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INTRODUCTION mitral valve prolapse(MVP) is a common disease in women, causing chest pain and palpitation, due to structural and functional valve abnormality, sometime associated with gastro-esophageal-reflux-disease(GERD).This is a challenging clinical problem in clinical practice,requires targeted diagnostic assessment,to identify the underlying causes of the symptoms because treatment needs to be tailored,according to the causes themselves, to resolve the symptoms. Our aim is to assess the prevalence of GERD in a population of postmenopausal women affected by MVP and if there is any correlation between the two conditions. PATIENTS AND METHODS MVP diagnosis was performed by echocardiograpic examination,according to ASE(American-Society-Echocardiography) criteria. 289 consecutive MVP women,symptomatic for chest pain and palpitation,were included,250 consecutive women without MVP, symptomatic for chest pain and palpitation were control group(CG).GERD diagnosis was performed according to 2013 ACG(American-College-Gastroenterology) criteria,women affected by thyroid disorders, all heart disease, including mitral disease with moderate or severe mitral regurgitation,gastrointestinal diseases assessed by gastroscopy were excluded. RESULTS 31(11%) women were affected by GERD,among 289 with MVP, 11(4.4%) women were affected by GERD,among 250 on CG,Chi-squared 8.1,Odds ratio 2.7,c.i.95%,p

Arterial hypertension is a systemic condition characterized by elevated blood pressure in the vascular system. Despite the great effort of scientific community to sensitize population to the problem, enforcing the preventive and treatment measures, this condition continues to be responsible for a large portion of global mortality, as it represents one of the major modifiable risk factors of cardiovascular disease. The significant and substantial clinical implications of high blood pressure on cardiovascular morbidity and mortality are explained by the effect of hypertension on specific organs, particularly sensitive to the effects of changes in blood pressure, resulting cardiac remodeling, cerebrovascular disease, renal failure, atherosclerotic vascular disease, and retinopathy, hence the term "target organ damage". The aim of this review is to give an overview of several noninvasive tools useful in the detection of organ damage related to arterial hypertension.

Background Coronary atherosclerosis is a frequent complication of type 2 diabetes mellitus (DM2). Considering the contiguity with the vascular wall, perivascular adipose tissue (PVAT) could play a crucial role in the pathogenic microenvironment of atherosclerosis. The PVAT attenuation index (p-FAI) is a non-invasive marker that reveals the change in peri-coronary adipose tissue (PCAT). High values of p-FAI are associated with increased cardiovascular mortality and poor prognosis. Emerging as an indication, contributor to, and therapeutic target for atherosclerosis, PCAT warrants further investigation in DM2. Purpose We aimed to characterize the association of PCAT by p-FAI and DM2, and to compare coronary inflammation in DM2 versus non DM2 patients with coronary artery disease (CAD), and versus healthy controls. Methods 15 consecutive DM2 patients (9 male, age 63±10 years) without symptoms/signs of cardiovascular disease were included in the study and compared to 8 non DM2 patients with CAD and 13 healthy volunteers without cardiovascular diseases, matched for age and sex. All patients and controls underwent coronary computed tomography angiography (CCTA) for the evaluation of coronary arteries and p-FAI. All scans were performed using a 320-slice multidetector computed tomography (Toshiba Aquilion) and a prospective ECG-triggered sequential acquisition. p-FAI analysis was performed using a dedicated workstation (Aquarius iNtuition Edition version 4.4.13. P3; TeraRecon Inc., Foster City, CA, USA). The proximal 40-mm segment of the right coronary artery (RCA) was identified and the inner and the outer wall were automatically traced, excluding the 10 mm from the ostium. The adipose tissue localized within a radial distance from the outer wall equal to a medium diameter of the RCA was evaluated. Voxel histograms of CT attenuation were traced and included between −190 to −30 HU within the PCAT volume. p-FAI was calculated as the median CT attenuation value of PCAT of the proximal 40-mm segment of the RCA (Figure 1). Results CAD was present in 10 DM2 patients (5 males, aged 63.1±10.5 years); in 5 DM2 patients (4 males, aged 63±11 years) epicardial coronary arteries were normal. p-FAI was higher in DM2 patients than in healthy controls (p=0.004). The presence of CAD did not impact on p-FAI in DM2 patients, presenting a comparable value (p=0.37). p-FAI was higher in DM2 patients with CAD than in non DM2 patients with CAD (p=0.04). Moreover, p-FAI was higher in DM2 patients without CAD than in non DM2 patients with CAD (p=0.002, Figure 2). Finally, p-FAI was not different in non DM2 patients with CAD compared to healthy controls (p=0.65), suggesting the limited role of CAD in the progression of peri-coronary inflammation when compared to DM2. Conclusions Coronary inflammation evaluated by p-FAI measurement was higher in DM2 patients, also without CAD. Therefore, our results suggest that DM2 is a determinant of coronary inflammation stronger than CAD. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Introduction Multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII) are two modalities of treating type 1 diabetes mellitus (T1DM). The benefits of CSII on long-term metabolic control and outcomes compared to those of MDI are still debated. We investigated both vascular function and myocardial performance in T1DM adolescents on MDI or CSII treatment. Methods One hundred twenty-three T1DM subjects (mean age 14.16±2.55 years), 63 on MDI regimen, 60 on CSII, and 57 controls were enrolled. Anthropometric and biochemical characteristics were evaluated. Ultrasound assessments of carotid intima-media thickness (cIMT), flow-mediated dilatation of brachial artery, anteroposterior diameter of the infrarenal abdominal aorta (APAO), and transthoracic echocardiography were performed. Results T1DM subjects on the CSII regimen showed better glycemic control than those on MDI, expressed as glycated haemoglobin (HbA1c). c-IMT and APAO were higher in MDI than CSII patients (0.61±0.11 mm vs. 0.56±0.07 mm, p=0.04; 13.61±3.29 mm vs. 11.65±1.84 mm, p=0.01, respectively). Left and right Tei index and left E/e’ ratio were higher in MDI than CSII subjects (0.82±0.40 vs. 0.52±0.19, p=0.002; 0.86±0.41 vs. 0.64±0.1, p=0.02; 5.89±2.0 vs. 4.73±1.59, p=0.02, respectively). Multiple regression analyses showed that glucose level, HbA1c and diabetes onset were significantly related to vascular and echocardiographic parameters in MDI and CSII patients. Conclusions CSII regimen in T1DM adolescents improves glycemic control and seems to ameliorate endothelial function and global myocardial performance as compared to MDI therapy.

