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Coronary microvascular dysfunction (CMD) may cause symptoms of myocardial ischemia (microvascular angina [MVA]), but recent studies suggested that it might also contribute to the syndrome of heart failure with preserved ejection fraction (HFpEF). In this study we assessed the relation of CMD with findings of HFpEF in MVA patients.We enrolled 36 consecutive patients with MVA, in whom we assessed: 1) coronary blood flow (CBF) response to adenosine and cold pressor test (CPT) by color-Doppler echocardiography of the left anterior descending coronary artery; 2) complete echocardiographic examination; 3) N-terminal-pro-B-natriuretic peptide (NT-proBNP); 4) grade of dyspnea by the modified Medical Research Scale.Among patients, 15 had definite HFpEF findings (group 1), 12 had equivocal HFpEF findings (group 2) and 9 had no evidence of HFpEF findings (group 3). Group 1 patients were older, had more cardiovascular risk factors and higher NT-proBNP levels (P=0.018), and showed a higher prevalence of diastolic dysfunction. Left ventricle dimensions and systolic function, however, did not differ among groups. Dyspnea was also not significantly different among groups (P=0.19). CBF to adenosine was 1.85±0.47, 1.78±0.40 1.49±0.32 in group 1, 2 and 3, respectively (P=0.13). Similarly, CBF response to CPT was 1.57±0.4, 1.49±0.2 and 1.45±0.3 in the 3 groups, respectively (P=0.74). Both CBF response to adenosine and CPT showed no relation with the severity of dyspnea symptoms.Our data suggest that in patients with MVA there is no relation between the grade of impairment of coronary microvascular dilatation and findings of HFpEF.

Background A sizeable number of patients with a diagnosis of non-ST segment elevation acute coronary syndrome show non-obstructive coronary artery disease. In this study we assessed whether differences in vascular and cardiac autonomic function exist between non-ST segment elevation acute coronary syndrome patients with obstructive or non-obstructive coronary artery disease. Methods and results Systemic endothelium-dependent and independent vascular dilator function (assessed by flow-mediated dilation and nitrate-mediated dilation of the brachial artery, respectively) and cardiac autonomic function (assessed by time-domain and frequency-domain heart rate variability parameters) were assessed on admission in 120 patients with a diagnosis of non-ST segment elevation acute coronary syndrome. Patients were divided into two groups according to coronary angiography findings: (a) 59 (49.2%) with obstructive coronary artery disease (≥50% stenosis in any epicardial arteries); (b) 61 (50.8%) with non-obstructive coronary artery disease. No significant differences between the two groups were found in both flow-mediated dilation (5.03 ± 2.6 vs. 5.40 ± 2.5%, respectively; P = 0.37) and nitrate-mediated dilatation (6.79 ± 2.8 vs. 7.30 ± 3.4%, respectively; P = 0.37). No significant differences were also observed between the two groups both in time-domain and frequency-domain heart rate variability variables, although the triangular index tended to be lower in obstructive coronary artery disease patients (30.2 ± 9.5 vs. 33.9 ± 11.6, respectively; P = 0.058). Neither vascular nor heart rate variability variables predicted the recurrence of angina, requiring emergency room admission or re-hospitalisation, during 11.3 months of follow-up. Conclusions Among patients admitted with a diagnosis of non-ST segment elevation acute coronary syndrome we found no significant differences in systemic vascular dilator function and cardiac autonomic function between those with obstructive coronary artery disease and those with non-obstructive coronary artery disease.

