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.

Mortality and Costs of Cardiac Implantable Electronic Device (CIED) Infections According to the Therapeutic Approach: A Single-Center Cohort Study.

Background: Cardiac device infections are serious adverse events associated with considerable morbidity and mortality, significant costs, and increased healthcare utilization. The aim of this study is to calculate the costs of treatment of cardiac implantable electrostimulation device (CIED)-related infections for different types of infection (local or systemic) and therapeutic approaches. Patients and Methods: Single-center cohort (1985-2018). The costs of the CIED-related infections were analyzed according to initial treatment (antimicrobial treatment exclusively, local approach, or transvenous lead extraction (TLE)). Total costs (including those for hospitalization stay, drugs, extraction material, and newly implanted devices) were assigned to each case until its final resolution. Results: A total of 380 cases (233 local and 147 systemic infections) were analyzed. The average cost of systemic infection was EUR 34,086, mainly due to hospitalization (78.5%; mean: 24 ± 14 days), with a mortality rate of 10.8%. Local infection had a mortality rate of 2.5% (mainly related to the extraction procedure) and an average cost of EUR 21,790, which was higher in patients with resynchronization therapy devices and defibrillators (46% of total costs). Surgical procedures limited to the pocket for local infections resulted in a high rate of recurrence (87%), evolved to systemic infections in 48 patients, and had a higher cost compared to TLE (EUR 42,978 vs. EUR 24,699; p < 0.01). Conclusions: The costs of treating CIED-related infections are high and mainly related to the type of treatment and length of hospitalization. Complete device removal is always the most effective approach and is a cost-saving strategy.

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.

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort.

OBJECTIVES: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). METHODS: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. RESULTS: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. CONCLUSION: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective.

Non-nosocomial Healthcare-Associated Infective Endocarditis: A Distinct Entity? Data From the GAMES Series (2008-2021).

Background: Patients who acquire infective endocarditis (IE) following contact with the healthcare system, but outside the hospital, are classified as having non-nosocomial healthcare-associated IE (HCIE). Our aim was to characterize HCIE and establish whether its etiology, diagnosis, and therapeutic approach suggest it should be considered a distinct entity. Methods: This study retrospectively analyzes data from a nationwide, multicenter, prospective cohort including consecutive cases of IE at 45 hospitals across Spain from 2008 to 2021. HCIE was defined as IE detected in patients in close contact with the healthcare system (eg, patients receiving intravenous treatment, hemodialysis, or institutionalized). The prevalence and main characteristics of HCIE were examined and compared with those of community-acquired IE (CIE) and nosocomial IE (NIE) and with literature data. Results: IE was diagnosed in 4520 cases, of which 2854 (63%) were classified as CIE, 1209 (27%) as NIE, and 457 (10%) as HCIE. Patients with HCIE showed a high burden of comorbidities, a high presence of intravascular catheters, and a predominant staphylococcal etiology, Staphylococcus aureus being identified as the most frequent causative agent (35%). They also experienced more persistent bacteremia, underwent fewer surgeries, and showed a higher mortality rate than those with CIE (32.4% vs 22.6%). However, mortality in this group was similar to that recorded for NIE (32.4% vs 34.9%, respectively, P = .40). Conclusions: Our data do not support considering HCIE as a distinct entity. HCIE affects a substantial number of patients, is associated with a high mortality, and shares many characteristics with NIE.

Infective Endocarditis in Diabetic Patients: A Different Profile with Prognostic Consequences.

Background. Infective Endocarditis (IE) is a severe condition. Diabetes mellitus (DM) has been associated with a poor prognosis in other settings. Our aim was to describe the profile and prognosis of IE with and without DM and to analyze the prognostic relevance of DM-related organ damage. Methods. Retrospective analysis of the Spanish IE Registry (2008−2020). Results. The cohort comprises 5590 IE patients with a mean age of 65.0 ± 15.5 years; 3764 (67.3%) were male. DM was found in 1625 patients (29.1%) and 515 presented DM-related organ damage. DM prevalence during the first half of the study period was 27.6% vs. 30.6% in the last half, p = 0.015. Patients with DM presented higher in-hospital mortality than those without DM (521 [32.1%] vs. 924 [23.3%], p < 0.001) and higher one-year mortality (640 [39.4%] vs. 1131 [28.5%], p < 0.001). Among DM patients, organ damage was associated with higher in-hospital (200 [38.8%] vs. 321 [28.9%], p < 0.001) and one-year mortality (247 [48.0%] vs. 393 [35.4%], p < 0.001). Multivariate analyses showed an independent association of DM with in-hospital (odds ratio [OR] = 1.34, 95% confidence interval [CI]: 1.16−1.55, p < 0.001) and one-year mortality (OR = 1.38, 95% CI: 1.21−1.59, p < 0.001). Among DM patients, organ damage was independently associated with higher in-hospital (OR = 1.37, 95% CI: 1.06−1.76, p = 0.015) and one-year mortality (OR = 1.59, 95% CI = 1.26−2.01, p < 0.001) Conclusions. The prevalence of DM among patients with IE is increasing and is already above 30%. DM is independently associated with a poor prognosis, particularly in the case of DM with organ damage.

