Prevalence and Prognostic Impact of Stroke in a National Cohort of Infective Endocarditis.

BACKGROUND: Stroke is a common complication of infective endocarditis (IE). Our aim was to describe the prevalence and prognostic impact of stroke in a national prospective cohort of IE. METHODS: Consecutive inclusion at 46 Spanish hospitals between 2008 and 2021. RESULTS: Out of 5667 IE cases, 1125 had acute stroke (19.8%): 811 ischemic strokes (618 cardioembolic strokes, 193 cardioembolic strokes with hemorrhagic transformation, 4 transient ischemic attacks, 3 lacunar infarctions), 125 intracranial hemorrhages, and 29 other neurological complications (cerebral abscesses, encephalitis, meningitis, seizures). Compared to patients without stroke, those with stroke had a similar mean age (69 years) but were more frequently female (68.2% vs. 63.7%, p=0.04) and had a higher incidence of intracardiac complications (35% vs 30%, p=0.01), surgical indication (69.9% vs 65.9%, p=0.001), in-hospital mortality (40.9% vs. 22.0%, p<0.001), and one-year mortality (46.2% vs 27.9%, p<0.001). The following variables were independently associated with stroke: mitral location (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.34-1.8, p<0.001), vascular phenomenon (OR 2.9, 95% CI 2.4-3.6, p=0.0001), acute renal failure (OR 1.2, 95% CI 1.0-1.4, p=0.021), septic shock (OR 1.3, CI 1.1-1.6, p=0.007), sepsis (OR 1.3, CI 1.1-1.6, p=0.005), surgery indicated but not performed (OR 1.4, 95% CI 1.2-1.7, p<0.001), community-acquired IE (OR 1.2, 95% CI 1-1.4, p=0.017), and peripheral embolization (OR 1.6, CI 1.4-1.9, p <0.001). Stroke was an independent predictor of in-hospital (OR 2.1, 95% CI: 1.78-2.51, p<0.001) and one-year mortality (hazard ratio 1.9, 95% CI 1.6-2.5). CONCLUSIONS: One fifth of patients with IE have concomitant stroke. Stroke is associated with mortality.

Analysis of Vascular Smooth Muscle Cells from Thoracic Aortic Aneurysms Reveals DNA Damage and Cell Cycle Arrest as Hallmarks in Bicuspid Aortic Valve Patients.

Thoracic aortic aneurysm (TAA) is mainly sporadic and with higher incidence in the presence of a bicuspid aortic valve (BAV) for unknown reasons. The lack of drug therapy to delay TAA progression lies in the limited knowledge of pathophysiology. We aimed to identify the molecular hallmarks that differentiate the aortic dilatation associated with BAV and tricuspid aortic valve (TAV). Aortic vascular smooth muscle cells (VSMCs) isolated from sporadic TAA patients with BAV or TAV were analyzed by mass spectrometry. DNA oxidative damage assay and cell cycle profiling were performed in three independent cohorts supporting proteomics data. The alteration of secreted proteins was confirmed in plasma. Stress phenotype, oxidative stress, and enhanced DNA damage response (increased S-phase arrest and apoptosis) were found in BAV-TAA patients. The increased levels of plasma C1QTNF5, LAMA2, THSB3, and FAP confirm the enhanced stress in BAV-TAA. Plasma FAP and BGN point to an increased inflammatory condition in TAV. The arterial wall of BAV patients shows a limited capacity to counteract drivers of sporadic TAA. The molecular pathways identified support the need of differential molecular diagnosis and therapeutic approaches for BAV and TAV patients, showing specific markers in plasma which may serve to monitor therapy efficacy.

Spatial Metabolomics Identifies LPC(18:0) and LPA(18:1) in Advanced Atheroma With Translation to Plasma for Cardiovascular Risk Estimation.

