AIMS:Infective endocarditis (IE) remains associated with high mortality despite diagnostic & therapeutic advances. The impact of social deprivation (SD), a key determinant of cardiovascular health, remains unclear. We evaluated the influence of SD in IE within a universal healthcare system. METHODS AND RESULTS:1740 IE patient visits from three centers in London (King's College Hospital NHS Foundation Trust, Guy's & St. Thomas' NHS Foundation Trust and Barts Health NHS Trust) between December 2013 and March 2023 were included. SD was measured using the Index of Multiple Deprivation, with patients stratified into High (N = 638), Medium (N = 576) and Low (N = 526) groups. Patient and admission characteristics, diagnostic imaging, clinical management, outcomes and variables influencing mortality were assessed. All-cause mortality at 30 days and 1 year was significantly higher in the High SD group (P = 0.030 and P = 0.004 respectively). The high SD group were more likely to be female (P < 0.001), from Asian (P < 0.001) or Black (P < 0.001) self-reported racial groups and had more co-morbidity, including more people who inject drugs (P < 0.001). The high SD group presented with higher white cell count (P = 0.025), C-reactive protein (P = 0.001) and higher rates of right-sided IE (P = 0.028). A causative organism was established in 77.1% of cases, with no differences between groups. There were significantly lower rates of surgery in the High SD group (P < 0.001), and significantly more patients managed conservatively despite having a surgical indication (P = 0.003). CONCLUSION:These findings suggest that greater co-morbidity, higher inflammatory markers and reduced surgical intervention contribute to higher mortality in socially deprived patients within a universal healthcare system.

BACKGROUND:Prosthetic valve infective endocarditis (PVE) is one of the most severe complications after valve implantation. Early diagnosis and identification of paravalvular complications are essential to determine optimal timing of surgery. Our aim is to assess the diagnostic performance of Computed Tomography Coronary Angiography (CTCA) versus Transoesophageal echocardiography (TOE) for the detection of valvular and paravalvular complications of PVE against the reference standard of surgical inspection. METHODS:Fifty-two patients who underwent pre-operative CTCA and TOE for the assessment of prosthetic valve IE were included. Imaging findings of vegetation, abscess/pseudoaneurysm, leaflet perforation and dehiscence were compared with intra-operative findings. Significant ancillary findings on CTCA likely to impact surgical planning were also reported. RESULTS:Median age was 64 years and 66 ​% were male. Surgical inspection revealed vegetations in 39 cases; CTCA had a sensitivity of 81.6 ​% specificity 90.9 ​%, AUC 0.876; TOE had a sensitivity of 97.4 ​%, specificity 72.7 ​%, AUC 0.807. Surgical inspection revealed abscess/pseudoaneurysm in 29 cases; CTCA had a sensitivity of 86.2 ​%, specificity 95.2 ​%, AUC 0.886; TOE had a sensitivity of 55.2 ​%, specificity 90.5 ​% (p ​< ​0.001), AUC 0.749. Significant ancillary findings on CTCA were identified in 24 (46 ​%) of patients. CONCLUSION:CTCA demonstrates higher diagnostic accuracy for paravalvular complications of PVE compared to TOE; a critical finding that necessitates early surgical intervention. Additionally, CTCA provides valuable ancillary information that can influence surgical planning. CTCA demonstrates comparable performance to TOE in identifying vegetations. Echocardiography remains superior for evaluating valve perforation, and dehiscence. A combined approach utilising both echocardiography and CTCA is recommended.

Abstract Background Guidelines suggest treating fully penicillin-susceptible Enterococcus faecalis strains causing infective endocarditis with amoxicillin combined with gentamicin or ceftriaxone, but clinical evidence to support this practice is limited and monotherapy cohorts were excluded from studies. We describe antibiotic treatment, complications, and outcomes in patients with Enterococcus faecalis infective endocarditis, specifically comparing monotherapy versus combination therapy. Methods Retrospective analysis of prospectively collected cohort of patients with definite or possible infective endocarditis from 2 English centres between 2006 and 2021. The primary outcome was 30-day mortality. Secondary outcomes included acute kidney injury, relapse, and clinical cure. Results 178 individuals were included: median age was 72 years (interquartile range 60–79), male sex majority (138, 78%) and mostly native valve endocarditis (108, 61%). Thirty-nine patients (22%) received monotherapy (penicillin/glycopeptide/linezolid/daptomycin), 128 (72%) combination with gentamicin, 11 (6%) combination with ceftriaxone. Patients on combination therapy with gentamicin had a statistically significant lower 30-day mortality than those treated with monotherapy (21 (16.4%) versus 15 (38.5%) p = 0.035) and higher rates of clinical cure (101 (78.9%) versus 23 (59.0%) p = 0.018). Patient receiving gentamicin were more likely to experience acute kidney injury (64 (50%) versus 11 (28.2%) p = 0.057). Ceftriaxone combination was associated with poor outcomes, but the sample size was small. Conclusion Patients treated with combination gentamicin therapy had better clinical outcomes than patients treated with monotherapy. Low-dose gentamicin regimens were associated with acute kidney injury. Patients treated with combinations were different to those treated with monotherapy and confounding remains a concern with observational analyses. An adequately powered clinical trial is needed to determine optimal treatment of enterococcal endocarditis. Clinical trial number Not applicable.

