Infective endocarditis in HIV-infected patients. Analysis of a national cohort.

BACKGROUND: There is limited recent evidence about infective endocarditis (IE) in HIV-infected patients. Our aim was to compare IE according to HIV infection presence. METHODS: Consecutive inclusion of IE patients at 46 Spanish hospitals between 2008 and 2021. RESULTS: From 5667 patients, 99 were HIV-infected (1·7%; 50 intravenous drugs users). Compared to patients without HIV, HIV-infected patients were more frequently male (84% vs. 67%), had younger median age (46 vs. 69 years), and less comorbidities, except liver disease (52% vs. 9%) and intravenous drug use (51% vs. 1%). They had more common tricuspid location (36% vs. 5%) and community-acquired IE (82% vs. 63%), vascular (29% vs. 17%) and cutaneous (22% vs. 7%) foci of infection, and Staphylococcus aureus aetiology (46% vs. 22%). Vegetations (84% vs. 72%), vascular phenomena (17% vs. 9%), splenomegaly (30% vs. 11%), and embolisation (41% vs 21%) were also more common. Surgical indication and surgery were less frequent in HIV-infected patients (54% vs 67%, 28% vs 47%, respectively). Median CD4 count in HIV-infected patients was 318 cells/mm3. In-hospital mortality (23% vs. 26%) and one-year mortality (25% vs. 32%) were similar in both groups. HIV infection was not independently associated with in-hospital (odds ratio 1·1, 95% CI 0·6-1·9) nor one-year mortality (hazard ratio 0·8, 95% CI 0·4-1·3). CONCLUSIONS: In the combined antiretroviral therapy era, less than 2% of IE patients have HIV infection. HIV-infected patients have a different clinical profile than those without HIV, but the presence of HIV does not seem to impact on IE prognosis.

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 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%): 818 ischemic strokes (811 cardioembolic strokes (193 with hemorrhagic transformation), 4 transient ischemic attacks, 3 lacunar infarctions), 127 intracranial hemorrhages, and 27 other neurological complications (cerebral abscesses, encephalitis, and meningitis). 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 1-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, 95% CI = 1.1-1.6, p = 0.007), sepsis (OR = 1.3, 95% 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, 95% 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 1-year mortality (hazard ratio = 1.9, 95% CI = 1.6-2.5). CONCLUSION: One-fifth of patients with IE have concomitant stroke. Stroke is associated with mortality.

Inhibition of adenylyl cyclase 8 prevents the upregulation of Orai1 channel, which improves cardiac function after myocardial infarction.

The upregulation of Orai1 and subsequent store-operated Ca2+ entry (SOCE) has been associated with adverse cardiac remodeling and heart failure (HF). However, the mechanism underlying Orai1 upregulation and its role in myocardial infarction remains unclear. Our study investigated the role of Orai1 in activating adenylyl cyclase 8 (AC8) and cyclic AMP (cAMP) response element-binding protein (CREB), as well as its contribution to cardiac dysfunction induced by ischemia and reperfusion (I/R). We found that I/R evoked an increase in the expression of Orai1 and AC8 in rats' hearts, resulting in a substantial rise in diastolic Ca2+ concentration ([Ca2+]i), and reduced ventricular contractions. The expression of Orai1 and AC8 was also increased in ventricular biopsies of post-ischemic HF patients. Mechanistically, we demonstrate that I/R activation of Orai1 stimulated AC8, which produced cAMP and phosphorylated CREB. Subsequently, p-CREB activated the ORAI1 promoter, resulting in Orai1 upregulation and SOCE exacerbation. Intramyocardial administration of AAV9 carrying AC8 short hairpin RNA decreased the expression of AC8, Orai1 and CREB, which restored diastolic [Ca2+]i and improved cardiac contraction. Therefore, our data suggests that the axis composed by Orai1/AC8/CREB plays a critical role in I/R-induced cardiac dysfunction, representing a potential new therapeutic target to limit the progression of the disease toward HF.

Analysis of sex differences in the clinical presentation, management and prognosis of infective endocarditis in Spain.