BACKGROUND: The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each arterial tunica. We aimed first to identify, in a spatially resolved manner, the specific metabolic changes in plaque, media, adventitia, and cardiac tissue between control and atherosclerotic murine aortas. Second, we assessed their translatability to human tissue and plasma for cardiovascular risk estimation. METHODS: In this observational study, mass spectrometry imaging (MSI) was applied to identify region-specific metabolic differences between atherosclerotic (n=11) and control (n=11) aortas from low-density lipoprotein receptor-deficient mice, via histology-guided virtual microdissection. Early and advanced plaques were compared within the same atherosclerotic animals. Progression metabolites were further analyzed by MSI in 9 human atherosclerotic carotids and by targeted mass spectrometry in human plasma from subjects with elective coronary artery bypass grafting (cardiovascular risk group, n=27) and a control group (n=27). RESULTS: MSI identified 362 local metabolic alterations in atherosclerotic mice (log2 fold-change ≥1.5; P≤0.05). The lipid composition of cardiac tissue is altered during atherosclerosis development and presents a generalized accumulation of glycerophospholipids, except for lysolipids. Lysolipids (among other glycerophospholipids) were found at elevated levels in all 3 arterial layers of atherosclerotic aortas. LPC(18:0) (lysophosphatidylcholine; P=0.024) and LPA(18:1) (lysophosphatidic acid; P=0.025) were found to be significantly elevated in advanced plaques as compared with mouse-matched early plaques. Higher levels of both lipid species were also observed in fibrosis-rich areas of advanced- versus early-stage human samples. They were found to be significantly reduced in human plasma from subjects with elective coronary artery bypass grafting (P<0.001 and P=0.031, respectively), with LPC(18:0) showing significant association with cardiovascular risk (odds ratio, 0.479 [95% CI, 0.225-0.883]; P=0.032) and diagnostic potential (area under the curve, 0.778 [95% CI, 0.638-0.917]). CONCLUSIONS: An altered phospholipid metabolism occurs in atherosclerosis, affecting both the aorta and the adjacent heart tissue. Plaque-progression lipids LPC(18:0) and LPA(18:1), as identified by MSI on tissue, reflect cardiovascular risk in human plasma.

Treatment For Infected Frozen Elephant Trunk Prosthesis Caused by Propionibacterium acnes: A Surgical Challenge

ABSTRACT In this article, we present the case of a 47-year-old man who underwent Bentall-Bono procedure and frozen elephant trunk prosthesis implantation due to severe aortic regurgitation and aortic dilatation with a second-time endovascular stent-graft repair in descending aorta. Over eight years, a subacute graft infection by Propionibacterium acnes was developed, culminating in cardiogenic shock secondary to severe aortic regurgitation due to a complete aortic root dehiscence because of multiple aortic pseudoaneurysms. The patient underwent emergency surgery in which the replacement of the graft by a biological valve tube was performed accompanied by a complete debranching of the three supra-aortic vessels.

Treatment For Infected Frozen Elephant Trunk Prosthesis Caused by Propionibacterium acnes: A Surgical Challenge.

In this article, we present the case of a 47-year-old man who underwent Bentall-Bono procedure and frozen elephant trunk prosthesis implantation due to severe aortic regurgitation and aortic dilatation with a second-time endovascular stent-graft repair in descending aorta. Over eight years, a subacute graft infection by Propionibacterium acnes was developed, culminating in cardiogenic shock secondary to severe aortic regurgitation due to a complete aortic root dehiscence because of multiple aortic pseudoaneurysms. The patient underwent emergency surgery in which the replacement of the graft by a biological valve tube was performed accompanied by a complete debranching of the three supra-aortic vessels.

Outcomes of rapid deployment aortic valve replacement with concomitant cardiac procedures.

Background: Rapid deployment aortic valve replacement (RD-AVR) has been recently introduced with encouraging results. Outcomes of isolated RD-AVR include good hemodynamic profile, facilitation of minimally invasive techniques, and reduction of surgical times. However, role of this prosthesis in concomitant surgery is not well known. Methods: In 2016, we formed a registry to monitor the introduction of this prosthesis, RApid Deployment Aortic Replacement (RADAR). We aim to report mid-term outcomes focusing on patients who had RD-AVR combined with other surgical procedures. Results: Between July 2012 and February 2021, 370 patients were included in this registry (mean age, 75.8±8.0 years; 64.32% male; mean EuroSCORE II, 3.5±2.8). Of these, 128 (34.59%) had concomitant procedures including myocardial revascularization surgery in 69 patients (53.91%), surgery on the ascending aorta in 34 (26.56%), and procedures on other valves in 10 patients (7.81%). There were no significant differences between the isolated AVR and concomitant AVR groups in postoperative complications, in-hospital mortality (4.72% vs. 3.32%, P=0.524), or hemodynamic behavior of these prostheses. Three-year survival was 83.73% and 89.89% in the isolated and concomitant AVR group respectively. There was no difference in survival between the two groups (log-rank test, P=0.4124). Conclusions: Our results support the safety and efficacy of the Edwards INTUITY valve system even in complex aortic valve disease with additional cardiac procedures. RD-AVR could become a useful tool for concomitant surgeries where surgical times are expected to be prolonged.

