Different prognostic significance of coronary artery and aortic valve calcium in patients with chest pain.

OBJECTIVES: Coronary artery calcification (CorCa) identifies high cardiovascular risk in the general population. In this setting, aortic valve calcification (AoCa) showed contradictory results. Our goal has been to assess the prognostic power of CorCa and AoCa in patients with chest pain who underwent an ECG-gated cardiac multidetector CT (cardiac-MDCT). METHODS: A total of 528 patients without previous known coronary artery disease, with chest pain who underwent a cardiac-MDCT multidetector, were retrospectively recruited. The primary endpoint included death, acute coronary syndrome, stroke, and heart failure. RESULTS: A total of 61 patients (11.6%) had an event during a mean follow-up of almost 6 years (5.95 ± 2.98). The most frequent event was acute coronary syndrome (6.4%). Total mortality was 4.5%. Patients with CorCa > 0 had more events than those without CorCa (17.3% versus 4.3%; p < 0.001). Likewise, when only patients without AoCa were considered (n = 118), clinical events were more frequent in those with CorCa (12.7% versus 3.6%; p = 0.004). After excluding patients with coronary artery disease, events were more frequent in those with CorCa (12.6% versus 4.3%; p = 0.004). The higher the Agatston score, the more frequent the events. Patients with AoCa > 0 had more events than those without (16.5% versus 7.3%; p < 0.001), but in patients without CorCa, no difference in events was seen (6.2% versus 3.6%; p = 0.471). A Cox regression analysis showed age, smoking, prior stroke, and CorCa but not AoCa to be independently related to events. CONCLUSIONS: In summary, CorCa, but not AoCa, is related to cardiovascular events in patients with chest pain who undergo a cardiac-MDCT. CLINICAL RELEVANCE STATEMENT: We show that coronary artery calcification, but not aortic valve calcification, detected in a coronary CT scan is tightly related to cardiovascular events. Although this is a message already shown by other groups in the general population, we do believe that this work is unique because it is restricted to patients with chest pain sent to coronary CT. In other words, our work deals with what we face in our routine everyday practice. KEY POINTS: • The presence and the amount of coronary artery calcification are associated with cardiovascular events in patients with chest pain. • Aortic valve calcification is not associated with cardiovascular events in patients with chest pain.

Clinical characteristics and outcomes of aortic prosthetic valve endocarditis: comparison between transcatheter and surgical bioprostheses.

PURPOSE: Most data regarding infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) comes from TAVI registries, rather than IE dedicated cohorts. The objective of our study was to compare the clinical and microbiological profile, imaging features and outcomes of patients with IE after SAVR with a biological prosthetic valve (IE-SAVR) and IE after TAVI (IE-TAVI) from 6 centres with an Endocarditis Team (ET) and broad experience in IE. METHODS: Retrospective analysis of prospectively collected data. From the time of first TAVI implantation in each centre to March 2021, all consecutive patients admitted for IE-SAVR or IE-TAVI were prospectively enrolled. Follow-up was monitored during admission and at 12 months after discharge. RESULTS: 169 patients with IE-SAVR and 41 with IE-TAVI were analysed. Early episodes were more frequent among IE-TAVI. Clinical course during hospitalization was similar in both groups, except for a higher incidence of atrioventricular block in IE-SAVR. The most frequently causative microorganisms were S. epidermidis, Enterococcus spp. and S. aureus in both groups. Periannular complications were more frequent in IE-SAVR. Cardiac surgery was performed in 53.6% of IE-SAVR and 7.3% of IE-TAVI (p=0.001), despite up to 54.8% of IE-TAVI patients had an indication. No differences were observed about death during hospitalization (32.7% vs 35.0%), and at 1-year follow-up (41.8% vs 37.5%), regardless of whether the patient underwent surgery or not. CONCLUSION: Patients with IE-TAVI had a higher incidence of early prosthetic valve IE. Compared to IE-SAVR, IE-TAVI patients underwent cardiac surgery much less frequently, despite having surgical indications. However, in-hospital and 1-year mortality rate was similar between both groups.

