Perioperative trajectory of plasma viscosity: A prospective, observational, exploratory study in cardiac surgery.

OBJECTIVE: Plasma viscosity is one of the critical factors that regulate microcirculatory flow but has received scant research attention. The main objective of this study was to evaluate plasma viscosity in cardiac surgery with respect to perioperative trajectory, main determinants, and impact on outcome. METHODS: Prospective, single center, observational study, including 50 adult patients undergoing cardiac surgery with cardiopulmonary bypass between February 1, 2020 and May 31, 2021. Clinical perioperative characteristics, short term outcome, standard blood analysis, plasma viscosity, total proteins, and fibrinogen concentrations were recorded at 10 distinct time points during the first perioperative week. RESULTS: The longitudinal analysis showed that plasma viscosity is strongly influenced by proteins and measurement time points. Plasma viscosity showed a coefficient of variation of 11.3 ± 1.08 for EDTA and 12.1 ± 2.1 for citrate, similarly to total proteins and hemoglobin, but significantly lower than fibrinogen (p < .001). Plasma viscosity had lower percentage changes compared to hemoglobin (RANOVA, p < .001), fibrinogen (RANOVA, p < .001), and total proteins (RANOVA, p < .001). The main determinant of plasma viscosity was protein concentrations. No association with outcome was found, but the study may have been underpowered to detect it. CONCLUSION: Plasma viscosity had a low coefficient of variation and low perioperative changes, suggesting tight regulation. Studies linking plasma viscosity with outcome would require large patient cohorts.

Iatrogenic Iliac Arteriovenous Fistula Management after Lumbar Discectomy Surgeries: A Case Report and Review of the Literature.

Iatrogenic iliac arteriovenous fistula (IAVF) is an extremely rare complication after lumbar discectomy surgery (LDS), with potentially life-threatening consequences. An IAVF results from the close anatomic relation between the iliac vessels and the last lumbar vertebrae and the corresponding discs. We report the case of a 45-year-old woman who developed a large right IAVF 3 years after L4-L5-S1 laminectomy. The arteriovenous fistula (AVF) was successfully treated with an endovascular technique using a WALLSTENT self- expanding stent. The postoperative period was uneventful, and the patient was discharged from the hospital in good general condition on the third postoperative day.

Authorship: from credit to accountability. Reflections from the Editors' Network.

The Editors' Network of the European Society of Cardiology provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

Echocardiographic features of Fabry cardiomyopathy-Comparison with hypertrophy-matched sarcomeric hypertrophic cardiomyopathy.

BACKGROUND: The concept of "red flags" has been particularly useful in the etiologic diagnosis of cardiomyopathies such as Fabry disease, as early detection is often essential for treatment response and outcomes. The present study sought to describe the echocardiographic features that may differentiate Fabry cardiomyopathy from sarcomeric hypertrophic cardiomyopathy (HCM). METHODS: Forty patients with left ventricular (LV) hypertrophy were prospectively included and divided into two groups: the Fabry group (20) and the sarcomeric HCM group (20). The two groups were matched for LV hypertrophy (similar maximum wall thickness and indexed LV mass) and age. All patients underwent full echocardiographic evaluation including ventricular strain analysis. RESULTS: The Fabry group had significantly lower LV ejection fraction (63 ± 7 vs 72 ± 7%, P = .001) and higher LV end-systolic diameter (28 ± 7 vs 22 ± 5 mm, P = .004). LV hypertrophy in Fabry patients was more often concentric, with a significantly lower interventricular septum/posterior wall ratio (1.22 ± 0.63 vs 1.55 ± 0.66, P = .001). Fabry patients had more reduced regional longitudinal strain in the inferolateral part of the LV (-9 ± 5 vs -16 ± 7%), and RV free wall longitudinal strain was also worse in Fabry patients (-23 ± 6 vs -28 ± 5%, P = .027). CONCLUSION: These parameters are promising echocardiographic features to identify patients with Fabry cardiomyopathy and may help for the detection and subsequent management of these patients.

Plasma α-synuclein and cognitive impairment in the Parkinson's Associated Risk Syndrome: A pilot study.

