Search

Aims The aim of our study is to assess the ability of left atrial (LA) strain values to improve left ventricular and diastolic pressure (LVEDP) non-invasive estimation as compared with traditional echocardiographic indexes in the acute phase of Takotsubo syndrome (TTS) and to predict adverse in-hospital outcomes in this population. Methods and results Consecutive TTS patients were prospectively enrolled. Left ventricular and diastolic pressure was measured at the time of catheterization. Transthoracic echocardiography was performed within 48 h from hospital admission. In-hospital complications (acute heart failure, death from any cause, and life-threatening arrhythmias) were collected. A total of 62 patients were analysed (72.2 ± 10.1 years, female 80%) and in-hospital complications occurred in 25 (40.3%). Left ventricular and diastolic pressure mean value was 24.53 ± 7.92 mmHg. Left atrial reservoir and pump strain values presented higher correlation with LVEDP (r −0.859, P < 0.001 and r −0.848, P < 0.001, respectively) in comparison with E/e ′ ratio, left atrial volume index (LAVi), and tricuspid regurgitation (TR) peak velocity. In addition, at receiver-operating characteristic curve analysis, LA reservoir and pump strain resulted to be better predictors of LVEDP above the mean of our population [0.909 (95% CI 0.818–0.999, P < 0.001) and 0.889 (95% CI 0.789–0.988, P < 0.001)], respectively] as compared with E/e′ ratio, LAVi, and TR peak velocity. Finally, LA reservoir strain resulted to be an independent predictor of worse in-hospital outcomes, together with LVEDP and left ventricular ejection fraction (all P < 0.001). Conclusion In our study, lower LA reservoir and pump strain values were better predictors of LVEDP as compared with traditional echocardiographic indexes in the acute phase of TTS syndrome. Moreover, LA reservoir strain was an independent predictor of adverse in-hospital outcomes.

Introduction: Left ventricular (LV) hypertrophy is the main feature of cardiac involvement in Anderson-Fabry disease (FD), but the right ventricle (RV) is also frequently affected. Previous studies failed to demonstrate an independent association between conventional parameters of RV performance and outcomes in FD. Nevertheless, if RV free wall strain (RV-FWS), assessed by 2D speckle tracking analysis, may provide a better prognostication is currently unknown. Methods: We retrospectively evaluated the association between RV-FWS and the occurrence of cardiovascular events in a cohort of 56 patients with FD. The study endpoint comprises cardiovascular mortality, severe heart failure symptoms, new-onset atrial fibrillation and major arrhythmias requiring device implantation. Results: Reduced RV-FWS, defined by values lower than 23%, was found in 25 (45%) patients. During a median follow-up of 47 months, 16 (29%) patients met the study endpoint. A ROC-curve analysis confirmed the threshold of reduced RV-FWS (

Recent studies suggested that early repolarization (ER)/J wave at the electrocardiogram (ECG) is associated with increased risk of sudden death and ventricular arrhythmias in patients with acute myocardial infarction. In this study, we prospectively assessed whether ER/J wave has any long-term prognostic implications in patients with stable ischemic heart disease (IHD). We enrolled consecutive clinically stable patients with documented IHD, referred to undergo a routine ECG. ER (typical concave ST-segment elevation) and J wave were diagnosed according to prospectively defined criteria. The final population included 617 patients with documented IHD (455 men; age 68.1 ± 11 years). ER/J wave was found in 138 patients (22.4%), 13 of whom (2.1%) showed ER and 133 (21.6%) a J wave. At a follow-up of 8.1±2.9 years, 160 deaths occurred (25.9%), 60 (9.7%) attributed to cardiovascular causes. Total mortality was lower in patients with versus those without ER/J wave (18.8% vs 28.0%; hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.40 to 0.93, p = 0.02). The difference, however, was not significant after adjustment for confounding clinical variables (HR 0.78, 95% CI 0.51 to 1.19, p = 0.25). No significant difference was found in cardiovascular death between patients with (7.2%) and those without (10.4%) ER/J wave (adjusted HR 0.78, 95% CI 0.40 to 1.55, p = 0.48). Similar results were obtained for ER and J wave separately, and for ECG location of ER/J wave (inferior or lateral/precordial) and type of J wave (notched or slurred). The ER/J wave pattern at the ECG is not associated with increased risk of long-term mortality in clinically stable patients with a documented history of IHD.

Little is known about prevalence and predictors of myocardial infarction with non-obstructive coronary arteries (MINOCA) in Fabry disease (FD) and hypertrophic cardiomyopathy (HCM). We assessed and compared the prevalence and predictors of MINOCA in a large cohort of HCM and FD patients.In this multicenter, retrospective study we enrolled 2870 adult patients with HCM and 267 with FD. The only exclusion criterion was documented obstructive coronary artery disease. MINOCA was defined according to guidelines. For each patient we collected clinical, ECG and echocardiographic data recorded at initial evaluation.Overall, 36 patients had MINOCA during a follow-up period of 4.5 ± 11.2 years. MINOCA occurred in 16 patients with HCM (0.5%) and 20 patients with FD (7.5%; p lt; 0.001). The difference between the 2 groups was highly significant, also after adjustment for the main clinical, ECG and echocardiographic variables (OR 6.12; 95%CI 2.80-13.3; p lt; 0.001). In the FD population MINOCA occurred in 17 out of 96 patients with left ventricle hypertrophy (LVH, 17.7%) and in 3 out of 171 patients without LVH (1.7%; OR 12.0; 95%CI 3.43-42.3; p lt; 0.001). At multivariable analysis, voltage criteria for LVH at ECG (OR 7.3; 95%CI 1.93-27.7; p = 0.003) and maximal LV wall thickness at echocardiography (OR 1.15; 95%CI 1.05-1.27; p = 0.002) maintained an independent association with MINOCA. No major significant differences were found in clinical, ECG and echocardiographic findings between HCM patients with or without MINOCA.MINOCA was rare in HCM patients, and 6-fold more frequent in FD patients. MINOCA may be considered a red flag for FD and aid in the differential diagnosis from HCM.

