Acute Q Fever Endocarditis: A Paradigm Shift Following the Systematic Use of Transthoracic Echocardiography During Acute Q Fever.

BACKGROUND: As Q fever, caused by Coxiella burnetii, is a major health challenge due to its cardiovascular complications, we aimed to detect acute Q fever valvular injury to improve therapeutic management. METHODS: In the French national reference center for Q fever, we prospectively collected data from patients with acute Q fever and valvular injury. We identified a new clinical entity, acute Q fever endocarditis, defined as valvular lesion potentially caused by C. burnetii: vegetation, valvular nodular thickening, rupture of chorda tendinae, and valve or chorda tendinae thickness. To determine whether or not the disease was superimposed on an underlying valvulopathy, patients' physicians were contacted. Aortic bicuspidy, valvular stenosis, and insufficiency were considered as underlying valvulopathies. RESULTS: Of the 2434 patients treated in our center, 1797 had acute Q fever and 48 had acute Q fever endocarditis. In 35 cases (72%), transthoracic echocardiography (TTE) identified a valvular lesion of acute Q fever endocarditis without underlying valvulopathy. Positive anticardiolipin antibodies (>22 immunoglobulin G-type phospholipid units [GPLU]) were independently associated with acute Q fever endocarditis (odds ratio [OR], 2.7 [95% confidence interval {CI}, 1.3-5.5]; P = .004). Acute Q fever endocarditis (OR, 5.2 [95% CI, 2.6-10.5]; P < .001) and age (OR, 1.7 [95% CI, 1.1-1.9]; P = .02) were independent predictors of progression toward persistent C. burnetii endocarditis. CONCLUSIONS: Systematic TTE in acute Q fever patients offers a unique opportunity for early diagnosis of acute Q fever endocarditis and for the prevention of persistent endocarditis. Transesophageal echocardiography should be proposed in men, aged >40 years, with anticardiolipin antibodies >60 GPLU when TTE is inconclusive or negative.

Marseille scoring system for empiric treatment of infective endocarditis.

Despite advances in medical, surgical, and critical care, infective endocarditis (IE) remains associated with considerable morbidity and mortality. We evaluated the performance of the Marseille score, including clinical data and biological tests obtained within 2 h, to identify patients at high risk of IE in order to initiate early antimicrobial treatment. This was secondarily confirmed using modified ESC criteria combined with molecular testing and (18)fluorodeoxyglucose-positron emission tomography/computed tomography as diagnostic tools. In a prospective cohort study, we enrolled 484 patients with cardiovascular predisposition and clinical suspicion of IE from 2011 to 2013. The final diagnosis was definite IE in 123 patients and possible IE in 107. Marseille score was calculated adding one point for each present parameter (range 0-9). This score includes clinical, epidemiological (male, fever, splenomegaly, clubbing, vascular disease and stroke) and biological criteria (Leucocytes >10,000/mm3, sedimentation rate (SR) > 50/mm or C reactive protein >10 mg/L and hemoglobin <100 g/l). A score of 2 or more performed best in predicting IE in patients with predisposing heart lesions. Sensitivity was better on left-side heart lesions (94%) than on right-side heart lesions (85%) (p = 0.04) and better for valvulopathy (94%) than intra cardiac devices (84%) (p = 0.02). The predictive positive value of prosthetic valves was greater than that of native valves (p = 0.02). Using our simple Marseille score combined with our standardized diagnostic procedures would help improve IE management by focusing on early empiric treatment within 2 h of admission for patients with cardiac predisposition factors.

Evaluation of empirical treatment for blood culture-negative endocarditis.