Background: The aim of this study was to assess the role of cardiac and vascular parameters as all-cause mortality determinants in patients suffering from gynecological cancers. Methods: This was an observational, prospective, non-randomized, and non-controlled study. Forty-seven consecutive patients (mean age: 58 ± 13 years) were enrolled after cancer staging. All patients underwent evaluation of vascular (common carotid intima-media thickness (mean C-IMT), flow-mediated dilation of the brachial artery (FMD), and antero-posterior diameter of the infrarenal abdominal aorta (APAO)) and cardiac function and morphology before cancer-related interventions. A 6-year follow-up was carried out to assess the overall survival of the whole population. Results: Twenty patients (42%) died by the time of the 6-year follow-up. The brachial artery FMD values were higher in the survivors than the non-survivors (9.71 ± 3.53% vs. 6.13 ± 2.62%, p &lt, 0.001), as well as the LVEF (60.8 ± 3.0% vs. 57.8 ± 4.4%, p = 0.009). There were no differences in the mean C-IMT, APAO, and other echocardiographic parameters. ROC curve analysis identified a baseline LVEF &lt, 57% and FMD value &lt, 5.8% as the best cut-offs. Kaplan–Meier evaluation showed that the LVEF, tricuspid annular plane systolic excursion, and FMD were the best predictors of all-cause mortality, although only the LVEF and FMD were confirmed in multivariate Cox regression analysis. Conclusions: The LVEF and brachial artery FMD are independent prognostic determinants in patients with gynecological cancers.

Funding Acknowledgements Type of funding sources: None. Background Left ventricular thrombosis (LVT) is a possible complication following myocardial infarction (MI). Besides infarct size, risk factors for LVT include ST-elevated MI (STEMI), anterior and apical location, reduced left ventricular ejection fraction (LVEF) and the presence of microvascular obstruction. Echocardiography quantified myocardial strain has been associated with LVT following MI. Recently, global longitudinal strain, calculated with feature tracking (FT) - CMR, emerged as an independent predictor of major cardiovascular events following MI. Anyway, the relationship between abnormalities on FT-CMR and LVT following MI is still unexplored. Aim of our study is to investigate the possible association between abnormal strain on FT-CMR and LVT following apical STEMI. Methods We performed a retrospective analysis including all patients with a previous apical STEMI, who underwent CMR at our Institute between August 2013 and October 2020. Patients with ongoing anticoagulant therapy were excluded. Differences in global and segmental strain on CMR between patients with and without LVT were tested in a propensity-matched sample, using LVEF, age, gender, time from MI diagnosis and number of LV segments with transmural late gadolinium enhancement (LGE) as covariates to assign propensity score. Furthermore, difference in terms of apical to global radial strain percentual deviation (AGD), calculated as [(Global Radial Strain – Apical Radial Strain)/Global Radial Strain] * 100, was tested. Results Of 356 patients with apical STEMI undergoing CMR at our center, 37 (10.4%) were diagnosed with LVT. After performing a propensity score matching, we obtained a sample of 36 pairs, with a mean age of 65 (SD 11) years, and a median EF of 35% (IQR 27-42); 59 (82%) of them were male. A significant difference in terms of apical radial strain was found between the two groups, with a median strain of 10.75 (IQR 6.8–16.5) in patients without LVT compared to a value of 5.25 (IQR 2.7–9-6) in patients with LVT (p = 0.007). No differences were found in terms of global longitudinal, radial and circumferential strain (p = 0.19, p= 0.2 and p= 0.49 respectively) and segmental circumferential and longitudinal strain. When considering the AGD parameter, a significant difference was found between the two groups, with a median deviation of 12% (IQR -20; +48) in patients without LVT and 51% (IQR +47; +75) in patients with LVT (p= 0.0003). Furthermore, an AGD value of 26% was found to be the most accurate in terms of sensitivity and specificity applying a Receiver Operating Characteristic (ROC) curve analysis (AUC 0.74; CI 0.62-0.85). Conclusions Among patients with transmural MI involving LV apex, reduced apical radial strain on FT-CMR is associated with the presence of LV thrombosis. Furthermore, among patients developing LV thrombi, a greater apical radial strain deviation from the global one was found, with a threshold value of 26% at ROC curve analysis.

