Device innovation in cardiovascular medicine: a report from the European Society of Cardiology Cardiovascular Round Table.

Research performed in Europe has driven cardiovascular device innovation. This includes, but is not limited to, percutaneous coronary intervention, cardiac imaging, transcatheter heart valve implantation, and device therapy of cardiac arrhythmias and heart failure. An important part of future medical progress involves the evolution of medical technology and the ongoing development of artificial intelligence and machine learning. There is a need to foster an environment conducive to medical technology development and validation so that Europe can continue to play a major role in device innovation while providing high standards of safety. This paper summarizes viewpoints on the topic of device innovation in cardiovascular medicine at the European Society of Cardiology Cardiovascular Round Table, a strategic forum for high-level dialogue to discuss issues related to the future of cardiovascular health in Europe. Devices are developed and improved through an iterative process throughout their lifecycle. Early feasibility studies demonstrate proof of concept and help to optimize the design of a device. If successful, this should ideally be followed by randomized clinical trials comparing novel devices vs. accepted standards of care when available and the collection of post-market real-world evidence through registries. Unfortunately, standardized procedures for feasibility studies across various device categories have not yet been implemented in Europe. Cardiovascular imaging can be used to diagnose and characterize patients for interventions to improve procedural results and to monitor devices long term after implantation. Randomized clinical trials often use cardiac imaging-based inclusion criteria, while less frequently trials randomize patients to compare the diagnostic or prognostic value of different modalities. Applications using machine learning are increasingly important, but specific regulatory standards and pathways remain in development in both Europe and the USA. Standards are also needed for smart devices and digital technologies that support device-driven biomonitoring. Changes in device regulation introduced by the European Union aim to improve clinical evidence, transparency, and safety, but they may impact the speed of innovation, access, and availability. Device development programmes including dialogue on unmet needs and advice on study designs must be driven by a community of physicians, trialists, patients, regulators, payers, and industry to ensure that patients have access to innovative care.

Fatal Human Alphaherpesvirus 1 Infection in Free-Ranging Black-Tufted Marmosets in Anthropized Environments, Brazil, 2012-2019.

Human alphaherpesvirus 1 (HuAHV1) causes fatal neurologic infections in captive New World primates. To determine risks for interspecies transmission, we examined data for 13 free-ranging, black-tufted marmosets (Callithrix penicillata) that died of HuAHV1 infection and had been in close contact with humans in anthropized areas in Brazil during 2012-2019. We evaluated pathologic changes in the marmosets, localized virus and antigen, and assessed epidemiologic features. The main clinical findings were neurologic signs, necrotizing meningoencephalitis, and ulcerative glossitis; 1 animal had necrotizing hepatitis. Transmission electron microscopy revealed intranuclear herpetic inclusions, and immunostaining revealed HuAHV1 and herpesvirus particles in neurons, glial cells, tongue mucosal epithelium, and hepatocytes. PCR confirmed HuAHV1 infection. These findings illustrate how disruption of the One Health equilibrium in anthropized environments poses risks for interspecies virus transmission with potential spillover not only from animals to humans but also from humans to free-ranging nonhuman primates or other animals.

Poisoning by Nierembergia veitchii: Effects on vascular smooth muscle cells in the pathogenesis of enzootic calcinosis.

Vascular mineralization is a hallmark of enzootic calcinosis. Histopathological, ultrastructural, and immunohistochemical investigations were performed on the external carotid arteries of seven sheep naturally poisoned by Nierembergia veitchii. Histologically, moderate to marked hyperplasia of the tunica intima was observed without mineralization. The tunica media exhibited mild to severe mineralization and osteochondroid metaplasia. Sheep with enzootic calcinosis showed arterial overexpression of osteopontin and tissue-nonspecific alkaline phosphatase and immunolabeling for osteonectin and osteocalcin in both intima and media layers of the tested arteries. The main ultrastructural finding in the tunica media was a marked phenotypic change of vascular smooth muscle cells from a contractile phenotype (VSMC-C) into a synthetic phenotype (VSMC-S). In the tunica media, VSMC-S produced matrix and extracellular vesicles, forming mineralizable granules associated with arterial mineralization. VSMC-S were also present in the tunica intima, but matrix and extracellular vesicles and mineralization were not observed. The absence of matrix and extracellular vesicles in the intimal hyperplasia, even in the presence of noncollagenous bone proteins, tissue-nonspecific alkaline phosphatase, and vitamin D receptors, reinforces the hypothesis that the presence of matrix and extracellular vesicles are crucial for the development of vascular mineralization in enzootic calcinosis. It is proposed that the two different VSMC-S phenotypes in calcinosis are due to the expression of at least two genetically different types of these cells induced by the action of 1,25(OH)2D3.