Cardiac protection induced by urocortin-2 enables the regulation of apoptosis and fibrosis after ischemia and reperfusion involving miR-29a modulation.

Urocortin-2 (Ucn-2) has demonstrated cardioprotective actions against myocardial ischemia-reperfusion (I/R) injuries. Herein, we explored the protective role of Ucn-2 through microRNAs (miRNAs) post-transcriptional regulation of apoptotic and pro-fibrotic genes. We determined that the intravenous administration of Ucn-2 before heart reperfusion in a Wistar rat model of I/R recovered cardiac contractility and decreased fibrosis, lactate dehydrogenase release, and apoptosis. The infusion of Ucn-2 also inhibited the upregulation of 6 miRNAs in revascularized heart. The in silico analysis indicated that miR-29a and miR-451_1∗ are predicted to target many apoptotic and fibrotic genes. Accordingly, the transfection of neonatal rat ventricular myocytes with mimics overexpressing miR-29a, but not miR-451_1∗, prevented I/R-induced expression of pro- and anti-apoptotic genes such as Apaf-1, Hmox-1, and Cycs, as well as pro-fibrotic genes Col-I and Col-III. We also confirmed that Hmox-1, target of miR-29a, is highly expressed at the mRNA and protein levels in adult rat heart under I/R, whereas, Ucn-2 abolished I/R-induced mRNA and protein upregulation of HMOX-1. Interestingly, a significant upregulation of Hmox-1 was observed in the ventricle of ischemic patients with heart failure, correlating negatively with the left ventricle ejection fraction. Altogether, these data indicate that Ucn-2, through miR-29a regulation, provides long-lasting cardioprotection, involving the post-transcriptional regulation of apoptotic and fibrotic genes.

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.

Mural Endocarditis: The GAMES Registry Series and Review of the Literature.

INTRODUCTION: Mural infective endocarditis (MIE) is a rare type of endovascular infection. We present a comprehensive series of patients with mural endocarditis. METHODS: Patients with infectious endocarditis (IE) from 35 Spanish hospitals were prospectively included in the GAMES registry between 2008 and 2017. MIEs were compared to non-MIEs. We also performed a literature search for cases of MIE published between 1979 and 2019 and compared them to the GAMEs series. RESULTS: Twenty-seven MIEs out of 3676 IEs were included. When compared to valvular IE (VIE) or device-associated IE (DIE), patients with MIE were younger (median age 59 years, p < 0.01). Transplantation (18.5% versus 1.6% VIE and 2% DIE, p < 0.01), hemodialysis (18.5% versus 4.3% VIE and 4.4% DIE, p = 0.006), catheter source (59.3% versus 9.7% VIE and 8.8% DIE, p < 0.01) and Candida etiology (22.2% versus 2% DIE and 1.2% VIE, p < 0.01) were more common in MIE, whereas the Charlson Index was lower (4 versus 5 in non-MIE, p = 0.006). Mortality was similar. MIE from the literature shared many characteristics with MIE from GAMES, although patients were younger (45 years vs. 56 years, p < 0.001), the Charlson Index was lower (1.3 vs. 4.3, p = 0.0001), catheter source was less common (13.9% vs. 59.3%) and there were more IVDUs (25% vs. 3.7%). S. aureus was the most frequent microorganism (50%, p = 0.035). Systemic complications were more common but mortality was similar. CONCLUSION: MIE is a rare entity. It is often a complication of catheter use, particularly in immunocompromised and hemodialysis patients. Fungal etiology is common. Mortality is similar to other IEs.

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.

miR-30b-5p Downregulation as a Predictive Biomarker of Coronary In-Stent Restenosis.

In-stent restenosis (ISR) is one of the main limitations of percutaneous coronary intervention (PCI) therapy with drug-eluting stents (DES) implantation. The aim of this study was to determine if circulating microRNAs (miRNAs) have diagnostic capability for determining ISR in a cohort of matched patients. Blood samples were collected from 55 patients who underwent previously PCI and were readmitted for a new coronary angiography. Patients were divided into subgroups comprising patients who presented ISR or not (non-ISR). A microarray analysis determined that up to 49 miRNAs were differentially expressed between ISR and non-ISR patients. Of these, 10 miRNAs are related to vascular smooth muscle and endothelial cells proliferation, migration, and differentiation, well-known hallmarks of vascular remodeling. Additionally, we identified that the expression of miR-30b-5p is significantly lower in serum samples of ISR patients, as compared to non-ISR. A further analysis demonstrated that miR-30b-5p provides better values of the receiver operator characteristic curve than other miRNAs and biochemical parameters. Finally, the in-silico analysis suggests that miR-30b-5p is predicted to target 62 genes involved in different signaling pathways involved in vascular remodeling. In conclusion, we determined for the first time that circulating mi-R30b-5p can reliably prognose restenosis in patient with implanted DES, which could be potentially helpful in the establishment of an early diagnosis and therapy of ISR.