Funding Acknowledgements Type of funding sources: None. Background. Arrhythmic mitral valve prolapse (MVP) is characterized by left ventricular (LV) fibrosis in the basal inferolateral wall and papillary muscles. We hypothesized that LV fibrosis are driven by excessive mechanical forces acting on myocardial susceptible cells, representing the last step in the MVP-induced myocardial stretch process. Purpose. We aimed to evaluate the LV myocardial deformation, using strain assessed with cardiac magnetic resonance (CMR), in arrhythmic MVP patients with normal LV ejection fraction (LVEF) and absent/trivial mitral regurgitation (MR) and its correlation with the presence of LV fibrosis, detected by late gadolinium enhancement (LGE) in post-contrast CMR images. Methods. We enrolled consecutive arrhythmic MVP patients with normal LVEF and no/trivial MR. Sixty-nine (39 female; median age: 40 years) patients without MVP, arrhythmias or cardiovascular history served as control group. All patients underwent CMR for identification of LGE and evaluation of LV myocardial deformation. Results. A total of 66 patients were enrolled (47 female; median age: 44 years). In the overall MVP population, LGE was present in 41 patients (62.1%). MVP patients without LGE (25 patients, 37.9%) presented a higher global radial (median: 42.19 vs 33; p

Background Inflammatory bowel diseases (IBD) may be complicated by extraintestinal manifestations (EIM). Both conditions may be implicated in the overall increase of cardiovascular (CV) risk profile of the patients. The study aimed to assess CV risk in IBD patients with EIMs in relation to the stages of both diseases. Methods A total of 70 (38 men, mean age 51.7±12.4 years) patients with IBD and 22 controls (12 men, mean age 49.2±13.6 years) were enrolled. All patients and controls were screened for extraintestinal manifestations and underwent physical and anthropometric examinations, standard laboratory investigations, ultrasound evaluation of carotid arteries and flow-mediated vasodilatation (FMD). Patients were divided into four groups in relation to their active or remission stage of disease: 1. IBD+ EIM+; 2. IBD+ EIM-; 3. IBD- EIM+; 4. IBD- EIM-. Results The groups were homogenous according to their clinical characteristics. Patients with both IBD and EIM in active phase showed significantly lower values in FMD than controls (p=0.024). Carotid intima-media thickness values (cIMT) were similar among groups. Patients with active phases of IBD and/or EIM showed statistically significant lower values in FMD measurements (p=0.0008 and p=0.0011, respectively). Multivariate regression did not reveal any independent predictors for FMD values. Conclusions The active phase of IBD or EIM or both may promote endothelial dysfunction in patients, thus increasing their CV risk profile. Patients in remission phase showed endothelial function similar at controls.

A significant change of platelet number may be a risk factor for atherosclerotic cardiovascular disease. The aim of this study was to investigate the association between platelet number and early signs of atherosclerosis, evaluated by carotid intima-media thickness (c-IMT), in a apparently healthy population mainly represented by obese subjects.As many as 961 subjects, 686 women and 275 men, aged between 18 and 74 years, were enrolled in the study. Of these, 54 individuals (5.6% of all subjects) were normal weight, 259 individuals (27.0% of all subjects) were overweight, and 648 individuals (67.4% of all subjects) were obese. Waist circumference (WC) and blood glucose, insulin, total cholesterol, high and low density lipoprotein cholesterol, triglycerides and platelet count were also detected in all subjects, who underwent carotid echo color doppler ultrasound to measure c-IMT. c-IMT was significantly and positively associated to age (r = 0.204, P 0.0001), fasting glucose (r = 0.073, P 0.0240), total cholesterol (r = 0.096, P = 0.0031), and systolic and diastolic blood pressure (r = 0.140, P 0.0001 and r = 0.119, P 0.0003 respectively); c-IMT was significantly and negatively correlated with platelet count (r = -0.165, P 0.0001). Only age (P 0.0001) and systolic blood pressure (P = 0.0393), positively, and platelet number (P 0.0001), negatively, were significantly and independently associated to c-IMT in a final multiple regression analysis.Lower platelet number represented an independent determinant of c-IMT in a population, mainly represented by obese patients. These results suggest that a decrease of platelet number may well be an early defensive mechanism in subjects developing the thickening of carotid artery.