Plasma total and nervous system derived exosomal (NDE) α-synuclein have been determined as potential biomarkers of Parkinson's disease (PD). To explore the utility of plasma α-synuclein in the prodromal phase of PD, plasma total and NDE α-synuclein were evaluated in baseline and 2-year follow-up samples from 256 individuals recruited as part of the Parkinson's Associated Risk Syndrome (PARS) study. The results demonstrated that baseline and longitudinal increases in total α-synuclein predicted progression of cognitive decline in hyposmic individuals with dopamine transporter (DAT) binding reduction. On the other hand, a longitudinal decrease in NDE α-synuclein predicted worsening cognitive scores in hyposmic individuals with DAT binding reduction. Finally, in individuals with faster DAT progression, decreasing NDE/total α-synuclein ratio was associated with a larger reduction in DAT from baseline to follow-up. These results suggest that, though underlying mechanisms remain to be defined, alterations in plasma total and NDE α-synuclein concentrations are likely associated with PD progression, especially in the aspect of cognitive impairment, at early stages of the disease.

Right ventricular remodeling in athletes and in arrhythmogenic cardiomyopathy.

OBJECTIVE: Changes in right ventricular (RV) structure and function following prolonged endurance training in athletes arise due to its unique anatomy and physiology. Arrhythmogenic cardiomyopathy (AC) should be differentiated from electrical, functional and structural adaptation of the heart in response to repetitive intense physical activity due to the negative contribution of exercise on AC progression and arrhythmic risk. DESIGN: For this review we performed a systematic search of the PubMed database up to October 2017 using terms and keywords pertaining to RV, athlete's heart (AH), AC, sudden cardiac death. RESULTS: This review summarizes currently available data on the impact of exercise on cardiac structure and function, discusses the debatable hypothesis of exercise-induced RV remodeling, compares the common features and search for distinctive characteristics between AH and AC. CONCLUSION: Exercise has a more profound impact on the structure and function of the RV than of the left ventricle. Differentiating physiologic RV remodeling following prolonged endurance exercise from subclinical cardiac pathology can be challenging. A multimodality approach is recommended to differentiate between exercise-induced physiological adaptations and cardiomyopathy.

α-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation.

Malformed α-Synuclein (α-syn) aggregates in neurons are released into the extracellular space, activating microglia to induce chronic neuroinflammation that further enhances neuronal damage in α-synucleinopathies, such as Parkinson's disease. The mechanisms by which α-syn aggregates activate and recruit microglia remain unclear, however. Here we show that α-syn aggregates act as chemoattractants to direct microglia toward damaged neurons. In addition, we describe a mechanism underlying this directional migration of microglia. Specifically, chemotaxis occurs when α-syn binds to integrin CD11b, leading to H2O2 production by NADPH oxidase. H2O2 directly attracts microglia via a process in which extracellularly generated H2O2 diffuses into the cytoplasm and tyrosine protein kinase Lyn, phosphorylates the F-actin-associated protein cortactin after sensing changes in the microglial intracellular concentration of H2O2. Finally, phosphorylated cortactin mediates actin cytoskeleton rearrangement and facilitates directional cell migration. These findings have significant implications, given that α-syn-mediated microglial migration reaches beyond Parkinson's disease.

Cerebrospinal fluid α-synuclein contributes to the differential diagnosis of Alzheimer's disease.

INTRODUCTION: The ability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid ß peptide 1-42, total tau, and phosphorylated tau) to discriminate AD from related disorders is limited. Biomarkers for other concomitant pathologies (e.g., CSF α-synuclein [α-syn] for Lewy body pathology) may be needed to further improve the differential diagnosis. METHODS: CSF total α-syn, phosphorylated α-syn at Ser129, and AD CSF biomarkers were evaluated with Luminex immunoassays in 367 participants, followed by validation in 74 different neuropathologically confirmed cases. RESULTS: CSF total α-syn, when combined with amyloid ß peptide 1-42 and either total tau or phosphorylated tau, improved the differential diagnosis of AD versus frontotemporal dementia, Lewy body disorders, or other neurological disorders. The diagnostic accuracy of the combined models attained clinical relevance (area under curve ∼0.9) and was largely validated in neuropathologically confirmed cases. DISCUSSION: Combining CSF biomarkers representing AD and Lewy body pathologies may have clinical value in the differential diagnosis of AD.

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors' Network.

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship- emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors' Network of the European Society of Cardiology.

Is Right Ventricular Remodeling in Pulmonary Hypertension Dependent on Etiology? An Echocardiographic Study.