BACKGROUND:Atrial fibrillation (AF)-induced cardiomyopathy (AIC) is characterised by reversible left ventricular (LV) dysfunction after restoration of sinus rhythm (SR). The need for continued guideline-directed medical therapy (GDMT) for heart failure after LV ejection fraction (LVEF) recovery in AIC after catheter ablation (CA) is unclear. METHODS:This multicentre cohort study across 12 UK centres included adults undergoing index AF ablation (June 2019-June 2024) with LVEF <50% preablation and recovery to ≥50% at three timepoints: preablation; early postablation (≥4 weeks) and late postablation (≥3 months or ≥3 months post-GDMT withdrawal). Patients were stratified post recovery of LVEF after CA. The primary outcome was mean LVEF at late follow-up; secondary outcomes included absolute change in LVEF, LV end-diastolic diameter (LVEDD) and SR maintenance. RESULTS:88 patients met inclusion enrolment criteria (61.7±10.6 years old; 91% male), of which 50 (56.8%) continued full-dose GDMT and 38 (43.2%) withdrew ≥50% of GDMT. In the GDMT-withdrawn group, mean GDMT classes decreased from 2.97±0.88 to 1.03±0.79 (p<0.001). At late follow-up, mean LVEF was comparable (56.3%±3.8% GDMT-continued vs 56.8%±5.5% GDMT-withdrawn; p=0.59), as was LVEF change (1.2% vs 0.4%; p=0.48). One relapse occurred in each group secondary to an acute coronary syndrome (2.0% vs 2.6%; p=1). LVEDD remained stable (p>0.8). SR was maintained in 82.0% vs 92.1% of patients; p=0.17. CONCLUSIONS:Selective GDMT withdrawal after sustained LVEF recovery and rhythm control did not compromise LV systolic function, remodelling or rhythm maintenance. This supports the study of personalised de-escalation strategies in AIC in prospective trials.

Between July 2024 and January 2025, five male patients in their early 20s to early 50s were confirmed with infective endocarditis associated with non-toxigenic Corynebacterium diphtheriae in England. Three were known to have experienced homelessness. All five used non-intravenous recreational drugs. Disease progression was rapid, four patients required surgical intervention, one died. Whole-genome sequencing and multilocus sequence type (MLST) analysis identified four individuals as ST559. Clinicians and substance use services have been alerted and enhanced surveillance implemented. A prevalence study is planned.

Multiple guidelines exist for the diagnosis and management of heart failure with preserved ejection fraction (HFpEF). We systematically reviewed current guidelines and recommendations, developed by national and international medical organizations, on the management of HFpEF in adults to aid clinical decision-making. We searched MEDLINE and EMBASE on 28 February 2024 for publications over the last 10 years as well as websites of organizations relevant to guideline development. Of the 10 guidelines and recommendations retrieved, 7 showed considerable rigour of development and were subsequently retained for analysis. There was consensus on the definition of HFpEF and the diagnostic role of serum natriuretic peptides and resting transthoracic echocardiography. Discrepancies were identified in the thresholds of serum natriuretic peptides and transthoracic echocardiography parameters used to diagnose HFpEF. There was agreement on the general pharmacological and supportive management of acute and chronic HFpEF. However, differences exist in strategies to identify and address specific phenotypes. Contemporary guidelines for HFpEF management agree on measures to avoid its development and the consideration of cardiac transplantation in advanced diseases. There were discrepancies in recommended frequency of surveillance for patients with HFpEF and sparse recommendations on screening for HFpEF in the general population, use of diagnostic scoring systems, and the role of newly emerging therapies.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce cardiovascular rehospitalisation in heart failure with reduced ejection fraction (HFrEF) patients. However, it is unknown whether initiating SGLT2i during an inpatient stay for a HFrEF exacerbation results in better outcomes versus initiation post-discharge in a cohort of diabetic and non-diabetic patients. This study compares cardiovascular rehospitalisation, heart failure specific rehospitalisation, cardiovascular death, and all-cause death between patients initiated on SGLT2i as an inpatient versus post-discharge. A retrospective study of four hospitals in England involving 184 patients with HFrEF exacerbations between March 2021 and June 2022 was performed. Cardiovascular rehospitalisation, heart failure specific rehospitalisation, cardiovascular death, and all-cause death were compared between the two groups using Cox regression. A Cox proportionalhazards model was fitted to determine predictors of cardiovascular rehospitalisation. There were 148 (80.4%) individuals who received SGLT2i as an inpatient, while 36 (19.6%) individuals received SGLT2i post-discharge. Median followup was 6.5 months for inpatients and 7.5 months for post-discharge patients (p=0.522). SGLT2i inpatients had significantly reduced cardiovascular rehospitalisations (22.3%) versus post-discharge patients (44.4%) (p=0.005), and significantly reduced heart failure specific rehospitalisations (10.1%) versus post-discharge patients (27.8%) (p=0.018). There was no significant difference in all-cause death (p=0.743) and cardiovascular death (p=0.816) between the two groups. Initiating SGLT2i post-discharge was an independent predictor of cardiovascular rehospitalisation (hazard ratio 2.40, 95% confidence interval 1.31 to 4.41, p=0.005). In conclusion, inpatient SGLT2i initiation for HFrEF exacerbations may reduce cardiovascular and heart failure specific rehospitalisation versus initiation postdischarge. In the absence of contraindications, clinicians should consider initiating SGLT2i once patients are clinically stable during inpatient HFrEF admissions.

