Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease.

INTRODUCTION AND PURPOSE: Bicuspid aortic valve (BAV) disease is associated with faster aortic valve degeneration and a high incidence of aortic stenosis (AS). In this study, we aimed to identify differences in the pathophysiology of AS between BAV and tricuspid aortic valve (TAV) patients in a multiomics study integrating metabolomics and transcriptomics as well as clinical data. METHODS: Eighteen patients underwent aortic valve replacement due to severe aortic stenosis: 8 of them had a TAV, while 10 of them had a BAV. RNA sequencing (RNA-seq) and proton nuclear magnetic resonance spectroscopy (1H-NMR) were performed on these tissue samples to obtain the RNA profile and lipid and low-molecular-weight metabolites. These results combined with clinical data were posteriorly compared, and a multiomic profile specific to AS in BAV disease was obtained. RESULTS: H-NMR results showed that BAV patients with AS had different metabolic profiles than TAV patients. RNA-seq also showed differential RNA expression between the groups. Functional analysis helped connect this RNA pattern to mitochondrial dysfunction. Integration of RNA-seq, 1H-NMR and clinical data helped create a multiomic profile that suggested that mitochondrial dysfunction and oxidative stress are key players in the pathophysiology of AS in BAV disease. CONCLUSIONS: The pathophysiology of AS in BAV disease differs from patients with a TAV and has a specific RNA and metabolic profile. This profile was associated with mitochondrial dysfunction and increased oxidative stress.

Influence of body mass index on recurrence of atrial fibrillation after electrical cardioversion.

BACKGROUND: Several studies have shown an independent relationship between body mass index (BMI) and the incidence of atrial fibrillation (AF). However, little is known about the influence of BMI on AF recurrence after electrical cardioversion (ECV). METHODS: We selected 1121 patients who reverted to sinus rhythm after scheduled ECV and were included in three prospective Spanish registries of ECV in persistent AF. The patients were classified according to baseline BMI into three categories (normal weight, overweight, obesity). We assessed the influence of BMI on the rate of AF recurrence at 3 months. RESULTS: We identified 538 patients (48%) who had AF recurrence in the first 3 months after successful ECV. The patients who suffered AF recurrence had a higher BMI than those who remained in sinus rhythm (29.66±4.57 vs. 28.87±4.64 Kg/m2, respectively; p = 0.004). We observed a higher incidence of AF recurrence in the overweight and obese patients (BMI ≥25 kg/m2) than in those classified as normal weight (50.5% vs. 35.6%, respectively; p<0,001). BMI≥25 Kg/m2 was shown to be independently related to of AF recurrence in the multivariate analysis (OR = 1.75, 95% confidence interval = 1.20-2.58; p = 0.004). CONCLUSIONS: Increased BMI is independently related to AF recurrence after ECV. BMI should also be taken into account when making decisions about the indication for ECV in persistent AF.

Hemolytic Anemia After Surgical Mitral Valve Repair Treated With Transcatheter Edge-to-Edge Device.

An 80-year-old woman with mitral valve repair failure was admitted with hemolytic anemia secondary to the impact of a regurgitant jet on the annuloplasty ring. Transcatheter repair to treat both mitral regurgitation and hemolysis was favored because of surgical risk. Transcatheter edge-to-edge repair represents an alternative for treating hemolysis associated with mitral regurgitation. (Level of Difficulty: Advanced.).

Glycoprotein and Lipoprotein Profiles Assessed by 1H-NMR and Its Relation to Ascending Aortic Dilatation in Bicuspid Aortic Valve Disease.