OBJECTIVES: Much progress has been made in understanding the main causes of blood culture-negative endocarditis (BCNE). Few studies concerning BCNE treatment (due to previous antibiotics used or fastidious pathogens) are available. We performed this study to evaluate the effectiveness of our therapeutic protocol in BCNE, based on compliance with the protocol, outcome and 1 year mortality. PATIENTS AND METHODS: We collected prospectively and analysed retrospectively cases of BCNE between 2002 and 2014, using a simplified and standardized protocol developed by our multidisciplinary team. We apply two kinds of protocols to treat BCNE, which include only four intravenous antimicrobial agents: amoxicillin, vancomycin, gentamicin and amphotericin B. RESULTS: We had 177 patients with definite BCNE. There were 154 (87.0%) patients treated with both appropriate antimicrobial agents and appropriate duration of treatment. We analysed the causes of inappropriate treatment in 13 (7.3%) cases and inappropriate duration in 10 (5.6%) cases. The treatment changes were justified in all cases except one of discharge against medical advice. The fatality rate was 5.1% (nine cases) and all deaths occurred in the group of patients who were treated with appropriate treatment; however, four deaths were not attributable to empirical treatment failure. Concerning the other deaths, the lack of surgical management, in association with empirical treatment, could explain our protocol's failure, such as poorly tolerated surgery. CONCLUSIONS: Our protocol is efficient and our mortality rate was low, compared with the literature review. This may result from a strategy that uses a sampling procedure and a standardized protocol at the same time.

Fatal Neisseria macacae infective endocarditis: first report.

INTRODUCTION: Neisseria macacae is a Gram-negative diplococcus, found in the oropharynx of healthy Rhesus Monkeys. Infections caused by N. macacae in humans are extremely rare. CASE PRESENTATION: We present here the first case of N. macacae infective endocarditis in a 65-year-old man with a native aortic valve infection complicated by a peri-aortic abscess. N. macacae was isolated from blood culture and was found on the cardiac valve using 16S rDNA detection. Despite an appropriate antibiotic therapy, and aortic homograft replacement, and mitral repair, the patient died 4 days after surgery from a massive hemorrhagic stroke.

Impact of the SARS-CoV-2 Pandemic on the Management and Prognosis of Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) is a serious condition which is difficult to diagnose and to treat, both medically and surgically. OBJECTIVES: The objective of this study was to evaluate the impact of the SARS-CoV-2 pandemic on the management of patients with IE. METHODS: We conducted a single-centre retrospective study including patients hospitalized for IE during the pandemic (Group 2) compared with the same period the year before (Group 1). We compared clinical, laboratory, imagery, therapeutic, and patient outcomes between the two groups. RESULTS: A total of 283 patients were managed for possible or definite IE (164 in Group 1 and 119 in Group 2). There were more intravenous drug-related IE patients in Group 2 (p = 0.009). There was no significant difference in surgery including intra-cardiac device extraction (p = 0.412) or time to surgery (p = 0.894). The one-year mortality was similar in both groups (16% versus 17.7%, p = 0.704). The recurrence rate was not significantly different between the two groups (5.9% in Group 2 versus 9.1% in Group 1, p = 0.311). CONCLUSIONS: The SARS-CoV-2 pandemic did not appear to have had a negative impact on the management of patients with IE. Maintenance of the activities of the endocarditis team within the referral centre probably contributed to this result. Nevertheless, the high proportion of intravenous drug-addicted patients in the pandemic cohort suggests that the SARS-CoV-2 pandemic had a major psychosocial impact.

Atrioventricular conduction disorders in aortic valve infective endocarditis.

BACKGROUND: Aortic valve infective endocarditis may be complicated by high-degree atrioventricular block in up to 10-20% of cases. AIM: To assess high-degree atrioventricular block occurrence, contributing factors, prognosis and evolution in patients referred for aortic infective endocarditis. METHODS: Two hundred and five patients referred for aortic valve infective endocarditis between January 2018 and March 2021 were included in this study. A comprehensive assessment of clinical, electrocardiographic, biological, microbiological and imaging data was conducted, with a follow-up carried out over 1 year. RESULTS: High-degree atrioventricular block occurred in 22 (11%) patients. In univariate analysis, high-degree atrioventricular block was associated with first-degree heart block at admission (odds ratio 3.1; P=0.015), periannular complication on echocardiography (odds ratio 6.9; P<0.001) and severe biological inflammatory syndrome, notably C-reactive protein (127 vs 90mg/L; P=0.011). In-hospital mortality (12.7%) was higher in patients with high-degree atrioventricular block (odds ratio 4.0; P=0.011) in univariate analysis. Of the 16 patients implanted with a permanent pacemaker for high-degree atrioventricular block and interrogated, only four (25%) were dependent on the pacing function at 1-year follow-up. CONCLUSIONS: High-degree atrioventricular block is associated with high inflammation markers and periannular complications, especially if first-degree heart block is identified at admission. High-degree atrioventricular block is a marker of infectious severity, and tends to raise the in-hospital mortality rate. Systematic assessment of patients admitted for infective endocarditis suspicion, considering these contributing factors, could indicate intensive care unit monitoring or even temporary pacemaker implantation in those at highest risk.