Aims Global longitudinal strain (GLS) is a hallmark of cardiac damage in mitral regurgitation (MR). GLS > −18% in patients with severe organic MR (OMR) and normal LV ejection fraction (LVEF) is an independent predictor of postoperative LV dysfunction. While it is known that GLS is impaired in less than severe functional ischaemic MR (FMR), the value of GLS in less than severe OMR is not known. We aimed to determine prevalence and determinants of any GLS impairment in OMR, in comparison to FMR. Methods We retrospectively evaluated 51 consecutive patients (33 OMR and 18 FMR) with mild-to-moderate, moderate and moderate-to-severe MR (Table*). Overall, GLS was higher in OMR than FMR (17.9±4.5 vs. 10.3±5.3, P Results However, no significant difference was found in GLS between mild-to-moderate, moderate and moderate-to-severe MR patients within OMR (17.7±4.7 vs. 16.9±3.9 vs. 22.4±3, respectively, P>0.05), as well as FMR (9.8±6.6 vs. 10.7±5.3 vs. 10.4±5.3, respectively, P>0.05) groups. GLS correlated directly with left ventricular (LV) ejection fraction (EF) in both OMR (r=0.69, P0.05). Conclusions In patients with OMR, GLS may be reduced, despite normal LVEF, in less than severe MR. Prevalence and degree of GLS impairment in OMR is less than in FMR. In OMR, as well as in FMR, GLS impairment is independent of entity of MR, but rather correlates with LVMi, maybe reflecting impact of myocardial fibrosis derived by increased LVMi on GLS.

Aims In ST-elevation myocardial infarction (STEMI), subtle tissutal changes in remote myocardium predict long-term left ventricular (LV) remodelling and prognosis, independently of infarct size and microvascular obstruction. Whether there is a subclinical dysfunction of remote myocardium, detectable by longitudinal strain (LS) at echocardiography, and whether it varies in different locations of STEMI and with adenosine (ADO) challenge, is still unknown. Methods and results Fifty-three patients (age 65 ± 12.5 years, 44 male, 20 anterior and 33 non-anterior, P = 0.01) underwent rest/stress echocardiography at 7 ± 2 days after successfully treated STEMI, and at 6-months follow-up. Global LS (GLS), ischaemic and remote LS (iLS and rLS) were analysed in anterior and non-anterior STEMI. Both at rest and at follow-up, GLS was stratified by ejection fraction (EF) into three groups: EF Conclusions In the subacute phase, anterior STEMI shows the worst impairment of LS in both ischaemic and remote regions. Strain reserve to ADO is absent in remote myocardium, as well as in ischaemic zone, regardless of MI location. Global, ischaemic and remote LS may improve at follow-up.

Aims Myocardial fibrosis has been found in papillary muscles (PM) and basal segment of left ventricular (LV) inferior-lateral wall in patients with mitral valve prolapse (MVP), which may be due to stretch from valve. Moreover, ST-segment depression is common in patients with MVP, despite low prevalence of epicardial coronary artery disease, and it is attributed to microvascular dysfunction or myocardial stretch. Longitudinal strain (LS) correlates with myocardial fibrosis, while dipyridamole stress echocardiography (DSE) identifies microvascular dysfunction. We aimed at assessing morphology and function of PM and left ventricular walls at rest and during DSE by LS, and at determining prevalence of microvascular dysfunction in patients with MVP. Methods and results Seven consecutive patients with MVP (age 55.4 ± 15.7 years, 57% female) and LV ejection fraction 64 ± 5% underwent DSE. Length and LS of PM were measured at rest and retrospectively compared with those of patients with ischaemic heart disease (n = 8, age 67.1 ± 10.1 years, 37% female) and healthy controls (n = 8, age 39.6 ± 13.3 years, 50% female). LS of PM and LV was also determined at rest and during stress in MVP. Length of PM did not differ among groups, but in MVP, posterior PM was longer than the anterior PM (24 ± 3.8 vs. 20.6 ± 3.6 mm, P = 0.028). Significant difference in resting PM LS was found among groups (overall P = 0.04), with PM LS value in MVP (16.7 ± 7.1%) intermediate between ischaemic (14.2 ± 3.2%) and controls (20.5 ± 2.7%). No difference was found between rest and stress LS of PM in MVP. Global LS tended to increase in MVP during DSE compared to rest (23.1 ± 3.8% vs. 21.1 ± 2.6%, respectively, P = 0.07), while no significant difference between rest and stress LS was found in every LV myocardial segments. Nevertheless, in MVP, LS of LV inferior-lateral wall tended to improve under DSE in patients with mild regurgitation (19.7 ± 4.6 vs. 14.2 ± 5 at rest), but to decrease (16 ± 6.1 vs. 20.3 ± 2.3 at rest) in patients with severe mitral regurgitation (P = 0.006 for interaction). ST-segment depression was elicited by DSE in 29% of MVP. No significant difference in echocardiographic parameters was found between patients with and without ST-segment depression. Conclusions In MVP, sub-valvular apparatus may have peculiar morpho-functional features. DSE does not alter LS of PM, neither of LV walls, except for inferior-lateral wall, which impairs in severe mitral regurgitation. Prevalence of microvascular dysfunction is comparable to that of the general population.