INTRODUCTION: The bicuspid aortic valve (BAV) confers a high risk of ascending aorta dilatation (AAoD), although its progression seems highly variable. Furthermore, the implication of lipoprotein metabolism and inflammation in the mechanisms that underlie AAoD is not fully established. The aim of this study consisted of evaluating the impact of the lipoprotein and glycoprotein profiles in AAOD as well as its progression in BAV aortopathy. METHODS: Using 1H-nuclear magnetic resonance (1H-NMR), we analyzed and compared the lipoprotein and glycoprotein profiles of plasma samples from 152 BAV patients with dilated and nondilated ascending aorta. Additionally, these profiles were also compared for 119 of these patients who were prospectively followed-up clinically and by echocardiography in the long-term (5 years). Ascending aorta dilation velocity (mm/year) was calculated for this analysis. RESULTS: Several parameters related to the lipoprotein profile including remnant cholesterol, small LDL and IDL-cholesterol were found to be significantly increased in the dilated group compared to those in the nondilated group. The glycoprotein A-nuclear magnetic resonance (NMR) signal, a novel inflammation biomarker, was also observed to be increased in the dilated group. After performing multivariate analysis, remnant cholesterol remained an independent variable related to AAoD. In the long-term follow-up, proatherogenic lipoprotein parameters were related to ascending aorta dilatation velocity ascending. After a lineal regression analysis, non-HDL particles remained as an independent predictor of ascending aorta dilation velocity. CONCLUSIONS: Patients with BAV and AAoD presented a more pro-atherogenic profile assessed by 1H-NMR, especially related to triglyceride-rich lipoproteins. This pro-atherogenic profile seems to contribute to the higher growth rate of ascending aorta diameter.

Improvement in Atrial Fibrillation-Related Symptoms After Cardioversion: Role of NYHA Functional Class and Maintenance of Sinus Rhythm.

BACKGROUND: The European Heart Rhythm Association (EHRA) score is a proven and validated tool for assessing the symptoms of atrial fibrillation (AF). Little is known about the variables related to this score and how it changes after cardioversion. METHODS: We analyzed 744 patients undergoing elective cardioversion in whom AF-related symptoms were assessed at baseline and after 6 months of follow-up using the EHRA score. We assessed the association between the EHRA score and other clinical and echocardiographic variables at baseline and after 6 months of follow-up. RESULTS: At 6 months of follow-up, we observed a reduction in the EHRA score in 50% and worsening in 2.8% of patients who remained in sinus rhythm (SR) compared with 34.6% and 11.3%, respectively, of patients with AF episodes (p<0.0001). Patients who maintained SR at 6 months were less symptomatic than those with AF (EHRA score 1.13 ± 0.35 vs 1.42 ± 0.59; p<0.0001). The independent predictors for reduction in the EHRA score after cardioversion were NYHA ≥II at baseline and maintenance of SR (p<0.0001). CONCLUSION: The greatest improvement in AF-related symptoms was in patients who remained in SR at 6 months after cardioversion and in patients with worse NYHA functional class at baseline.

Immunological and virological efficacy of different antiretroviral regimens initiated during acute/recent HIV infection.

OBJECTIVES: Antiretroviral treatment (ART) during acute/recent HIV infection decreases transmission and optimizes immune recovery but the optimal ART-regimen in this setting is unknown. The objectives were to analyze the virological efficacy, immunological reconstitution and tolerability of different ART-regimens at 3 years after starting ART during acute/recent HIV infection. DESIGN: Retrospective cohort study of consecutive acutely/recently infected patients who started ART within 6 months postinfection. METHODS: We compared regimens based on protease-inhibitors (N = 28), integrase-strand-transfer-inhibitors (InSTI, N = 87) and nonnucleoside-reverse-transcriptase-inhibitors (N = 22). Virological suppression (viral load <50 copies/ml), immune reconstitution (CD4 T-cell count >900 cells/µl and CD4/CD8 ratio >1) and adverse events leading to ART discontinuation at 1 and 3 years were compared. RESULTS: Baseline characteristics were comparable among groups. Overall viral suppression at 1 (96%) and 3 years (99%) was comparable in all ART regimens and, InSTI group, comparable for dolutegravir and elvitegravir within InSTIs. CD4 T-cell counts at 1 year were comparable in all ART regimens. Overall proportion of patients reaching CD4 cell count more than 900 cells/µl and CD4/CD8 ratio more than 1 was 36% and 40% and 46% and 63% at 1 and 3 years, respectively with no differences among ART regimens. Starting ART during the earliest Fiebig stages (I-V vs. VI) was associated with higher rates of CD4 cell count more than 900 cells/µl at 3 years (P = 0.027). Discontinuation due to adverse events was more frequent with nonnucleoside-reverse-transcriptase-inhibitors compared with other ART classes. CONCLUSION: Viral suppression and immunological recovery were excellent, with no differences between ART regimens. Earlier ART initiation was associated with a higher proportion of long-term immunological recovery.