Abstract Background Emphasis is placed on the link between oral health and Infective Endocarditis (IE), particularly around odontogenic infections and specific dental procedures. The Adult Dental Health Survey in 2009 showed 45% of adults in the UK required dental intervention typically associated with developing IE. Antibiotic prophylaxis in this context is not without controversy. With gum and periodontic disease endemic, is the modern issue one of generalised poor oral health as a risk factor for IE? Purpose To determine the impact of oral health on risk and outcome in IE. Terminology SDCEP published dental guidelines of when to consider AP against IE for dental procedures. It identifies dental procedures that can cause transient bacteraemia. Methodology Data were collected from October 2020-Januaury 2023 in 123 patients with confirmed IE at a central London cardiac surgical centre. Patients had a focussed dental assessment with history, intraoral examination and dental panoramic radiograph to determine the risk and extent of oral disease. Results Average age was 54.2years. 77/123 (63%) had native IE (NVE) and 46 (37%) prosthetic (PVE). 17 (37%) cultured oral organisms from blood (Table 1); 8 (47%) of these organisms are associated with active dental disease (decay, periodontal disease, dental infection). Organisms can be found in Table 2. However, 93/123 (76%) had oral caries requiring dental treatment, irrespective of typical portal of entry for that organism. The proposed dental treatment posed a high risk for causing IE in 70%. 93/123 (76%) needed further dental treatment within six months rendering only 12% of patients orally stable. Oral organisms were seen more frequently in NVE (41/77) vs PVE (17/46). There was no difference in the incidence of dental disease requiring treatment (77% NVE vs 74% PVE). Whilst 27% of PVE had had recent (within 4 months) dental treatment compared to 73% NVE, only 1 PVE patient grew an oral commensal compared to 82% of NVE patients. Conclusion Prevention of IE is key to reducing the morbidity and mortality of this disease. We see oral commensals causing IE in 47%, with only 12% of this modern IE cohort dentally stable. Despite this, there was no difference in rates of dental disease requiring invasive treatment when stratified by oral vs non-oral organisms. A robust public health strategy is required to reduce the risk of oral disease driving IE.

Background Infective endocarditis (IE) is a rare, highly morbid condition with 17% in-hospital mortality. A total of 25–30% require surgery and there is ongoing debate with regard to markers predicting patient outcomes and guiding intervention. This systematic review aims to evaluate all IE risk scores currently available. Methods Standard methodology (PRISMA guideline) was used. Papers with risk score analysis for IE patients were included, with attention to studies reporting area under the receiver-operating characteristic curve (AUC/ROC). Qualitative analysis was carried out, including assessment of validation processes and comparison of these results to original derivation cohorts where available. Risk-of-bias analysis illustrated according to PROBAST guidelines. Results Of 75 articles initially identified, 32 papers were analyzed for a total of 20 proposed scores (range 66–13,000 patients), 14 of which were specific for IE. The number of variables per score ranged from 3 to 14 with only 50% including microbiological variables and 15% including biomarkers. The following scores had good performance (AUC > 0.8) in studies proposing the score (often the derivation cohort); however fared poorly when applied to a new cohort: PALSUSE, DeFeo, ANCLA, RISK-E, EndoSCORE, MELD-XI, COSTA, and SHARPEN. DeFeo score demonstrated the largest discrepancy with initial AUC of 0.88, compared to 0.58 when applied to different cohorts. The inflammatory response in IE has been well documented and CRP has been found to be an independent predictor for worse outcomes. There is ongoing investigation on alternate inflammatory biomarkers which may assist in IE management. Of the scores identified in this review, only three have included a biomarker as a predictor. Conclusion Despite the variety of available scores, their development has been limited by small sample size, retrospective collection of data and short-term outcomes, with lack of external validation, limiting their transportability. Future population studies and large comprehensive registries are required to address this unmet clinical need.