Background: Coronary microvascular dysfunction (CMD) is usually evaluated measuring coronary flow velocity reserve (CFVR). A more comprehensive analysis of CFVR including additional consideration of the associated logical companion-CFVR, where hyperemic diastolic coronary flow velocity may act as surrogate, was applied in this study to elucidate the mechanism of CMD in psoriasis. Methods and results: Coronary flow velocity reserve was analysed using transthoracic echocardiographs of 127 psoriasis patients (age 36 ± 8 years; 104 males) and of 52 sex- and age-matched healthy controls. CFVR determination was repeated in the patient subgroup (n = 78) receiving anti-inflammatory therapy. Baseline and hyperemic microvascular resistance (MR) were calculated. CMD was defined as CFVR ≤ 2.5. Four endotypes of CMD were identified referring to concordant or discordant impairments of hyperemic flow or CFVR. We evaluated the companion-CFVR, as derived from the quadratic mean of hyperemic and diastolic flow velocity at rest. Coronary flow parameters, including CFVR (p = 0.01), were different among the two endotypes having CFVR > 2.5. Specifically, all 11 (14%) patients with CFVR deterioration despite therapy, belonged to endotype 1, and had higher baseline and hyperemic MR (p

The introduction of high-sensitivity cardiac troponin allowed identifying a proportion of subjects with chest pain and electrocardiographic changes suggestive of myocardial infarction showing &lt, 50% coronary artery stenosis. PFAI is a coronary CT marker proved to predict outcome in ischemic heart disease. Based on CMR findings, patients were divided into myocarditis (n = 15), MINOCA (n = 14) and TTS (n = 9) groups. The aim was to estimate the value of pFAI in these groups compared to 12 controls. To evaluate the coronary inflammation “time course,” 20 patients underwent CMR and coronary CT scan within 8 days from the onset, the others within 60 days. There were higher values of pFAI in myocarditis (−86.45 HU), MINOCA (−84.63 HU) and TTS (−84.79 HU) compared to controls (−96.02 HU, p = 0.0077). Among patients who underwent CT within 8 days from onset, the MINOCA had a significantly higher pFAI value (−76.91 HU) compared to the control group (−96.02 HU, p = 0.0001). In the group that underwent CT later than 8 days, elevated pFAI values persisted only in the myocarditis and TTS groups, and there was no difference between MINOCA and controls. Our study shows that in patients with a diagnosis of MINOCA, there is acute coronary inflammation, which is more evident within one week from the acute event but tends to disappear with time.

Background According to expert opinion, orthostatic hypotension (OH) associated to a change in heart rate (ΔHR) less than 15 bpm suggests neurogenic OH (NOH). Recently, the ratio between HR and systolic blood pressure changes at 3 min of tilt test (ΔHR/ΔSBP) has been proposed as a better index than the ΔHR cut-off of 17 bpm. Our aim was to validate these indexes based on HR in an independent cohort of patients who performed cardiovascular reflex tests according to standardized procedures at our Institution. Methods We applied the HR indexes to all cardiovascular reflex tests that fulfilled the following criteria: (1) presence of classical OH at tilt test, (2) reliable Valsalva manoeuvre (VM), (3) absence of heart disease. We classified OH according to VM (absence of overshoot = NOH), and verified how many were correctly identified by ΔHR/ΔSBP (≤0.49 neurogenic) and ΔHR (≤17 and ≤15 neurogenic). Results We identified 369 tests with OH. Based on VM, 335 were NOH. The ΔHR/ΔSBP ≤ 0.49 identified NOH with a sensitivity of 91% and a specificity of 59%, the ΔHR ≤ 17 bpm with 88% sensitivity and 38% specificity, and the ΔHR ≤ 15 bpm with 84% sensitivity and 50% specificity. Conclusion In our cohort, the ΔHR/ΔSBP ratio had a good sensitivity but a limited specificity to identify NOH. This easily applicable test may represent a valuable screening tool in a clinical setting to identify patients who need further detailed autonomic testing to confirm the neurogenic origin of OH.