Multimodality imaging in marantic endocarditis associated with cancer: a multicentric cohort study.

AIMS: We aimed to assess the role of multimodality imaging (MMI) in the diagnosis of marantic endocarditis (ME) associated with cancers and to describe the clinical characteristics, management, and outcome of these patients. METHODS AND RESULTS: In a retrospective multicentric study including four tertiary centres for the treatment of endocarditis in France and Belgium, patients with a diagnosis of ME were included. Demographic, MMI [echocardiography, computed tomography (CT), and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)], and management data were collected. Long-term mortality was analysed. Between November 2011 and August 2021, 47 patients with a diagnosis of ME were included. Mean age was 65 ± 11 years. ME occurred in 43 cases (91%) on native valves. Vegetations were detected by echocardiography in all cases and in 12 cases (26%) by CT. No patient had an increased cardiac 18F-FDG valve uptake. The most common cardiac valve involved was aortic (34 cases, 73%). Twenty-two patients (46%) had a known cancer before ME, and 25 cases (54%) were diagnosed thanks to multimodality imaging. 18FDG PET/CT was performed in 30 patients (64%) and allowed a new diagnosis of cancer in 14 patients (30%). Systemic embolism was frequent (40 patients, 85% of cases). Forty-one patients (87%) were treated medically with anticoagulation therapy. One-year mortality was 55% (26 patients). CONCLUSION: ME remains associated with a high risk of complications and death.

Impact of cardiac surgery on left-sided infective endocarditis with intermediate-length vegetations.

OBJECTIVE: The best strategy to manage patients with left-sided infective endocarditis (IE) and intermediate-length vegetations (10-15 mm) remains uncertain. We aimed to evaluate the role of surgery in patients with intermediate-length vegetations and no other European Society of Cardiology guidelines-approved surgical indication. METHODS: We retrospectively enrolled 638 consecutive patients admitted to three academic centres (Amiens, Marseille and Florence University Hospitals) between 2012 and 2022 for left-sided definite IE (native or prosthetic) with intermediate-length vegetations (10-15 mm). We compared four clinical groups: medically (n=50) or surgically (n=345) treated complicated IE, medically (n=194) or surgically (n=49) treated uncomplicated IE. RESULTS: Mean age was 67±14 years. Women were 182 (28.6%). The rate of embolic events on admission was 40% in medically treated and 61% in surgically treated complicated IE, 31% in medically treated and 26% in surgically treated uncomplicated IE. The analysis of all-cause mortality showed the lowest 5-year survival rate for medically treated complicated IE (53.7%). We found a similar 5-year survival rate for surgically treated complicated IE (71.4%) and medically treated uncomplicated IE (68.4%). The highest 5-year survival rate was observed in surgically treated uncomplicated IE group (82.4%, log-rank p<0.001). The analysis of the propensity score-matched cohort estimated an HR of 0.23 for uncomplicated IE treated surgically compared with medical therapy (p=0.005, 95% CI: 0.079 to 0.656). CONCLUSIONS: Our results suggest that surgery is associated with lower all-cause mortality than medical therapy in patients with uncomplicated left-sided IE with intermediate-length vegetations even in the absence of other guideline-based indications.

Clinical and Echocardiographic Features of Patients With Infective Endocarditis and Bicuspid Aortic Valve According to Echocardiographic Definition of Valve Morphology.

