new oral anticoagulant. It is of utmost importance to know how treatment should be started, how you should switch from warfarin, which patients should be maintained on warfarin, how and when cardioversion, catheter ablation or appendage closure should be performed, what drug and food interactions may affect these medications, and how treatment adherence may be improved to avoid therapy discontinuation. An accurate examination of the risk of bleeding is also provided, with special reference to laboratory monitoring of renal and hepatic function, timing for discontinuing these medications prior to surgery, and treatment of patients with major and minor bleeding.

[Cardiovascular risk profile and lifestyle habits in a cohort of Italian cardiologists. Results of the SOCRATES survey]. / Profilo di rischio cardiovascolare e stili di vita in una coorte di cardiologi Italiani. risultati della survey SOCRATES (Survey on Cardiac Risk Profile and Lifestyle Habits in a Cohort of Italian Cardiologists).

OBJECTIVES: To offer a snapshot of the personal health habits of Italian cardiologists, the Survey on Cardiac Risk Profile and Lifestyle Habits in a Cohort of Italian Cardiologists (SOCRATES) study was undertaken. BACKGROUND: Cardiologists' cardiovascular profile and lifestyle habits are poorly known worldwide. METHODS: A Web-based electronic self-reported survey, accessible through a dedicated website, was used for data entry, and data were transferred via the web to a central database. The survey was divided in 4 sections: baseline characteristics, medical illnesses and traditional cardiovascular risk factors, lifestyle habits and selected medication use. The e-mail databases of three national scientific societies were used to survey a large and representative sample of Italian cardiologists. RESULTS: During the 3-month period of the survey, 1770 out of the 5240 cardiologists contacted (33.7%) completed and returned one or more sections of the questionnaire. More than 49% of the participants had 1 out of 5 classical risk factors (e.g. hypertension, hypercholesterolemia, active smoking, diabetes and previous vascular events). More than 28% of respondents had 2 to 5 risk factors and only 22.1% had none and therefore, according to age and sex, could be considered at low-intermediate risk. Despite the reported risk factors, more than 90% of cardiologists had a self-reported risk perception quantified as mild, such as low or intermediate. Furthermore, overweight/obesity, physical inactivity and stress at work or at home were commonly reported, as well as a limited use of cardiovascular drugs, such as statins or aspirin. CONCLUSIONS: The average cardiovascular profile of Italian cardiologist is unlikely to be considered ideal or even favorable according to recent statements and guidelines regarding cardiovascular risk. Thus, there is a large room for improvement and a need for education and intervention.

[New evidences on the use of aldosterone receptor antagonists in left ventricular dysfunction: from myocardial infarction to heart failure]. / Nuove evidenze sull'impiego degli antialdosteronici nella disfunzione ventricolare sinistra: spironolattone ed eplerenone. Dal postinfarto allo scompenso cardiaco.

Heart failure and myocardial infarction result in considerable consumption of healthcare resources. Therefore, there is interest in the availability of drug therapies that can favorably modify their prognosis in the post-acute phase, reducing mortality and rehospitalization rates. Aldosterone antagonists represent a class of drugs which offer advantages in these settings, in addition to those obtained with beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, even though attention should be drawn to their potential adverse effects. In particular, eplerenone exhibits a better safety profile than spironolactone. Since it has very little affinity for glucocorticoid, androgen and progesterone receptors, eplerenone has less antiandrogenic and progestagenic effects, resulting in a lower incidence of gynecomastia. The EPHESUS study showed that eplerenone can reduce mortality in the short and long term and the rate of new hospitalizations after a myocardial infarction complicated by heart failure. In addition, in the EMPHASIS-HF study eplerenone reduced cardiovascular mortality and hospitalizations after mild heart failure (NYHA class IIa). Despite these important results, which confirmed those obtained with spironolactone in severe heart failure in the RALES study, aldosterone antagonists are still underutilized. In particular, eplerenone is not yet available in Italy, although it is recommended by the latest European Society of Cardiology guidelines.

[Coronary stenting and surgery: perioperative management of antiplatelet therapy in patients undergoing surgery after coronary stent implantation]. / Stent coronarico e chirurgia: la gestione perioperatoria della terapia antiaggregante nel paziente portatore di stent coronarico candidato a intervento chirurgico.