AIMS: Survival in patients (pts) with pulmonary hypertension (PH) differs between subgroups at similar levels of pressure overload. We set to analyze right ventricular (RV) morphology and function in different types of PH using conventional and deformation imaging echocardiography. MATERIAL AND METHODS: Thirty-four pts with PH: 12 pts with idiopathic pulmonary arterial hypertension (IPAH, 42.2 ± 13 years), 11 pts with chronic thromboembolic PH (CTEPH, 50.8 ± 12 years), 11 pts with Eisenmenger syndrome [ES 41.2 ± 15 years, 4 with atrial septal defect (ASD) and 7 with ventricular septal defect (VSD)], and 13 age-matched healthy individuals (38.1 ± 15 years) were evaluated. The following echocardiographic parameters were measured: echo-derived systolic pulmonary pressure (sPAPecho), RV end-diastolic diameter (RVEDD), RV wall thickness (RVWT), TAPSE, RV fractional area change (RVFAC), Tei index, peak systolic velocity of the tricuspid ring (S't), and speckle tracking-derived RV free wall strain. Furthermore, right heart catheterization (RHC) was performed in pts with PH and mean, and systolic pulmonary artery pressure (mPAPcath, sPAPcath), cardiac output (CO), cardiac index (COi), and pulmonary vascular resistance (PVR) were noted. RESULTS: The levels of mPAPcath and sPAPcath were similar between pts with PH (pANOVA = NS). Patients with ES had higher COi compared to other groups (2.94 ± 0.79, 2.28 ± 0.69, and 1.74 ± 0.46 L/min/m(2) for pts with ES, IPAH, and CTEPH respectively, pANOVA = 0.004, P post hoc ES versus all other groups < 0.05). TAPSE, Tei index, and S't were similar between groups and impaired versus controls (pANOVA < 0.001, P post hoc between groups of patients = NS). Patients with ES had better RVFAC (41.1 ± 9, 30.5 ± 10.8, 23.2 ± 9.8%) and RV free wall strain (-20.6 ± 3.5, -16.3 ± 7.5, -10.8 ± 5%), as well as an increased thickness of the RV free wall compared to other groups of patients (9.2 ± 1.5, 7.2 ± 1 and 7.2 ± 1.6 mm for pts with ES, IPAH and CTEPH, respectively) (pANOVA<0.001, P post hoc <0.05 ES versus all other groups). RVFAC and RV free wall strain significantly correlated with COi (r = 0.53, P = 0.006 and r = -0.77, P < 0.001, respectively). CONCLUSION: Patients with ES have a more hypertrophied RV free wall, better RV performance as assessed by RVFAC and RV free wall strain and increased COi compared to other types of PH. Furthermore, RV performance appears to be less dependent on the level of pressure overload. These findings could contribute to the better survival profile of patients with ES.

CNS tau efflux via exosomes is likely increased in Parkinson's disease but not in Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) and Parkinson's disease (PD) involve tau pathology. Tau is detectable in blood, but its clearance from neuronal cells and the brain is poorly understood. METHODS: Tau efflux from the brain to the blood was evaluated by administering radioactively labeled and unlabeled tau intracerebroventricularly in wild-type and tau knock-out mice, respectively. Central nervous system (CNS)-derived tau in L1CAM-containing exosomes was further characterized extensively in human plasma, including by single molecule array technology with 303 subjects. RESULTS: The efflux of Tau, including a fraction via CNS-derived L1CAM exosomes, was observed in mice. In human plasma, tau was explicitly identified within L1CAM exosomes. In contrast to AD patients, L1CAM exosomal tau was significantly higher in PD patients than controls and correlated with cerebrospinal fluid tau. CONCLUSIONS: Tau is readily transported from the brain to the blood. The mechanisms of CNS tau efflux are likely different between AD and PD.

Cerebrospinal fluid α-synuclein predicts cognitive decline in Parkinson disease progression in the DATATOP cohort.

Most patients with Parkinson disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although α-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and α-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess α-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing α-synuclein (phase 1 to phase 2 change of -0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between α-synuclein and motor symptoms. Longitudinally, lower α-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall α-synuclein × time interaction effect coefficient, -0.12 (P = 0.037); delayed recall, -0.05 (P = 0.002); New Dot Test, -0.03 (P = 0.002)]. Thus, α-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation.

The left ventricle in aortic stenosis--imaging assessment and clinical implications.

