TMAD enters the toolbox for evaluating selected heart transplant patients.

Adaptation of the heart is often a blessing for the patient, but sometimes a diagnostic challenge for the responsible physician. The clinical difficulty may be enhanced when employing diagnostic tools that are hard to interpret. Ratio-based metrics are notorious in this respect, and particularly risky in the follow-up evaluation of heart transplant patients. However, measures expressed as physical units contribute to a comprehensive clinical evaluation and guide proper patient management.

Pervasive and diffuse muscle activity during REM sleep and non-REM sleep characterises multiple system atrophy in comparison with Parkinson's disease.

Multiple system atrophy (MSA) and Parkinson's disease (PD) may share overlapping features particularly at early disease stage, including sleep alterations, but have profoundly different prognoses. Certain sleep phenomena and disorders of motor control are more prevalent in multiple system atrophy, such as REM sleep behaviour disorder (RBD). We quantitatively tested whether pervasive muscle activity during sleep occurs in subjects with multiple system atrophy versus Parkinson's disease. Laboratory polysomnographic studies were performed in 50 consecutive subjects with Parkinson's disease and 26 age- and gender-matched subjects with multiple system atrophy at <5 years from disease onset. The distributions of normalised electromyographic activity of submentalis, wrist extensor, and tibialis anterior muscles in different wake-sleep states during the night were analysed. Subjects with multiple system atrophy had significantly higher activity of submentalis, wrist extensor, and tibialis anterior muscles than subjects with Parkinson's disease during non-REM sleep, including separately in stages N1, N2, and N3, and during REM sleep, but not during nocturnal wakefulness. The activity of wrist extensor and tibialis anterior muscles during non-REM sleep and the activity of tibialis anterior muscles during REM sleep were also significantly higher in subjects with multiple system atrophy and RBD than in subjects with Parkinson's disease and RBD. In conclusion, with respect to Parkinson's disease, multiple system atrophy is characterised by a pervasive and diffuse muscle overactivity that involves axial and limb muscles and occurs not only during REM sleep, but also during non-REM sleep and between subjects with comorbid RBD.

Cardiac magnetic resonance imaging of arrhythmogenic cardiomyopathy: evolving diagnostic perspectives.

Arrhythmogenic cardiomyopathy (ACM) is a genetically determined heart muscle disease characterized by fibro-fatty myocardial replacement, clinically associated with malignant ventricular arrhythmias and sudden cardiac death. Originally described a disease with a prevalent right ventricular (RV) involvement, subsequently two other phenotypes have been recognized, such as the left dominant and the biventricular phenotypes, for which a recent International Expert consensus document provided upgrade diagnostic criteria (the 2020 "Padua Criteria"). In this novel workup for the diagnosis of the entire spectrum of phenotypic variants of ACM, including left ventricular (LV) variants, cardiac magnetic resonance (CMR) has emerged as the cardiac imaging technique of choice, due to its capability of detailed morpho-functional and tissue characterization evaluation of both RV and LV. In this review, the key role of CMR in the diagnosis of ACM is outlined, including the supplemental value for the characterization of the disease variants. An ACM-specific CMR study protocol, as well as strengths and weaknesses of each imaging technique, is also provided. KEY POINTS: • Arrhythmogenic cardiomyopathy includes three different phenotypes: dominant right, biventricular, and dominant left. • In 2020, diagnostic criteria have been updated and cardiac magnetic resonance has emerged as the cardiac imaging technique of choice. • This aim of this review is to provide an update of the current state of art regarding the use of CMR in ACM, with a particular focus on novel diagnostic criteria, CMR protocols, and prognostic significance of CMR findings in ACM.

Multiparametric analysis of coronary flow in psoriasis using a coronary flow reserve companion.

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 < 0.0001, both). Interestingly, while CFVR was comparable in patients with worsened versus those with improved CFVR, the companion-CFVR could discriminate by being lower in patients with worsened CFVR (p = 0.01). CONCLUSIONS: The reduced CFVR in psoriasis is driven by decreased companion-CFVR, combined with increased hyperemic MR. Adoption of the mandatory companion-CFVR enables a personalized characterization superior to that achieved by exclusive consideration of CFVR.