Contemporary comparison of infective endocarditis caused by Candida albicans and Candida parapsilosis: a cohort study.

Among 1655 consecutive patients with infective endocarditis treated from 1998 to 2020 in three tertiary care centres, 16 were caused by Candida albicans (CAIE, n = 8) and Candida parapsilosis (CPIE, n = 8). Compared to CAIE, CPIE were more frequently community-acquired. Prosthetic valve involvement was remarkably more common among patients with CPIE. CPIE cases presented a higher rate of positive blood cultures at admission, persistently positive blood cultures after antifungals initiation and positive valve cultures. All patients but four underwent cardiac surgery. Urgent surgery was more frequently performed in CPIE. No differences regarding in-hospital mortality were documented, even after adjusting for therapeutic management.

Dyslipidemia and Inflammation as Hallmarks of Oxidative Stress in COVID-19: A Follow-Up Study.

Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not well known. This study aimed to comprehensively evaluate their possible association during the evolution of COVID-19. This is an observational prospective study. The primary endpoint was to analyze the association between lipid peroxidation, lipid, and inflammatory profiles in COVID-19 patients. A multivariate regression analysis was employed. The secondary endpoint included the long-term follow-up of lipid profiles. COVID-19 patients presented significantly lower values in their lipid profile (total, low, and high-density lipoprotein cholesterol) with greater oxidative stress and inflammatory response compared to the healthy controls. Lipid peroxidation was the unique oxidative parameter with a significant association with the total cholesterol (OR: 0.982; 95% CI: 0.969-0.996; p = 0.012), IL1-RA (OR: 0.999; 95% CI: 0.998-0.999; p = 0.021) IL-6 (OR: 1.062; 95% CI: 1.017-1.110; p = 0.007), IL-7 (OR: 0.653; 95% CI: 0.433-0.986; p = 0.042) and IL-17 (OR: 1.098; 95% CI: 1.010-1.193; p = 0.028). Lipid abnormalities recovered after the initial insult during long-term follow-up (IQR 514 days); however, those with high LPO levels at hospital admission had, during long-term follow-up, an atherogenic lipid profile. Our study suggests that oxidative stress in COVID-19 is associated with derangements of the lipid profile and inflammation. Survivors experienced a recovery in their lipid profiles during long-term follow-up, but those with stronger oxidative responses had an atherogenic lipid profile.

Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19.

BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19). METHODS AND RESULTS: We performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein >88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia <1000 (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up. CONCLUSION: Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.

Interferons Are Pro-Inflammatory Cytokines in Sheared-Stressed Human Aortic Valve Endothelial Cells.

Calcific aortic valve disease (CAVD) is an athero-inflammatory process. Growing evidence supports the inflammation-driven calcification model, mediated by cytokines such as interferons (IFNs) and tumor necrosis factor (TNF)-α. Our goal was investigating IFNs' effects in human aortic valve endothelial cells (VEC) and the potential differences between aortic (aVEC) and ventricular (vVEC) side cells. The endothelial phenotype was analyzed by Western blot, qPCR, ELISA, monocyte adhesion, and migration assays. In mixed VEC populations, IFNs promoted the activation of signal transducers and activators of transcription-1 and nuclear factor-κB, and the subsequent up-regulation of pro-inflammatory molecules. Side-specific VEC were activated with IFN-γ and TNF-α in an orbital shaker flow system. TNF-α, but not IFN-γ, induced hypoxia-inducible factor (HIF)-1α stabilization or endothelial nitric oxide synthase downregulation. Additionally, IFN-γ inhibited TNF-α-induced migration of aVEC. Also, IFN-γ triggered cytokine secretion and adhesion molecule expression in aVEC and vVEC. Finally, aVEC were more prone to cytokine-mediated monocyte adhesion under multiaxial flow conditions as compared with uniaxial flow. In conclusion, IFNs promote inflammation and reduce TNF-α-mediated migration in human VEC. Moreover, monocyte adhesion was higher in inflamed aVEC sheared under multiaxial flow, which may be relevant to understanding the initial stages of CAVD.

Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With ST-Segment Elevation Myocardial Infarction and Left Ventricular Dysfunction.

RATIONALE: Allogeneic cardiac stem cells (AlloCSC-01) have shown protective, immunoregulatory, and regenerative properties with a robust safety profile in large animal models of heart disease. OBJECTIVE: To investigate the safety and feasibility of early administration of AlloCSC-01 in patients with ST-segment-elevation myocardial infarction. METHODS AND RESULTS: CAREMI (Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With STEMI and Left Ventricular Dysfunction) was a phase I/II multicenter, randomized, double-blind, placebo-controlled trial in patients with ST-segment-elevation myocardial infarction, left ventricular ejection fraction ≤45%, and infarct size ≥25% of left ventricular mass by cardiac magnetic resonance, who were randomized (2:1) to receive AlloCSC-01 or placebo through the intracoronary route at days 5 to 7. The primary end point was safety and included all-cause death and major adverse cardiac events at 30 days (all-cause death, reinfarction, hospitalization because of heart failure, sustained ventricular tachycardia, ventricular fibrillation, and stroke). Secondary safety end points included major adverse cardiac events at 6 and 12 months, adverse events, and immunologic surveillance. Secondary exploratory efficacy end points were changes in infarct size (percentage of left ventricular mass) and indices of ventricular remodeling by magnetic resonance at 12 months. Forty-nine patients were included (92% male, 55±11 years), 33 randomized to AlloCSC-01 and 16 to placebo. No deaths or major adverse cardiac events were reported at 12 months. One severe adverse events in each group was considered possibly related to study treatment (allergic dermatitis and rash). AlloCSC-01 elicited low levels of donor-specific antibodies in 2 patients. No immune-related adverse events were found, and no differences between groups were observed in magnetic resonance-based efficacy parameters at 12 months. The estimated treatment effect of AlloCSC-01 on the absolute change from baseline in infarct size was -2.3% (95% confidence interval, -6.5% to 1.9%). CONCLUSIONS: AlloCSC-01 can be safely administered in ST-segment-elevation myocardial infarction patients with left ventricular dysfunction early after revascularization. Low immunogenicity and absence of immune-mediated events will facilitate adequately powered studies to demonstrate their clinical efficacy in this setting. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02439398.

Short-course antibiotic regimen compared to conventional antibiotic treatment for gram-positive cocci infective endocarditis: randomized clinical trial (SATIE).

BACKGROUND: Most serious complications of infective endocarditis (IE) appear in the so-called "critical phase" of the disease, which represents the first days after diagnosis. The majority of patients overcoming the acute phase has a favorable outcome, yet they remain hospitalized for a long period of time mainly to complete antibiotic therapy. The major hypothesis of this trial is that in patients with clinically stable IE and adequate response to antibiotic treatment, without signs of persistent infection, periannular complications or metastatic foci, a shorter antibiotic time period would be as efficient and safe as the classic 4 to 6 weeks antibiotic regimen. METHODS: Multicenter, prospective, randomized, controlled open-label, phase IV clinical trial with a non-inferiority design to evaluate the efficacy of a short course (2 weeks) of parenteral antibiotic therapy compared with conventional antibiotic therapy (4-6 weeks). SAMPLE: patients with IE caused by gram-positive cocci, having received at least 10 days of conventional antibiotic treatment, and at least 7 days after surgery when indicated, without clinical, analytical, microbiological or echocardiographic signs of persistent infection. Estimated sample size: 298 patients. INTERVENTION: Control group: standard duration antibiotic therapy, (4 to 6 weeks) according to ESC guidelines recommendations. Experimental group: short-course antibiotic therapy for 2 weeks. The incidence of the primary composite endpoint of all-cause mortality, unplanned cardiac surgery, symptomatic embolisms and relapses within 6 months after the inclusion in the study will be prospectively registered and compared. CONCLUSIONS: SATIE will investigate whether a two weeks short-course of intravenous antibiotics in patients with IE caused by gram-positive cocci, without signs of persistent infection, is not inferior in safety and efficacy to conventional antibiotic treatment (4-6 weeks). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04222257 (January 7, 2020). EudraCT 2019-003358-10.