Intracoronary provocation testing with acetylcholine (ACh) is crucial for the diagnosis of functional coronary alterations in patients with suspected myocardial ischaemia and non-obstructive coronary arteries.Our intention was to assess the safety and predictive value for major adverse cardiovascular and cerebrovascular events (MACCE) in patients presenting with ischaemia with non-obstructive coronary arteries (INOCA) or with myocardial infarction with non-obstructive coronary arteries (MINOCA).We prospectively enrolled consecutive INOCA or MINOCA patients undergoing intracoronary ACh provocation testing.A total of 317 patients were enrolled: 174 (54.9%) with INOCA and 143 (45.1%) with MINOCA. Of these, 185 patients (58.4%) had a positive response to the ACh test. Complications during ACh provocative testing were all mild and transient and occurred in 29 (9.1%) patients, with no difference between patients with positive or negative responses to ACh testing, nor between INOCA and MINOCA patients. A history of paroxysmal atrial fibrillation, moderate/severe diastolic dysfunction and a higher QT dispersion at baseline electrocardiogram were independent predictors of complications. MACCE occurred in 30 patients (9.5%) during a median follow-up of 22 months. The incidence of MACCE was higher among patients with a positive ACh test (24 [13.0%] vs 6 [4.5%], p=0.017), and a positive ACh test was an independent predictor of MACCE.ACh provocation testing is associated with a low risk of mild and transient complications, with a similar prevalence in both INOCA and MINOCA patients. Importantly, ACh provocation testing can help to identify patients at higher risk of future clinical events, suggesting a net clinical benefit derived from its use in this clinical setting.

Few data are available on the prevalence of right ventricle (RV) systolic dysfunction, assessed including RV strain, and RV to pulmonary artery (PA) coupling in patients with aortic stenosis (AS) submitted to TAVI and the early effect of the procedure. We performed standard and speckle tracking echocardiography in 80 patients with severe AS the day before TAVI and within 48 h after TAVI. In all patients we measured TAPSE/PASP (cut-off for RV-PA uncoupling 0.31) and in 60/80 we were able to analyze RV global longitudinal strain (RV-GLS) and RV free wall strain (RV-FWS). RVFAC and TAPSE were impaired in 8.3% while RV-GLS and RV-FWS in 45% and 33.3% respectively before TAVI. TAPSE/PASP 0.31 was documented in 7/80 patients (8.7%) before TAVI. These subjects differed from patients with TAPSE/PASP ≥ 0.31 for: enlarged left ventricular (LV) end-diastolic and end-systolic volumes (p 0.001), worst LV ejection fraction (p 0.001) and RVFAC (p 0.001), worst RV-GLS and RV-FWS (p = 0.01 and p = 0.03) and bigger right atrium (RA) area (p 0.001). After TAVI, RV systolic function did not improve while PASP significantly decreased (p = 0.005) driving the improvement of TAPSE/PASP (p = 0.01). Patients with TAPSE/PASP improvement (51%) differed from the others for worst pre-TAVI diastolic function (E/e' p = 0.045), RVFAC (p = 0.042), RV-GLS (p = 0.049) and RA area (p = 0.02). RV-GLS unveils RV systolic dysfunction in as much as 45% of patients with AS vs only 8.3% revealed by conventional echocardiography. RV systolic function does not significantly improve early after TAVI while RV-PA coupling does. Patients with lower TAPSE/PASP at baseline have worst LV and RV systolic function as well as larger RA. Patients who improve TAPSE/PASP after TAVI are those with worst diastolic function, RV systolic function and larger RA at baseline.

Background Transcatheter aortic valve implantation (TAVI) in the treatment of severe aortic stenosis has considerably grown in the latest years. There are limited data, however, about predictors of long-term prognosis in this population. Particularly, whether arrhythmic burden is associated with clinical outcome has poorly been investigated. Methods We performed 24-hour 3-channel ECG Holter recording (HM) in 284 consecutive patients who underwent TAVI for severe aortic stenosis at our Center within 30 days from a successful procedure (average 10.2 days, range 2-30). For each patient we obtained the number of premature ventricular complexes (PVCs) and the presence of non-sustained ventricular tachycardia (NSVT, ≥3 PVCs with a rate ≥100 bpm). Assessment of clinical events at follow-up was performed by clinical visits or telephone interview of patients or relatives (in case of fatal events). The primary end-point of the study was a composite of cardiovascular death and resuscitation from cardiac arrest (CVE); total mortality was assessed as secondary end-point. Results Frequent PVCs (≥30/hour) and episodes of NSVT were found in 49 (20.2%) and 52 (21.4%) patients, respectively. Clinical outcome was obtained for 243 patients (85.6%). At an average follow-up of 3.5 year (range 1.0-8.6), CVE occurred in 25 patients (8.8%) and 64 died (22.5%). Frequent PVCs at HM were detected in 11/25 (44.0%) and 38/218 (17.4%) patients with and without CVE, respectively (p=0.006). Episodes of NSVT were detected in 9/25 (36.0%) and 43/218 (19.7%) patients with and without CVE, respectively (p=0.07). Furthermore, frequent PVCs were present in 18/64 (28.1%) and 31/179 (17.3%) patients dead and alive, respectively (p=0.07), whereas NSVT episodes were detected in 17/64 (26.6%) and 35/179 (19.6%) patients dead and alive, respectively (p=0.29). Frequent PVCs maintained independent association with CVE after correction for confounding variables at multivariable analysis (HR 2.63; 95 CI 1.05-6.62; p=0.04). Conclusions Our data indicate that assessment of ventricular arrhythmic burden after TAVI is helpful to identify patients at increased risk of cardiovascular death/cardiac arrest during medium follow-up.