The management of antiplatelet therapy in patients with coronary stents undergoing surgery is a growing clinical problem and often represents a matter of debate between cardiologists and surgeons. It has been estimated that about 4-8% of patients undergoing coronary stenting need to undergo surgery within the next year. Surgery represents one of the most common reasons for premature antiplatelet therapy discontinuation, which is associated with a significant increase in mortality and major adverse cardiac events, in particular stent thrombosis. In addition, surgery confers an additional risk of perioperative cardiac ischemic events, being high in these patients because of the pro-inflammatory and pro-thrombotic effects of surgery. Current international guidelines recommend to postpone non-urgent surgery for at least 6 weeks after bare metal stent implantation and for 6-12 months after drug-eluting stent implantation. However, these recommendations provide little support with regard to managing antiplatelet therapy in the perioperative phase in case of urgent operations and/or high hemorrhagic risk. Furthermore, ischemic and hemorrhagic risk is not defined in detail on the basis of clinical and procedural characteristics. Finally, guidelines shared with cardiologists and surgeons are lacking. The present consensus document provides practical recommendations on the management of antiplatelet therapy in the perioperative period in patients with coronary stents undergoing surgery. Cardiologists and surgeons contributed equally to its creation. An ischemic risk stratification has been provided on the basis of clinical and procedural data. All surgical interventions have been defined on the basis of the hemorrhagic risk. A consensus on the most appropriate antiplatelet regimen in the perioperative phase has been reached on the basis of the ischemic and hemorrhagic risk. Dual antiplatelet therapy should not be withdrawn for surgery at low bleeding risk, whereas aspirin should be continued perioperatively in the majority of surgical operations. In the event of interventions at high risk for both bleeding and ischemic events, when oral antiplatelet therapy withdrawal is required, perioperative treatment with short-acting intravenous glycoprotein IIb/IIIa inhibitors (tirofiban or eptifibatide) should be considered.

Risk stratification and prognosis of patients with known or suspected coronary artery disease by use of supine bicycle exercise stress echocardiography.

BACKGROUND: The aim of this study was to assess the long-term predictive values of supine bicycle exercise stress echocardiography (ESE), and the ESE additional role compared to other traditional clinical and rest echocardiographic variables, in 607 patients with low, intermediate and high pretest risk of cardiac events. METHODS: Clinical status and long-term outcome were assessed for a mean period of 46 months (range 12-60 months). ESE was performed for the diagnosis of suspected coronary artery disease (CAD) in 267 patients (43.9%), and for risk stratification of known CAD in 340 patients (56.1%). At baseline, the mean value of wall motion score index (WMSI) was 1.22 +/- 0.36, and the mean left ventricular ejection fraction was 58.5 +/- 10.9%. RESULTS: ESE was positive for ischemia in 210 patients (34.9%), while ECG was suggestive for ischemia in 157 patients (25.8%). During the test only 97 patients (15.9%) experienced angina. At peak effort, the mean WMSI was 1.38 +/- 0.46. A low workload was achieved by 158 patients (26.1%). During the follow-up period there were 222 events, including 82 hard events (36.9%), 48 deaths (21.6%) and 34 acute non-fatal myocardial infarction (15.3%). At stepwise multivariate model, cigarette smoking (p < 0.01), peak WMSI (p < 0.001), ESE positive for ischemia (p < 0.001) and low workload (p < 0.01) were the only independent predictors of cardiac death, while positive ESE, peak WMSI, angina during the test and hypercholesterolemia were the only independent determinants of hard cardiac events. The cumulative 5-year mean survival rate according to ESE response was 95.9% in patients with negative ESE, and 83.7% in patients with positive ESE (log rank 13.6; p < 0.00001). CONCLUSIONS: ESE yields prognostic information in known or suspected CAD, especially in patients with intermediate pretest risk level. The combined evaluation of clinical variables and other ESE variables, such as peak WMSI and exercise capacity, may further select patients at greatest risk of cardiac death in the overall population.

Prognostic value of supine bicycle exercise stress echocardiography in patients with known or suspected coronary artery disease.