Global longitudinal strain by CMR improves prognostic stratification in acute myocarditis presenting with normal LVEF.

BACKGROUND: Prognostic stratification of acute myocarditis (AM) presenting with normal left ventricular ejection fraction (LVEF) relies mostly on late gadolinium enhancement (LGE) characterization. Left ventricular peak global longitudinal strain (LV-GLS) measured by feature tracking analysis might improve prognostication of AM presenting with normal LVEF. METHODS: Data of patients undergoing cardiac magnetic resonance (CMR) for clinically suspected AM in seven European Centres (2013-2020) were retrospectively analysed. Patients with AM confirmed by CMR and LVEF ≥50% were included. LGE was visually characterized: localized versus. non-localized, subepicardial versus midwall. LV-GLS was measured by dedicated software. The primary outcome was the first occurrence of an adverse cardiovascular event (ACE) including cardiac death, life-threatening arrhythmias, development of heart failure or of LVEF <50%. RESULTS: Of 389 screened patients, 256 (66%) fulfilled inclusion criteria: median age 36 years, 71% males, median LVEF 60%, median LV-GLS -17.3%. CMR was performed at 4 days from hospitalization. At 27 months, 24 (9%) patients experienced ≥1 ACE (71% developed LVEF <50%). Compared to the others, they had lower median LV-GLS values (-13.9% vs. -17.5%, p = .001). At Kaplan-Meier analysis, impaired LV-GLS (both considered as > -20% or quartiles), non-localized and midwall LGE were associated with ACEs. Patients with LV-GLS ≤-20% did not experience ACEs. LV-GLS remained associated with ACEs after adjustment for non-localized and midwall LGE. CONCLUSION: In AM presenting with LVEF ≥50%, LV-GLS provides independent prognostic value over LGE characterization, improving risk stratification and representing a rationale for further studies of therapy in this cohort.

Tracheostomy is associated with increased survival in Multiple System Atrophy patients with stridor.

BACKGROUND AND PURPOSE: Stridor treatment in multiple system atrophy (MSA) mainly comprises tracheostomy or continuous positive airway pressure (CPAP), but guidelines for the use of these treatments are lacking. The aim of the study was to evaluate the predictive value of stridor treatment in an MSA cohort. METHODS: This is a retrospective and prospective monocentric cohort study including MSA patients evaluated at least once a year during the disease course. Stridor was video-polysomnography confirmed. The time of stridor treatment (CPAP or tracheostomy) and latency from stridor onset were collected. Survival and predictors of survival were calculated. RESULTS: A total of 182 (107 males, mean age at disease onset 57.3 ± 8.4 years) MSA patients were included in the study; 141 were deceased at the time of study. Of the total sample, 75 patients were diagnosed with stridor: 22 patients were treated with tracheostomy and 29 with CPAP, whilst 24 patients did not receive treatment. Treatment with tracheostomy showed longer survival compared with both treatment with CPAP or no treatment (incidence rate of death 12 vs. 21 vs. 23 per 100 person-years, respectively). Tracheostomy remained an independent factor associated with longer survival (hazard ratio 0.38, p = 0.029), also after adjustment for other confounders and latency for stridor treatment. CONCLUSIONS: This is the largest monocentric and long-term follow-up study comparing survival between tracheostomy and CPAP in MSA patients with stridor. Treatment with tracheostomy showed longer survival compared with both treatment with CPAP or no treatment. A careful multidisciplinary approach is required for the management of MSA patients with stridor.

Chest pain and palpitations in postmenopausal women with mitral valve prolapse: is there a gastro-oesophageal origin?