INTRODUCTION: Sex-dependent differences of infective endocarditis (IE) have been reported. Women suffer from IE less frequently than men and tend to present more severe manifestations. Our objective was to analyse the sex-based differences of IE in the clinical presentation, treatment, and prognosis. MATERIAL AND METHODS: We analysed the sex differences in the clinical presentation, modality of treatment and prognosis of IE in a national-level multicentric cohort between 2008 and 2018. All data were prospectively recorded by the GAMES cohort (Spanish Collaboration on Endocarditis). RESULTS: A total of 3451 patients were included, of whom 1105 were women (32.0%). Women were older than men (mean age, 68.4 vs 64.5). The most frequently affected valves were the aortic valve in men (50.6%) and mitral valve in women (48.7%). Staphylococcus aureus aetiology was more frequent in women (30.1% vs 23.1%; p<0.001).Surgery was performed in 38.3% of women and 50% of men. After propensity score (PS) matching for age and estimated surgical risk (European System for Cardiac Operative Risk Evaluation II (EuroSCORE II)), the analysis of the matched cohorts revealed that women were less likely to undergo surgery (OR 0.74; 95% CI 0.59 to 0.91; p=0.05).The observed overall in-hospital mortality was 32.8% in women and 25.7% in men (OR for the mortality of female sex 1.41; 95% CI 1.21 to 1.65; p<0.001). This statistical difference was not modified after adjusting for all possible confounders. CONCLUSIONS: Female sex was an independent factor related to mortality after adjusting for confounders. In addition, women were less frequently referred for surgical treatment.

Non-HACEK gram negative bacilli endocarditis: Analysis of a national prospective cohort.

BACKGROUND: Infective endocarditis (IE) due to non-HACEK bacilli (Haemophilus species, Actinobacillus, Cardiobacterium, Eikenella, or Kingella) is uncommon and poorly described. The objectives of this study were to describe non-HACEK Gram-Negative Bacilli (GNB) IE cases and compare characteristic of IE produced by Enterobacterales and non-fermenting (NF) GNB. METHODS: From January 2008 to December 2018, 3910 consecutive patients with definitive IE diagnosis, defined with Modified Duke criteria, either clinical or pathological criteria (e.g. demonstration of non-HACEK GNB in valve culture)were prospectively included. RESULTS: A total of 104 IE cases were caused by non-HACEK GNB (2.6%). Compared to IE due to other microorganisms (excluding HACEK GNB), patients with non-HACEK GNB IE presented with higher age (71 years [IQR 62-78] vs 68 years [IQR: 57-77]; p = 0.026), higher proportion of women (52% vs 31.5%, p < 0.001), higher Charlson Index (5 [IQR: 4-8] vs 4 [IQR 3-7], p = 0.003) and higher in-hospital mortality (36.5% vs 27.1%, p = 0.034). Enterobacterales cases were more frequently associated with genitourinary focus (32.8% vs 5.0%, p = 0.001). NFGNB endocarditis more frequently affected right valves (20.0% vs. 6.3%, p = 0.033), had more common healthcare-related acquisition (67.5% vs. 43.7%, p = 0.030) and venous catheter as focus (40.0% vs. 17.2%, p = 0.019). In the multivariant model, factors related with hospital mortality were: age (OR 1.05, 95%CI 1.00-1.09, p = 0.042), prosthetic valve (OR 2.31, 95%CI 0.90-5.88, p = 0.080), and not performing surgery when indicated (OR 3.60, 95%CI 1.17-11.05, p = 0.025).Patients treated with quinolone combination had lower mortality (OR 0.29; 95%CI 0.09-0.96; p = 0.043). CONCLUSION: Non-HACEK GNB IE is a rare infection characterized by affecting elderly patients with high comorbidity, nosocomial acquisition and unfavorable outcome. Age, prosthetic valve and not performing surgery when indicated are associated with mortality.

Infective endocarditis in patients with solid organ transplantation. A nationwide descriptive study.

BACKGROUND: Solid organ transplantation (SOT) implies immunosuppression and frequent health care contact. Our aim was to compare the characteristics of patients with infective endocarditis (IE) and SOT against those without SOT. METHODS: We used data from the Spanish Collaboration on Endocarditis during the period 2008-2018. RESULTS: We identified 4794 cases of IE, 85 (1.8%) in SOT (56 kidney, 18 liver, 8 heart, 3 lung). Thirteen patients with other transplantation types (bone marrow, hematopoietic precursors, and cornea) were excluded from the analysis. Compared with patients without SOT, patients with SOT had lower median age (61 vs. 69 years, p<0.001), more comorbidities (mean age-adjusted Charlson index 5.7±2.9 vs. 4.9±2.9, p=0.004), a lower prevalence of native valvular heart disease (29.4 vs. 45.4%, p=0.003), more in-hospital and healthcare-related IE (70.5% vs. 36.3%, p<0.001) and staphylococcal etiology (57.7% vs. 39.7%, p=0.001). Patients with SOT had more frequent kidney function worsening (47.1% vs. 34.6%, p=0.02), septic shock (25.9% vs. 12.1 %, p<0.001), sepsis (27.1% vs. 17.2%, p=0.02), and less surgery indication (54.1% vs 66.3%, p=0.02) and surgery (32.9% vs. 46.3%, p=0.01) than patients without SOT. There were no significant differences in mortality: inhospital (30.6% SOT vs. 25.6% without SOT, p=0.31), 1-year (38.8% SOT vs. 31.9% without SOT, p=0.18). CONCLUSIONS: Most IE in SOT recipients are nosocomial and over 70% are health care-related. Half have previously normal heart valves and almost 60% are due to Staphylococcus spp. infections. Mortality seems to be similar to non-SOT counterparts.