Abstract Background/intro Cardiac device-related infective endocarditis (CDRIE) is a rare but serious complication of cardiac device insertion with a high mortality rate. Cardiac devices are increasingly being implanted in older patients amid an ageing population with more comorbidities. Our centre is a large cardiac surgery referral centre in London. The centre implants a large number of cardiac devices per year (an average of 2168 per year from 2016 - 2019). The IE multidisciplinary team (IE MDT) manages approximately 150 IE referrals from the region per year. Purpose We aimed to describe a cohort of patients with CRDIE, referred to the IE MDT over 5 years (2015-2020), to generate a contemporary representation of patients with CDRIE. Methods We carried out a retrospective review of all referrals to the IE MDT between 2015 and 2020, identifying all patients with CDRIE - infection extending to the electrode leads, cardiac valve lead(s) or endocardial surface (ESC). All patients who were discussed at the IE MDT between October 2015 and March 2020 were screened, based on inclusion criteria according to the ESC's definition of CDRIE. Patients who had an infection of the cardiac device pocket with no evidence of IE were excluded. Results 60 out of 928 IE patients had confirmed CRDIE after discussion in the IE MDT from 10/2015 and 03/2020. The average age of the cohort was 70.3 (male =44, 73%). 61.7% of the devices were PPM (n=37), 10% were ICD, 20% were CRT-D, and 8.3% were CRT-P. The average duration of device therapy before removal was 64 months. 66.7% of devices were extracted (n=40) and 33.3% were managed medically (n=20). 43.3% of the cohort had prosthetic valves (n=26), and 13.3% of the total cohort had tissue aortic valve implants (TAVI) (n=8). 85% had a transesophageal echo (TOE) procedure (n=51) and 61.7% went on to have a PET CT scan (n=37). The overall inpatient mortality was 25% (n=15), rising to 45% at 12 months (n=27). Patients managed medically had a significantly higher mortality at 6 and 12 months compared to those who received an extraction and antibiotics (figure 1). There was no difference in left or right ventricular systolic function pre- and post- treatment on average or degree of tricuspid regurgitation. Medically managed patients were frailer by Charlson Index (average Charlson Index score 3) than surgically managed patients (average Charlson Index score 2). Conclusions In a retrospective assessment of CRDIE, we found that there is a low incidence of CRDIE complicating cardiac device insertion at BHC when compared to the national average. We found that surgical removal improves the likelihood of survival at 6 and 12 months when compared to medical management in those with a severe Charlson score, suggesting that even in cases of frailty and multiple morbidities, device extraction is preferable (figure 2).Survival curve of all CDRIE patientsSurvival curve in the severely frail

HomeJournal of the American Heart AssociationVol. 11, No. 16Infective Endocarditis Remains a Deadly Disease—It's Bad News, Especially When Staphylococci and Enterococci Are Involved: A Call to Action Open AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessEditorialPDF/EPUBInfective Endocarditis Remains a Deadly Disease—It's Bad News, Especially When Staphylococci and Enterococci Are Involved: A Call to Action Christopher P. Primus and Simon Woldman Christopher P. PrimusChristopher P. Primus *Correspondence to: Christopher P. Primus, MBBS, Specialised Cardiology Division, Barts Heart Centre, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, United Kingdom. Email: E-mail Address: [email protected] https://orcid.org/0000-0002-7464-5210 , Barts Heart Centre, , St Bartholomew's Hospital, Barts Health NHS Trust, , London, , United Kingdom, and Simon WoldmanSimon Woldman https://orcid.org/0000-0003-2156-4019 , Barts Heart Centre, , St Bartholomew's Hospital, Barts Health NHS Trust, , London, , United Kingdom, , University College London, , London, , United Kingdom, Originally published10 Aug 2022https://doi.org/10.1161/JAHA.122.026788Journal of the American Heart Association. 2022;11:e026788This article is a commentary on the followingTemporal Changes, Patient Characteristics, and Mortality, According to Microbiological Cause of Infective Endocarditis: A Nationwide StudyOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: August 10, 2022: Ahead of Print In this issue of the Journal of the American Heart Association (JAHA), Østergaard and colleagues present data drawn from national registries across Denmark, providing clear insight to the common pathogens and associated outcomes following a first episode of infective endocarditis (IE).1 Understanding the predictors of poor outcome and identifying modifiable patient‐ and disease‐related factors are key to building an evidence‐based approach to tackle the high morbidity and mortality associated with IE. Danish registries provide a unique opportunity to achieve this, with individual citizens traceable across pseudoanonymized national databases.The Danish National Patient Registry holds information on every hospital admission in Denmark since 1977, with International Classification of Diseases, Tenth Revision (ICD‐10) coded diagnoses obtained from patient discharge paperwork. Although coding relating to IE is not without pitfalls, the authors identified patients with a first diagnosis of IE from 2010 to 2017 with a combination of ICD‐10 codes previously identified as having good positive predictive value for IE.2 This allowed linking of patients with first‐time IE to clinical, microbiological, and outcome registries, containing key demographic and comorbidity data. Over