BACKGROUND AND AIM: Mitral valve prolapse (MVP) is a common disease in women, causing chest pain and palpitation due to structural and functional valve abnormality, and is sometimes associated with gastro-oesophageal reflux disease (GERD). This is a challenging clinical problem in clinical practice and 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. AIM: To assess the prevalence of GERD in a population of postmenopausal women affected by MVP and determine if there is any correlation between the two conditions. METHODS: The MVP diagnosis was performed using echocardiograpy examination, according to American Society Echocardiography criteria. Two hundred and eighty-nine consecutive MVP women, symptomatic for chest pain and palpitation, were included; 250 consecutive women without MVP, symptomatic for chest pain and palpitation, were the control group (CG). The GERD diagnosis was made according to 2013 American College Gastroenterology criteria; women affected by thyroid disorders, all heart disease, including mitral disease with moderate or severe mitral regurgitation, and gastrointestinal diseases assessed using gastroscopy were excluded. RESULTS: Among 289 women with MVP, 31 (11%) women were affected by GERD, and among 250 in the CG, 11 (4.4%) women were affected by GERD: Chi-squared 8.1; odds ratio 2.7; P < 0.0044. Twenty-six (9%) women affected by GERD, with MVP, presented with mild mitral regurgitation, and 7 (2.8%) women in the CG presented with mild mitral regurgitation as well: Chi-squared 8.95; odds ratio 3.4; 95% CI, P < 0.0028. DISCUSSION AND CONCLUSIONS: GERD is relatively common in women with MVP. Moreover, women with MVP are approximately three times more likely to be affected by GERD; the two conditions are correlated in a statistically high significant way. GERD assessment needs to be included into routine follow-up strategies in women with MVP to optimise medical therapy, improvinge symptom relief for better quality of life.

The Impairment in Kidney Function in the Oral Anticoagulation Era. A Pathophysiological Insight.

The need for anticoagulation in patients with atrial fibrillation (AF) is fundamental to prevent thromboembolic events. Direct oral anticoagulants (DOACs) recently demonstrated to be superior, or at least equal, to Warfarin in reducing the risk for stroke/systemic embolism and preventing major bleeding and intracranial hemorrhages. The AF population often suffers from chronic kidney disease (CKD). Indeed, the relationship between AF and renal function is bidirectional: AF can trigger kidney failure, while kidney impairment can promote alterations able to enhance AF. Therefore, there are concerns regarding prescriptions of anticoagulants to patients with AF and CKD. The worsening in kidney function can be effectively due to anticoagulants administration. Warfarin has been recognized to promote acute kidney injury in case of excessive anticoagulation levels. Nevertheless, further mechanisms can induce the chronic worsening of renal function, thus leading to terminal kidney failure as observed in post-hoc analysis from registration trials and dedicated observational studies. By contrast, DOACs seem to protect kidneys from injuries more efficiently than Warfarin, although they still continue to play a role in promoting some kidney lesions. However, the exact mechanisms remain unknown. This narrative review aimed to discuss the influence of oral anticoagulants on renal impairment as well as to overview potential pathophysiological mechanisms related to this clinical complication.

Circadian and state-dependent core body temperature in people with spinal cord injury.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To analyze the circadian rhythm and state-dependent modulation of core body temperature (Tcore) in individuals with spinal cord injury (SCI) under controlled environmental conditions. SETTING: Institute of the Neurological Sciences of Bologna, Italy. METHODS: We assessed 48-h rectal Tcore and sleep-wake cycle by means of video-polygraphic recording in five cervical SCI (cSCI), seven thoracic SCI (tSCI), and seven healthy controls under controlled environmental conditions. RESULTS: cSCI showed higher night-time Tcore values with reduced nocturnal decrease, higher MESOR and earlier acrophase compared with tSCI and controls (p < 0.05 in all comparisons). The mean Tcore values during wake and non-rapid eye movement (NREM) and rapid eye movement (REM) sleep stages were higher in cSCI compared with tSCI and controls (p < 0.05). Tcore variability throughout the 24 h differed significantly between cSCI, tSCI, and controls. CONCLUSIONS: cSCI had higher Tcore values without physiological night-time fall compared with controls and tSCI, and a disrupted Tcore circadian rhythm. Furthermore, SCI individuals did not display the physiological state-dependent Tcore modulation. The disconnection of the sympathetic nervous system from its central control caused by the SCI could affect thermoregulation including Tcore modulation during sleep. It is also possible that the reduced representation of deep sleep in people with SCI impairs such ability. Further studies are necessary to evaluate whether improvement of sleep could ameliorate thermoregulation and vice versa.

REM sleep behavior disorder, autonomic dysfunction and synuclein-related neurodegeneration: where do we stand?