Long-term impact of early initiation of enzyme replacement therapy in 34 MPS VI patients: A resurvey study.

Patients with mucopolysaccharidosis type VI (MPS VI) present with a wide range of disease severity and clinical manifestations, with significant functional impairment and shortened lifespan. Enzyme replacement therapy (ERT) with galsulfase has been shown to improve clinical and biochemical parameters including patient survival, quality of life and growth. The present study is a resurvey of 34 Brazilian MPS VI patients with rapidly progressive disease (classical phenotype) who initiated ERT with galsulfase under five years of age and had been on ERT until data collection in 2019, with few exceptions (n = 4 patients who died before 2019). Anthropometric measures, urinary glycosaminoglycans, and data regarding cardiac, orthopedic, neurologic, sleep apnea, hearing and ophthalmologic outcomes were filled in by specialists. Pubertal development, clinical complications, hospitalizations, and surgeries were also assessed. In this resurvey study, treatment with galsulfase has shown to be safe and well tolerated in MPS VI patients who initiated ERT under the age of 5 years and who have been undergoing ERT for approximately 10 years. Mortality rate suggests that early initiation of ERT may have a positive impact on patients' survival, improving but not preventing disease progression and death. MPS VI patients on ERT also showed improved growth velocity and the pubertal development was normal in all surviving patients. Follow-up data on pneumonia and hospitalization suggest that early ERT may have a protective effect against major respiratory complications. Cardiac valve disease progressed since their prior evaluation and spinal cord compression was observed in a large number of patients, suggesting that these disease complications were not modified by ERT.

Immune System Efficiency in Cancer and the Microbiota Influence.

The immune system plays a critical role in preventing cancer development and progression. However, the complex network of cells and soluble factor that form the tumor microenvironment (TME) can dictate the differentiation of tumor-infiltrating leukocytes and shift the antitumor immune response into promoting tumor growth. With the advent of cancer immunotherapy, there has been a reinvigorated interest in defining how the TME shapes the antitumor immune response. This interest brought to light the microbiome as a novel player in shaping cancer immunosurveillance. Indeed, accumulating evidence now suggests that the microbiome may confer susceptibility or resistance to certain cancers and may influence response to therapeutics, particularly immune checkpoint inhibitors. As we move forward into the age of precision medicine, it is vital that we define the factors that influence the interplay between the triad immune system-microbiota-cancer. This knowledge will contribute to improve the therapeutic response to current approaches and will unravel novel targets for immunotherapy.

Past appendectomy may be related to early cognitive dysfunction in Parkinson's disease.

INTRODUCTION: The vermiform appendix is a potential site of initiation of Parkinson's disease (PD) pathology. We hypothesized that the appendectomy earlier in life may alter the clinical expression of PD. OBJECTIVE: To explore the effects of appendectomy prior to onset of PD motor symptoms on patients' symptoms, in particular on cognitive dysfunction. METHODS: Two hundred and sixty-two consecutive PD patients were asked about past history of appendectomy and underwent an evaluation, which included the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale (H&Y), Schwab & England Independence Scale (S&E), Dementia Rating Scale-2 (DRS-2), Apathy Evaluation Scale, Hospital Anxiety and Depression Scale, and Brief Smell Identification Test. Motor symptoms were evaluated in OFF and ON states. Non-parametric group comparisons and logistic regressions were used for data analyses. RESULTS: Thirty-one patients (11.8%) had history of appendectomy prior to PD onset. These patients had more severe motor symptoms (UPDRS-III and H&Y) and lower functional independence (S&E) in ON and had higher frequency of cognitive dysfunction (DRS-2 Initiation/Perseveration, Conceptualization, and Memory subscales) (p < 0.05). The association between history of appendectomy and cognitive dysfunction was evident only in patients with late onset PD (≥ 55 years) and with disease duration ≤ 5 years. History of appendectomy remained statistically associated with impairment on DRS-2 Conceptualization and Memory subscales, when demographic and clinical variables were considered. CONCLUSION: History of appendectomy appears to alter the clinical expression of late onset PD, with early cognitive impairment, more severe motor symptoms in ON, and poorer functional independence under anti-parkinsonian medication.