Aortic stenosis has an increasing prevalence in the context of aging population. In these patients non-invasive imaging allows not only the grading of valve stenosis severity, but also the assessment of left ventricular function. These two goals play a key role in clinical decision-making. Although left ventricular ejection fraction is currently the only left ventricular function parameter that guides intervention, current imaging techniques are able to detect early changes in LV structure and function even in asymptomatic patients with significant aortic stenosis and preserved ejection fraction. Moreover, new imaging parameters emerged as predictors of disease progression in patients with aortic stenosis. Although proper standardization and confirmatory data from large prospective studies are needed, these novel parameters have the potential of becoming useful tools in guiding intervention in asymptomatic patients with aortic stenosis and stratify risk in symptomatic patients undergoing aortic valve replacement.This review focuses on the mechanisms of transition from compensatory left ventricular hypertrophy to left ventricular dysfunction and heart failure in aortic stenosis and the role of non-invasive imaging assessment of the left ventricular geometry and function in these patients.

Targeted discovery and validation of plasma biomarkers of Parkinson's disease.

Despite extensive research, an unmet need remains for protein biomarkers of Parkinson's disease (PD) in peripheral body fluids, especially blood, which is easily accessible clinically. The discovery of such biomarkers is challenging, however, due to the enormous complexity and huge dynamic range of human blood proteins, which are derived from nearly all organ systems, with those originating specifically from the central nervous system (CNS) being exceptionally low in abundance. In this investigation of a relatively large cohort (∼300 subjects), selected reaction monitoring (SRM) assays (a targeted approach) were used to probe plasma peptides derived from glycoproteins previously found to be altered in the CNS based on PD diagnosis or severity. Next, the detected peptides were interrogated for their diagnostic sensitivity and specificity as well as the correlation with PD severity, as determined by the Unified Parkinson's Disease Rating Scale (UPDRS). The results revealed that 12 of the 50 candidate glycopeptides were reliably and consistently identified in plasma samples, with three of them displaying significant differences among diagnostic groups. A combination of four peptides (derived from PRNP, HSPG2, MEGF8, and NCAM1) provided an overall area under curve (AUC) of 0.753 (sensitivity: 90.4%; specificity: 50.0%). Additionally, combining two peptides (derived from MEGF8 and ICAM1) yielded significant correlation with PD severity, that is, UPDRS (r = 0.293, p = 0.004). The significance of these results is at least two-fold: (1) it is possible to use a targeted approach to identify otherwise very difficult to detect CNS related biomarkers in peripheral blood and (2) the novel biomarkers, if validated in independent cohorts, can be employed to assist with clinical diagnosis of PD as well as monitoring disease progression.

Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson's disease.

Extracellular α-synuclein is important in the pathogenesis of Parkinson's disease (PD) and also as a potential biomarker when tested in the cerebrospinal fluid (CSF). The performance of blood plasma or serum α-synuclein as a biomarker has been found to be inconsistent and generally ineffective, largely due to the contribution of peripherally derived α-synuclein. In this study, we discovered, via an intracerebroventricular injection of radiolabeled α-synuclein into mouse brain, that CSF α-synuclein was readily transported to blood, with a small portion being contained in exosomes that are relatively specific to the central nervous system (CNS). Consequently, we developed a technique to evaluate the levels of α-synuclein in these exosomes in individual plasma samples. When applied to a large cohort of clinical samples (267 PD, 215 controls), we found that in contrast to CSF α-synuclein concentrations, which are consistently reported to be lower in PD patients compared to controls, the levels of plasma exosomal α-synuclein were substantially higher in PD patients, suggesting an increased efflux of the protein to the peripheral blood of these patients. Furthermore, although no association was observed between plasma exosomal and CSF α-synuclein, a significant correlation between plasma exosomal α-synuclein and disease severity (r = 0.176, p = 0.004) was observed, and the diagnostic sensitivity and specificity achieved by plasma exosomal α-synuclein were comparable to those determined by CSF α-synuclein. Further studies are clearly needed to elucidate the mechanism involved in the transport of CNS α-synuclein to the periphery, which may lead to a more convenient and robust assessment of PD clinically.

Cardiac structure and function and insulin resistance in morbidly obese patients: does superobesity play an additional role?