the 8 years of study, 4123 admissions with IE were included in analyses, with no significant difference in incidence. Outcome data were available for both inpatient stay and in the medium term, with a median follow‐up period of 2.3 years (interquartile range 0.4–4.6 years). This allowed for identification of trends over time, accounting for captured patient characteristics and causative organism. Interestingly, in the more recent quartile of study, patients were older, had proportionally more prosthetic valve IE, and were more likely to have a past history of cancer and diabetes compared with earlier time periods.1Staphylococci were the leading causative organism in IE (28.1%), followed by Streptococci (26.0%) and Enterococci (15.5%) with blood culture negative IE (BCNIE) accounting for 18.9% of cases.1 This is in line with international registries showing falling rates of streptococcal IE and climbing staphylococcal and enterococcal IE.3, 4 However, there was no temporal change in the proportion of IE secondary to these organisms in the period of study. This does, however, reflect the shift in causative organism over the past 20 years, associated with the climbing incidence of invasive procedures and a population with a longer life expectancy.5, 6, 7 These relate not only to cardiac interventions with climbing rates of valve surgery, the evolution of transcatheter aortic valve implantation, and cardiac implantable devices but also to indwelling vascular catheters associated with dialysis and the management of cancer.3, 5Given the important role of viridans streptococci in IE, an increased population health focus on improving oral health and dental hygiene may also contribute to falling rates of streptococcal disease.8, 9 An inevitable impact of this change in causative organism has been a shift from subacute bacterial IE to rapid deterioration with an acute presentation for staphylococcal disease, in particular. This demands new treatment paradigms for the diagnosis and management of IE, with many patients seeking evaluation of fever later in their illness. This is despite guidance for patients deemed at high risk, including those with valvular heart disease, prosthetic heart valves, and previous IE; this has been particularly evident during the COVID‐19 pandemic.10, 11, 12, 13 Although Staphylococcus aureus is a known predictor of poor outcome in IE, only 13.6% of patients underwent operative intervention in the current study, compared with 20.1% of those with streptococcal IE, 24.3% with enterococcal IE, and 21.1% with BCNIE.1Despite high rates of morbidity and mortality, IE remains a rare disease, and this may explain in part why health care services are ill equipped to deliver rapid diagnostics to patients with IE that may well be life saving. This is highlighted in the current study, and other large international registries, where almost 1 in 5 cases were BCNIE (18.9%).1, 3, 4 This is despite established diagnostic pathways to identify the causative pathogen in this scenario, including the use of 16S rDNA polymerase chain reaction technology.3, 12, 13 This phenomenon is reflected in the current study, with a statistically significant decline in the proportion of BCNIE over the period of study from 24.1% in 2010 to 18.4% in 2017.1 Further promising work continues in this area, with the emerging technologies of both metagenomics to identify bacterial DNA in resected valve tissue and proteomics to capture proteins pathognomonic of certain bacteria and fungi.14, 15 Critically, identifying the causative organism will allow more targeted therapeutics, reducing toxicity and improving outcomes for this group in particular.The paradigm shift in the timing of surgery in IE has been adopted in international guidelines, with a move away from the concept of achieving sterility and operating late, toward early surgery to avoid heart failure, intractable sepsis, irreversible structural damage, and death.12, 13 This move led to reduced all‐cause mortality in a large meta‐analysis, favoring surgery before 7 days compared with 8 to 21 days, with an odds ratio (OR) of 0.61 (95% CI, 0.50–0.74), albeit with a possible higher rate of recurrence in the early surgery group.16 The modern approach to the management of IE is to therefore actively identify the established indications for surgical intervention in every patient at the time of diagnosis, and regularly thereafter, as a part of a multidisciplinary expert IE team.12, 17, 18 Despite this, the EuroENDO (European Infective Endocarditis) registry identified 69.3% of patients had an indication for surgery, with only 51.2% of patients actually undergoing surgical intervention; the remaining 18.1% had the highest rates of mortality.3 Of those undergoing surgery, just 31.5% went to the operating theater emergently or urgently, with 32.0% operated beyond the first week and 36.5% electively. In the current study, the population statistics preclude identification of surgical indications; however operative rates declined steadily from 24.8% in 2010 to 2011 to 17.6% in 2016 to 2017.1 If we are to reduce mortality in IE further, it is imperative we reconfigure our services to improve response times, training a cohort of cardiologists to identify IE early and manage it aggressively, and a further cohort of cardiac surgeons and anesthetists who operate upon these patients on a regular basis.The most striking findings from Østergaard and colleagues however, relate to in‐hospital versus medium‐term mortality.Overall in‐hospital mortality was comparable to other European countries in the contemporary era at 18.7%, with highest mortality rates in S. aureus IE (28.2%) compared with just 11.1% in