Coronary pseudoaneurysm after Bentall-Bono intervention: A novel treatment to a rare surgery complication.

We present a rare case of a coronary pseudoaneurysm after a Bentall-Bono procedure. During a routine follow-up computed tomography scan, a pseudoaneurysm located between the aorta and the proximal portion of the right coronary artery was diagnosed. Contrast extravasation was observed with partial thrombosis of the pseudoaneurysm. Coronary angiography and intravascular ultrasound were performed showing the point of contrast extravasation dependent of the right coronary artery in its proximal portion. An angioplasty procedure was performed sealing the pseudoaneurysm with the implantation of a covered stent. After an uneventful postoperative follow-up, the patient was discharged home. Learning objective: The development of a coronary artery pseudoaneurysm (CAP) after complex cardiac surgeries, like Bentall-Bono procedure, could be a life-threatening condition. The possible derived complications of CAP are rupture, compression of surrounding structures, or coronary ischemia.Although surgical approach to a CAP may have an extremely high surgical risk, most of the cases require a complex surgical repair. We describe a novel possible treatment option by angioplasty and sealing of the CAP with the implantation of a covered stent.

Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting.

Atherosclerosis is the predominant pathology associated to premature deaths due to cardiovascular disease. However, early intervention based on a personalized diagnosis of cardiovascular risk is very limited. We have previously identified metabolic alterations during atherosclerosis development in a rabbit model and in subjects suffering from an acute coronary syndrome. Here we aim to identify specific metabolic signatures which may set the basis for novel tools aiding cardiovascular risk diagnosis in clinical practice. In a cohort of subjects with programmed coronary artery bypass grafting (CABG), we have performed liquid chromatography and targeted mass spectrometry analysis in urine and plasma. The role of vascular smooth muscle cells from human aorta (HA-VSMCs) was also investigated by analyzing the intra and extracellular metabolites in response to a pro-atherosclerotic stimulus. Statistically significant variation was considered if p value < 0.05 (Mann-Whitney test). Urinary trimethylamine N-oxide (TMAO), arabitol and spermidine showed higher levels in the CVrisk group compared with a control group; while glutamine and pantothenate showed lower levels. The same trend was found for plasma TMAO and glutamine. Plasma choline, acetylcholine and valine were also decreased in CVrisk group, while pyruvate was found increased. In the secretome of HA-VSMCs, TMAO, pantothenate, glycerophosphocholine, glutathion, spermidine and acetylcholine increased after pro-atherosclerotic stimulus, while secreted glutamine decreased. At intracellular level, TMAO, pantothenate and glycerophosphocholine increased with stimulation. Observed metabolic deregulations pointed to an inflammatory response together with a deregulation of oxidative stress counteraction.

Early renal and vascular damage within the normoalbuminuria condition.