Prevalence, clinical characteristics and outcome of severe primary HIV-1 infection: A prospective cohort study.

BACKGROUND: Severe cases of primary HIV infection have been described in patients presenting with neurological involvement, AIDS defining events or other life-threatening events. These severe forms have not been fully studied. OBJECTIVES: To determine the prevalence and characteristics of severe PHI in a hospital-based cohort of primary HIV infection, and the response to the early initiation of antiretroviral therapy (ART) at 12 months. METHODS: Every patient with PHI attending Hospital Clínic of Barcelona (1997-2015) was evaluated. Severe PHI was defined using clinical, analytical and immunological criteria. Chi-squared test was used for categorical variables and Student's t-test for quantitative variables. RESULTS: 33% of 224 PHI patients (95% CI: 26.84%-39.16%) had a severe PHI. These patients had more symptoms, abnormal analytical parameters and hospital admissions. The severe PHI group had a significantly higher viral load although no differences were observed at 12 months in terms of viral suppression or CD4 count recovery. None died during PHI. CONCLUSIONS: Up to one third of patients in our cohort presented with a severe PHI, which was associated with higher hospitalization rates and higher plasma HIV RNA viral load. However, severe forms were not associated to a worse clinical, immunological or virological outcome at 12 months.

PD-L1 Blockade Differentially Impacts Regulatory T Cells from HIV-Infected Individuals Depending on Plasma Viremia.

Blocking the PD-1/PD-L1 pathway has emerged as a potential therapy to restore impaired immune responses in human immunodeficiency virus (HIV)-infected individuals. Most reports have studied the impact of the PD-L1 blockade on effector cells and neglected possible effects on regulatory T cells (Treg cells), which play an essential role in balancing immunopathology and antiviral effector responses. The aim of this study was to define the consequences of ex vivo PD-L1 blockade on Treg cells from HIV-infected individuals. We observed that HIV infection led to an increase in PD-1+ and PD-L1+ Treg cells. This upregulation correlated with disease progression and decreased under antiretroviral treatment. Treg cells from viremic individuals had a particularly high PD-1 expression and impaired proliferative capacity in comparison with Treg cells from individuals under antiretroviral treatment. PD-L1 blockade restored the proliferative capacity of Treg cells from viremic individuals but had no effect on its suppressive capacity. Moreover, it increased the viral production in cell cultures from viremic individuals. This increase in viral production correlated with an increase in Treg cell percentage and a reduction in the CD4/Treg and CD8/Treg cell ratios. In contrast to the effect of the PD-L1 blockade on Treg cells from viremic individuals, we did not observe a significant effect on the proliferative capacity of Treg cells from individuals in whom viremia was controlled (either spontaneously or by antiretroviral treatment). However, PD-L1 blockade resulted in an increased proliferative capacity of HIV-specific-CD8 T cells in all subjects. Taken together, our findings suggest that manipulating PD-L1 in vivo can be expected to influence the net gain of effector function depending on the subject's plasma viremia.

Stent implantation in variant angina refractory to medical treatment.