streptococcal IE.1 This translated to an OR of 3.5 (95% CI, 2.7–4.4) for S. aureus IE, OR of 2.0 (95% CI, 1.5–2.6) for BCNIE, OR of 1.8 (95% CI, 1.2–2.7) for coagulase negative Staphylococci (CoNS), and OR of 1.5 (95% CI, 1.0–2.3) for enterococcal IE. A similar distribution of risk was seen for 1‐year mortality, albeit ≈10% higher in absolute values.1However, at a median follow‐up of 2.3 years (interquartile range 0.4–4.6 years) mortality rates were astounding: 74.4% for enterococcal IE, 70.1% for S. aureus, 62.4% for BCNIE and coagulase negative Staphylococci IE, and 58.5% for streptococcal IE. This higher rate of mortality for patients with enterococcal disease, compared with S. aureus, was identified only when differentiating mortality at time from discharge compared with admission.1 This suggests that although S. aureus IE is high risk at presentation, if patients survive their admission, they do better compared with their counterparts with enterococcal disease, who are older with more comorbidities.To put these findings in context, mortality rates in observational studies of patients with heart failure between 2000 and 2009 to 2010 show a 1‐year mortality of 20% and a 5‐year mortality of 53% to 67%.19, 20 Even without the anticipated real‐world reduction in mortality with novel heart failure pharmacotherapy, the mortality in IE is significantly worse than in heart failure. Yet most countries spend very little on the organization of IE services in comparison with heart failure.In conclusion, the present study highlights significant mortality in IE, with Staphylococci as the leading causative organism in an unselected cohort of patients with IE. When adjusting for inpatient mortality, the prognosis following enterococcal IE is also poor. Patient characteristics are important factors in relation to the causative organism, particularly in relation to intracardiac prosthetic material and indwelling long‐term vascular catheters.The very high rates of medium‐term mortality are a serious concern, and as a community we must strive to identify and address modifiable risk factors to improve outcome. To achieve this, we must innovate in diagnostics, adopt a mindset of active consideration and adoption of early surgery, and develop robust pathways that facilitate working in expert teams.DisclosuresNone.Footnotes*Correspondence to: Christopher P. Primus, MBBS, Specialised Cardiology Division, Barts Heart Centre, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, United Kingdom. Email: christopher.primus@nhs.netThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.See Article by Østergaard et al.For Disclosures, see page 3.References1 Østergaard L, Voldstedlund M, Bruun NE, Bundgaard H, Iversen K, Køber N, Christensen JJ, Rosenvinge FS, Jarløv JO, Moser C, et al. Temporal changes, patient characteristics, and mortality, according to microbiological cause of infective endocarditis: a nationwide study. J Am Heart Assoc. 2022; 11:e025801. doi: 10.1161/JAHA.122.025801LinkGoogle Scholar2 Fawcett N, Young B, Peto L, Quan TP, Gillott R, Wu J, Middlemass C, Weston S, Crook DW, Peto TEA, et al. 'Caveat emptor': the cautionary tale of endocarditis and the potential pitfalls of clinical coding data—an electronic health records study. BMC Med. 2019; 17:169. doi: 10.1186/s12916-019-1390-xCrossrefMedlineGoogle Scholar3 Habib G, Erba PA, Iung B, Donal E, Cosyns B, Laroche C, Popescu BA, Prendergast B, Tornos P, Sadeghpour A, et al. Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC‐EORP EURO‐ENDO (European infective endocarditis) registry: a prospective cohort study. Eur Heart J. 2019; 40:3222–3232. doi: 10.1093/eurheartj/ehz620CrossrefMedlineGoogle Scholar4 Murdoch DR, Corey GR, Hoen B, Miró JM, Fowler VG, Bayer AS, Karchmer AW, Olaison L, Pappas PA, Moreillon P, et al. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century. Arch Intern Med. 2009; 169:463.CrossrefMedlineGoogle Scholar5 Cahill TJ, Prendergast BD. Infective endocarditis. Lancet. 2016; 387:882–893. doi: 10.1016/S0140-6736(15)00067-7CrossrefMedlineGoogle Scholar6 Talha KM, Baddour LM, Thornhill MH, Arshad V, Tariq W, Tleyjeh IM, Scott CG, Hyun MC, Bailey KR, Anavekar NS, et al. Escalating incidence of infective endocarditis in Europe in the 21st century. Open Heart. 2021; 8:e001846. doi: 10.1136/openhrt-2021-001846CrossrefMedlineGoogle Scholar7 Pant S, Patel NJ, Deshmukh A, Golwala H, Patel N, Badheka A, Hirsch GA, Mehta JL. Trends in infective endocarditis incidence, microbiology, and valve replacement in the United States from 2000 to 2011. J Am Coll Cardiol. 2015; 65:2070–2076. doi: 10.1016/j.jacc.2015.03.518CrossrefMedlineGoogle Scholar8 GBD 2017 Oral Disorders Collaborators , Bernabe E, Marcenes W, Hernandez CR, Bailey J, Abreu LG, Alipour V, Amini S, Arabloo J, Arefi Z, Arora A, et al. Global, regional, and national levels and trends in burden of oral conditions from 1990 to 2017: a systematic analysis for the Global Burden of Disease 2017 Study. J Dent Res. 2020; 99:362–373. doi: 10.1177/0022034520908533CrossrefMedlineGoogle Scholar9 Lockhart PB, Brennan MT, Thornhill M, Michalowicz BS, Noll J, Bahrani‐Mougeot FK, Sasser HC. Poor oral hygiene as a risk factor for infective endocarditis–related bacteremia. J Am Dent Assoc. 2009; 140:1238–1244. doi: 10.14219/jada.archive.2009.0046CrossrefMedlineGoogle Scholar10 Havers‐Borgersen E, Fosbøl EL, Butt JH, Petersen JK, Dalsgaard A, Kyhl F, Schou M, Phelps M, Kragholm K, Gislason GH, et al. Incidence of infective endocarditis during the coronavirus disease 2019 pandemic: a nationwide study. Int J Cardiol Heart Vasc. 2020; 31:100675. doi: 10.1016/j.ijcha.2020.100675CrossrefMedlineGoogle Scholar11 Escolà‐Vergé L, Cuervo G, de Alarcón A, Sousa D, Barca LV, Fernández‐Hidalgo N; IE COVID‐19 Investigators . Impact of the COVID‐19 pandemic on the diagnosis, management and prognosis of infective endocarditis. Clin Microbiol Infect. 