BACKGROUND: The influence of different bicuspid aortic valve (BAV) morphology in the clinical course of infective endocarditis (IE) has not yet been investigated. This study aimed to describe the clinical and echocardiographic features of IE in patients with BAV (BAVIE) according to valve morphology. METHODS: Patients with definite BAVIE prospectively enrolled in 4 high-volume referral centers from 2000 to 2019 were evaluated and divided into 2 groups according to the echocardiographic definition of fused BAV morphology: right-left coronary (RL type) and right noncoronary or left noncoronary (non-RL type) cusp fusion. All patients were followed up for 1 year. RESULTS: One hundred thirty-eight patients with BAVIE were included (77.7% male; median age, 52 [36.83-61.00] years): 112 patients with RL type (81%) and 26 patients with non-RL type BAV (19%), with no significant differences in age, sex, and comorbidities between groups. Although 43% of the cohort had known BAV, the referral was late after symptom onset, particularly for the RL phenotype; time from symptom onset to hospitalization >30 days (31.3% vs 11.5%; P = .032) and New York Heart Association class ≥ II (64.3% vs 42.3%; P = .039) were more frequent in patients with RL type BAV than in patients with non-RL type BAV. Conversely, patients with non-RL type BAV had a higher incidence of hemorrhagic stroke (19.2% vs 5.4%; P = .034) and high-grade atrioventricular block (11.5% vs 0.9%; P = .021). Streptococcus viridans was more frequently isolated in patients with non-RL type BAV than in patients with RL type BAV (44% vs 24.1%; P = .045). No difference in short- and intermediate-term mortality was observed between groups. CONCLUSIONS: Clinical profile and echocardiographic features in BAVIE patients may differ according to valve morphology, and patients with BAVIE appear to be referred late, even when BAV disease is previously known.

Influence of the healthcare pathway on the outcome of patients with infective endocarditis.

AIMS: To determine the prognosis of patients treated for infective endocarditis (IE) according to their healthcare pathway. To assess how the ESC guidelines are implemented concerning the performance of transoesophageal echocardiography, the use of antibiotic therapy, and the performance of valve surgery; and to compare the epidemiological profile of IE according to the type of centres in which the patients are hospitalized. METHODS AND RESULTS: In a prospective multicentric study including 22 hospitals in the South-East of France, 342 patients were classified into three groups according to their healthcare pathway: 119 patients diagnosed and taken care entirely in a reference centre or hospital with cardiac surgery [Referral Center (RC) group], 111 patients diagnosed and initially taken care in a non-RC (NRC), then referred in a centre including cardiac surgery [transferred to the Referral Center (TRC) group] and 112 patients totally taken care in the NRC (NRC group). One-year mortality was 26% (88 deaths) and was not significantly different between Groups 1 and 2 (20 vs. 21%, P = 0.83). Patients in the NRC group had a higher mortality (37%) compared with patients in the RC and TRC groups (P < 0.001). ESC guidelines were not implemented similarly depending on the healthcare pathway (P = 0.04). Patients in the NRC group were significantly older (P < 0.001) and had more comorbidities (P < 0.001) than patients treated in referral centres. CONCLUSION: Prognosis of patients with IE is influenced by their healthcare pathway. Patients treated exclusively in NRC have a worse prognosis than patients treated in referral or surgical centres.

A Massive Number of Extracellular Tropheryma whipplei in Infective Endocarditis: A Case Report and Literature Review.

Whipple's disease (WD) is a chronic multisystemic infection caused by Tropheryma whipplei. If this bacterium presents an intracellular localization, associated with rare diseases and without pathognomonic signs, it is often subject to a misunderstanding of its physiopathology, often a misdiagnosis or simply an oversight. Here, we report the case of a patient treated for presumed rheumatoid arthritis. Recently, this patient presented to the hospital with infectious endocarditis. After surgery and histological analysis, we discovered the presence of T. whipplei. Electron microscopy allowed us to discover an atypical bacterial organization with a very large number of bacteria present in the extracellular medium in vegetation and valvular tissue. This atypical presentation we report here might be explained by the anti-inflammatory treatment administrated for our patient's initial diagnosis of rheumatoid arthritis.

