Background: An extensive use of transesophageal echocardiography (TEE) has recently been suggested for the diagnosis of infective endocarditis (IE). In this study, we investigated whether among patients with negative transthoracic echocardiography (TTE), subgroups can be identified among whom TEE can be avoided/delayed. Methods: We conducted a retrospective study of 637 consecutive patients who underwent TEE for suspected IE. We selected 375 patients with negative TTE. For each patient, we obtained age, sex, blood culture (BC), blood exams, evidence of embolism, presence of moderate/severe heart valve disease, valve prostheses, and intracardiac devices. Results: IE was eventually diagnosed in 56 patients. Variables independently associated with IE at multivariate analysis included positive BC (OR 3.45; p = 0.006), evidence of embolism (OR 13.0; p < 0.001), bioprosthetic heart valves (OR 4.31; p < 0.001) and platelet count < 150,000/mL (OR 2.47; p = 0.014). In patients without any of these predictors for IE (n = 81), only 1 had a diagnosis of IE and no in-hospital IE-related deaths occurred. Among patients with negative BC (n = 127), IE prevalence increased with the number of other predictors, but IE-related mortality was 0%. IE prevalence (10.8%) and IE related in-hospital mortality (2.7%) were also rather low in patients with a positive blood culture without any other independent predictors for IE but were 20% (IE-related mortality 3.8%) and 71% (IE-related mortality 28.6%) in those with only one or 2–3 other IE predictors, respectively. Conclusions: Our data suggest that, among patients with suspected IE and negative TTE, subgroups can be identified in whom TEE might be safely avoided or delayed.

Background: Intracoronary acetylcholine testing may induce epicardial coronary artery spasm (CAS) or coronary microvascular spasm (CMVS) in patients with angina syndromes but non-obstructive coronary artery disease, but their causal role in individual patients is not always clear. In this prospective, observational single-center study, we aimed to assess whether (1) the induction of myocardial ischemia/angina by electrocardiogram (ECG) exercise stress test (EST) differs between patients showing different results in response to acetylcholine testing (i.e., CAS, CMVS, or no spasm); (2) the preventive administration of short-acting nitrates has any different effects on the EST of those patients who showed a positive basal EST. We expected that if exercise-induced angina and/or ischemic ECG changes are related to CAS, they should improve after nitrates administration, whereas they should not significantly improve if they are caused by CMVS. Methods: We enrolled 81 patients with angina syndromes and non-obstructive coronary artery disease, who were divided into three groups according to acetylcholine testing: 40 patients with CAS (CAS-group), 14 with CMVS (CMVS-groups), and 27 with a negative test (NEG-group). All patients underwent a basal EST (B-EST). Patients with a positive B-EST repeated the test 24–48 h later, 5 min after the administration of short-acting nitrates (N-EST). Results: There were no significant differences among the groups in terms of the B-EST results. B-EST was positive in eight (20%) patients in the CAS-group, seven (50%) in the CMVS-group, and six (22%) in the NEG-group (p = 0.076). N-EST, performed in eight, six, and five of these patients, also showed similar results in the three groups. Furthermore, the N-EST results also did not significantly differ compared to B-EST in any group, remaining positive in seven (87.5%), four (66.7%), and four (80%) patients in the CAS-group, CMVS-group, and NEG-group, respectively (p = 0.78). Conclusions: Our data show that patients with angina and non-obstructive coronary artery disease show largely comparable results of the ECG exercise stress test and similar poor effects of short-acting nitrates on abnormal ECG exercise stress test results. On the whole, our findings suggest caution in attributing to the results of Ach testing a definite causal role for the clinical syndrome in individual patients.

Background: Pharmacologic therapy guided by invasive coronary function tests (CFTs) may improve symptomatic outcomes in patients with angina and non-obstructive coronary artery disease (ANOCA). In this study, we specifically aimed to investigate whether the induction of coronary microvascular spasm (CMVS) by the acetylcholine (Ach) test predicts a better therapeutic effect of calcium-channel blocker therapy compared to beta-blocker therapy. Methods: We enrolled 31 ANOCA patients, who were divided into two groups according to the result of Ach testing: 16 patients with CMVS (CMVS group) and 15 patients with a negative test (NEG group). Patients with Ach-induced epicardial spasm were excluded. In an open-label crossover trial, patients were randomly assigned to each receive, for a period of 4 weeks, either metoprolol (50 mg twice daily) or diltiazem (120 mg twice daily). At the end of each 4-week period, patients underwent an ECG–exercise stress test (EST) and were invited to fill out the Seattle Angina Questionnaire (SAQ). Results: No significant differences were found between metoprolol and diltiazem in terms of SAQ scores, and ECG-EST results were also largely comparable with the two drug treatments, both in the CMVS group and the NEG group. In particular, the SAQ summary score was 63.1 ± 24 and 66.0 ± 25 (p = 0.59) for metoprolol and diltiazem, respectively, in the CMVS group, and 70.9 ± 17 and 74.3 ± 16 (p = 0.37) with the two drugs, respectively, in the NEG group. Conclusions: Our small open-label study shows that patients with ANOCA with negative Ach test or Ach-induced CMVS show largely comparable short-term symptomatic outcomes and ECG-EST results when treated with either metoprolol or diltiazem.