Feasibility of using magnetic nanoparticles in water disinfection.

Disinfection is a crucial step during the water treatment process due to the significant risks of water contamination with human and animal excreta. The development of innovative disinfection technologies that can be applied at water point of use, avoiding contamination problems in water distribution systems and reservoirs, are needed. Thus, the present work aimed at assessing the disinfection efficiency of iron oxide magnetic nanoparticles (MNPs) modified with different compounds, such as carbon nanotubes, copper and silver, in water solutions contaminated with bacteria. Kinetic and influence of nanoparticles concentration experiments, performed with Escherichia coli, allowed to define the optimal reaction conditions to apply in batch experiments (1 min of contact time and 50 mg/mL of MNPs). During these experiments, CuFeO/CNT, C-FeO@CVD750 and 5% Ag/FeO were selected as the most efficient presenting log reduction values of 2.99, 1.50 and 2.11, respectively; however, experiments performed with Staphylococcus aureus suspension and a mixed bacterial suspension (E. coli + S. aureus) allowed to observe a slight decrease in nanomaterials efficiency, which was more evident for C-FeO@CVD750 and 5% Ag/FeO materials achieving efficiencies of 94 and 83% (corresponding log reductions of 1.26 and 0.77, respectively). CuFeO/CNT nanoparticles proved to be the most efficient material for both bacteria removal presenting an efficiency of 99% (corresponding log reduction of 1.99) for the mixed bacterial suspension. These nanoparticles proved to have great stability over successive experiments, and the low leaching values of the metals present in their composition after reaction proved the resistance and efficiency of these magnetic nanoparticles.

Automated, machine learning-based, 3D echocardiographic quantification of left ventricular mass.

BACKGROUND: Although 3D echocardiography (3DE) circumvents many limitations of 2D echocardiography by allowing direct measurements of left ventricular (LV) mass, it is seldom used in clinical practice due to time-consuming analysis. A recently developed 3DE machine learning (ML) approach allows automated determination of LV mass. We aimed to evaluate the accuracy of this new approach by comparing it to cardiac magnetic resonance (CMR) reference and to conventional 3DE volumetric analysis. METHODS: We prospectively studied 23 patients who underwent 3DE (Philips EPIQ) and CMR imaging on the same day. Single-beat wide-angle 3D datasets of the left ventricle were acquired. LV mass was quantified using the new automated software (Philips HeartModel) with manual corrections when necessary and using conventional volumetric analysis (TomTec). CMR analysis was performed by manual slice-by-slice tracing of LV endo- and epicardial boundaries. Reproducibility of the ML approach was assessed using repeated measurements and quantified by intra-class correlation (ICC) and coefficients of variation (CoV). RESULTS: Automated LV mass measurements were feasible in 20 patients (87%). The results were similar to CMR-derived values (Bland-Altman bias 5 g, limits of agreement ±37 g) and also to the conventional 3DE analysis (bias 7 g, ±27 g). Processing time was considerably shorter: 1.02 ± 0.24 minutes (CMR: 2.20 ± 0.13 minutes; TomTec: 2.36 ± 0.09 minutes), although manual corrections were performed in most patients. Repeated measurements showed high reproducibility: ICC = 0.99; CoV = 4 ± 5%. CONCLUSIONS: 3D Echocardiography analysis of LV mass using novel ML-based algorithm is feasible, fast, and accurate and may thus facilitate the incorporation of 3DE measurements of LV mass into clinical practice.

Transthoracic Echocardiography to Assess Aortic Regurgitation after TAVR: A Comparison with Periprocedural Transesophageal Echocardiography.