INTRODUCTION: From newfound parasomnia to a marker of future synucleinopathy, since its first description in 1986, REM sleep behavior disorder (RBD) has been systematically tackled from virtually many viewpoints in basic, translational, and clinical studies. The time delay between RBD and synucleinopathy onset offers an exceptional window for observation and design of neuroprotective trials. In the last few years, research has focused on characterizing possible differences within RBD patients in order to draw potential profiles more or less susceptible to further neurodegeneration. Attention has been drawn towards autonomic dysfunction in RBD as one of such variables. OVERVIEW: In this review, REM sleep physiology and relevant brain anatomy is briefly mentioned and integrated with neuroanatomical and physiological concepts regarding the central autonomic network. A detailed summary of works showing the presence of autonomic dysfunction in RBD is provided, and clinical and electrophysiological features of RBD in synucleinopathies are discussed. A short overview of RBD in other neurodegenerative diseases is also provided.

Percutaneous Edge-to-Edge Transcatheter Mitral Valve Repair: Current Indications and Future Perspectives.

Mitral regurgitation (MR) is the most prevalent valvular heart disease (VHD) and represents an important cause of heart failure. Medical therapy has a limited role in improving symptoms and does not hinder the progression of valvular disease. Surgery is the treatment of choice for severe symptomatic MR; valve repair is currently the preferred surgical approach because it reduces peri-operative mortality and ensures a good medium- to long-term survival outcome. Nevertheless, a non-negligible proportion of patients with indications for surgical correction are considered to be at prohibitive perioperative risk, mainly because of old age and multiple comorbidities. The introduction of percutaneous interventions to clinical practice has changed the natural history of this population. Percutaneous edge-to-edge transcatheter mitral valve repair (Mitraclip®, Abbott Vascular, Menlo Park, CA) is a state-of-the-art therapy for approaching MR in patients with a high surgical risk. Despite having been only recently introduced, this transvenous transfemoral percutaneous intervention has already been performed in more than 40,000 subjects worldwide, with reassuring post-operative results in terms of safety, feasibility, mortality and morbidity. Since Mitraclip® is considered to be minimally invasive, it is currently indicated in "frail" patients with severe comorbidities. We provide a critical review of the literature to clarify current indications, procedural details, patient selection criteria, and future perspectives for this innovative technique.

Postoperative outcome of body core temperature rhythm and sleep-wake cycle in third ventricle craniopharyngiomas.

OBJECTIVE One of the more serious risks in the treatment of third ventricle craniopharyngiomas is represented by hypothalamic damage. Recently, many papers have reported the expansion of the indications for the endoscopic endonasal approach (EEA) to be used for these tumors as well. The aim of this study was to assess the outcome of sleep-wake cycle and body core temperature (BCT), both depending on hypothalamic control, in patients affected by craniopharyngiomas involving the third ventricle that were surgically treated via an EEA. METHODS All consecutive adult patients with craniopharyngiomas that were treated at one center via an EEA between 2014 and 2016 were prospectively included. Each patient underwent neuroradiological, endocrinological, and ophthalmological evaluation; 24-hour monitoring of the BCT rhythm; and the sleep-wake cycle before surgery and at follow-up of at least 6 months. RESULTS Ten patients were included in the study (male/female ratio 4:6, mean age 48.6 years, SD 15.9 years). Gross-total resection was achieved in 8 cases. Preoperative BCT rhythm was pathological in 6 patients. After surgery, these disturbances resolved in 2 cases, improved in another 3, and remained the same in 1 patient; also, 1 case of de novo onset was observed. Before surgery the sleep-wake cycle was pathological in 8 cases, and it was restored in 4 patients at follow-up. After surgery the number of patients reporting diurnal naps increased from 7 to 9. CONCLUSIONS The outcome of the sleep-wake cycle and BCT analyzed after EEA in this study is promising. Despite the short duration of the authors' experience, they consider these results encouraging; additional series are needed to confirm the preliminary findings.

Left ventricular fibrosis in arrhythmic mitral valve prolapse: quantification and comparison of semi-automated techniques assessed by cardiac magnetic resonance.