Inflammatory bowel diseases have been recognized as predisposing factors to atherosclerosis and thrombotic events, involving both the venous and the arterial circulatory systems. We report the case of a 70-year-old man who presented with ST elevation myocardial infarction during the active phase of ulcerative colitis (UC). Because of the ongoing hematochezia, after successful revascularization of the culprit vessel, the patient was medicated with Clopidogrel, in place of one of the more powerful new oral P2Y12 inhibitors that currently represent the gold standard therapy. Few days later a second elective percutaneous coronary intervention (PCI) on a non-culprit vessel ensued in a life-threatening early massive stent thrombosis involving the left main. During and after emergency PCI antiplatelet therapy was upgraded to Abciximab and Ticagrelor; this therapy proved successful in handling the massive stent thrombosis in the absence of severe bleeding complications. This case is unique and paradigmatic of the complex management of patients with coexisting active UC and acute coronary syndromes; it demonstrates as in this setting the balance between hemorrhagic and ischemic risk is labile and tricky to assess.

Introduction The primary endpoint of this study was to determine the prevalence of coronary artery disease (CAD) and coronary artery calcium score (CACS) using coronary computed tomography angiography (CCTA) among patients with polyvascular atherosclerosis (PVA). Secondary endpoints were to evaluate the prevalence of cardiovascular risk factors and determine the predictors of PVA. Methods The presence of atherosclerotic disease was assessed using ultrasonographic vascular examination in 515 asymptomatic patients. All patients with presence of stenosis over 50% and moderate-to-severe cardiovascular risk profile underwent CCTA to identify atherosclerotic coronary disease. Results Among 515 participants, 143 patients had no evidence of atherosclerotic plaque. Of the 372 patients with atherosclerotic plaque, 184 patients had single-vessel disease, 111 patients had double-vessel disease and 77 patients had triple-vessel disease; among these patients, those who also presented with stenosis > 50% underwent CCTA. Coronary stenosis categories included: normal (6.4%); haemodynamically insignificant (34.6%); intermediate (28.7%); significant (26.6%); and total artery occlusion (3.7%). Based on the coronary vessel involved, the patients were categorised as having single- (41.0%), double- (42.0%) or triple- (17.0%) coronary disease. CACS was significantly higher in patients with double- or triple-vessel disease when compared to those with single-vessel disease. Conclusion Our study confirmed not only the high sensitivity of CCTA for highlighting CAD, but also its negative predictive value for excluding the presence of coronary stenosis or ischaemia. We found good correlation between PVA and CACS, and were able to confirm the risk factors for PVA.

Primary prevention of cardiovascular events in older adults is a relevant problem, due to lack of evidence for safe and efficacious therapy, its costs and elderly quality of life, Italy’s aging population is constantly increasing, so cardiovascular disease (CVD) primary prevention in the elderly is a prime objective. Life expectancy has dramatically increased over the last 2 decades, the proportion of individuals aged 80 years and older has grown rapidly in Europe and the United States, but cost / effective ratio of CVD prevention through risk factors control is debated. It is therefore important to implement cardiovascular risk factors estimation in the elderly to maximize the quality of life of patients and to lengthen their healthy life expectancy, choosing the better treatment for each patient sharing the choice with himself when it is possible, always remembering that elderly patients often have multiple co-morbidities that require a high number of concurrent medications; this may increase the risk for drug-drug interactions, thereby reducing the potential benefits of CVD prevention therapy. Nevertheless, CVD is not an inevitable concomitant of aging. Sometimes, autopsy in the elderly reveals atheroma-free coronary arteries, a normal-sized heart and unscarred valves. All primary prevention strategy decisions should consider estimated life expectancy and overall function and not just the cardiovascular event risks, magnitude and time to benefit or harm, potentially altered adverse effect profiles, and informed patient preferences. CVD primary prevention needs to be more implemented in the elderly, this might contribute to improve health status and quality of life in this growing population if correctly performed.

ObjectiveTo retrospectively describe clinical and instrumental features of a cohort of patients with at least a 5-year history of idiopathic autonomic failure (IAF) longitudinally evaluated at the Autonomic Unit of the University of Bologna (IAF-Bo cohort).MethodsWe identified patients with at least a 5-year history of IAF who were referred to our department from 1989 to 2016 and evaluated at least once a year during the disease course. Clinical and instrumental data were collected from medical records. Clinical variables were categorized as early if presenting within 3 years from disease onset. Predictors associated with conversion to other synucleinopathies were identified in a Cox regression analysis.ResultsThe IAF-Bo cohort included 50 patients (39 male, 19 deceased at the last follow-up). At the last follow-up visit, 34 patients retained IAF phenotype (ncIAF group), while 16 developed a CNS synucleinopathy (converters group). Specific clinical and instrumental features were represented differently in the converters and ncIAF groups. The converters group showed a higher risk of death than the ncIAF group. Early onset of urinary dysfunction, early onset of REM sleep behavior disorder, and a Valsalva ratio ≥1.25 were identified as variables associated with phenoconversion.ConclusionsThis is one of the largest studies on the natural history of a cohort of patients with at least a 5-year history of IAF, showing a percentage of phenoconversion of 32%. We demonstrated that specific clinical and instrumental features entail an increased probability of phenoconversion. These findings could contribute to a better definition of the nature of IAF and to the identification of early markers of phenoconversion.