BACKGROUND: We aimed to compare periprocedural transesophageal echocardiography (TEE) with postprocedural transthoracic echocardiography (TTE) for the diagnosis of aortic regurgitation (AR). METHODS AND RESULTS: TEE and TTE images of 163 transcatheter aortic valve replacement (TAVR) patients (mean age 81 ± 8 years; 56% men) were reviewed separately and blinded to each other as well as to all clinical data. The median time between TEE during TAVR (TEE/TAVR) and TTE was 4 days (IQR 2-10 days). After TAVR, 48% of the patients had at least trace AR by TEE, 56% by angiography and 67% by TTE. The majority of AR was paravalvular (78%). More patients were classified with mild-to-moderate AR by TTE than by TEE (44 vs. 22%, p < 0.01). When examining the 46 patients with AR by TTE which was not at TEE/TAVR, both systolic and diastolic blood pressure (SBP and DBP) were significantly higher during TTE than during TEE (mean ΔSBP = 9 ± 4 mm Hg and mean ΔDBP = 6 ± 2 mm Hg, p < 0.01 for both). No differences in BP between TEE and TTE were found among patients with no AR or among those who had AR in both studies. At a median follow-up of 185 days (IQR 39-424 days), the overall mortality was 17%, but this was not associated with the presence of AR on TTE or TEE. CONCLUSIONS: Patients' hemodynamic conditions may result in underdiagnosis of paravalvular regurgitation in periprocedural TEE. Our findings suggest that a postprocedural evaluation for AR by TTE could serve as a reasonable alternative to TEE for the evaluation of AR.

Rapid analysis of cocaine and metabolites in urine using microextraction in packed sorbent and GC/MS.

Cocaine is still one of the most abused drugs worldwide and, as such, it is often screened for in driving-under-the-influence or workplace drug - testing scenarios. A large number of samples have usually to be processed in those situations, and this requires fast and simple extraction procedures for the detection and quantification of the drugs. The present work describes an ultrafast and fully validated procedure for the simultaneous detection and quantification of cocaine and its two main metabolites, ecgonine methyl ester and benzoylecgonine, in urine using microextraction by packed sorbent and GC-MS. A small sample volume (200 µL) was used, and a fast extraction procedure together with a microwave-assisted derivatization (800 W, 2 min) allowed the quantification of all analytes in a range of 25 to 1000 ng/mL (r 2 > 0.99). Inter-day precision revealed coefficients of variation (CVs) lower than 10% for all analytes at the tested concentration levels, with an accuracy within a ±7% interval, with the exception of EME's lowest calibrator (±17%). Intra-day CVs were lower than 15% at the studied concentration levels, with a mean relative error within a ±13% interval. Recoveries ranged from 14.5 to 37.2% (EME), 67.0 to 83.3% (cocaine), and 24.6 to 43.5% (BEG), allowing the limits of detection and quantification to be set at 25 ng/mL for all compounds. Graphical Abstract Schematized analysis of cocaine and metabolites in urine by MEPS- GC/MS.

Cardiac structure and function and leisure-time physical activity in the elderly: The Atherosclerosis Risk in Communities Study.

AIMS: Adults who engage in leisure-time physical activity (LTPA) have a reduced risk of developing heart failure. We hypothesized that high levels of LTPA are associated with diminished adverse age-related changes in cardiac structure and function. METHODS AND RESULTS: We studied 4342 Atherosclerosis Risk in Communities Study participants free of cardiovascular disease who underwent standardized echocardiography. In a cross-sectional analysis, we related LTPA (poor, intermediate, or ideal) to cardiac structure and function. We also related cumulative average LTPA over 24 years and changes in LTPA categories to echocardiographic measures. Cross-sectional analysis demonstrated that ideal LTPA, compared with poor LTPA, was associated with better diastolic function [prevalence of normal diastolic function: 39.8% vs. 31.5%, P < 0.001; mean E/E' ratio (95% CI): 9.8 (9.6, 9.9) vs. 10.4 (10.2, 10.5), P = 0.001] and better systolic function [left-ventricular (LV) longitudinal strain: -18.3 (-18.4, -18.2) vs. -17.9 (-18.0, -17.8), P < 0.001] after adjusting for age, sex, race, and centre. Higher cumulative average LTPA over 24 years or an improvement in LTPA category were also, respectively, related to a more favourable E/E' ratio (P < 0.0001, P = 0.004) and longitudinal LV strain (P = 0.0002, P = 0.002). CONCLUSION: Ideal LTPA, higher average levels of LTPA over a 24-year period, and an improvement in LTPA even later in life were associated with more favourable indices of LV diastolic and systolic function in older adults. Sustaining higher levels of LTPA, and even increasing physical activity later in life, may be beneficial for older adults in attenuating expected age-related changes in cardiac structure and function.