Impact of Valve Culture in the Prognosis of Active Left-sided Infective Endocarditis.

BACKGROUND: The culture of removed cardiac tissues during cardiac surgery of left-sided infective endocarditis (LSIE) helps to guide antibiotic treatment. Nevertheless, the prognostic information of a positive valve culture has never been explored. METHODS: Among 1078 cases of LSIE consecutively diagnosed in 3 tertiary centers, we selected patients with positive blood cultures who underwent surgery during the active period of infection and in whom surgical biological tissues were cultured (n = 429). According to microbiological results, we constructed 2 groups: negative valve culture (n=218) and concordant positive valve culture (CPVC) (n=118). We compared their main features and performed a multivariable analysis of in-hospital mortality. RESULTS: Patients with CPVC presented more nosocomial origin (32% vs 20%, P = .014), more septic shock (21% vs 11%, P = .007), and higher Risk-E score (29% vs 21%, P = .023). Their in-hospital mortality was higher (35% vs 19%, P = .001), despite an earlier surgery (3 vs 11 days from antibiotic initiation, P < .001). Staphylococcus species (61% vs 42%, P = .001) and Enterococcus species (20% vs 9%, P = .002) were more frequent in the CPVC group, whereas Streptococcus species were less frequent (14% vs 42%, P < .001). Independent predictors for in-hospital mortality were renal failure (odds ratio [OR], 2.6 [95% confidence interval {CI}, 1.5-4.4]), prosthesis (OR, 1.9 [95% CI, 1.1-3.5]), Staphylococcus aureus (OR, 1.8 [95% CI, 1.02-3.3]), and CPVC (OR, 2.3 [95% CI, 1.4-3.9]). CONCLUSIONS: Valve culture in patients with active LSIE is an independent predictor of in-hospital mortality.

Calcification Induced by Type I Interferon in Human Aortic Valve Interstitial Cells Is Larger in Males and Blunted by a Janus Kinase Inhibitor.

Objective- Calcific aortic valve disease is the most prevalent valvulopathy in Western countries. An unanticipated pathogenetic clue involving IFN (interferon) was disclosed by the finding of constitutive type I IFN activity associated with aortic valve calcification in children with the atypical Singleton-Merten syndrome. On this basis, the role of type I IFN on inflammation and calcification in human aortic valve interstitial cells (AVIC) was examined. Approach and Results- IFN-α was weakly proinflammatory but potentiated lipopolysaccharide-mediated activation of NF (nuclear factor)-κB and the ensuing induction of proinflammatory molecules in human AVIC. Stimulation with IFN-α and in combination with lipopolysaccharide promoted osteoblast-like differentiation characterized by increased osteoblastic gene expression, BMP (bone morphogenetic protein)-2 secretion, and ectopic phosphatase activity. Sex differences were observed. Likewise, IFN-α treatment of human AVICs in osteogenic medium resulted in increased formation of calcific nodules. Strikingly, IFN-α-mediated calcification was significantly higher in AVICs from males, and was blocked by tofacitinib, a JAK (Janus kinase) inhibitor, and by a BMP antagonist. A female-specific protective mechanism involving the activation of PI3K-Akt (protein kinase B) pathways and cell survival was disclosed. Females exhibited higher levels of BCL2 in valve cells and tissues and lower annexin V staining on cell stimulation. Conclusions- IFN-α acts as a proinflammatory and pro-osteogenic cytokine in AVICs, its effects being potentiated by lipopolysaccharide. Results also uncovered sex differences with lower responses in female AVICs and sex-specific mechanisms involving apoptosis. Data point to JAK/STAT (signal transducer and activator of transcription) system as a potential therapeutic target for calcific aortic valve disease.