Left ventricular (LV) hypertrophy is the main feature of Fabry cardiomyopathy (FC), but the right ventricle (RV) is also frequently affected. Previous studies failed to demonstrate an independent association between RV hypertrophy or conventional parameters of RV function and the occurrence of adverse outcomes in patients with FC. Nevertheless, if RV free wall strain (RV-FWS), assessed by 2D speckle tracking analysis, may provide a better prognostication is currently unexplored. We retrospectively evaluated the association between RV-FWS and the occurrence of cardiovascular events in a cohort of 28 patients with FC. The study endpoint comprises the occurrence of cardiovascular mortality, severe heart failure symptoms, new-onset atrial fibrillation, bradyarrhythmias requiring pacemaker implantation and sustained ventricular tachyarrhythmias. The median value of RV-FWS was 21.4% (interquartile range:17.1-23.9%) and a total of 18 (64%) patients showed reduced RV-FWS ( In Conclusion, impaired RV-FWS was not independently associated with the occurrence of cardiovascular events in FC, confirming previous observations that prognosis is mainly driven by the severity of LV cardiomyopathy.

Background The clinical impact of valvular heart disease (VHD) in adult congenital heart disease (ACHD) patients is unascertained. Aim of our study was to assess the prevalence and clinical impact of severe VHD (S-VHD) in a real-world contemporary cohort of ACHD patients. Methods Patients followed-up at our ACHD Outpatient Clinic were enrolled. Clinical characteristics and echocardiographic data were prospectively entered into a digitalized medical records database. VHD at the first access was evaluated and graded according to VHD guidelines. Clinical data at follow-up were collected. Results A total of 390 patients were included and S-VHD was present in 101 (25.9%) patients. Over a median follow-up time of 26 months (IQR: 12-48), the primary composite endpoint occurred in 76 patients (19.5%). The cumulative primary endpoint-free survival was significantly lower in patients with S-VHD vs patients with non-severe VHD (Log rank p 45 mmHg. Conclusion In ACHD patients, the presence of S-VHD is independently associated with the occurrence of cardiovascular mortality and hospitalization. The prognostic value of S-VHD is incremental above other established prognostic markers.

Background Left main coronary artery disease (LMCAD) heavily affects prognosis of patients with suspected CAD. Thus, its identification/exclusion is an important step in the assessment of these patients. Although being the gold standard to identify LMCAD, invasive coronary angiography (ICA) is burdened by some risks, while coronary computed tomography angiography (CCTA) has still limited availability, quite high costs and associated radiologic risks. In the past decades, several studies demonstrated the utility of ECG exercise stress test (EST) for the identification of LM disease in patients with suspected CAD. However, the pre-test probability of CAD of subjects undergoing EST has significantly changed in the last decades. Accordingly, in this study we aimed to assess the predictive value of EST for the presence/absence of LMCAD in a contemporary population of patients with suspected CAD. Methods We retrospectively enrolled 495 consecutive patients, referred to our Center between years 2018 and 2021 because of suspected CAD, who underwent both an EST (standard treadmill Bruce protocol) and ICA (within 12 months of the EST). Patients with a history of coronary artery bypass surgery were excluded. Results Overall, 24 patients (4.8%) were found to have LMCAD at ICA. Among clinical variables, only male gender (p=0.025) and smoking (p=0.003) were associated with LMCAD. A number of ECG leads with EST-induced ST-segment depression (STD) ≥5 and a maximal STD ≥2 mm were more frequently found in patients with, compared to those without LMCAD (29.2 vs 9.8%, p=0.003; and 58.3 vs 24.8%, p Conclusions Our data indicate that EST continues to be a valuable tool for predicting the presence/absence of LMCAD in contemporary populations of patients with suspected coronary artery disease.