Background and aims Diabetes mellitus (DM) is a risk factor for left ventricle (LV) diastolic dysfunction. Aim of this study was to investigate whether endothelial and/or autonomic dysfunction are associated with LV diastolic dysfunction in DM patients. Methods We studied 84 non-insulin-dependent type II DM (T2DM) patients with no heart disease by assessing: 1) LV diastolic function by echocardiography; 2) peripheral vasodilator function, by measuring flow-mediated dilation (FMD) and nitrate-mediate dilation (NMD); 3) heart rate variability (HRV) on 24-hour Holter electrocardiographic monitoring. Results Twenty-five patients (29.8%) had normal LV diastolic function, while 47 (55.9%) and 12 (14.3%) showed a mild and moderate/severe diastolic dysfunction, respectively. FMD in these 3 groups was 5.25±2.0, 4.95±1.6 and 4.43±1.8% (p=0.42), wherease NMD was 10.8±2.3, 8.98±3.0 and 8.82±3.2%, respectively (p=0.02). HRV variables did not differ among groups. However, the triangular index tended to be lower in patients with moderate/severe (p=0.09) and a significant correlation was found between the E/e' ratio and both the triangular index (r=-0.26; p=0.022) and LF amplitude (r=-0.29; p=0.011). Conclusions In T2DM patients an impairment of endothelium-independent, but not endothelium-dependent, dilatation seems associated with LV diastolic dysfunction. The possible role of cardiac autonomic dysfunction in diastolic dysfunction deserves investigation in larger populations of patients. This article is protected by copyright. All rights reserved.

"Early repolarization" (ER) is a frequent finding at standard electrocardiogram (ECG). In this study we assessed whether ER is associated with an increased risk of events, as recently suggested by some studies. We prospectively enrolled 4,176 consecutive subjects without any heart disease who underwent routine ECG recording. ER was diagnosed in case of typical concave ST-segment elevation ≥0.1 mV; a J wave was diagnosed when the QRS showed a notch or a slur in its terminal part. In this study we compared the 6-year outcome of all 687 subjects with ER/J wave and 687 matched subjects without ER/J wave (controls). Both groups included 335 males and 352 females, and age was 48.8 ± 18 years. Overall, 145 deaths occurred (11%), only 11 of which attributed to cardiac causes. No sudden death was reported. Cardiac deaths occurred in 5 (0.8%) and 6 (0.9%) ER/J wave subjects and controls, respectively (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.26 to 2.80, p = 0.79). Both ER (OR 1.68, 95% CI 0.21 to 13.3, p = 0.62) and J wave (OR 0.91, 95% CI 0.28 to 3.00, p = 0.88) showed no association with cardiac death. Total mortality was 11.5% in the ER/J wave group and 10.6% in the control group (OR 1.10, 95% CI 0.78 to 1.56, p = 0.58). Both ER (OR 0.44, 95% CI 0.16 to 1.24, p = 0.12) and J wave (OR 1.20, 95% CI 0.85 to 1.70, p = 0.30) showed also no association with all-cause death. In subjects without any evidence of heart disease, we found no significant association of ER/J wave with the risk of cardiac, as well as all-cause, death at medium-term follow-up.