Alcohol consumption and risk of heart failure: the Atherosclerosis Risk in Communities Study.

AIM: Alcohol is a known cardiac toxin and heavy consumption can lead to heart failure (HF). However, the relationship between moderate alcohol consumption and risk for HF, in either men or women, remains unclear. METHODS AND RESULTS: We examined 14 629 participants of the Atherosclerosis Risk in Communities (ARIC) study (54 ± 6 years, 55% women) without prevalent HF at baseline (1987-89) who were followed for 24 ± 1 years. Self-reported alcohol consumption was assessed as the number of drinks/week (1 drink = 14 g of alcohol) at baseline, and updated cumulative average alcohol intake was calculated over 8.9 ± 0.3 years. Using multivariable Cox proportional hazards models, we examined the relation of alcohol intake with incident HF and assessed whether associations were modified by sex. Overall, most participants were abstainers (42%) or former drinkers (19%), with 25% reporting up to 7 drinks per week, 8% reporting ≥7 to 14 drinks per week, and 3% reporting ≥14-21 and ≥21 drinks per week, respectively. Incident HF occurred in 1271 men and 1237 women. Men consuming up to 7 drinks/week had reduced risk of HF relative to abstainers (hazard ratio, HR 0.80, 95% CI 0.68-0.94, P = 0.006); this effect was less robust in women (HR 0.84, 95% CI 0.71-1.00, P = 0.05). In the higher drinking categories, the risk of HF was not significantly different from abstainers, either in men or in women. CONCLUSION: In the community, alcohol consumption of up to 7 drinks/week at early-middle age is associated with lower risk for future HF, with a similar but less definite association in women than in men. These findings suggest that despite the dangers of heavy drinking, modest alcohol consumption in early-middle age may be associated with a lower risk for HF.

Appendectomy may delay Parkinson's disease Onset.

BACKGROUND: Alpha-synuclein (α-Syn) is particularly abundant in the vermiform appendix, which makes this structure an anatomical candidate for the initiation of Parkinson's disease (PD) pathology. We hypothesized that history of appendectomy might affect PD clinical onset. METHODS: A total of 295 PD patients enrolled in a comprehensive observational study were asked about past history of appendectomy. Cox's regression, with a time-dependent covariate, explored the effects of appendectomy on age at PD onset. RESULTS: Thirty-four patients (11.5%) had appendectomy before PD onset. There was no significant effect of appendectomy on age at PD onset for the entire cohort (P = 0.153). However, among patients with late onset (≥55 years), we found evidence that those with past appendectomy had more years of life without PD symptoms than patients without appendectomy (P = 0.040). No association was found for the young-onset group (P = 0.663). CONCLUSIONS: An apparent relationship was observed between appendectomy and PD onset in the late PD cohort.

Cognitive reserve in multiple sclerosis: Protective effects of education.

BACKGROUND: Recent data suggest that cognitive reserve modulates the adverse effects of multiple sclerosis (MS) pathology on cognitive functioning; however, the protective effects of education in MS are still unclear. OBJECTIVE: To explore education as an indicator of cognitive reserve, while controlling for demographic, clinical and genetic features. METHODS: A total of 419 MS patients and 159 healthy comparison (HC) subjects underwent a comprehensive neuropsychological (NP) assessment, and answered the Hospital Anxiety and Depression Scale. Based on the HC data, MS patients' NP scores were adjusted for sex, age and education; and the estimated 5(th) percentile (or 95(th) percentile, when appropriate) was used to identify any deficits. Patients also performed the Mini-Mental State Examination (MMSE); and their human leucocyte antigen HLA-DRB1 and apolipoprotein E (ApoE) genotypes were investigated. RESULTS: Patients with higher education were less likely (p < 0.05) to have cognitive deficits than those with lower education, even when controlling for other covariates. Other significant predictors of cognitive deficit were: age, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), and a progressive course. No significant association was found with the HLA-DRB1*15:01 or ApoE ε4 alleles. CONCLUSIONS: These results provide support to the use of education as a proxy of cognitive reserve in MS and stress the need to take into account education when approaching cognition in MS.