OBJECTIVE: A continuous association between albuminuria and cardiorenal risk exists further below moderately increased albuminuria ranges. If only based in albumin to creatinine ratio (ACR) higher than 30 mg/g, a significant percentage of individuals may be out of the scope for therapeutic management. Despite epidemiological outcomes, the identification of biochemical changes linked to early albuminuria is underexplored, and normoalbuminuric individuals are usually considered at no risk in clinical practice. Here, we aimed to identify early molecular alterations behind albuminuria development. METHODS: Hypertensive patients under renin-angiotensin system (RAS) suppression were classified as control, (ACR < 10 mg/g) or high-normal (ACR = 10-30 mg/g). Urinary protein alterations were quantified and confirmed by untargeted and targeted mass spectrometry. Coordinated protein responses with biological significance in albuminuria development were investigated. Immunohistochemistry assays were performed in human kidney and arterial tissue to in situ evaluate the associated damage. RESULTS: A total of 2663 identified proteins reflect inflammation, immune response, ion transport and lipids metabolism (P value ≤ 0.01). A1AT, VTDB and KNG1 varied in high-normal individuals (P value < 0.05), correlated with ACR and associated with the high-normal condition (odds ratio of 20.76, 6.00 and 7.04 were found, respectively (P value < 0.001)). After 12 months, protein variations persist and aggravate in progressors to moderately increased albuminuria. At tissue level, differential protein expression was found in kidney from individuals with moderately increased albuminuria and atherosclerotic aortas for the three proteins, confirming their capacity to reflect subclinical organ damage. CONCLUSION: Early renal and vascular damage is molecularly evidenced within the normoalbuminuria condition.

Two giant sinus of Valsalva pseudoaneurysms as a casual finding.

BACKGROUND: Pseudoaneurysms of the sinus of Valsalva are infrequent cardiac pathologies that usually involve a single sinus. MATERIAL AND METHODS: We present a case of a 63-year-old male who was diagnosed with ascending aortic aneurysm during a routine echocardiogram. CONCLUSION: We report here a patient with giant pseudoaneurysms of two sinuses of Valsalva who successfully underwent a sinus of Valsalva reconstruction.

Non-syndromic thoracic aortic aneurysm: cellular and molecular insights.

Thoracic aortic aneurysm (TAA) develops silently and asymptomatically and is a major cause of mortality. TAA prevalence is greatly underestimated, it is usually diagnosed incidentally, and its treatment consists mainly of prophylactic surgery based on the aortic diameter. The lack of effective drugs and biological markers to identify and stratify TAAs by risk before visible symptoms results from scant knowledge of its pathophysiological mechanisms. Here we integrate the structural impairment affecting non-syndromic non-familial TAA with the main cellular and molecular changes described so far and consider how these changes are interconnected through specific pathways. The ultimate goal is to define much-needed novel markers of TAA, and so the potential of previously identified molecules to aid in early diagnosis/prognosis is also discussed. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Analysis of urinary exosomal metabolites identifies cardiovascular risk signatures with added value to urine analysis.

BACKGROUND: Subclinical atherosclerosis may result in fatal cardiovascular (CV) events, but the underlying mechanisms and molecular players leading to disease are not entirely understood. Thus, novel approaches capable of identifying the factors involved in pathological progression and providing a better understanding of the subjacent mechanisms are needed. Extracellular vesicles (EVs) have been shown to have numerous biological functions, and their metabolome has recently generated interest as a source of novel biomarkers. The metabolic content of the exosomes has been so far unexplored in cardiovascular disease (CVD), and here, we developed an analytical strategy aimed at probing urinary exosomal metabolite content and its association to CV risk. RESULTS: Direct analysis of the exosomes without metabolite extraction was evaluated by high-resolution magic angle spinning (1H HR-MAS). Other two methodologies for the analysis of exosomal metabolites by 1H NMR were set up, based on methanol or organic solvents sequential extraction. The three methods were compared in terms of the number of detected signals and signal to noise ratio (S/N). The methanol method was applied to identify altered metabolites in the urinary exosomes of subjects with programmed coronary artery by-pass grafting (CABG) versus a control group. Target mass spectrometry (MS) was also performed for differential analysis. The clinical performance of exosomal metabolites of interest in CVD was investigated, and the added value of the exosomes compared to urine analysis was evaluated. Based on S/N ratio, simplicity, reproducibility, and quality of the spectrum, the methanol method was chosen for the study in CVD. A cardiometabolic signature composed by 4-aminohippuric acid, N-1-methylnicotinamide, and citric acid was identified in urinary exosomes. Directly in urine, 4-aminohippuric acid and citric acid do not show variation between groups and changes in N-1-methylnicotinamide are less pronounced, proving the added value of exosomes. CONCLUSIONS: We set up a novel methodology to analyze metabolic alterations in urinary exosomes and identified a cardiometabolic signature in these microvesicles. This study constitutes the first evidence of a role for the exosomal metabolism in CVD and demonstrates the possibility to evaluate the urinary exosomal metabolic content by NMR and MS.