Characteristics and Outcome of Acute Heart Failure in Infective Endocarditis: Focus on Cardiogenic Shock.

BACKGROUND: Studies investigating the impact of cardiogenic shock (CS) on endocarditis are lacking. METHODS: Prospectively collected cohort from 35 Spanish centers (2008-2018). Logistic regression analyses were performed to identify risk factors for developing CS and predictors of mortality. RESULTS: Among 4856 endocarditis patients, 1652 (34%) had acute heart failure (AHF) and 244 (5%) CS. Compared with patients without AHF and AHF but no CS, patients with CS presented higher rates of surgery (40.5%, 52.5%, and 68%; P < .001) and in-hospital mortality (16.3%, 39.1%, and 52.5%). Compared with patients with septic shock, CS patients presented higher rates of surgery (42.5% vs 68%; P < .001) and lower rates of in-hospital and 1-year mortality (62.3% vs 52.5%, P = .008, and 65.3% vs 57.4%, P = .030). Severe aortic and mitral regurgitation (OR [95% CI], 2.47 [1.82-3.35] and 3.03 [2.26-4.07]; both P < .001), left-ventricle ejection fraction <60% (1.72; 1.22-2.40; P = .002), heart block (2.22; 1.41-3.47; P = .001), tachyarrhythmias (5.07; 3.13-8.19; P < .001), and acute kidney failure (2.29; 1.73-3.03; P < .001) were associated with higher likelihood of developing CS. Prosthetic endocarditis (2.03; 1.06 -3.88; P = .032), Staphylococcus aureus (3.10; 1.16 -8.30; P = .024), tachyarrhythmias (3.09; 1.50-10.13; P = .005), and not performing cardiac surgery (11.40; 4.83-26.90; P < .001) were associated with a higher risk of mortality. CONCLUSIONS: AHF is common among patients with endocarditis. CS is associated with high mortality and should be promptly identified and assessed for cardiac surgery.

Outcomes of Isolated Tricuspid Valve Surgery.

BACKGROUND: Isolated tricuspid valve surgery is a rarely performed procedure and traditionally is associated with a bad prognosis, although its clinical outcomes still are little known. The aim of this study was to assess the short- and long-term clinical outcomes obtained at our center after isolated tricuspid valve surgery as treatment for severe tricuspid regurgitation. METHODS: This retrospective study included 71 consecutive patients with severe tricuspid regurgitation who underwent isolated tricuspid valve surgery between December 1996 and December 2017. Perioperative and long-term mortality, tricuspid valve reoperation, and functional class were analyzed after follow up. RESULTS: Regarding surgery, 7% of patients received a De Vega annuloplasty, 14.1% an annuloplasty ring, 11.3% a mechanical prosthesis, and 67.6% a biological prosthesis. Perioperative mortality was 12.7% and no variable was shown to be predictive of this event. After a median follow up of 45.5 months, long-term mortality was 36.6%, and the multivariate analysis identified atrial fibrillation as the only predictor (Hazard Ratio 3.014, 95% confidence interval 1.06-8.566; P = 0.038). At the end of follow up, 63.6% of survivors had functional class I. CONCLUSIONS: Isolated tricuspid valve surgery was infrequent in our center. Perioperative mortality was high, as was long-term mortality. However, a high percentage of survivors were barely symptomatic after follow up.

Infective endocarditis in patients with cardiac implantable electronic devices: a nationwide study.

AIMS: Patients with infective endocarditis (IE) frequently have cardiac implantable electronic devices (CIEDs). Here, we aim to define the clinical profile and prognostic factors of IE in these patients. METHODS AND RESULTS: Infective endocarditis cases were prospectively identified in the Spanish National Endocarditis Registry. From 3996 IE, 708 (17.7%) had a CIED and 424 CIED-related IE (lead vegetation). Patients with a CIED were older (68 ± 11 vs. 73 ± 8 years); had more comorbidities {pulmonary disease [176 (24.8%) vs. 545 (16.7%)], renal disease [239 (33.8%) vs. 740 (22.7%)], diabetes [248 (35.0%) vs. 867 (26.6%)], and heart failure [348 (49.2%) vs. 978 (29.9%)]}; and fewer complications {intracardiac destruction [106 (15%) vs. 1077 (33.1%)], heart failure [215 (30.3%) vs. 1340 (41.1%)], embolism [107 (15.1%) vs. 714 (21.9%)], and neurological involvement [77 (10.8%) vs. 702 (21.5%)]} (all P-values <0.001) in comparison to subjects without a CIED. In-hospital mortality was similar in patients with and without CIED [171 (24.2%) vs. 881 (27.0%), P = 0.82]. In subjects with a CIED, CIED-related IE was independently associated with in-hospital survival: odds ratio (OR) 0.4 [95% confidence interval (CI) 0.3-0.7, P = 0.001]. Surgery was independently associated with in-hospital survival in CIED-related IE: OR 0.4 (95% CI 0.2-0.7, P = 0.004); but not in subjects with valve IE and no CIED lead involvement: OR 0.9 (95% CI 0.5-1.7, P = 0.77). CONCLUSION: Over a sixth of IE patients have a CIED. This group of patients is older, with more comorbidities and fewer IE-related complications in comparison to subjects without a CIED. In-hospital mortality was similar in patients with and without a CIED.