Background Although the detection of a rise and/or fall pattern of cardiac troponin (cTn) serum levels in presence of a clinical context of acute myocardial ischemia, represents the main criterion for the diagnosis of acute myocardial infarction (AMI), troponins may increase in various conditions of myocardial injury different from ischemic myocardial necrosis or simply following myocardial ischemia, in the absence of cell necrosis. Some studies found that troponins also increase after physical exertion and other types of stressful stimuli in the absence of obstructive CAD and myocardial ischemia. No previous study, however, investigated the relation between cTn serum levels and the extent of myocardial ischemia in patients with a suspect of CCS. Methods We prospectively enrolled consecutive patients undergoing an elective stress myocardial perfusion scintigraphy (MPS) because of a clinical suspicion of obstructive coronary artery disease (CAD). Patients were divided into 3 groups based on the evidence and degree of stress-induced MI at MPS: 1) group 1, no MI (≤4%); 2) group 2, mild MI (5-10%); 3) group 3, moderate-to-severe MI (≥10%). High sensitivity (hs)-cTnI was measured immediately before (T0) and 1 hour (T1) and 4 hours (T2) after the stress test. A successive evaluation of patients was performed at 24 months. Results One-hundred consecutive patients (64 males; age 65.5±9.5 years) were enrolled in the study. Serum hs-cTnI concentrations significantly increased after MPS, compared to baseline, in the whole population, from (median, interquartile range) 3.9 (2.5-6.1) ng/L at T0, to 4.2 (2.8-7.3) ng/L at T1 (p Conclusions In patients with suspected CAD, stress MPS induces an increase of cTnI that is independent of the induction and the extent of myocardial ischemia and is mainly related to myocardial work, as indicated by HR achieved during the test.

Background Takotsubo syndrome (TTS) is associated with a non-negligible risk of in-hospital complications. Elevated left ventricular filling pressures (LVFP) showed to predict adverse outcomes in this population. Recently, LA reservoir and LA pump strain, demonstrated a close correlation with increased LVFP in unselected patients. The aim of our study is to assess the ability of LA strain analysis to improve non-invasive estimation of LVFP and to predict IH complications in TTS patients. Methods We prospectively enrolled patients with confirmed TTS diagnosis. LVEDP was assessed invasively at the time of catheterization. Transthoracic echocardiography was performed within 48 hours from hospital admission. In-hospital complications were collected, including occurrence of acute heart failure, death from any cause and life-threatening arrhythmias. Results A total of 62 patients were analysed (72.2±10.1 years, female 80%). In-hospital complications occurred in 25 (40.3%). Patients who experienced IH complications had higher LVEDP and lower LVEF, LA reservoir strain and LA pump strain values compared to patients without IH complications (all p24.5 mmHg in comparison with E/e’, LAVi and tricuspid regurgitation (TR) peak velocity. Moreover, the incorporation of LA strain values in a multivariable model including E/e’ ratio, LAVi and TR peak velocity to predict a LVEDP>24.5 mmHg led to a significant incremental predictive value (p=0.002). Conclusion In patients with TTS, lower LA reservoir and pump strain values correlate with increased LVEDP and improve non-invasive estimation of LVFP. LA strain analysis may be an easy tool to individuate subjects at higher risk of in-hospital complications.

Background Myocardial bridging (MB) is a congenital epicardial coronary abnormality, in which a segment of the artery runs through the myocardium, determining dynamic stenosis during systole. Whether MB can be responsible by itself for myocardial ischemia remains unclear. Thus, we aimed to evaluate whether the dynamic stenosis related to MB can cause signs and symptoms of myocardial ischemia. Methods We enrolled 41 consecutive patients who underwent coronary angiography because of chest pain suspected for ischemic heart disease and were found to have MB in the absence of any significant flow-limiting coronary stenosis and any other cardiac disease. A group of 14 patients who also underwent coronary angiography because of chest pain suspected for ischemic heart disease, but found to be free of any coronary or cardiac abnormality (including MB) and also showed negative results at exercise stress test (EST) served as controls. All enrolled patients underwent a maximal treadmill EST according to standard Bruce protocol. A complete echocardiographic examination was performed at rest and at peak exercise. Results Baseline EST parameters were comparable between groups, whereas peak diastolic blood pressure (pDBP) was slightly higher in the MB group (p=0.044). No clinically significant differences were found in baseline echocardiographic parameters, although the E wave deceleration time (DcT) was longer (p=0.038) and global longitudinal strain (GLS) was higher (p=0.05) in the MB group. During exercise, left ventricular ejection fraction (LVEF) improved significantly in both groups (p Moreover, among MB patients, no differences were found in stress echocardiographic results between those with positive vs. those with negative EST. Conclusions We failed to demonstrate any significant ischemic impairment of LV systolic and diastolic function at maximal EST in patients with MB. Moreover, we also failed to demonstrate any LV dysfunction in MB patients that developed ECG signs of myocardial ischemia during EST, as compared to those without evidence of myocardial ischemia. Thus, our data question about the ability of MB itself to trigger significant myocardial ischemia in clinical practice.

Background A significant proportion of patients recovering from SARS-CoV-2 infection (Covid-19) complain a wide variety of bothersome symptoms, including symptoms potentially related to cardiac involvement, that may significantly impair their quality of life (post-Covid or long-Covid syndrome). However, full diagnostic investigation usually does not reveal significant structural or functional cardiac abnormalities. Whether cardiac autonomic dysfunction and/or endothelial dysfunction may play a role in post-COVID-19 symptoms, however, has poorly been investigated. Methods We prospectively enrolled 63 young adult patients (age 18-55 years) without any previous cardiovascular disease, referred to our “Post-COVID-19” Day Hospital ward for a clinical follow-up after 3 months from SARS-CoV-2 infection. In all patients endothelium-dependent vasodilator function was assessed non-invasively by measuring the change of brachial artery diameter in response to hyperaemia after 5 minutes of forearm ischemia (flow-mediated dilatation, FMD); furthermore, endothelium-independent vasodilator function was assessed by measuring the change of brachial artery diameter in response to sublingual nitro-glycerine (25 µg) (nitrate-mediated dilatation, NMD). A 24-hour ECG Holter monitoring (HM) was performed to assess cardiac autonomic function by obtaining time-domain and frequency-domain parameters of heart rate variability (HRV). Results Symptoms of potential cardiac origin (dyspnoea on exertion, chest pain, arrhythmic symptoms) were referred by 47 patients (74.6%, Group 1), whereas 16 (25.4%, Group 2) were free from any possible cardiac symptom. The two groups did not differ in age, sex and cardiovascular risk factors. FMD was 7.29±3.4% and 7.01±2.3% in Group 1 and 2, respectively (p=0.77), whereas NMD was 11.1±3.8% and 14.2±4.9 in the two groups, respectively (p=0.013). No significant differences were observed for HRV parameters between the two groups (see Table). Conclusions Our data do not support a role for both endothelial dysfunction and cardiac autonomic dysfunction in the persistence of symptoms of potential cardiac origin in patients with a recent SARS-CoV-2 infection. The lower endothelium-independent arterial vasodilator found in these patients, however, deserves further investigation.