Clinical Profile and Prognosis of Patients with Left-Sided Infective Endocarditis with Surgical Indication Who Are Not Operated.

Approximately a quarter of patients with infective endocarditis (IE) who have surgical indication only receive antibiotic treatment. Their short-term prognosis is dismal. We aimed to describe the characteristics of this group of patients to evaluate the mortality according to the cause of rejection and type of surgical indication and to analyze their prognostic factors of mortality. From 2005 to 2022, 1105 patients with definite left-sided IE were consecutively attended in three tertiary hospitals. Of them, 912 (82.5%) had formal surgical indication according to the most recent European Guidelines available in each period of the study and 303 (33%) only received medical treatment. These were older, had more comorbidities and higher in-hospital (46% vs. 24%; p < 0.001) and one year mortality (57.1% vs. 27.6%; p < 0.001) than operated patients. The main reason for surgical rejection was high surgical risk (57.1%) and the highest mortality when the cause were severe neurological conditions (76%). When the endocarditis team took the decision not to operate (25.5% of the patients), in-hospital (7%) and one-year mortality (17%) were low. In-hospital mortality associated with each surgical indication was 67% in heart failure, 53% in uncontrolled infection and 45% in prevention of embolisms (p < 0.001). Heart failure (OR: 2.26 CI95%: 1.29-3.96; p = 0.005), Staphylococcus aureus (OR: 3.17; CI95%: 1.72-5.86; p < 0.001) and persistent infection (OR: 5.07 CI95%: 2.85-9.03) are the independent risk factors of in-hospital mortality. One third of the patients with left-sided IE and formal surgical indication are rejected for surgery. In-hospital mortality is very high, especially when heart failure is the indication for surgery and when severe neurological conditions the reason for rejection. Short term prognosis of patients rejected by a specialized endocarditis team is favorable.

Evolution and Prognostic Significance of Patient-Reported Symptoms After Intervention in Severe Aortic Stenosis.

OBJECTIVE: To describe the evolution of symptoms in patients with symptomatic severe aortic stenosis (sSAS) undergoing valve replacement, the predictors of the persistence of these symptoms, and their prognostic significance. The evolution of symptoms after intervention in sSAS and their association with outcome are unknown. PATIENTS AND METHODS: Data from patients with sSAS who underwent intervention were collected. All-cause mortality and cardiovascular mortality were considered events. The evolution of symptoms and their association with events were studied. RESULTS: In this study, 451 consecutive patients with sSAS and no other valvular or coronary disease who were alive 30 days after intervention were included. Before valve replacement, 133 of the 451 patients (29.5%) had congestive heart failure requiring hospitalization. Of the remaining 318 patients, 287 (90.2%) had dyspnea on effort, 129 (40.6%) had angina, and 59 had syncope (18.6%). Symptoms disappeared after intervention in 192 of the 451 patients (42.6%) and remained in 259 (57.4%): 193 dyspnea, 9 angina, 17 syncope, and 60 admission for heart failure. Syncope on effort persisted in 4 of 33 patients (12.1%) and at rest in 11 of 20 (55.0%; P<.001). Age, body mass index, previous admission for heart failure, and chronic obstructive pulmonary disease were independently related to persistence of symptoms. Over a median follow-up of 56 months in our cohort of 451 patients, 129 deaths were registered (28.6%), 40 of which were cardiovascular (8.9%). Age, chronic obstructive pulmonary disease, chronic kidney disease, atrial fibrillation, heart failure, and persistence of symptoms were independently associated with all-cause mortality. CONCLUSION: Symptoms attributed to SAS remain after intervention in a high proportion of patients, particularly dyspnea on effort and syncope at rest. The persistence of symptoms after intervention identifies patients with poor outcome.