Impact of dual-chamber pacing with closed loop stimulation on quality of life in patients with recurrent reflex vasovagal syncope: results of the SPAIN study.

AIMS: Reflex vasovagal syncope (VVS) is the most common cause of syncope and patients with recurrent episodes may severely impair quality of life (QoL). This pre-specified analysis evaluated whether the clinically significant reduction in syncope burden demonstrated by dual-chamber pacing with closed loop stimulation (DDD-CLS) reported in the SPAIN trial translates into improved QoL. METHODS AND RESULTS: Patients aged ≥40 years with ≥5 VVS episodes and cardioinhibitory response induced by head-up tilt testing were included. Patients were randomized 1:1 to active DDD-CLS pacing algorithm for 12 months followed by sham DDI mode for the remaining 12 months (Group A) or vice versa (Group B). QoL was assessed using the Short Form-36 (SF-36) health survey, Physical Component Score (PCS), and Mental Component Score (MCS) before randomization (baseline) and at 12- and 24-month follow-up. Fifty-four patients were enrolled from 11 participating centres. No significant carryover effect was detected for any variable, and the only period effect was observed in the vitality subdomain (P = 0.033). Mean SF-36 scores were higher in the DDD-CLS group vs. the DDI group for the eight subdomains and significantly different in physical role, bodily pain, and vitality (P < 0.05). The analysis of component summary scores indicated that DDD-CLS benefited both mental and physical components with significant differences in PCS when compared with the DDI group. CONCLUSION: Dual-chamber pacing with closed loop stimulation determined a significant and clinically relevant improvement in QoL across both mental and physical components in patients with recurrent VVS. REGISTRATION: Closed Loop Stimulation for Neuromediated Syncope (SPAIN Study); NCT01621464.

Dual-Chamber Pacing With Closed Loop Stimulation in Recurrent Reflex Vasovagal Syncope: The SPAIN Study.

BACKGROUND: Pacing in vasovagal syncope remains controversial. OBJECTIVES: The authors evaluated dual-chamber pacing with closed loop stimulation (DDD-CLS) in patients with cardioinhibitory vasovagal syncope. METHODS: This randomized, double-blind, controlled study included Canadian and Spanish patients age ≥40 years, with high burden syncope (≥5 episodes, ≥2 episodes in the past year), and a cardioinhibitory head-up tilt test (bradycardia <40 beats/min for 10 s or asystole >3 s). Patients were randomized to either DDD-CLS pacing for 12 months followed by sham DDI mode pacing at 30 pulses/min for 12 months (group A), or sham DDI mode for 12 months followed by DDD-CLS pacing for 12 months (group B). Patients in both arms crossed-over after 12 months of follow-up or when a maximum of 3 syncopal episodes occurred within 1 month. RESULTS: A total of 46 patients completed the protocol; 22 were men (47.8%), and mean age was 56.30 ± 10.63 years. The mean number of previous syncopal episodes was 12 (range 9 to 20). The proportion of patients with ≥50% reduction in the number of syncopal episodes was 72% (95% confidence interval [CI]: 47% to 90%) with DDD-CLS compared with 28% (95% CI: 9.7% to 53.5%) with sham DDI mode (p = 0.017). A total of 4 patients (8.7%) had events during DDD-CLS and 21 (45.7%) during sham DDI (hazard ratio: 6.7; 95% CI: 2.3 to 19.8). Kaplan-Meier curve was significantly different between groups in time to first syncope: 29.2 months (95% CI: 15.3 to 29.2 months) versus 9.3 months (95% CI: 6.21 months, NA; p < 0.016); odds ratio: 0.11 (95% CI: 0.03 to 0.37; p < 0.0001). CONCLUSIONS: DDD-CLS pacing significantly reduced syncope burden and time to first recurrence by 7-fold, prolonging time to first syncope recurrence in patients age ≥40 years with head-up tilt test-induced vasovagal syncope compared with sham pacing. (Closed Loop Stimulation for Neuromediated Syncope [SPAIN Study]; NCT01621464).