Hyperglycemia is frequent in patients with ST elevation myocardial infarction (STEMI) and is associated with adverse outcome. Aim of our study was to evaluate the correlation between admission plasma glucose level (PGL) and coronary arteries flow velocity.We enrolled 149 STEMI patients successfully treated with primary percutaneous coronary intervention (pPCI). The study population was divided into two groups based on PGL (or140 mg/dl) and on history of diabetes, and the groups compared in terms of corrected TIMI frame count (cTFC).Hyperglycemic patients had a significantly higher cTFC in both the culprit (p 0.0001) and non-culprit vessel (p: 0.0002); diabetes history impairs as well cTFC of the culprit (p 0.0001) and non-culprit vessel (p: 0.0001). Within the subpopulation of diabetic patients hyperglycemic ones showed higher cTFC in both the culprit (p 0.0013) and non-culprit vessel (p: 0.0006). Moreover in the whole population cTFC values of both arteries increase linearly with the increment of admission PGL.Admission PGL affects coronary flow of both culprit and non-culprit vessel. The impairment of coronary flow is also demonstrated in known diabetic patients, suggesting to consider hyperglycemia an additional risk factor. We finally demonstrated for the first time a positive linear relationship between PGL and cTFC.

Pure autonomic failure is challenging as it can be the presenting feature of a central nervous system syncleinopathy such as Parkinson’s disease (PD) or multiple system atrophy (MSA). Because the prognosis of MSA and PD is so different, predictive features for a possible conversion can be extremely valuable. In this paper, we report three cases (two with autopsy-proven diagnosis) that had isolated AF for many years before converting to MSA or PD. Of all the tests that were performed during the premotor stage, Iodine-123-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy was predictive of the conversion to MSA. We suggest that MIBG myocardial scintigraphy, when performed in patients with isolated AF, may be a valuable predictor of conversion to MSA. On the contrary, the role of such test in parkinsonian patients irrespective of the presence of AF is still to be clarified.

Spontaneous coronary artery dissection (SCAD) is a separation of the coronary wall layers, not related to trauma, medical procedures or atherosclerosis. The dissection causes the blood entry in the vascular wall with the consequent formation of a false lumen and intramural hematoma (IMH). Two pathogenetic mechanisms have been proposed to explain SCAD: a “primary” rupture of coronary endothelium or the rupture of the “vasa vasorum”. Clinical presentation and severity of manifestations are variable, ranging from complete absence of symptoms to acute coronary syndrome (ACS), cardiogenic shock, cardiac arrest or sudden cardiac death. Despite coronary angiography is the first-line examination, by supplying two-dimensional images of the lumen, it does not always allow an incontrovertible diagnosis of SCAD. New intravascular imaging techniques, such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS), have been recently introduced and may be extremely helpful in assessing the coronary wall integrity, thus improving coronary angiography diagnostic accuracy. Because of the lack of large randomized trials comparing different strategies, the optimal treatment of SCAD is still controversial. The first-line approach is conservative and based on medical therapy. Nevertheless, in particular situations an invasive approach is necessary. In the last years, several new strategies have improved the way to perform percutaneous coronary interventions (PCI), such as new generation drug eluting stents (DES), bio-resorbable scaffolds (BRS), sirolimus self-expandable stent (SES), drug eluting balloons (DEB), and cutting balloon. Cardiac artery bypass graft (CABG) is an even more invasive method to restore coronary flow and should be considered in urgent/emergent settings when PCI is not feasible or has failed. Cause the therapeutic approach of SCAD can be substantially different from that of atherosclerotic coronary artery disease, an accurate diagnosis is crucial to set up the best treatment strategy.