PURPOSE: Left ventricular (LV) fibrosis has a key role in arrhythmogenesis in patients with mitral valve prolapse (MVP). Cardiac magnetic resonance identifies LV fibrosis by using late gadolinium enhancement (LGE) technique. LGE assessment and quantification in patients with MVP lacks of standardization protocols. METHODS: 66 MVP patients with normal systolic function and without significant regurgitation were enrolled. Semi-automated gray-scale thresholding techniques using full width at half maximum (FWHM) and 2, 3 and 5 standard deviation (SD) above the remote myocardium were used and compared with the visual assessment, considered as the gold standard. RESULTS: LGE was identified in 41 MVP patients (62%) and quantified. The mean quantity of LGE visually assessed was 2.40 ± 1.07% or 1.40 ± 0.82 g. With FWHM, LGE resulted 3.56 ± 1.23% or 1.99 ± 1.13 g. Using thresholding, the mean LGE quantity was 9.2 ± 3.1% or 4.82 ± 2.28 g for 2-SD, 5.72 ± 1.75% or 3.06 ± 1.47 g for 3-SD and 2.36 ± 0.99% or 1.29 ± 0.79 g for 5-SD. The 5-SD measurement in percentage demonstrated a good correlation with LGE quantification visually assessed (2.40 ± 1.07 vs. 2.363 ± 0.9909, p = 0.543). When compared with the gold standard, the 5-SD threshold quantification, both in percentage and in grams, revealed the least intra-observer (respectively, ICC: 0.976 and 0.966) and inter-observer variability (respectively ICC: 0.948 and 0.935). CONCLUSION: The 5-SD gray-scale threshold technique in percentage revealed the best correlation with the visual assessment and an optimal reproducibility in MVP patient.

The Degree of Cardiovascular Autonomic Dysfunction is not Different in GBA-Related and Idiopathic Parkinson's Disease Patients: A Case-Control Instrumental Evaluation.

Background: Increased prevalence of cardiovascular autonomic failure might play a key role on Parkinson's disease (PD) progression of glucocerebrosidase gene (GBA)-mutated patients, determining a malignant phenotype of disease in these patients. Objective: To objectively characterize, for the first time, the cardiovascular autonomic profile of GBA-mutated patients compared to idiopathic PD patients by means of cardiovascular reflex tests (CRTs). Methods: This is a case-control (1 : 2) study on PD patients belonging to well-characterized prospective cohorts. For each PD patient carrying GBA variants, two idiopathic PD patients, matched for sex and disease duration at CRTs, were selected. Patients recruited in these cohorts underwent a complete clinical and instrumental evaluation including specific autonomic questionnaires, CRTs and extensive genetic analysis. Results: A total of 23 GBA-PD patients (19 males, disease duration 7.7 years) were included and matched with 46 non-mutated PD controls. GBA-mutated patients were younger than controls (59.9±8.1 vs. 64.3±7.2 years, p = 0.0257) and showed a more severe phenotype. Despite GBA-mutated patients reported more frequently symptoms suggestive of orthostatic hypotension (OH) than non-mutated patients (39.1% vs 6.5%, p = 0.001), the degree of cardiovascular autonomic dysfunction, when instrumentally assessed, did not differ between the two groups, showing the same prevalence of neurogenic OH, delayed OH and cardiovascular reflex impairment (pathological Valsalva maneuver). Conclusion: GBA-PD patients did not show different instrumental cardiovascular autonomic pattern than non-mutated PD. Our findings suggested that symptoms suggestive of OH should be promptly investigated by clinicians to confirm their nature and improve patient care and management.

Determinants of Ventricular Arrhythmias in Mitral Valve Prolapse.