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.

2D speckle tracking echocardiography (2DSTE) is superior to standard echocardiography in the assessment of subtle right ventricle (RV) systolic dysfunction. In this study we aimed to: 1) test the hypothesis that 2DSTE may unveil subtle RV systolic dysfunction in patients with Fabry disease; 2) investigate whether the physiologic difference between the 3-segment (RV-FWS) and the 6-segment (RV-GLS) RV strain (∆RV strain) is preserved in Fabry patients.Standard echocardiography and 2DSTE were performed in 49 Fabry patients and 49 age- and sex-matched healthy controls. Fabry patients were divided in two groups according to the presence/absence of left ventricular hypertrophy (LVH+: left ventricular wall thickness 12 mm, 49% of total Fabry patients). RV systolic function assessed by standard echocardiography was normal in the majority of Fabry patients (92%) while RV-GLS and RV-FWS were impaired in about 40%. RV-GLS and RV-FWS were significantly worse in patients LVH+ vs LVH- and vs controls (RV-GLS: LVH+ vs LVH-: -18.4 ± -4.3% vs -23.8 ± -3.1% p0.001; LVH+ vs controls: -18.4 ± -4.3% vs -23.9 ± -2.8% p0.001; RV-FWS: LVH+ vs LVH-: -21.8 ± -5.3% vs -26.7 ± -3.8% p = 0.002, LVH+ vs controls -21.8 ± -5.3% vs -26.8 ± -3.9% p0.001). No difference was found between LVH- patients and controls in both RV-GLS (p = 0.65) and RV-FWS (p = 0.79). ∆RV strain was similar among the groups.In Fabry cardiomyopathy impaired RV-GLS and RV-FWS is a common finding, while RV strain is preserved in Fabry patients without overt cardiac involvement. The physiologic difference between RV-FWS and RV-GLS is maintained in Fabry patients, regardless of the presence of cardiomyopathy.

The paradigm for the management of patients presenting with angina and/or myocardial ischemia has been historically centered on the detection and treatment of obstructive coronary artery disease (CAD). However, in a considerable proportion (30-50%) of patients undergoing coronary angiography, obstructive CAD is excluded. Thus, functional mechanisms may be involved in determining myocardial ischemia and should be investigated. In particular, coronary vasomotor disorders both at epicardial and at microvascular level may play a crucial role, but a definitive diagnosis of these disorders can at times be difficult, given the transience of symptoms, and often requires the use of coronary provocative tests. Of importance, these tests may provide relevant information on the pathogenic mechanism of myocardial ischemia, allowing physicians to tailor the therapies of their patients. Furthermore, several studies underscored the important prognostic information deriving from the use of coronary provocative tests. Nevertheless, their use in clinical practice is currently limited and mainly restricted to specialized centers, with only a minority of patients receiving a benefit from this diagnostic approach. In this review, we explain the pathophysiological bases for the use of provocative tests, along with their clinical, prognostic and therapeutic implications.

Background. Continuous glucose monitoring (CGM) shows in more detail the glycaemic pattern of diabetic subjects and provides several new parameters (“glucometrics”) to assess patients’ glycaemia and consensually guide treatment. A better control of glucose levels might result in improvement of clinical outcome and reduce disease complications. This study aimed to gather an expert consensus on the clinical and prognostic use of CGM in diabetic patients at high cardiovascular risk or with heart disease.Methods. A list of 22 statements concerning type of patients who can benefit from CGM, prognostic impact of CGM in diabetic patients with heart disease, CGM use during acute cardiovascular events and educational issues of CGM were developed. Using a two-round Delphi methodology, the survey was distributed online to 42 Italian experts (21 diabetologists and 21 cardiologists) who rated their level of agreement with each statement on a 5-point Likert scale. Consensus was predefined as more than 66% of the panel agreeing/disagreeing with any given statement.Results. Forty experts (95%) answered the survey. Every statement achieved a positive consensus. In particular, the panel expressed the feeling that CGM can be prognostically relevant for every diabetic patient (70%) and that is clinically useful also in the management of those with type 2 diabetes not treated with insulin (87.5%). The assessment of time in range (TIR), glycaemic variability (GV) and hypoglycaemic/hyperglycaemic episodes were considered relevant in the management of diabetic patients with heart disease (92.5% for TIR, 95% for GV, 97.5% for time spent in hypoglycaemia) and can improve the prognosis of those with ischaemic heart disease (100% for hypoglycaemia, 90% for hyperglycaemia) or with heart failure (87.5% for hypoglycaemia, 85% for TIR, 87.5% for GV). The experts retained that CGM can be used and can impact the short- and long-term prognosis during an acute cardiovascular event. Lastly, CGM has a recognized educational role for diabetic subjects.Conclusions. According to this Delphi consensus, the clinical and prognostic use of CGM in diabetic patients at high cardiovascular risk is promising and deserves dedicated studies to confirm the experts’ feelings.