BACKGROUND: Vasospastic angina usually responds well to medical treatment. HYPOTHESIS: The present study describes our experience in patients who received a coronary stent because of recurrent variant angina refractory to medical treatment and evaluates stent implantation as an alternative treatment. MATERIALS AND METHODS: Between March 1998 and February 2005, recurrent variant angina was diagnosed in 22 patients admitted to our coronary care unit. Of these, five patients (22.7%), were refractory to pharmacologic treatment. Coronary angiography and coronary stents were indicated. Clinical follow-up was 29 +/- 6 months. RESULTS: Stenting was performed during diagnostic coronary angiography in two patients. In the other three patients, the stent was implanted 24-48 h later. We observed coronary spasm recurrences proximal or distal to the stent in four patients-two during the stent implantation procedure and the other two in the coronary care unit within 48 h post angioplasty. Three patients where treated with additional stenting and the fourth patient improved with pharmacologic treatment. During follow-up three patients remained asymptomatic. The fourth patient had diffuse in-stent restenosis in the third month, and the fifth patient showed a de novo lesion in the treated segment 2 years later. CONCLUSIONS: Stent implantation in patients with recurrent variant angina refractory to medical treatment may be an alternative treatment in carefully selected, clinically unstable patients. Spasm recurrences may occur in other segments of the treated artery, probably due to the diffuse nature of the disease. Immediate and continued surveillance is recommended because of the risk of adverse clinical events.

Transient biventricular dysfunction following pericardiocentesis.

We report the case of a 41-year-old woman admitted to the hospital due to cardiac tamponade as the first manifestation of a pulmonary neoplasm. The patient developed an early biventricular dysfunction and pulmonary edema after removal of the pericardial effusion, with complete recovery within ten days. Since transient ventricular dysfunction after pericardiocentesis is a very unusual complication, we present a review of the different mechanisms suggested in the literature to explain the pathophysiology of this rare phenomenon.

[Acute coronary events among spectators in a soccer stadium]. / Eventos coronarios agudos entre los espectadores de un estadio de fútbol.

The aim of this study was to describe acute coronary syndromes (ACS) with a substantial emotional component in spectators of professional league competition sports events. The study was done at the Barcelona soccer team's home stadium. We recorded cases of ACS that occurred during official competition matches during the 2000-2001 season. A total of 7 episodes of ACS were recorded, 1 involving sudden death, 4 involving acute myocardial infarction and 2 involving angina pectoris. The victim of sudden death had a history of heart disease. The overall risk of ACS was 0.0056 episodes per 100,000 person-hours. We conclude that medical facilities at the stadium facilitated the initial diagnosis of ACS and ensured prompt initial treatment and transport to the reference hospital.

Eventos coronarios agudos entre los espectadores de un estadio de fútbol / Acute coronary events among spectators in a soccer stadium

El objetivo de este estudio fue describir los síndromes coronarios agudos (SCA) que se presentan durante los partidos de competición en un estadio de alto nivel en los que el componente emocional es importante. El estudio se realizó en el estadio del FC Barcelona. Se registraron los casos de SCA que se presentaron durante los partidos de competición oficial en la temporada 2000-2001.Se presentaron 7 episodios de SCA, 1 con muerte súbita,4 con infarto agudo de miocardio y 2 con angina inicial. La confirmación del diagnóstico se realizó en el hospital de referencia. El paciente con muerte súbita tenía antecedente de coronariopatía. El riesgo total de SCA fue de0,0056 episodios por 100.000 personas-hora. En conclusión, disponer de un servicio de asistencia médica en el estadio facilita el diagnóstico de los SCA, asegura su tratamiento inicial precoz y el traslado al hospital de referencia (AU)

The aim of this study was to describe acute coronary syndromes (ACS) with a substantial emotional component in spectators of professional league competition sports events. The study was done at the Barcelona soccer team’s home stadium. We recorded cases of ACS that occurred during official competition matches during the 2000-2001 season. A total of 7 episodes of ACS were recorded, 1 involving sudden death, 4 involving acutemyocardial infarction and 2 involving angina pectoris. The victim of sudden death had a history of heart disease. The overall risk of ACS was 0.0056 episodes per 100 000person-hours. We conclude that medical facilities at the stadium facilitated the initial diagnosis of ACS and ensured prompt initial treatment and transport to the reference hospital (AU)