Imaging to select and guide transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is indicated for patients with severe aortic stenosis and high or prohibitive surgical risk. Patients' selection requires clinical and anatomical selection criteria, being the later determined by multimodality imaging evaluation. Echocardiography, multislice computed tomography (MSCT), angiography, and cardiovascular magnetic resonance (CMR) are the methods available to determine the anatomical suitability for the procedure. Imaging assists in the selection of bioprosthesis type, prosthetic sizing and in the decision of the best vascular access. In this review, we present our critical appraisal on the use of imaging to best patients' selection and procedure guidance in TAVI.

Ozonation of bezafibrate over ceria and ceria supported on carbon materials.

Two catalysts containing ceria dispersed on the surface of multi-walled carbon nanotubes and activated carbon were investigated as ozonation catalysts for the mineralization of bezafibrate (BZF). The results were compared with those obtained in the absence of the catalyst and in the presence of the parent carbon materials, as well as in the presence of ceria (CeO2). Carbon materials containing ceria showed an interesting catalytic effect. Both materials enhanced the mineralization of BZF relatively to single ozonation and ozonation catalysed by the corresponding carbon materials. In the catalytic ozonation with these materials, both surface and bulk reactions are supposed to occur. The BZF ozonation catalysed by CeO2 leaded to the highest mineralization degrees, indicating that the reaction mechanism followed in the presence of CeO2 (free radical oxidation in solution) leads to the formation of intermediates more easily degradable, mainly after 120 min of reaction. Some primary products and refractory final oxidation compounds in single and catalytic ozonation of BZF were followed. The original chlorine present on the BZF molecule is completely converted to chloride anion and part of the nitrogen is mainly converted to NO3- along with smaller amounts of NO2- and NH4+. Microtox tests revealed that simultaneous use of ozone and CeO2 originated lower acute toxicity.

Iron deficiency status irrespective of anemia: a predictor of unfavorable outcome in chronic heart failure patients.

OBJECTIVE: To assess the prognostic significance of iron deficiency (ID) in a chronic heart failure (CHF) outpatient population. METHODS AND RESULTS: We prospectively evaluated 127 patients with stable CHF and left ventricular ejection fraction ≤45%. Clinical and analytical data as well as information regarding the occurrence of the composite endpoint of overall mortality and nonfatal cardiovascular events were assessed. Among the 127 patients enrolled [81% men, median age: 62 years (25th-75th percentile: 53-68)], 46 (36%) patients had ID. Women, patients with higher plasma brain natriuretic peptide levels (>400 pg/ml) and with right ventricular systolic dysfunction presented ID more frequently (p < 0.05 for all). At 225 ± 139 days of follow-up, the composite endpoint occurred in 15 (12%) patients. It was more frequent in ID (24 vs. 5%, p = 0.001) and anemic patients (25 vs. 8%, p = 0.014). In a Cox regression analysis, ID was associated with a higher likelihood of composite endpoint occurrence (HR 5.00, 95% CI 1.59-15.78, p = 0.006). In a multivariable analysis adjusted for clinical variables, including the presence of anemia, ID remained a significant predictor of the composite endpoint (HR 5.38, 95% CI 1.54-18.87, p = 0.009). CONCLUSION: In a CHF outpatient population, ID carried a higher risk of unfavorable outcome, irrespectively of the presence of anemia.

Determinants of clinical improvement after surgical replacement or transcatheter aortic valve implantation for isolated aortic stenosis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement (SAVR) in patients with aortic stenosis (AS) and high surgical risk. Hemodynamic performance after TAVI is superior, but the impact of reverse remodeling on clinical improvement is controversial. We aim to address the differences in hemodynamic changes between SAVR and TAVI, and its correlation with LV remodeling and clinical improvement at 6 months follow-up. METHODS: Forty-two patients treated by TAVI were compared with 45 SAVR patients with a stented bioprosthesis. Clinical, 2D and 3D echocardiographic data were prospectively obtained before and six months after intervention. RESULTS: Patients had similar distribution for sex, body surface area and AS severity. TAVI patients were older, more symptomatic and had more comorbidities. They also had higher LV filling pressures, larger 3D indexed left atrium volume, but similar 3D indexed LV mass. At 6 months, TAVI patients had greater clinical improvement and higher effective orifice area index (EAOI), but only SAVR patients already had a significant decrease in 3D indexed LV mass and diastolic volume. In univariate analysis older age, NYHA class ≥ III, increase in EAOI and TAVI were related with functional class improvement. After multivariate analysis only NYHA class ≥ III (OR 8.81, CI:2.13-36.52; p=0.003) and an increase in EAOI ≥ 105% (OR 3.87, CI:1.02-14.70; p=0.04) were predictors of clinical improvement. CONCLUSIONS: At 6 months, functional class improvement was greater after TAVI. Higher initial NYHA class and an increase in EAOI ≥ 105% were independently associated with functional enhancement. It is debatable if left ventricular remodeling is determinant for functional class improvement.