2021; 27:660–664. doi: 10.1016/j.cmi.2020.11.022CrossrefMedlineGoogle Scholar12 Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta J‐P, Del Zotti F, Dulgheru R, El Khoury G, Erba PA, Iung B, et al. 2015 ESC guidelines for the management of infective endocarditis. Eur Heart J. 2015; 36:3075–3128. doi: 10.1093/eurheartj/ehv319CrossrefMedlineGoogle Scholar13 Baddour LM, Wilson WR, Bayer AS, Fowler VG, Tleyjeh IM, Rybak MJ, Barsic B, Lockhart PB, Gewitz MH, Levison ME, et al. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications. Circulation. 2015; 132:1435–1486. doi: 10.1161/CIR.0000000000000296LinkGoogle Scholar14 Million M, Gaudin M, Melenotte C, Chasson L, Edouard S, Verdonk C, Prudent E, Amphoux B, Meresse S, Dorent R, et al. Metagenomic analysis of microdissected valvular tissue for etiological diagnosis of blood culture‐negative endocarditis. Clin Infect Dis. 2020; 70:2405–2412. doi: 10.1093/cid/ciz655CrossrefMedlineGoogle Scholar15 Snipsøyr MG, Wiggers H, Ludvigsen M, Stensballe A, Vorum H, Poulsen SH, Rasmussen LM, Petersen E, Honoré B. Towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysis. Int J Infect Dis. 2020; 96:73–81. doi: 10.1016/j.ijid.2020.02.026CrossrefMedlineGoogle Scholar16 Anantha Narayanan M, Mahfood Haddad T, Kalil A, Kanmanthareddy A, Suri R, Mansour G, Destache C, Baskaran J, Mooss A, Wichman T, et al. Early versus late surgical intervention or medical management for infective endocarditis: a systematic review and meta‐analysis. Heart. 2016; 102:950–957. doi: 10.1136/HEARTJNL-2015-308589CrossrefMedlineGoogle Scholar17 Botelho‐Nevers E, Thuny F, Casalta JP, Richet H, Gouriet F, Collart F, Riberi A, Habib G, Raoult D. Dramatic reduction in infective endocarditis–related mortality with a management‐based approach. Arch Intern Med. 2009; 169:1290–1298. doi: 10.1001/archinternmed.2009.192CrossrefMedlineGoogle Scholar18 Chirillo F, Scotton P, Rocco F, Rigoli R, Borsatto F, Pedrocco A, De Leo A, Minniti G, Polesel E, Olivari Z. Impact of a multidisciplinary management strategy on the outcome of patients with native valve infective endocarditis. Am J Cardiol. 2013; 112:1171–1176. doi: 10.1016/J.AMJCARD.2013.05.060CrossrefMedlineGoogle Scholar19 Gerber Y, Weston SA, Redfield MM, Chamberlain AM, Manemann SM, Jiang R, Killian JM, Roger VL. A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010. JAMA Intern Med. 2015; 175:996–1004. doi: 10.1001/jamainternmed.2015.0924CrossrefMedlineGoogle Scholar20 Tsao CW, Lyass A, Enserro D, Larson MG, Ho JE, Kizer JR, Gottdiener JS, Psaty BM, Vasan RS. Temporal trends in the incidence of and mortality associated with heart failure with preserved and reduced ejection fraction. JACC Heart Fail. 2018; 6:678–685. doi: 10.1016/j.jchf.2018.03.006CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesTemporal Changes, Patient Characteristics, and Mortality, According to Microbiological Cause of Infective Endocarditis: A Nationwide StudyLauge Østergaard, et al. Journal of the American Heart Association. 2022;11 August 16, 2022Vol 11, Issue 16 Article InformationMetrics Copyright © 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.122.026788PMID: 35946465 Originally publishedAugust 10, 2022 Keywordsheart valve diseaseinfective endocarditismortalityorganismpopulation studynationwide studyEditorialsblood stream infectionPDF download SubjectsCardiovascular SurgeryEpidemiologyInfectious EndocarditisMortality/SurvivalRisk Factors

Background and purpose NO is a vasodilator and independent modulator of cardiac remodelling. Commonly, in cardiac disease (e.g., heart failure), endothelial dysfunction (synonymous with NO deficiency) has been implicated in increased BP, cardiac hypertrophy and fibrosis. Currently, no effective therapies replacing NO have succeeded in the clinic. Inorganic nitrate (NO3-), through chemical reduction to nitrite and then to NO, exerts potent BP lowering, but whether it might be useful in treating undesirable cardiac remodelling is not known. Experimental approach We analysed demographics in a nested age- and sex-matched case-control study of hypertensive patients with or without left ventricular hypertrophy (NCT03088514) and assessed the effects of dietary nitrate in mouse models of cardiac dysfunction. Key results Lower plasma nitrite concentrations and vascular dysfunction accompanied cardiac hypertrophy and fibrosis in patients. In mouse models of cardiac remodelling, restoration of circulating nitrite levels using dietary nitrate improved endothelial dysfunction through targeting the xanthine oxidoreductase-driven increase in levels of H2O2 and superoxide, and decreased cardiac fibrosis through NO-mediated block of SMAD phosphorylation leading to improvements in cardiac structure and function. Conclusions and implications Dietary nitrate offers easily translatable therapeutic options for delivery of NO and thereby treatment of cardiac dysfunction.

Transient receptor potential cation channel subfamily V member 1 (TRPV1) is localized to sensory C‐fibres and its opening leads to membrane depolarization, resulting in neuropeptide release and neurogenic inflammation. However, the identity of the endogenous activator of TRPV1 in this setting is unknown. The arachidonic acid metabolites 12‐hydroperoxyeicosatetraenoyl acid (12‐HpETE) and 20‐hydroxyeicosatetraenoic acid (20‐HETE) have emerged as potential endogenous activators of TRPV1. However, whether these lipids underlie TRPV1‐mediated neurogenic inflammation remains unknown.