The autonomic nervous system (ANS) regulates physiologic processes occurring without conscious control through the sympathetic and the parasympathetic systems. Since the ANS is one of the major determinants of heart rate (HR), evaluation of HR variability is a powerful instrument to quantify sympathetic and parasympathetic activations. Traditional techniques in the frequency domain are not applicable to short non-stationary signals like the RR intervals during the Valsalva maneuver (VM). The aim of this work was to validate the wavelet approach in analyzing the VM: 14 healthy subjects and 9 with autonomic failure underwent two or more VMs for a total of 68 tests. A Daubechies-16 form mother wavelet and the powers associated with the sympathetic (LF band) and parasympathetic (HF) activities were calculated. Each VM performed by the same healthy subject presented similar morphologies for the RR series and LF and HF powers. The inter-subject comparison showed a good agreement in morphology with a greater variability in sympathetic and parasympathetic activations. Pathological subjects presented a good RR series repeatability without any correlation in LF and HF powers. The wavelet approach is a good methodology to discriminate normal from pathological subjects and further longitudinal evaluation are required.

Sleep disorders (SDs) are one of the most frequent non-motor symptoms of Parkinson’s disease (PD), usually increasing in frequency over the course of the disease and disability progression. SDs include nocturnal and diurnal manifestations such as insomnia, REM sleep behavior disorder and excessive daytime sleepiness. The causes of sleep disorders in PD are numerous, including the neurodegeneration process itself, which can disrupt the networks regulating the sleep-wake cycle and deplete a large number of cerebral amines possibly playing a role in the initiation and maintenance of sleep. Despite the significant prevalence of SDs in PD patients, few clinical trials on SDs treatment have been conducted. Our aim is to critically review the principal therapeutic options for the most common SDs in PD. The appropriate diagnosis and treatment of SDs in PD can lead to the consolidation of nocturnal sleep, the enhancement of daytime alertness and the amelioration of the quality of life of the patients.

The prevalence of heart failure among diabetic patients is high, also in those with normal blood pressure and without coronary artery disease, even when electrocardiogram (ECG) is normal. The goal of our study was to assess the prevalence of left ventricular diastolic dysfunction (LVDD) among diabetic women (DW) and its correlation with glycosylated hemoglobin (HbA1c) levels, obesity status, and ECG parameters.A group of 456 consecutive normotensive postmenopausal women affected by type 2 diabetes, diagnosed over 5 years, were enrolled. One hundred normotensive non-diabetic postmenopausal women were included as a control group (CG). Rest ECG and trans-thoracic echocardiogram and Doppler were performed.LVDD was present in 103 (23.3%) out of 456 DW, and 8 out of 100 women in CG (8%), p0.001. There was no difference in mean age between the two groups: 56 ± 13 and 55 ± 3, respectively (p = 0.3). There were 191 (41.9%) DW with body mass index (BMI)30 kg/m². Among those, there were 56 (12.3%) with significant prevalence of LVDD, while there were 49 (10.7%) with BMI30 kg/m², p0.005. DW with HbA1c7.5% comprised a group of 243 (53.3%) patients. Among those, there were 45 (9.9%) with higher prevalence of LVDD, and 15 (3.3%) with HbA1c7.5%, p0.01. Out of a group of 147 (32.2%) DW with abnormal ECG , 21 had LVDD (4.6%), p = 0,1, and 84 (18.8%) had LVDD with normal ECG.Our data prove a high prevalence of LVDD in asymptomatic diabetic postmenopausal women. This finding is closely related with HbA1c levels and obesity status, not with abnormal ECG, which is a unique cardiologic test recommended by current guidelines in all diabetic patients. We conclude that early detection of high level of HbA1c and obesity (30 kg/m²) may identify women with major risk to develop LVDD. Furthermore, a simple ECG, when normal, is not enough to assess a normal LV diastolic function.

Dual antiplatelet therapy improves angiographic results of primary percutaneous coronary intervention (pPCI) in patients with STEMI. The new oral P2Y12 inhibitors (P2Y12-I) prasugrel and ticagrelor are the gold-standard drugs because of a faster and more intense effect when compared to clopidogrel.

Background: The goal of STEMI treatment is early reperfusion. The new oral P2Y12 inhibitors (P2Y12-I) prasugrel and ticagrelor demonstrated to improve angiographic results of primary percutaneous coronary intervention (pPCI) and clinical prognosis, but their onset of action is significantly impaired

Pietro Scicchitano,1 Francesca Cortese,1 Gabriella Ricci,1 Santa Carbonara,1 Michele Moncelli,1 Massimo Iacoviello,1 Annagrazia Cecere,1 Michele Gesualdo,1 Annapaola Zito,1 Pasquale Caldarola,2 Domenico Scrutinio,3 Rocco Lagioia,3 Graziano Riccioni,4 Marco Matteo Ciccone1 1Section of Cardiovascular Diseases, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Policlinico, Bari, Italy; 2Section of Cardiovascular Diseases, Policlinic, San Paolo Hospital, Bari, Italy; 3Section of Cardiovascular Diseases, Fondazione Maugeri, Cassano Murge, Italy; 4Intensive Cardiology Care Unit, San Camillo de Lellis Hospital, Manfredonia, Foggia, Italy Abstract: Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies. Keywords: chronic heart failure, heart rate reduction, cardiac ischemic disease, heart-rate lowering drugs, funny current