Severe mitral regurgitation due to an extraordinary heart defect.

A previously non-described cause of mitral regurgitation is presented. An asymptomatic 50-year old male who was casually diagnosed of mitral valve Barlow's disease underwent cardiac surgery due to severe mitral regurgitation. In the operating theatre, a longitudinal fissure of 1.5-2.0 cm length, along the posterior mitral leaflet, was found responsible for the insufficiency. This defect had features of a potential congenital origin and it was successfully repaired with direct suture. Whether it is an atypical mitral cleft, a variation of Barlow's morphology spectrum or a new congenital heart defect remains unclear.

Cytoskeleton deregulation and impairment in amino acids and energy metabolism in early atherosclerosis at aortic tissue with reflection in plasma.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death globally, being atherosclerosis the main cause. Main risk factors are known and current effort is very much dedicated to improve prevention. However, the asymptomatic and silent course of atherosclerosis hampers an accurate and individualized risk evaluation. OBJECTIVES: Here we investigate subjacent molecular changes taking place in arterial tissue which can be ultimately translated in a measurable fingerprint in plasma. METHODS: First, we applied a combined approach to find out main molecular alterations at protein and metabolite level in response to early atherosclerosis development in a rabbit model. A potential reflection of all these alterations observed in aortic tissue was investigated in rabbit plasma and further analyzed in a translational study in human plasma from 62 individuals. RESULTS: Data link the structural remodeling taking place in atherosclerotic arteries in terms of loss of contractile properties and favored cellular migration, with an up-regulation of integrin linked kinase, tropomyosin isoform 2 and capping protein gelsolin-like, and a down-regulation of vinculin. A molecular response to oxidative stress is evidenced, involving changes in the glucose metabolism enzymes pyruvate kinase (PKM) and phosphoglycerate kinase (PGK), and pyruvate. Up-regulation of aspartate connects different changes observed in amino acid metabolism and, additionally, alterations in the phosphatidylcholine route of the glycerophospholipid metabolism were found. CONCLUSIONS: A specific molecular marker panel composed by PKM, valine and pyruvate is shown here linked to cardiovascular risk.

Combined endocardiectomy and bidirectional glenn shunt for right ventricular endomyocardial fibrosis.

We report the case of a young African woman with a history of right ventricular failure. Image studies suggested endomyocardial fibrosis affecting only the right side of the heart. The right ventricle was extremely small and restricted. The surgical approach entailed endocardectomy and a bidirectional cavopulmonary shunt to improve weaning off bypass and postoperative recovery, both of which were successfully achieved.

Successful removal of a floating thrombus in ascending aorta.

Free-floating thrombus in ascending aorta is a rare cause of peripheral embolism with potentially fatal consequences. We report the case of a young patient with syncope and sudden lumbar pain. Computed tomographic scan revealed a large pedunculated floating mass attached to the posterior wall of the ascending aorta, probably responsible of renal embolic infarction; transthoracic echocardiography confirmed the diagnosis. Surgery was urgently performed. The thrombus was excised, and was not related to atherosclerotic disease of the aortic wall. We conclude that once diagnosis is clear, urgent surgery must be considered to avoid any further embolic complications.

El desajuste paciente-prótesis moderado no aumenta de modo independiente la mortalidad a 30 días tras la sustitución aislada de válvula aórtica / Moderate patient-prosthesis mismatch has no independent effect on 30-day mortality after isolated aortic valve replacement