BACKGROUND:Patients with acute severe aortic regurgitation (AR) due to infective endocarditis can progress rapidly from the hemodynamically stable patient to pulmonary edema and cardiogenic shock. We sought to identify patients at risk of decompensation where emergent surgery should be undertaken. METHODS:We identified 90 patients with acute severe AR from the echocardiography laboratory database. Baseline clinical, hemodynamic (heart rate (HR) and blood pressure (BP)), and echocardiographic data including mitral filling, premature mitral valve closure (PMVC), and diastolic mitral regurgitation (DMR) were identified. The primary endpoint was subsequent development of pulmonary edema or severe hemodynamic instability. RESULTS:Patients who met the primary endpoint had a higher HR (98.5 bpm vs 80.5 bpm), lower diastolic BP (54 mm Hg vs 61.5 mm Hg), higher mitral E-wave velocity (113 cm/s vs 83 cm/s), higher E/e' ratio (12.4 vs 8), higher proportion of DMR (27.8% vs 7.4%), and PMVC (25% vs 9.3%) than patients who did not meet the endpoint. The proportion of patients with the primary endpoint increased as HR increased ((≤81 bpm) 3/30 (10%), (81-94 bpm) 11/31 (35.5%), (≥94 bpm) 22/29 (75.9%), P < .0001) and as the diastolic BP reduced ((≤54 mm Hg) 19/31 (61.3%), (54-63 mm Hg) 12/31 (38.7%), (≥63 mm Hg) 5/28 (17.9%), P = .003). Independent predictors were a higher HR (OR 1.08 (95% CI 1.04-1.13) P = .0003) and DMR (OR 4.71 (95% CI 1.23-18.09), P = .02). CONCLUSION:Decompensation in acute severe AR is common. Independent predictors of decompensation are increasing HR(≥94 bpm) and the presence of DMR. Those with these adverse markers should be considered for emergent surgery.

Type of funding sources: None. Diagnosis of blood culture negative infective endocarditis (BCNIE) is challenging, with positive microbiology key in the modified Duke Criteria (mDC). ESC IE Guidelines (2015) recommend the use of 18F-FDG PET/CT (PET) in cases where transoesophageal echocardiography (TOE) is equivocal and where cardiac implantable device-related IE (CIDRE) is suspected. We explored the role of PET to improve diagnostic certainty in the challenging cohort of BCNIE. Retrospective review of all suspected BCNIE patients undergoing PET (10/2015 to 01/2021). Myocardial suppression technique was used in all cases, and studies were assessed for valve/device avidity. Patients were classified as definite/possible/rejected IE by mDC pre- and post-PET, with incremental benefit assessed by net reclassification index (NRI) versus actual diagnosis. Actual diagnosis was defined by Endocarditis Team consensus or surgical specimen (where available) at a minimum of 2-months following index admission. PET was performed in 110/807 (13.6%) cases overall. BCNIE prevalence was 18% across the total cohort, with 25/110 (22.7%) PET studies in BCNIE patients (male = 17, mean age 65). (p = 0.16 for PET in BCNIE compared to overall). PET was undertaken in 8 CIDRE, 9 native IE (NVE) and 10 prosthetic IE (PVE); 2-patients had suspected CIDRE + PVE. TOE was performed in all cases, and surgery was required in 8/25 patients. IE was confirmed in 44% of cases. PET sensitivity, specificity, positive and negative predictive values were 73%, 93%, 89% and 81%, respectively. Addition of PET to the mDC improved re-classification to definite or rejected IE, with NRI 0.633 (positive NRI 0.3; negative 0.333), and added weight to the original mDC classification in 14/25 (56%) of cases. PET improves diagnostic certainty when combined with mDC in the evaluation of patients with BCNIE across NVE, PVE and CIDRE.

International guidance recognizes the shortcomings of the modified Duke Criteria (mDC) in diagnosing infective endocarditis (IE) when transoesophageal echocardiography (TOE) is equivocal. 18F-FDG PET/CT (PET) has proven benefit in prosthetic valve endocarditis (PVE), but is restricted to extracardiac manifestations in native disease (NVE). We investigated the incremental benefit of PET over the mDC in NVE. Dual-center retrospective study (2010-2018) of patients undergoing myocardial suppression PET for NVE and PVE. Cases were classified by mDC pre- and post-PET, and evaluated against discharge diagnosis. Receiver Operating Characteristic (ROC) analysis and net reclassification index (NRI) assessed diagnostic performance. Valve standardized uptake value (SUV) was recorded. 69/88 PET studies were evaluated across 668 patients. At discharge, 20/32 had confirmed NVE, 22/37 PVE, and 19/69 patients required surgery. PET accurately re-classified patients from possible, to definite or rejected (NRI: NVE 0.89; PVE 0.90), with significant incremental benefit in both NVE (AUC 0.883 vs 0.750) and PVE (0.877 vs 0.633). Sensitivity and specificity were 75% and 92% in NVE; 87% and 86% in PVE. Duration of antibiotics and C-reactive Protein level did not impact performance. No diagnostic SUV cut-off was identified. PET improves diagnostic certainty when combined with mDC in NVE and PVE.