Multiple system atrophy (MSA) is a neurodegenerative disease characterised by cardiovascular autonomic failure and/or urinary dysfunctions, associated with parkinsonism, cerebellar and/or corticospinal signs, usually leading to death after an average of 7 years. We describe the disease course of five patients diagnosed with probable MSA (4 with predominant parkinsonism and 1 with predominant cerebellar ataxia) who survived for more than 15 years and were followed throughout the disease course at our department. Cardiovascular autonomic dysfunction of any severity occurred late (mean latency from disease onset 9.4 ± 5 years) in this subgroup of MSA patients. The time of involvement of the urogenital system was more variable (from 0 to 14 years after disease onset) and manifested with symptoms of storage disorders (urinary urgency, frequency and incontinence) and erectile dysfunction in men. Conversely complains suggestive of urinary voiding dysfunction (incomplete bladder emptying and urinary retention) were not recorded and patients required catheterization only late in the disease course. In conclusion, our study showed that late onset of both cardiovascular autonomic failure and urinary voiding disorders may be positive prognostic factors in MSA irrespective of the MSA subtype.

INTRODUCTION: The exact clinical and prognostic significance and the therapeutic implications of asystole induced by head-up tilt test are still a matter of debate. METHODS: We assessed, by means of a semi-structured interview, the long-term outcome of cardioinhibitory syncope in all the patients who presented a tilt-induced sinus arrest of more than 3 s in our Autonomic Unit between 1996 and 2010. CONCLUSIONS: Although syncopal recurrences were common, tilt-induced asystole did not imply a poor prognosis in terms of death or major therapeutic procedures.

Background Objective of this study was to evaluate the acute cardiovascular and respiratory effects of switching on the deep brain stimulation in the follow up of nine Parkinson's disease patients with subthalamic nucleus stimulation and six cluster headache patients with posterior hypothalamic area stimulation. Methods Systolic and diastolic blood pressure, heart rate, and respiratory rate were monitored continuously during supine rest in both groups. Each patient was assessed in two conditions: resting supine with stimulator off and with stimulator on. Results In supine resting condition switching on the DBS induced no significant changes ( p > 0.05) in systolic and diastolic blood pressure as well as in heart rate and respiratory rate, in both groups of patients, either taking 1 min or 10 heartbeats as a sample for analysis. Conclusions Switching on the DBS does not modify heart rate, blood pressure nor respiratory rate in both Parkinson and cluster headache patients under resting conditions.

Background Coronary microvasculopathy has impact on prognosis in heart transplantation (HT). Distinct contributions by functional or structural alterations of coronary microcirculation in HT and their prognostic role have not been fully elucidated. Purpose We aimed to identify the mechanisms of coronary microvascular impairment in HT and their possible prognostic implications by applying a comprehensive analysis in a comparative study. Methods Included were 134 patients, surviving at least 5 years, with normal systolic function and no evidence of allograft vasculopathy or symptoms/signs of rejection. To permit comparison, 50 healthy volunteers without cardiovascular diseases, and matched for age and sex, served as controls. All underwent echocardiographic evaluation of microvascular function by the assessment of rest and hyperemic diastolic peak blood velocity (DPVr and DPVh). These paired data enable calculation of coronary flow velocity reserve (CFVR) and its inherent companion that is based on the quadratic mean: CFVRC = √{(DPVr)2 + (DPVh)2}. Additionally, basal and hyperemic coronary microvascular resistance (BMR and HMR) were estimated. A CFVR ≤2.5 was considered abnormal; the median value of DPVh (75 cm/s) and CFVRC (80 cm/s) were selected as cut-offs to classify patients. Results HT patients can be assigned to four groups, based on their CFVR and DPVh (Figure A): group 1 (n=32), discordant with preserved CFVR (3.1±0.4); group 2 (n=60), concordant with preserved CFVR (3.4±0.5); group 3 (n=31), concordant with impaired CFVR (1.8±0.3) and group 4 (n=11), discordant with impaired CFVR (2.0±0.2). Group 3 represents the structural microvascular remodeling with high HMR, while group 4 represents the functional remodeling with low BMR. Intriguingly, group 1 showed lower DPVr (p Conclusions A normal CFVR could hide detection of microvascular damage with high flow resistance and low flow velocities at rest. This microvasculopathy seems to be secondary to factors unrelated to HT (i.e., less rejections and more often diabetes). Being a dimensionless ratio, CFVR may miss some deaths, yet captured by CFVRC. Thus, the combined use of CFVR and CFVRC provides more complete clinical information on coronary microvasculopathy in HT. Funding Acknowledgement Type of funding source: None