Introducción y objetivos. La cuestión de si un desajuste paciente-prótesis moderado tras la sustitución aislada de la válvula aórtica puede aumentar la mortalidad a 30 días continúa abierta. El objetivo de este estudio es verificar si un desajuste moderado es un factor predictivo de carácter independiente respecto a la mortalidad temprana total o cardiaca tras la sustitución valvular aórtica. Métodos. Formaron la población del estudio 272 adultos (mediana de edad, 72 años; intervalo intercuartílico, 66-76 años) a los que se practicaron intervenciones de sustitución aislada de la válvula aórtica. Se consideró que había un desajuste moderado si el área efectiva del orificio indexada que se preveía era ≤ 0,85 y > 0,65 cm2/m2. Se consideró que había un desajuste grave si el área efectiva del orificio indexada prevista era ≤ 0,65 cm2/m2. El seguimiento a 30 días respecto a la supervivencia se cumplió en el 100% de los casos. Resultados. Se detectó un desajuste moderado en el 37,9% de los pacientes. No hubo ningún caso de desajuste grave. Un análisis multivariable identificó los siguientes factores predictivos independientes para la mortalidad total a 30 días: fracción de eyección ventricular izquierda < 50% (p = 0,03) y edad (p = 0,01). Las mismas variables pero con un mayor nivel de significación estadística eran factores predictivos de la supervivencia por causas cardiacas a 30 días: fracción de eyección ventricular izquierda < 50% (p = 0,006) y edad (p = 0,008). Nuestro análisis no identificó que el desajuste moderado fuera un factor predictivo de la mortalidad total o cardiaca a 30 días en nuestra muestra de estudio. Conclusiones. Nuestros resultados indican que la evidencia de que la implantación de la prótesis del tamaño medido en un anillo aórtico pequeño compromete la supervivencia del paciente está lejos de ser clara cuando el desajuste paciente-prótesis es moderado (AU)

Introduction and objectives. It is still not clear whether the presence of a moderate patient-prosthesis mismatch after isolated aortic valve replacement can increase 30-day mortality. The aim of this study was to determine whether a moderate mismatch is an independent predictor of early global or cardiac mortality after aortic valve replacement. Methods. The study involved 272 adult patients (median age, 72 years; interquartile range, 66-76 years) undergoing isolated aortic valve replacement. Moderate mismatch was considered to be present if the projected indexed effective orifice area was ≤0.85 and >0.65 cm2/m2. Severe mismatch was present if the projected indexed effective orifice area was ≤0.65 cm2/m2. Follow-up to assess survival at 30 days was carried out in 100% of patients. Results. Moderate mismatch was observed in 37.9% of patients. None had a severe mismatch. Multivariate analysis identified the following independent predictors of global mortality at 30 days: left ventricular ejection fraction <50 p=".01)." and age the same variables were identified as predictors of 30-day cardiac survival but at a higher level statistical significance: left ventricular ejection fraction <50 p=".008)." and age the analysis did not identify moderate mismatch as a predictor of global or cardiac 30-day mortality in our study population conclusions findings indicate that evidence inserting prosthesis measured size small aortic annulus compromises patient s survival is far from clear when patient-prosthesis (AU)

[Moderate patient-prosthesis mismatch has no independent effect on 30-day mortality after isolated aortic valve replacement]. / El desajuste paciente-prótesis moderado no aumenta de modo independiente la mortalidad a 30 días tras la sustitución aislada de válvula aórtica.

INTRODUCTION AND OBJECTIVES: It is still not clear whether the presence of a moderate patient-prosthesis mismatch after isolated aortic valve replacement can increase 30-day mortality. The aim of this study was to determine whether a moderate mismatch is an independent predictor of early global or cardiac mortality after aortic valve replacement. METHODS: The study involved 272 adult patients (median age, 72 years; interquartile range, 66-76 years) undergoing isolated aortic valve replacement. Moderate mismatch was considered to be present if the projected indexed effective orifice area was < or =0.85 and >0.65 cm2/m2. Severe mismatch was present if the projected indexed effective orifice area was < or =0.65 cm2/m2. Follow-up to assess survival at 30 days was carried out in 100% of patients. RESULTS: Moderate mismatch was observed in 37.9% of patients. None had a severe mismatch. Multivariate analysis identified the following independent predictors of global mortality at 30 days: left ventricular ejection fraction <50% (P=.03) and age (P=.01). The same variables were identified as predictors of 30-day cardiac survival, but at a higher level of statistical significance: left ventricular ejection fraction <50% (P=.006) and age (P=.008). The analysis did not identify moderate mismatch as a predictor of global or cardiac 30-day mortality in our study population. CONCLUSIONS: Our findings indicate that the evidence that inserting a prosthesis of the measured size in a small aortic annulus compromises the patient's survival is far from clear when the patient-prosthesis mismatch is moderate.