Aims To perform a comparative analysis of right ventricle (RV) myocardial mechanics, assessed by 2D speckle-tracking echocardiography (2D-STE), between patients with Fabry disease and patients with sarcomeric disease. Methods and results Patients with Fabry cardiomyopathy (FC) (n = 28) were compared with patients with sarcomeric hypertrophic cardiomyopathy (HCM), matched for degree of left ventricle hypertrophy (LVH) and demographic characteristics (n = 112). In addition, patients with Fabry disease and no LVH [phenotype-negative carriers of pathogenic α-galactosidase gene mutations (GLA LVH-)] (n = 28) were compared with age and sex-matched carriers of sarcomeric gene mutations without LVH [Phenotype-negative carriers of pathogenic sarcomeric gene mutations (Sarc LVH-)] (n = 56). Standard echocardiography and 2D-STE were performed in all participants. Despite a subtle impairment of RV global longitudinal strain (RV-GLS) was common in both groups, patients with FC showed a more prominent reduction of RV free wall longitudinal strain (RV-FWS) and lower values of difference between RV-FWS and RV-GLS (ΔRV strain), in comparison to individuals with HCM (P < 0.001 and P = 0.002, respectively). RV-FWS and ΔRV strain demonstrated an independent and additive value in discriminating FC from HCM, over the presence of symmetric LVH, systolic anterior motion of the mitral valve and RV hypertrophy. Similar results were found in GLA LVH- patients: they had worse RV-FWS and lower values of ΔRV strain as compared to Sarc LVH- patients (both P < 0.001). Conclusion Patients with FC show a specific pattern of RV myocardial mechanics, characterized by a larger impairment of RV-FWS and lower ΔRV strain in comparison to patients with HCM, which may be helpful in the differential diagnosis between these two diseases.

Aims The main severe complications of SARS-CoV-2 infection are pneumonia and respiratory distress syndrome. Recent studies, however, reported that cardiac injury, as assessed by troponin levels, is associated with a worse outcome in these patients. No study hitherto assessed whether the simple standard electrocardiogram (ECG) may be helpful for risk stratification in these patients. Methods and results We studied 324 consecutive patients admitted to our Emergency Department with a confirmed diagnosis of SARS-CoV-2 infection. Standard 12-lead ECG recorded on admission was assessed for cardiac rhythm and rate, atrioventricular and intraventricular conduction, abnormal Q/QS wave, ST segment and T wave changes, corrected QT interval, and tachyarrhythmias. At a mean follow-up of 31 ± 11 days, 44 deaths occurred (13.6%). Most ECG variables were significantly associated with mortality, including atrial fibrillation (P = 0.002), increasing heart rate (P = 0.002), presence of left bundle branch block (LBBB; P < 0.001), QRS duration (P, Graphical Abstract Graphical Abstract

Aims Right ventricular hypertrophy (RVH) is a common finding in Anderson–Fabry disease (AFD), but the prognostic role of right ventricular (RV) involvement has never been assessed. The aim of our study was to evaluate the prognostic significance of RVH and RV systolic function in AFD. Methods and results Forty‐five AFD patients (56% male patients) with extensive baseline evaluation, including assessment of RVH and RV systolic function, were followed‐up for an average of 51.2 ± 11.4 months. RV systolic function was assessed by standard and tissue Doppler echocardiography. Cardiovascular events were defined as new‐onset atrial fibrillation (AF), sustained ventricular arrhythmias, heart failure, or pacemaker/implantable cardioverter defibrillator implantation; renal events were defined as progression to dialysis and/or renal transplantation or significant worsening of glomerular filtration rate; and cerebrovascular events were defined as transient ischaemic attack or stroke. Fourteen patients (31.1%) presented RVH, while RV systolic function was normal in all cases. During the follow‐up period, 13 patients (28.8%, 11 male) experienced 18 major events, including two deaths. Cardiovascular events occurred in eight patients (17.7%). The most common event was pacemaker/implantable cardioverter defibrillator implantation (six patients, 13.3%), followed by AF (three cases, 6.6%). Only one case of worsening New York Heart Association class (from II to III and IV) was observed. Ischaemic stroke occurred in three cases (6.6%). Renal events were recorded in three patients (6.6%). At univariate analysis, several variables were associated with the occurrence of events, including RVH (HR: 7.09, 95% CI: 2.17 to 23.14, P = 0.001) and indexes of RV systolic function (tricuspid annular plane systolic excursion HR: 0.77, 95% CI: 0.62 to 0.96, P = 0.02; and RV tissue Doppler systolic velocity HR: 0.76, 95% CI: 0.61 to 0.93, P = 0.01). At multivariate analysis, proteinuria (HR:8.3, 95% CI: 2.88 to 23.87, P

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.