Bicaval TricValve Implantation in Patients With Severe Symptomatic Tricuspid Regurgitation: 1-Year Follow-Up Outcomes.

BACKGROUND: Several orthotopic transcatheter strategies have been developed to treat severe tricuspid regurgitation (TR); however, many patients are deemed unsuitable. Caval valve implantation with the TricValve system addresses this unmet need. OBJECTIVES: This study sought to determine the impact of TricValve on systemic congestion and quality of life (QOL) at 1 year. METHODS: The TRICUS (Safety and Efficacy of the TricValve® Transcatheter Bicaval Valves System in the Superior and Inferior Vena Cava in Patients With Severe Tricuspid Regurgitation) and TRICUS EURO studies were prospective, nonblinded, nonrandomized, single-arm trials representing the early-in-man experience of the TricValve system in NYHA functional class III or IV severe TR patients, optimally medicated and ineligible for open heart surgery, with significant caval backflow. The primary endpoint was QOL metrics and functional status. The 1-year results of the combined cohort are described here. RESULTS: Forty-four patients were included. Mean age was 76.2 ± 7.5 years, 81.0% were women, and the TRISCORE (risk score model for isolated tricuspid valve surgery) was 5.3 ± 1.3. Clinical improvement at 1 year was achieved in 42 (95.5%) patients, measured by (at least 1 of) an increase in ≥15 points from baseline in 12-item Kansas City Cardiomyopathy Questionnaire score, improvement to NYHA functional class to I or II, or an increase ≥40 m in the 6-minute walk test. There were 3 (6.8%) deaths at 1-year follow-up (1 cardiovascular), and the heart failure rehospitalization rate was 29.5%. Stent fracture, conduction system disturbances, or clinically significant leaflet thrombosis were not detected. Abolished hepatic vein backflow was achieved and persisted in 63.8% of the patients, contributing towards a reduction in congestive symptoms, N-terminal pro-B-type natriuretic peptide levels (P = 0.032), and diuretic treatment. CONCLUSIONS: Caval valve implantation with the TricValve system associated with meaningful 1-year clinical improvements in terms of QOL along with relatively low mortality rates. (TRICUS Study - Safety and Efficacy of the TricValve® Device; NCT03723239).

Measurement of vegetations in infective endocarditis: An inaccurate method to decide the therapeutical approach.

BACKGROUND: The European Society of Cardiology and American Heart Association guidelines give a central role to the maximal vegetation diameter in the indication for surgery to prevent embolism in left sided infective endocarditis. Vegetation measuring is likely to be inaccurate. The hypothesis herein, is that the vegetation diameter is not an appropriate surgical criterion given the variability of its measurement. METHODS: Two trained echocardiographers independently measured the maximal vegetation diameter by transesophageal echocardiogram of 76 vegetations in 67 consecutive patients with definite infective endocarditis in an off-line workstation. The interobserver variability was calculated by the interclass correlation coefficient. The relationship between the strength of agreement for the cut-off points of 10 and 15 mm was also calculated. Finally, the number of patients whose surgical indication would have changed depending on which operator measured the vegetation was evaluated. RESULTS: Interobserver interclass correlation coefficient in the measurement of the maximal longitudinal diameter of the vegetations was 0.757 (0.642-0.839). The strength of agreement of the interobserver analysis for the cut-off point of 10 mm was 0.533 (0.327-0.759). For the cut-off point of 15 mm it was 0.475 (0.270-0.679). If heart failure or uncontrolled infections had been absent, the surgical indication would have changed in a total of 33 patients (33/76; 43%) depending on which operator measured the vegetation. CONCLUSIONS: The variability in the measurements of the maximal longitudinal diameter by transesophageal echocardiogram is high. Surgical indications based on the cut-off points recommended by the international guidelines should be revised.