Mitral valve repair is better than mitral valve replacement in native mitral valve endocarditis: Results from a prospective matched cohort.

BACKGROUND: In native mitral valve infective endocarditis (NMIE), the respective values of mitral valve repair (MVRep) and replacement (MVR) are still debated. AIM: To compare MVRep and MVR in a large prospective matched cohort. METHODS: Between 2010 and 2017, all consecutive patients operated on for NMIE in our centre were included prospectively. Clinical and outcome features were compared between the two groups. Primary endpoint was event-free survival, including death, reoperation and relapse. Univariate and multivariable survival analyses and a propensity score analysis were performed. RESULTS: Among 152 patients, 115 (75.7%) underwent MVRep, and 37 (24.3%) MVR. Median follow-up was 28±22months. Surgery was performed during the active phase in 75.0% of patients (25.7% on an urgent basis). Compared with the MVRep group, patients in the MVR group were more frequently intravenous drug abusers (10.8% vs. 0.9%; P=0.016), had a more frequent history of rheumatic fever (13.5% vs. 0%; P=0.001), more aortic abscesses (16.7% vs. 3.5%; P=0.018), larger vegetations (16.6±8.1mm vs. 12.6±9.9mm; P=0.042) and poorer New York Heart Association status (P=0.006). Overall mortality was lower in the MVRep group than in MVR group (11.3% vs. 29.3%; P=0.018). Event-free survival was better in the MVRep group than in the MVR group in univariate analysis (hazard ratio: 2.72, 95% confidence interval: 1.34-5.52; P=0.004). Survival analysis in the propensity-matched cohort showed that MVRep was safer than MVR (log rank test: P=0.018). Multivariable analysis using the Cox proportional hazard model confirmed this finding (hazard ratio: 3.48, 95% confidence interval: 1.15-10.61; P=0.03). CONCLUSIONS: MVRep is feasible in most cases of NMIE and, when technically possible, should be preferred, even in urgent surgery.

Infective endocarditis with neurological complications: Delaying cardiac surgery is associated with worse outcome.

BACKGROUND: Infective endocarditis (IE) is associated with a high mortality rate, related in part to neurological complications. Studies suggest that valvular surgery should be performed early when indicated, but is often delayed by the presence of neurological complications. AIM: To assess the effect of delaying surgery in patients with IE and neurological complications and to identify factors predictive of death. METHODS: In a prospective, single-centre study in a referral centre for IE, all patients with IE underwent systematic screening for neurological complications. The primary outcome was 6-month death. In patients presenting with neurological complications, the prognosis according to surgical status was analysed and a Cox regression model used to identify variables predictive of death. RESULTS: Between April 2014 and January 2018, 351 patients with a definite diagnosis of left-sided IE were included. Ninety-four patients (26.8%) presented with at least one neurological complication. Fifty-nine patients (17.7%) died during 6-month follow-up. Six-month mortality rates did not differ significantly between patients with and without neurological complications (P=0.60). Forty patients had a temporary surgical contraindication because of neurological complications. During the period of surgical contraindication, seven of these patients (17.5%) died, six (15.0%) presented a new embolic event, and 12 (30.0%) presented cardiac or septic deterioration. In multivariable analysis, predictive factors of death in patients presenting with neurological complications were temporary surgical contraindication (hazard ratio 7.36, 95% confidence interval 1.61-33.67; P=0.010) and presence of a mechanical prosthetic valve (hazard ratio 16.40, 95% confidence interval 2.22-121.17; P=0.006). CONCLUSIONS: Patients with a temporary surgical contraindication due to neurological complications had a higher risk of death and frequent major complications while waiting for surgery. When indicated, the decision to postpone surgery in the early phase should be weighed against the risk of infectious or cardiac deterioration.

18F-fluorodeoxyglucose positron emission tomography/computed tomography for the diagnosis of native valve infective endocarditis: A prospective study.