Diffuse and focal epicardial coronary disease and coronary microvascular abnormalities may exist side-by-side. Identifying the contributions of each of these three players in the coronary circulation is a difficult task. Yet identifying coronary microvascular dysfunction (CMD) as an additional player in patients with coronary artery disease (CAD) may provide explanations of why symptoms may persist frequently following and why global coronary flow reserve may be more prognostically important than fractional flow reserve measured in a single vessel before percutaneous coronary intervention. This review focuses on the challenges of identifying the presence of CMD in the context of diffuse non-obstructive CAD and obstructive CAD. Furthermore, it is going to discuss the pathophysiology in this complex situation, examine the clinical context in which the interaction of the three components of disease takes place and finally look at non-invasive diagnostic methods relevant for addressing this question.

Funding Acknowledgements Type of funding sources: None. Background The right ventricle-pulmonary artery (RV-PA) coupling is a strong prognostic marker in several clinical settings, but only few studies focused on its role in repaired Tetralogy of Fallot (rToF) with pulmonary regurgitation (PR). Aim of this study was to assess whether differences exist in RV-PA coupling, estimated as by echocardiography, between patients with rToF and PR with (i-PVR) or without (ni-PVR) indication for pulmonary valve replacement (PVR). 3 Materials and Methods The study population included 40 rToF patients allocated to two groups: 20 i-PVR and 20 ni-PVR; 40 healthy controls were also included. All subjects underwent echocardiogram, while Cardiac magnetic resonance (CMR) was available in 27/40 rToF patients. RV-PA coupling was assessed by echocardiographic TAPSE/PASP and RV stroke volume/RV end systolic volume (RVSV/RVESV) by CMR. Results TAPSE was similar in i-PVR vs ni-PVR (19.0 ± 3.4 vs 18.8 ± 2.7 mm, p = 0.85) while RV-PA coupling was significantly worse in i-PVR vs ni-PVR (TAPSE/PASP 0.8 ± 0.3 vs 1.1 ± 0.5 mm/mmHg, p = 0.009) as well as in i-PVR vs controls (p = 0.02) while there was no difference between ni-PVR and controls (p = 0.29). CMR data confirmed the echo results, with a significant difference in RV-PA coupling between i-PVR and ni-PVR (RVSV/RVESV 0.9 ± 0.2 vs 1.2 ± 0.3 mL/min/mL, p = 0.01). Conclusions This study shows the presence of worse RV-PA uncoupling, despite normal RV systolic function, in rToF patients with indication to PVR. RV-PA coupling could be a sensitive marker of a progressive maladaptive RV response to long-standing volume overload in rToF prior to the onset of clinical symptoms and RV systolic dysfunction. Abstract Figure. example of an i-PVR patient

Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating "anatomical" and "functional" information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future.

Up to 50% of patients presenting with stable, mainly exercise-induced, chest pain and 10-20% of those admitted to hospital with chest pain suggesting an acute coronary syndrome show normal or near-normal coronary arteries at angiography. Coronary microvascular dysfunction (CMD) is a major cause of symptoms in these patients. However, controversial data exist about their prognosis. In this article, we critically review characteristics and results of the main studies that assessed clinical outcome of patients with angina chest pain and nonobstructive coronary artery disease presenting with either a stable angina pattern or an acute coronary syndrome. Published data indicate that the patients included in most studies are heterogeneous and a major determinant of clinical outcome is the presence of atherosclerotic, albeit not obstructive, coronary artery disease. Long-term prognosis seems instead excellent in patients with totally normal coronary arteries and a syndrome of CMD-related stable angina (microvascular angina). On the other hand, the prognostic impact of CMD in patients presenting with an acute coronary syndrome needs to be better assessed in future studies.

Congenital heart disease (CHD) and hypertrophic cardiomyopathy (HCM) are common features in patients affected by RASopathies. The aim of this study was to assess genotype- phenotype correlations, focusing on the cardiac features and outcomes of interventions for cardiac conditions, in a single-center cohort of 116 patients with molecularly confirmed diagnosis of RASopathy, and compare these findings with previously published data. All enrolled patients underwent a comprehensive echocardiographic examination. Relevant information was also retrospectively collected through the analysis of clinical records. As expected, significant associations were found between PTPN11 mutations and pulmonary stenosis (both valvular and supravalvular) and pulmonary valve dysplasia, and between SOS1 mutations and valvular defects. Similarly, HRAS mutations were significantly associated with HCM. Potential associations between less prevalent mutations and cardiac defects were also observed, including RIT1 mutations and HCM, SOS2 mutations and septal defects, and SHOC2 mutations and septal and valve abnormalities. Patients with PTPN11 mutations were the most likely to require both a primary treatment (transcatheter or surgical) and surgical reintervention. Other cardiac anomalies less reported until recently in this population, such as isolated functional and structural mitral valve diseases, as well as a sigmoid-shaped interventricular septum in the absence of HCM, were also reported. In conclusion, our study confirms previous data but also provides new insights on cardiac involvement in RASopathies. Further research concerning genotype/phenotype associations in RASopathies could lead to a more rational approach to surgery and the consideration of drug therapy in patients at higher risk due to age, severity, anatomy, and comorbidities.