Impact of transfer to reference centres and surgical timing on the prognosis of surgically treated patients with infective endocarditis: a prospective multi-centre cohort study.

OBJECTIVES: To compare outcomes in patients with infective endocarditis (IE) first treated in secondary hospitals and then transferred to reference centres for surgery with those in patients diagnosed in reference centres, and to evaluate the impact of surgery timing on prognosis. METHODS: Analysis of a prospective cohort of patients with active IE admitted to three reference centres between 1996 and 2022 who underwent cardiac surgery in the first month after diagnosis. Multi-variable analysis was performed to evaluate the impact of transfer to reference centres and time to surgery on 30-day mortality. Adjusted ORs with 95% CIs were calculated. RESULTS: Amongst 703 patients operated on for IE, 385 (54.8%) were referred cases. All-cause 30-day mortality did not differ significantly between referred patients and those diagnosed at reference centres (102/385 [26.5%] vs. 78/385 [24.5%], respectively; p 0.552). Variables independently associated with 30-day mortality in the whole cohort were diabetes (OR, 1.76 [95% CI, 1.15-2.69]), chronic kidney disease (OR, 1.83 [95% CI, 1.08-3.10]), Staphylococcus aureus (OR, 1.88 [95% CI, 1.18-2.98]), septic shock (OR, 2.76 [95% CI, 1.67-4.57]), heart failure (OR, 1.41 [95% CI, 0.85-2.11]), acute renal failure before surgery (OR, 1.76 [95% CI, 1.15-2.69]), and the interaction between transfer to reference centres and surgery timing (OR, 1.18 [95% CI, 1.03-1.35]). Amidst referred patients, time from diagnosis to surgery longer than a week was independently associated with 30-day mortality (OR, 2.19 [95% CI, 1.30-3.69]; p 0.003). CONCLUSION: Among referred patients, surgery performed >7 days after diagnosis was associated with two-fold higher 30-day mortality.

Sex Differences in Clinical Outcomes after Aortic Valve Intervention for Isolated Severe Aortic Stenosis.

There are known pathophysiologic and clinical differences according to sex in patients with aortic stenosis (AS). To evaluate if these differences persist after valve replacement, we conducted an observational study including 451 patients with symptomatic AS who survived aortic valve intervention (AVI) in two centers. Clinical data and mortality were evaluated at a mean follow-up of 5 years. 56% of patients were women. At baseline, women were older (80.6 vs. 78 years, p = 0.013), presented higher mean gradient (48 vs. 45 mmHg, p = 0.023), lower aortic valve area (0.70 vs. 0.74 cm2, p = 0.002) and higher systolic pulmonary artery pressure (36 vs. 33 mmHg, p = 0.016). They underwent percutaneous aortic valve replacement more frequently than men (47 vs. 35.9%, p = 0.017). At 5 years follow-up, women required more admissions due to heart failure (23 vs. 9%, p = 0.046) but they did not present higher cardiovascular nor overall mortality (27.7% vs. 29.8%, p = 0.741; 11.1 vs. 10.1%, p = 0.619, respectively). Female sex was an independent predictor of heart failure hospitalization at follow-up (HR 95% 1.16-4.22, p = 0.016). Women undergo AVI at a more advanced stage than men, resulting in a higher frequency of readmissions due to heart failure during the follow-up period, but not in higher mortality.

Feasibility of precise commissural and coronary alignment with balloon-expandable TAVI.