AIMS: To assess the prognostic significance of supine bicycle exercise stress echocardiography (ESE) for cardiac events, and the ESE additional role compared to other traditional clinical and echo variables, in patients with proven or suspected coronary artery disease (CAD). METHODS AND RESULTS: Clinical status and long-term outcome were assessed in 607 patients, for a mean period of 49.9 +/- 12.5 months. ESE was performed for the diagnosis of suspected CAD in 267 patients, and for the risk stratification in 340 patients. At baseline, the mean value of WMSI was 1.22 +/- 0.36, and the mean left ventricular ejection fraction was 58.2 +/- 10.9%. The ESE was positive for ischemia in 210 patients (34.9%), while the ECG was suggestive for ischemia in 157 patients. At peak effort, the mean WMSI was 1.38 +/- 0.46. Low work load was achieved by 158 patients (26.1%). During the follow-up period there were 222 events, including 48 cardiac deaths and 34 acute non-fatal myocardial infarction. By multivariable model, cigarette smoking, peak WMSI, positive ESE for ischemia and low work load were the only independent predictors of cardiac death. The cumulative 5-year mean survival rate according to ESE response was 95.9% in patients with negative ESE, and 81.7% in positive ESE (p < 0.00001). CONCLUSIONS: In patients with known or suspected CAD able to perform a physical stress, bicycle ESE is able to stratify patients at higher risk of cardiac events. The final report of an ESE performed for prognostic purpose should include both the assessment of induced dyssinergy and the evaluation of indexes of the extent and the severity of myocardial ischemia.

Noninvasive assessment of left and right internal mammary artery graft patency using transthoracic color Doppler echocardiography.

BACKGROUND: The aim of this study was to evaluate the patency of left and right internal mammary artery grafts respectively on the left anterior descending and right coronary artery by noninvasive transthoracic color Doppler echocardiography. METHODS: Thirty eight patients (34 males, 4 females, mean age 59 +/- 2 years), with a history of coronary artery bypass grafting for a total of 42 mammary artery grafts, were studied by means of color Doppler echocardiography at baseline and after vasodilation with dipyridamole infusion (0.56 mg/kg i.v. over 4 min). The evaluated echocardiographic parameters included: systolic (SPV) and diastolic peak velocities (DPV), systolic (SVI) and diastolic velocity-time integrals (DVI), and the DPV/SPV and DVI/SVI ratios. We also calculated the dipyridamole infusion to baseline ratio of the diastolic peak velocities (DPVdip/DPVbaseline), the index of internal mammary artery graft blood flow reserve and the percent DPV increment as an index of graft stenosis. RESULTS: On the basis of coronary angiography, two groups were selected: group A (36 mammary grafts) with patent grafts and group B (6 mammary grafts) with moderate or severe stenosis of the grafts. Group A had a predominant diastolic pattern with a DPV of 0.24 +/- 0.13 m/s, whereas group B had a predominant systolic pattern with a reduced DPV of 0.12 +/- 0.03 m/s (p < 0.01). Dipyridamole induced an increase in the DPV respectively of 86.8 +/- 64.4% in group A and 13.8 +/- 15.9% in group B (p < 0.001). Statistical analysis (Mann-Whitney test) revealed a significant difference between the two groups for the baseline DPV (p < 0.01), DVI (p < 0.05), DPV/SPV ratio (p < 0.005), DVI/SVI ratio (p < 0.05), and for the after dipyridamole infusion values: DPV (p < 0.0001), DVI (p < 0.005), DPV/SPV ratio (p < 0.001), and DVI/SVI ratio (p < 0.05). Multivariate analysis showed that the percent DPV increment, the DPVdip/DPVbaseline ratio and the baseline DPV were independent determinants of the stenosis as evaluated at angiography (beta = -0.38, p < 0.01; beta = -0.37, p < 0.01, and beta = -0.33, p < 0.05, respectively; cumulative r2 = 0.25, standard error 0.30 m/s, p < 0.005). CONCLUSIONS: The echocardiographic evaluation of the mammary grafts is a simple, noninvasive method for the assessment of the graft patency and of the functional status of the vessel. The percent DPV increment and baseline DPV were independent determinants of mammary graft stenosis.