OBJECTIVE: To evaluate the impact of superobesity, defined as body mass index (BMI) ≥50, on cardiac structure and function. METHODS: Using echocardiography, we studied 198 asymptomatic patients (mean age 48 ± 13 years, 29.3% were men) with a BMI ≥40. Insulin resistance was measured using the Homeostasis Model Assessment of insulin resistance (HOMA-IR). Patients were divided into 2 groups: morbidly obese (BMI ≥40 and <50; n = 160) and superobese (BMI ≥50; n = 38). RESULTS: There were no significant differences in age, gender, hypertension and diabetes between groups. Superobese patients had higher LV mass (66.0 ± 14.7 vs. 59.9 ± 11.9 g/m(2.7), p = 0.007), left ventricular (LV) end-diastolic (33.8 ± 7.7 vs. 31.5 ± 7.1 ml/m(2.7), p = 0.041) and end-systolic (12.2 ± 3.6 vs. 10.9 ± 2.8 ml/m(2.7), p = 0.016) volumes, left atrial volume (13.8 ± 4.5 vs. 12.2 ± 3.9 ml/m(2.7), p = 0.029), peak velocity of transmitral flow in early diastole/early diastolic peak myocardial velocity ratio (9.1 ± 2.6 vs. 8.2 ± 2.2, p = 0.03) and HOMA-IR (9.7 ± 7.3 vs. 7.3 ± 6.5, p = 0.047). LV ejection fraction was similar. CONCLUSIONS: Superobesity is associated with insulin resistance and a worse impact on cardiac remodeling and LV diastolic function than morbid obesity. Prospective studies are needed to evaluate whether such further classification of morbid obesity could stratify the cardiovascular risk in these patients more accurately.

Correlation between global longitudinal strain and QRS voltage on electrocardiogram in patients with left ventricular hypertrophy.

PURPOSE: Left ventricular hypertrophy (LVH) is as an independent risk factor. Discrepancies were reported between LV mass (LVM) estimated by echocardiography and electrocardiography (ECG) findings. We hypothesized that QRS voltage criteria may reflect not only anatomical changes (LVM) but also changes in LV function and we tested the relationship between QRS voltage and echocardiographic parameters of LV function in patients (pts) with different types of LVH. METHODS: We prospectively enrolled pts with LVH and preserved ejection fraction (LVEF >50%): 20 pts with isolated arterial hypertension, HTN, 20 pts with severe aortic stenosis, AS (indexed aortic valve area <0.6 cm(2)/m(2)), and 20 pts with symmetric hypertrophic cardiomyopathy, HCM. Standard 12-lead ECG (including Sokolow and Cornell voltage indices) and a comprehensive two-dimensional (2D) echocardiography were performed in all. Left ventricular mass was calculated according to Devereux formula. Global longitudinal strain (GLS) was assessed by speckle tracking echocardiography. RESULTS: A significant correlation was found between both ECG indices and LVM assessed by echocardiography. Moreover, significant correlations were found between Sokolow-Lyon voltage and LVEF (r = 0.26; P = 0.03), GLS (r = 0.59; P < 0.001) and E/e' average (r = 0.43; P < 0.001). Cornell voltage index correlated significantly only with GLS. In multivariable analysis GLS emerged as the only independent correlate of both Sokolow-Lyon (ß = 0.6, P < 0.001) and Cornell voltage indices (ß = 0.45, P < 0.001). CONCLUSION: These findings suggest that in pts with LVH, ECG should no longer be used only as a surrogate method for LVM estimation (structural changes only), but rather as an investigation complementary to imaging, incorporating information on overall LV remodeling (changes in structure and function).

Longitudinal assessment of tau and amyloid beta in cerebrospinal fluid of Parkinson disease.