BACKGROUND: Mitral valve prolapse (MVP) may be associated with ventricular arrhythmias (VA) even in the absence of significant valvular regurgitation. Curling, mitral annulus disjunction (MAD) and myocardial fibrosis (late gadolinium enhancement [LGE]) may account for arrhythmogenesis. OBJECTIVES: This study investigated the determinants of VA in patients with MVP without significant regurgitation. METHODS: This study included 108 patients with MVP (66 female; median age: 48 years) without valve regurgitation. All patients underwent 12-lead electrocardiography, 12-lead 24-hour electrocardiographic Holter monitoring, exercise stress test, and cardiac magnetic resonance. Patients were divided into 2 groups (arrhythmic and no-arrhythmic MVP), according to the presence of VA with a right bundle branch block pattern. RESULTS: The 62 patients (57%) with arrhythmic MVP showed: 1) higher MAD (median length: 6.0 vs 3.2 mm; P = 0.017); 2) higher prevalence of curling (79% vs 52%; P = 0.012); and 3) higher prevalence of left ventricular LGE (79% vs 52%; P = 0.012). Mediation analysis showed that curling had both a direct (P = 0.03) and indirect effect mediated by LGE (P = 0.04) on VA, whereas the association between MAD and VA was completely mediated by LGE. Patients with severe VA showed more pronounced morphofunctional alterations, in terms of MAD (7.0 vs 4.6 mm; P = 0.004) and presence and severity of curling (respectively, 91% vs 64%; P = 0.010; and 4 vs 3 mm; P = 0.004), compared to those without severe VA. CONCLUSIONS: In patients with MVP the occurrence of VA with right bundle branch block morphology is the expression of more severe morphologic, mechanical, and tissue alterations. Curling has both a direct and an indirect effect on VA.

Association of Angiotensin II Receptor Type 1 and Endothelin-1 Receptor Type A Agonistic Autoantibodies With Adverse Remodeling and Cardiovascular Events After Acute Myocardial Infarction.

BACKGROUND: The left ventricular remodeling (LVR) process has limited the effectiveness of therapies after myocardial infarction. The relationship between autoantibodies activating AT1R-AAs (angiotensin II receptor type 1-AAs) and ETAR-AAs (autoantibodies activating endothelin-1 receptor type A) with myocardial infarction has been described. Among patients with ST-segment-elevation myocardial infarction, we investigated the relationship between these autoantibodies with LVR and subsequent major adverse cardiac events. METHODS AND RESULTS: In this prospective observational study, we included 131 patients with ST-segment-elevation myocardial infarction (61±11 years of age, 112 men) treated with primary percutaneous coronary intervention. Within 48 hours of admission, 2-dimensional transthoracic echocardiography was performed, and blood samples were obtained. The seropositive threshold for AT1R-AAs and ETAR-AAs was >10 U/mL. Patients were followed up at 6 months, when repeat transthoracic echocardiography was performed. The primary end points were LVR, defined as a 20% increase in left ventricular end-diastolic volume index, and major adverse cardiac event occurrence at follow-up, defined as cardiac death, nonfatal re-myocardial infarction, and hospitalization for heart failure. Forty-one (31%) patients experienced LVR. The prevalence of AT1R-AAs and ETAR-AAs seropositivity was higher in patients with versus without LVR (39% versus 11%, P<0.001 and 37% versus 12%, P=0.001, respectively). In multivariable analysis, AT1R-AAs seropositivity was significantly associated with LVR (odds ratio [OR], 4.66; P=0.002) and represented a risk factor for subsequent major adverse cardiac events (OR, 19.6; P=0.002). CONCLUSIONS: AT1R-AAs and ETAR-AAs are associated with LVR in patients with ST-segment-elevation myocardial infarction. AT1R-AAs are also significantly associated with recurrent major adverse cardiac events. These initial observations may set the stage for a better pathophysiological understanding of the mechanisms contributing to LVR and ST-segment-elevation myocardial infarction prognosis.

Multiple system atrophy with prolonged survival: is late onset of dysautonomia the clue?

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.

Early diagnosis of subclinical left ventricular dysfunction in postmenopausal women with rheumatoid arthritis.

OBJECTIVE: Heart failure is the most frequent cause of death among patients affected by rheumatoid arthritis(RA), in which high prevalence is independent of traditional risk factors. An early diagnosis of subclinical heart failure may be made by assessing left ventricular diastolic dysfunction (LVDD) by Doppler Echocardiography. Our study aims to early identify LVDD in RA patients. METHODS: We enrolled 207 consecutive postmenopausal women (PMW) with normal electrocardiography and physical examination with a confirmed diagnosis of RA, for over one year, 200 PMW free from RA served as the control group (CG). All women underwent M-mode and two-dimensional Doppler echocardiography. RESULTS: A total of 72 women were affected by LVDD among 207 women with RA (34.8%), 46 among 200 women in the CG (23%), chi-squared 6.8, OR 1.8, confidence interval (CI) 95%, p < 0.009. For our RA women, the chance of being affected by LVDD has almost doubled. There were 70 women affected by LVDD among 72 hypertensive women with RA (97.2%). A total of 32 women were affected by LVDD among 98 hypertensive women in the CG (32.7%), chi-squared 72.1, OR 7.2, CI 95%, p < 0.009. Among hypertensive PMW in our population, the chance of being affected by LVDD has more than tripled. All LVDD subjects had abnormal diastolic function for all different degrees. CONCLUSION: We propose that PMW, affected by RA, have a significantly higher prevalence than CG of LVDD without clinical evidence of heart disease. Since the prevalence is even higher if they are hypertensive, we suggest a Doppler echocardiography examination for all women with a diagnosis of RA.