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.

Circulating miR-320a as a Predictive Biomarker for Left Ventricular Remodelling in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention.

Restoration of epicardial coronary blood flow, achieved by early reperfusion with primary percutaneous coronary intervention (PPCI), is the guideline recommended to treat patients with ST-segment-elevation myocardial infarction (STEMI). However, despite successful blood restoration, increasing numbers of patients develop left ventricular adverse remodelling (LVAR) and heart failure. Therefore, reliable prognostic biomarkers for LVAR in STEMI are urgently needed. Our aim was to investigate the role of circulating microRNAs (miRNAs) and their association with LVAR in STEMI patients following the PPCI procedure. We analysed the expression of circulating miRNAs in blood samples of 56 patients collected at admission and after revascularization (at 3, 6, 12 and 24 h). The associations between miRNAs and left ventricular end diastolic volumes at 6 months were estimated to detect LVAR. miRNAs were also analysed in samples isolated from peripheral blood mononuclear cells (PBMCs) and human myocardium of failing hearts. Kinetic analysis of miRNAs showed a fast time-dependent increase in miR-133a, miR-133b, miR-193b, miR-499, and miR-320a in STEMI patients compared to controls. Moreover, the expression of miR-29a, miR-29b, miR-324, miR-208, miR-423, miR-522, and miR-545 was differentially expressed even before PPCI in STEMI. Furthermore, the increase in circulating miR-320a and the decrease in its expression in PBMCs were significantly associated with LVAR and correlated with the expression of miR-320a in human failing myocardium from ischaemic origin. In conclusion, we determined the time course expression of new circulating miRNAs in patients with STEMI treated with PPCI and we showed that miR-320a was positively associated with LVAR.

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).

Repeated procedures at the generator pocket are a determinant of implantable cardioverter-defibrillator infection.

BACKGROUND: Rates of cardiac-device infections have increased in recent years, but the current incidence and risk factors for infection in patients with implantable cardioverter-defibrillators (ICDs) are not well known. HYPOTHESIS: The increasing number of ICD infections is related to accumulated pocket manipulations over time. METHODS: This single-center, prospective study included patients that underwent ICD implantation from 2008 to 2015. The endpoint was time to infection. Multivariate analysis was performed to identify independent risk factors related to infection. RESULTS: The study included a total of 570 patients, of whom 419 (73.5%) underwent a first implantation. Mean age was 59 ± 14 years, and 80% were male. During a median follow-up of 36 months (interquartile range, 18-61 months; 1887 patient-years), infection was identified in 26 patients (4.56%), an incidence of 14.9 × 1000 patient-years. Median time to infection was 9.7 months (interquartile range, 1.35-23.4 months), and 38.5% were late infections (beyond 12 months of follow-up). In patients with replacement implants, the incidence was 3-fold higher than in first implantations (27.7 vs 9.1 × 1000 patient-years; P = 0.002). Cox regression identified 2 independent predictors of ICD infection: cumulative number of interventions at the generator pocket (hazard ratio: 1.92, 95% confidence interval: 1.42-2.6, P < 0.001) and pocket hematoma (hazard ratio: 7.0, 95% confidence interval: 2.7-17.9, P < 0.0001). CONCLUSIONS: The incidence of infection in ICD patients is greater than previously reported, largely due to late infections. Each new cumulative intervention at the same generator pocket nearly doubles the risk of infection.

Infections in Cardiac Implantable Electronic Devices: Diagnosis and Management in a Referral Center.

INTRODUCTION AND OBJECTIVES: Infections in cardiac implantable electronic devices are increasing due to the expansion of the indications of these devices. The management of some aspects is controversial. Here, we report our broad experience. METHODS: Between 1985 and 2015, 325 infections (196 local and 129 systemic) were registered; 28.5% of them were referred from other centers: 229 pacemakers, 69 implantable cardioverter-defibrillators, and 27 patients with cardiac resynchronization therapy. The follow-up was at least 1 year after hospital discharge. RESULTS: Percutaneous traction (PCT) was the most frequent procedure (n=280) in local (n=166) and systemic infections (n=114), with complete extraction of the system in 82.5% of the patients, clinical success in 89%, and few complications (2 deaths attributable to the technique). Overall mortality was 1% in local infections and 8% in systemic infections. After 212 complete PCT, a new device was placed in 209: of these, a contralateral system was implanted in the same procedure in 152 (73%) and in a second procedure in 57, with no differences in relapses (2 in the 1-stage procedure, and 1 in the 2-stage procedure). CONCLUSIONS: Percutaneous traction in experienced hands has good results with very few complications. It is possible to perform contralateral implantation of the new device on the same day without increasing the risk of relapse.