Tau gene has been consistently associated with the risk of Parkinson disease in recent genome wide association studies. In addition, alterations of the levels of total tau, phosphorylated tau [181P], and amyloid beta 1-42 in cerebrospinal fluid have been reported in patients with sporadic Parkinson disease and asymptomatic carriers of leucine-rich repeat kinase 2 mutations, in patterns that clearly differ from those typically described for patients with Alzheimer disease. To further determine the potential roles of these molecules in Parkinson disease pathogenesis and/or in tracking the disease progression, especially at early stages, the current study assessed all three proteins in 403 Parkinson disease patients enrolled in the DATATOP (Deprenyl and tocopherol antioxidative therapy of parkinsonism) placebo-controlled clinical trial, the largest cohort to date with cerebrospinal fluid samples collected longitudinally. These initially drug-naive patients at early disease stages were clinically evaluated, and cerebrospinal fluid was collected at baseline and then at endpoint, defined as the time at which symptomatic anti-Parkinson disease medications were determined to be required. General linear models were used to test for associations between baseline cerebrospinal fluid biomarker levels or their rates of change and changes in the Unified Parkinson Disease Rating Scale (total or part III motor score) over time. Robust associations among candidate markers are readily noted. Baseline levels of amyloid beta were weakly but negatively correlated with baseline Unified Parkinson Disease Rating Scale total scores. Baseline phosphorylated tau/total tau and phosphorylated tau/amyloid beta were significantly and negatively correlated with the rates of the Unified Parkinson Disease Rating Scale change. While medications (deprenyl and/or tocopherol) did not appear to alter biomarkers appreciably, a weak but significant positive correlation between the rate of change in total tau or total tau/amyloid beta levels and the change of the Unified Parkinson Disease Rating Scale was observed. Notably, these correlations did not appear to be influenced by APOE genotype. These results are one of the very first pieces of evidence suggesting that tau and amyloid beta are critically involved in early Parkinson disease progression, potentially by a different mechanism than that in Alzheimer disease, although their applications as Parkinson disease progression markers will likely require the addition of other proteins.

Impact of associated significant aortic regurgitation on left ventricular remodeling and hemodynamic impairment in severe aortic valve stenosis.

OBJECTIVES: The left ventricular (LV) response to combined pressure and volume overload [aortic stenosis (AS) and aortic regurgitation (AR)] versus pressure overload (isolated AS)has not been systematically studied. We aimed to assess LV remodeling, functional and hemodynamic consequences inpatients with mixed aortic valve disease versus patients with isolated AS. METHODS: We enrolled 181 patients (67 ± 9 years,109 men) with severe AS (aortic valve area indexed to body surface area <0.6 cm 2 /m 2 ) who underwent preoperative cardiac catheterization and a complete echocardiogram. Pulmonary capillary wedge pressure (PCWP), LV end-diastolic pressure (LVEDP) and pulmonary artery pressure (PAP) were measured. RESULTS: One hundred and ten patients (group A)had isolated severe AS (AR 0­1) and 71 patients (group B)had mixed aortic valve disease (severe AS plus AR 2­3). Patients in group B were younger and in a higher New York Heart Association class (p < 0.01). Severity of AS was similar in both groups. Patients in group B had a higher indexed LV mass, a lower LV ejection fraction, and higher PCWP, LVED Pand PAP (all p ≤ 0.01). CONCLUSIONS: Patients with severe AS and significant AR are more symptomatic than patients with isolated severe AS. The increased burden due to the combined lesion induces pronounced LV remodeling and more severe hemodynamic consequences.

Right ventricular function predicts clinical response to specific vasodilator therapy in patients with pulmonary hypertension.

INTRODUCTION: We followed patients with pulmonary arterial hypertension (PAH) receiving specific vasodilator therapy and tested for predictors of clinical outcome. METHODS: Thirty-two patients (mean age 39 ± 15 years, 22 women, diagnosed with pulmonary hypertension; PH): 29 with PAH and 3 patients with inoperable chronic thromboembolic PH received therapy with either bosentan, sildenafil, or both and were evaluated with clinical parameters, biomarkers (B-type natriuretic peptide values), and echocardiography before receiving specific medication and every 3 months thereafter. A right heart catheterization was performed at baseline. A composite endpoint of death, worsening of functional class, or the need of a second vasodilator agent was used to define the clinical nonresponders. RESULTS: Patients were followed for 14 months (7.5-21). The endpoint was reached by 15 patients: four patients died (two idiopathic PAH and two PAH in context of Eisenmenger syndrome), seven patients showed 1 functional class worsening, and four patients needed to be switched to combination therapy. Patients who remained clinically stable or improved had at baseline a better cardiac output with a less remodeled right ventricle (RV) and better functioning RV (all P < 0.05). A RV fractional area change (RVFAC) lower than 25.7% and a RV global strain value higher than -13.4% predict with 87% sensitivity and 83% specificity (AUC 87.3%, P = 0.001) and 73% sensitivity and 91% specificity (AUC 84.2%, P = 0.003), respectively, patients who will deteriorate clinically under specific vasodilator therapy. A multivariate model showed RVFAC to be the only independent predictor of the endpoint with a HR of 0.87 (0.8-0.96), P = 0.007. CONCLUSIONS: Over an average period of 1 year, almost half of patients showed signs of clinical deterioration despite specific vasodilator therapy. Parameters of right ventricular morphology and function had prognostic value in these patients.