Association of autoantibodies targeting endothelin type-A receptors with no-reflow in ST-elevation myocardial infarction.

BACKGROUND AND AIMS: No-reflow (NR), where the coronary artery is patent after treatment of ST-elevation myocardial infarction (STEMI) but tissue perfusion is not restored, is associated with worse outcomes. We aimed to investigate the relationship between autoantibodies activating endothelin-1 receptor type A (ETAR-AAs) and NR after primary percutaneous coronary intervention (PPCI) in STEMI. METHODS: We studied 50 patients (age 59 ± 11 years, 40 males) with STEMI who underwent PPCI within 6 h after the onset of symptoms. Blood samples were obtained from all patients within 12 h following PPCI for ETAR-AA level measurement. The seropositive threshold was provided by the manufacturer (>10 U/ml). NR was assessed by cardiac magnetic resonance imaging (MVO, microvascular obstruction). As a control group, 40 healthy subjects matched for age and sex were recruited from the general population. RESULTS: MVO was observed in 24 patients (48%). The prevalence of MVO was higher in patients with ETAR-AAs seropositivity (72% vs. 38%, p = 0.03). ETAR-AAs were higher in patients with MVO (8.9 U/mL (interquartile range [IQR] 6.8-16.2 U/mL) vs. 5.7 U/mL [IQR 4.3-7.7 U/mL], p = 0.003). ETAR-AAs seropositivity was independently associated with MVO (OR 3.2, 95% CI 1.3-7.1; p = 0.03). We identified ≥6.74 U/mL as the best cut-off for prediction of MVO (sensitivity 79%; specificity 65%; NPV 71%; PPV 74%; accuracy 72%). CONCLUSIONS: The ETAR-AAs seropositivity is associated with NR in STEMI patients. These findings may open up new options in the management of myocardial infarction even if confirmation in a larger trial is needed.

Cardiac rupture in acute myocardial infarction: a cardiac magnetic resonance study.

AIMS: We assessed the feasibility of cardiac magnetic resonance (CMR) and the role of myocardial strain in the diagnostic work-up of patients with acute myocardial infarction (AMI) and a clinical suspicion of cardiac rupture (CR). METHODS AND RESULTS: Consecutive patients with AMI complicated by CR who underwent CMR were enrolled. Traditional and strain CMR findings were evaluated; new parameters indicating the relative wall stress between AMI and adjacent segments, named wall stress index (WSI) and WSI ratio, were analysed. A group of patients admitted for AMI without CR served as control. 19 patients (63% male, median age 73 years) met the inclusion criteria. Microvascular obstruction (MVO, P = 0.001) and pericardial enhancement (P < 0.001) were strongly associated with CR. Patients with clinical CR confirmed by CMR exhibited more frequently an intramyocardial haemorrhage than controls (P = 0.003). Patients with CR had lower 2D and 3D global radial strain (GRS) and global circumferential strain (in 2D mode P < 0.001; in 3D mode P = 0.001), as well as 3D global longitudinal strain (P < 0.001), than controls. The 2D circumferential WSI (P = 0.010), as well as the 2D and 3D circumferential (respectively, P < 0.001 and P = 0.042) and radial WSI ratio (respectively, P < 0.001 and P: 0.007), were higher in CR patients than controls. CONCLUSION: CMR is a safe and useful imaging tool to achieve the definite diagnosis of CR and an accurate visualization of tissue abnormalities associated with CR. Strain analysis parameters can give insights into the pathophysiology of CR and may help to identify those patients with sub-acute CR.