AimsThe “early repolarization” (ER) pattern and J wave are frequent findings on standard ECG. Controversial data have recently been reported about their prognostic implications in healthy subjects, but no longitudinal prospective study specifically designed to investigate their long-term prognostic value has hitherto been published.Methods and ResultsWe prospectively enrolled 4,176 consecutive subjects with no evidence of cardiovascular disease who were referred for standard ECG recording for routine check-ups or pre-operative assessments for non-cardiovascular surgery. ECGs were prospectively assessed for the presence of ER/J wave. A 10-year follow-up was available for 3,937 patients (94.3%), 660 of whom (16.8%) showed ER/J wave whereas 3,277 did not. A total of 644 deaths occurred (16.3%), 116 (2.95%) of which were attributed to cardiovascular causes. Both total and cardiovascular mortality adjusted for clinical and laboratory variables did not differ significantly between patients with vs. without ER/J wave (HR 0.94; 95% CI 0.75–1.19; p = 0.63 and HR 0.61; 95% CI 0.31–1.21; p = 0.16, respectively). No significant association with total and cardiovascular mortality was also found in pre-specified analyses for ER and J wave alone, ER/J wave detected in specific ECG regions (i.e., inferior, lateral, precordial), and type of J wave (notched or slurred).ConclusionIn this specifically designed prospective study of individuals without any evidence of cardiovascular disease, we found no significant association of ER/J wave with the risk of the total as well as cardiovascular mortality during long-term follow-up.

Background Individuals who contract coronavirus disease 2019 (COVID-19) can suffer with persistent and debilitating symptoms long after the initial acute illness. Heart rate (HR) profiles determined during cardiopulmonary exercise testing (CPET) and delivered as part of a post-COVID recovery service may provide insight into the presence and impact of dysautonomia on functional ability. Objective Using an active, working-age, post–COVID-19 population, the purpose of this study was to (1) determine and characterize any association between subjective symptoms and dysautonomia; and (2) identify objective exercise capacity differences between patients classified “with” and those “without” dysautonomia. Methods Patients referred to a post–COVID-19 service underwent comprehensive clinical assessment, including self-reported symptoms, CPET, and secondary care investigations when indicated. Resting HR >75 bpm, HR increase with exercise .05). Patients with dysautonomia demonstrated objective functional limitations with significantly reduced work rate (219 ± 37 W vs 253 ± 52 W; P

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 Cardiac troponin I (cTnI) is considered a marker of myocardial necrosis. However, several studies have shown that cTnI increases also after short episodes of myocardial ischaemia. Nevertheless, it is unknown whether the changes in cTnI show differences according to the cause of myocardial ischaemia. Thus, our study aimed to evaluate cTnI response to ischaemia in patients with stable coronary artery disease (CAD), patients with microvascular angina (MVA), and transient ischaemia induced during percutaneous coronary intervention (PCI). Methods and results We studied four groups of patients: (1) patients with stable angina and obstructive CAD (coronary stenosis ≥50% and/or fractional flow reserve Conclusions Hs-cTnI serum levels increase after EST, both in patients with obstructive CAD and coronary microvascular dysfunction (CMD), but a similar increase is also observed in healthy subjects. More consistent hs-cTnI level increase with later peak-level is observed in patients with obstructive CAD after transient ischaemia induced during PCI.

Aims Transcatheter aortic valve implantation (TAVI) has become a first-line treatment for most patients with severe aortic stenosis (AS) at intermediate/high surgical risk, resulting in significant improvement of clinical outcome. However, whether ventricular arrhythmias (VAs) or cardiac autonomic dysfunction influence outcome and whether TAVI has any effects on VAs and cardiac autonomic function is unknown. Thus, this study was aimed to investigate: I1) whether VAs and autonomic dysfunction [as assessed by heart rate variability (HRV)] are associated with clinical outcome and (2) the effects of TAVI on VAs and HRV, in patients with severe AS. Methods and results We studied 71 consecutive patients with severe aortic stenosis, admitted to our department of Cardiovascular Medicine to undergo TAVI. Patients with previous cardiac surgery, percutaneous coronary revascularization, acute coronary syndrome, and other significant heart valve disease or relevant comorbidities were excluded. The day before TAVI all patients underwent transthoracic Doppler echocardiography (TTDE), including global longitudinal strain (GLS) assessment, and 24-h ECG Holter monitoring (HM), to assess VA burden and HRV. A clinical follow-up was performed at 6 months from discharge. Furthermore, TTDE and 24-h HM were performed at follow-up in 38 (54.5%) and 29 (40.8%) patients, respectively. The primary endpoint was the occurrence of major clinical events (MACE), that include death, hospitalization for cardiac causes, pacemaker implantation, myocardial infarction, or stroke. Of 71 patients (48 female, mean age 80.5 ± 6.5 years) enrolled in the study, a 6-month clinical follow-up could be performed in 54 (76%). MACE occurred in 21 patients (38.9%), 8 of whom (14.8%) had hospitalization for heart failure, 13 (24%) required pacemaker implantation, and 3 had stroke (5.6%). Compared to baseline, at follow-up the mean aortic valve gradient (50.6 ± 11.4 vs. 8.38 ± 3.23 mmHg, P 10 per hour were detected in a higher number of patients at 6-month follow-up, compared to baseline (23.8% vs. 45.2%; P = 0.022). No significant differences were detected in most time-domain and frequency-domain HRV parameters. Unexpectedly, SDNNi (62.8 ± 19.1 vs. 41.9 ± 16.5; P = 0.008), RMSSD (54.6 ± 36.6 vs. 30.1 ± 17.9; P = 0.024) and VLF (56.4 ± 49.6 vs. 29 ± 12.7; P = 0.028) were found to be significantly higher at follow-up compared to baseline. Conclusions Our data show that, in patients with severe AS, TAVI does not seem to have significant effects on VA burden, despite echocardiographic and clinical improvement. Similarly, our data failed to show significant improvement of sympatho-vagal balance at follow-up compared to baseline in these patients.