Background Global longitudinal strain (LS) is a sensitive marker of ischemic myocardial damage and predicts adverse left ventricular (LV) remodeling and outcome, independently of infarct size. In healthy subjects, regional LS increases from LV base to apex and enhances under physical or pharmacological stress, while in ST-elevation myocardial infarction (STEMI), response to dobutamine depends on transmurality of necrosis. It is known that coronary flow reserve during adenosine (ADN) is impaired both in ischemic and remote myocardium, but effect of ADN on strain reserve has never been investigated. Similarly, LS response to ADN in ischemic (iLS) and remote (rLS) myocardium and their relative contribution to LV function and remodeling are still unknown. Methods 61 consecutive patients with first STEMI (26 anterior, 29 inferior, 6 lateral), treated by successful primary percutaneous coronary intervention (PCI) followed by PCI of non-culprit coronary arteries, underwent rest and stress ADN (140 mcg/kg/minutes in 90 seconds) echocardiography at discharge (7 ± 2 days after admission). LV end-diastolic volume indexed for body surface area (EDV), ejection fraction (EF) and wall motion score index (WMSI) were measured at rest, while GLS, iLS and rLS analysis was performed both at rest and during stress. Ischemic and remote myocardium was allocated, by standard LV segmentation, basing on the culprit coronary artery. Results Significant differences existed among anterior, inferior and lateral STEMI in median (iQr) EDV [52 (45-59) vs 45 (36-51) vs 48 (45–56) ml, respectively, p=.034 overall], EF [47 (37-58) vs 58 (53–61) vs 56 (46-60)%, respectively, p=.002 overall], WMSI [1.63 (1.38–2) vs 1.25 (1.19-1.47) vs 1.41 (1.30-1.75), respectively, p=.001 overall]. GLS differed among anterior, inferior and lateral STEMI both at rest [13.75 (11.63-16.1) vs 19.5 (17.15-22.4) vs 17.85 (17.02-19), respectively, p Conclusions In the subacute phase of STEMI, GLS, iLS and rLS are heterogeneous and depend on infarct site. After ADN, there is no strain reserve in ischemic neither in remote myocardium. This may reflect regional differences in the response of microcirculation and myocardium to ischemia or may underlie pre-existing pathophysiological differences in the coronary circulation

Previous studies of patients with primary stable microvascular angina showed excellent prognosis despite frequent recurrence of symptoms.1,2 Recent large studies challenged this view, however, reporting a sizeable rate of major adverse cardiovascular events (MACE) in patients with stable angina and no obstructive coronary artery disease.3,4 To get further insight into this clinical controversy, we performed long-term follow-up of a rather large population of patients with microvascular angina. We included in this study all patients with primary stable microvascular angina who participated in clinical investigations performed at our institute between 1991 and 2011. All patients had exercise-induced angina, positive exercise stress test, angiographically normal coronary arteries, and no other relevant cardiac or systemic disease.5 In suspected cases, coronary spasm was excluded by ergonovine test. Patients were carefully characterized for cardiovascular risk factors and symptoms. All patients gave their informed consent to participate in the study, which was approved by our institutional review board. Follow-up was done by clinical visits or structured telephone interview. In the case of death, its cause …

Background A sizeable proportion of patients with primary stable microvascular angina (MVA; exercise-induced angina, positive exercise stress test [EST], normal coronary arteries) have recurrent symptoms during follow-up. There have been no previous studies, however, on the long-term results of EST and their correlation with symptom outcome.Methods and Results:Follow-up EST was performed in 71 MVA patients at an average of 16.2 years (range, 5-25 years) from the first EST. Angina status was assessed on weekly frequency of angina episodes and nitroglycerin consumption and by whether symptoms had worsened, improved, or remained unchanged over time. At follow-up EST, 41 patients (group 1) had exercise-induced ischemia, whereas 30 patients (group 2) had negative EST. Compared to group 2, group 1 patients more frequently had exercise-induced dyspnea, and had a greater maximum ST-segment depression and a lower coronary blood flow response to adenosine and cold pressor test, but group 2 patients had a more frequent history of rest angina. No differences between the 2 groups were found at follow-up in angina status or change in symptom status during follow-up. Conclusions Electrocardiogram results improve significantly in a sizeable proportion of patients with MVA. Changes in EST results, however, were not associated with clinical outcome.