Spirito-Maron echocardiographic score: a marker for morphological and physiological assessment of patients with hypertrophic cardiomyopathy.

AIMS: The heterogeneous distribution of hypertrophy in hypertrophic cardiomyopathy (HCM) limits the echocardiographic conventional measurements accuracy in the evaluation of left ventricular hypertrophy (LVH). The aim of this study was to assess the correlation of the echocardiographic Spirito-Maron score (SMS) with left ventricle (LV) mass quantification by cardiac magnetic resonance (CMR) and with LV diastolic function. METHODS AND RESULTS: Left ventricle diastolic function parameters, SMS, LV mass (American Society of Echocardiography formula), and maximal wall thickness (MWT) were evaluated by two-dimensional (2D) transthoracic echocardiography. The SMS was obtained by adding the MWT of 4 LV segments, at the mitral valve or papillary muscles short-axis views. Echocardiographic parameters of LVH, including SMS, were correlated with LV mass obtained by CMR and with E/e' ratio. We included 45 patients (60% male, mean age 48 ± 18 years), who underwent 2D echocardiography. Twenty-two of them performed a CMR study. A positive correlation was found between SMS and CMR LV mass (r = 0.80; P < 0.001), whereas MWT (r = 0.62; P = 0.002) and the 2D LV mass (r = 0.60; P = 0.011) presented a lower correlation with CMR LV mass. The SMS was significantly correlated with E/e' ratio (r = 0.60; P = 0.007), whereas a nonsignificant correlation was found with MWT (r = 0.41; P = 0.081) and 2D LV mass (r = 0.22; P = 0.400). CONCLUSION: Spirito-Maron score presents a highly positive correlation with CMR LV mass and with diastolic dysfunction severity in HCM patients. SMS is a reliable quantitative LVH measurement method and seems to provide more comprehensive morphological and physiological information than 2D echocardiographic conventional parameters used to estimate LVH.

DRD3 Predicts Cognitive Impairment and Anxiety in Parkinson's Disease: Susceptibility and Protective Effects.

Background: A possible genetic contribution of dopamine D3 receptor (DRD3) to cognitive impairment in Parkinson's disease (PD) has yet to be investigated. Objective: To explore the effects of rs6280 (Ser9Gly) genotype on PD patients' cognitive performance and to clarify possible interactions with psychopathology. Methods: Two hundred and fifty-three consecutive PD patients underwent neurological and neuropsychological evaluations, which included: Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale (H&Y), Dementia Rating Scale-2 (DRS-2), and Hospital Anxiety and Depression Scale (HADS). rs6280 polymorphism was genotyped for all PD patients and for 270 ethnically matched healthy volunteers (HC). Non-parametric group comparisons and logistic regressions were used for data analyses. Results: rs6280 genotype did not differ between PD and HC groups. PD patients with rs6280 CC genotype had more impaired cognitive performance (i.e., <1st percentile of demographically adjusted norms) on DRS-2 subscales Initiation/Perseveration and Construction than those with TT genotype. These associations remained statistically significant when other covariates (e.g., demographic features, disease duration, severity of motor symptoms in OFF and ON states, anti-parkinsonian medication, and psychopathology symptoms) were taken into consideration. PD patients with rs6280 TC had less anxiety (i.e., HADS Anxiety≥11) than those with TT (p = 0.012). This association was also independent of other covariates. Conclusions: Study findings suggest that rs6280 CC genotype predisposes to executive dysfunction and visuoconstructional deficits, whereas the heterozygous genotype protects from anxiety in PD. These effects do not appear to be dependent of one another. rs6280 is not a genotypic susceptibility factor for PD.