INTRODUCTION AND OBJECTIVES: We aimed to describe the feasibility and preliminary outcomes of commissural alignment (CA) for the balloon-expandable transcatheter heart valve. METHODS: The relationship among native commissures and transcatheter aortic valve implantation neocommissures was analyzed in 10 consecutive patients with tricuspid severe aortic stenosis undergoing transcatheter aortic valve implantation after guided implantation based on computed tomography analysis with a self-developed software. CA was predicted by in silico bio-modelling in the 10 patients and the calculated rotation was applied during crimping. Degrees of CA and coronary overlap (CO) were measured through 1-month follow up computed tomography. Transvalvular residual gradients and the rate of paravalvular leak were also analyzed. RESULTS: Mean commissural misalignment was 16.7±8°. Four patients showed mild misalignment but none of them showed a moderate or severe degree of misalignment. The in silico model accurately predicted the final in vivo position with a correlation coefficient of 0.983 (95%CI, 0.966-0.992), P <.001. Severe CO with right coronary ostium occurred in 3 patients likely due to ostial eccentricity, and CO was not present with the left coronary artery in any of the patients. Mean transaortic gradient was 6.1±3.3mmHg and there were no moderate-severe paravalvular leaks. CONCLUSIONS: Patient-specific rotation during valve crimping based on preprocedural computed tomography is feasible with balloon-expandable devices and is associated with the absence of moderate or severe commissural misalignment and left main CO.

The three-noes right-sided infective endocarditis: An unrecognized type of right-sided endocarditis.

The "3 noes right-sided infective endocarditis" (3no-RSIE: no left-sided, no drug users, no cardiac devices) was first described more than a decade ago. We describe the largest series to date to characterize its clinical, microbiological, echocardiographic and prognostic profile. Eight tertiary centers with surgical facilities participated in the study. Patients with right-sided endocarditis without left sided involvement, absence of drug use history and no intracardiac electronic devices were retrospectively included in a multipurpose database. A total of 53 variables were analyzed in every patient. We performed a univariate analysis of in-hospital mortality to determine variables associated with worse prognosis. the study was comprised of 100 patients (mean age 54.1 ± 20 years, 65% male) with definite 3no-RSIE were included (selected from a total of 598 patients with RSIE of all the series, which entails a 16.7% of 3no-RSIE). Most of the episodes were community-acquired (72%), congenital cardiopathies were frequent (32% of the group of patients with previous known predisposing heart disease) and fever was the main manifestation at admission (85%). The microbiological profile was led by Staphylococci spp (52%). Vegetations were detected in 94% of the patients. Global in-hospital mortality was 19% (5.7% in patients operated and 26% in patients who received only medical treatment, P < .001). Non-community acquired infection, diabetes mellitus, right heart failure, septic shock and acute renal failure were more common in patients who died. the clinical profile of 3no-RSIE is closer to other types of RSIE than to LSIE, but mortality is higher than that reported on for other types of RSIE. Surgery may play an important role in improving outcome.

Contemporary Clinical Profile of Left-Sided Native Valve Infective Endocarditis: Influence of the Causative Microorganism.

Studies focused on the clinical profile of native valve endocarditis are scarce and outdated. In addition, none of them analyzed differences depending on the causative microorganism. Our objectives are to describe the clinical profile at admission of patients with left-sided native valve infective endocarditis in a contemporary wide series of patients and to compare them among the most frequent etiologies. To do so, we conducted a prospective, observational cohort study including 569 patients with native left-sided endocarditis enrolled from 2006 to 2019. We describe the modes of presentation and the symptoms and signs at admission of these patients and compare them among the five more frequent microbiological etiologies. Coagulase-negative Staphylococci and Enterococci endocarditis patients were the oldest (71 ± 11 years), and episodes caused by Streptococci viridans were less frequently nosocomial (4%). The neurologic, cutaneous or renal modes of presentation were more typical in Staphylococcus aureus endocarditis (28%, p = 0.002), the wasting syndrome of Streptococcus viridans (49%, p < 0.001), and the cardiac in Coagulase-negative Staphylococci, Enterococci and unidentified microorganism endocarditis (45%, 49% and 56%, p < 0.001). The clinical signs agreed with the mode of presentation. In conclusion, the modes of presentation and the clinical picture at admission were tightly associated with the causative microorganism in patients with left-sided native valve endocarditis.