BACKGROUND: 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) has recently been added as a major criterion in the European Society of Cardiology (ESC) 2015 infective endocarditis guidelines. PET/CT is currently used in patients with suspected prosthetic valve and cardiac device-related endocarditis. However, the value of the ESC classification and the clinical impact of PET findings are unknown in patients with native valve endocarditis (NVE). AIMS: Our aims were: to assess the value of the ESC criteria (including PET/CT) in NVE; to determine the usefulness of PET/CT concerning embolic detection; and to describe a new PET/CT feature (diffuse splenic uptake). METHODS: Between 2012 and 2017, 75 patients with suspected NVE were included prospectively, after exclusion of patients with uninterpretable or unfeasible PET/CT. Using gold standard expert consensus, 63 cases of infective endocarditis were confirmed and 12 were rejected. RESULTS: Significant valvular uptake was observed in 11 of 63 patients with definite NVE and in no patients who had the diagnosis of infective endocarditis rejected (sensitivity 17.5%, specificity 100%). Among the 63 patients with NVE, a peripheral embolism or mycotic aneurysm was observed in 20 (31.7%) cases. Application of the ESC criteria increased Duke criteria sensitivity from 63.5% to 69.8% (P<0.001), without a change in specificity. Diffuse splenic uptake was observed in 39 (52.0%) patients, including 37 (58.7%) with a final diagnosis of NVE (specificity 83.3%). CONCLUSIONS: 18F-FDG PET/CT has poor sensitivity but high specificity in the diagnosis of NVE. The usefulness of 18F-FDG PET/CT is high for embolic detection. Diffuse splenic uptake represents a possible new diagnostic criterion for NVE.

FDG-PET/CT Incidental Detection of Cancer in Patients Investigated for Infective Endocarditis.

Background: Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is an imaging technique largely used in the management of infective endocarditis and in the detection and staging of cancer. We evaluate our experience of incidental cancer detection by PET/CT during IE investigations and follow-up. Methods and Findings: Between 2009 and 2018, our center, which includes an "endocarditis team," managed 750 patients with IE in a prospective cohort. PET/CT became available in 2011 and was performed in 451 patients. Incidental diagnosis of cancer by PET/CT was observed in 36 patients and confirmed in 34 of them (7.5%) (colorectal n = 17; lung n = 7; lymphoma n = 2; melanoma n = 2; ovarian n = 2; prostate n = 1; bladder n = 1; ear, nose, and throat n = 1; brain n = 1). A significant association has been found between colorectal cancer and Streptococcus gallolyticus and/or Enterococcus faecalis [12/26 vs. 6/33 for other cancers, p = 0.025, odds ratio = 3.86 (1.19-12.47)]. Two patients had a negative PET/CT (a colon cancer and a bladder cancer), and two patients, with positive PET/CT, had a benign colorectal tumor. PET/CT had a sensitivity of 94-100% for the diagnosis of cancer in this patient. Conclusions: Whole-body PET/CT confirmed the high incidence of cancer in patients with IE and could now be proposed in these cases.

High-dose trimethoprim-sulfamethoxazole and clindamycin for Staphylococcus aureus endocarditis.

OBJECTIVE: The mortality rate for Staphylococcus aureus endocarditis remains as high as 20-30% despite improvements in medical and surgical treatment. This study evaluated the efficiency and tolerance of a combination of intravenous trimethoprim-sulfamethoxazole and clindamycin (T&C) +/- rifampicin and gentamicin, with a rapid switch to oral administration of T&C. METHODS: This before-after intervention study compared the outcomes of 170 control patients before introduction of the T&C protocol (2001-2011) with the outcomes of 171 patients in the T&C group (2012-2016). All patients diagnosed with S. aureus infective endocarditis and referred to the study centre between 2001 and 2016 were included. Between 2001 and 2011, the patients received a standardized antibiotic treatment: oxacillin or vancomycin for 6 weeks, plus gentamicin for 5 days. Since February 2012, the antibiotic protocol has included a high dose of T&C (intravenous, switched to oral administration on day 7). Rifampicin and gentamicin are also given in cases of cardiac abscess or persistent bacteraemia. RESULTS: The two groups were slightly different. On intention-to-treat analysis, global mortality (19% vs 30%, P=0.024), in-hospital mortality (10% vs 18%, P=0.03) and 30-day mortality (7% vs 14%, P=0.05) were lower in the T&C group. The mean duration of hospital stay was significantly shorter in the T&C group (30 vs 39 days; P=0.005). CONCLUSIONS: The management of S. aureus infective endocarditis using a rapid shift to oral administration of T&C reduced the length of hospital stay and the mortality rate.

Prognostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Infective Endocarditis.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is commonly used for the diagnosis of infective endocarditis (IE), but its prognostic value remains unknown. OBJECTIVES: This study sought to assess the prognostic value of 18F-FDG PET/CT in prosthetic valve endocarditis (PVE) and native valve endocarditis (NVE). METHODS: This study prospectively included 173 consecutive patients (109 PVE and 64 NVE) with definite left-sided IE who had an 18F-FDG PET/CT and were followed-up for 1 year. The primary endpoint was a composite of major cardiac events: death, recurrence of IE, acute cardiac failure, nonscheduled hospitalization for cardiovascular indication, and new embolic event. RESULTS: 18F-FDG PET/CT was positive in 100 (58%) patients, 83% (n = 90 of 109) in the PVE, and 16% (n = 10 of 64) in the NVE group. At a mean follow-up of 225 days (interquartile range: 199 to 251 days), the primary endpoint occurred in 94 (54%) patients: 63 (58%) in the PVE group and 31 (48%) in the NVE group. In the PVE group, positive 18F-FDG PET/CT was significantly associated with a higher rate of primary endpoint (hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.1 to 6.7; p = 0.04). Moderate to intense 18F-FDG valvular uptake was also associated with worse outcome (HR: 2.3; 95% CI: 1.3 to 4.5; p = 0.03) and to new embolic events in PVE (HR: 7.5; 95% CI: 1.24 to 45.2; p = 0.03) and in NVE (HR: 8.8; 95% CI: 1.1 to 69.5; p = 0.02). In the NVE group, 18F-FDG PET/CT was not associated with occurrence of the primary endpoint CONCLUSIONS: In addition to its good diagnostic performance, 18F-FDG PET/CT is predictive of major cardiac events in PVE and new embolic events within the first year following IE.

Synthetic oligorotaxanes exert high forces when folding under mechanical load.

Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems 1,2 . Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts 3-5 . Recently, combining the exquisite complexity of these two classes of molecules, donor-acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure 6-8 . Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 µs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

Apical four-chamber longitudinal left ventricular strain in patients with aortic stenosis and preserved left ventricular ejection fraction: analysis related with flow/gradient pattern and association with outcome.

Aims: To evaluate the prognostic value of apical four-chamber (A4-C) longitudinal strain (LS) in patients with aortic stenosis (AS). Methods and results: In a multicentre cohort, 582 patients (74.3 ± 10.9 years) with moderate or severe AS and preserved left ventricular (LV) ejection fraction (≥50%) were included in this retrospective study. Patients with severe AS were classified in four subgroups according to flow and gradient: low flow (LF) was defined as a stroke volume index <35 mL/m2 compared with normal flow (NF); low-gradient (LG) as a mean gradient <40 mmHg compared with high gradient (HG). The end point was all-cause of mortality. A4-C LS was measured by two-dimensional speckle tracking and was feasible in all patients. The degree of A4-C LV longitudinal dysfunction increased according to the severity and subgroups of severe AS: from the least to the most impaired: moderate AS, NF/HG, NF/LG, LF/HG, and LF/LG AS (P < 0.001). During a mean follow-up of 2.6 ± 0.2 years, 58(10%) patients died. The 2-year survival was 76.8% in patients with LF/LG vs. 89.3% in patients with other groups. The best threshold of A4-C LS associated with overall mortality was an absolute cut-off value of |13.75%|. According to this cut-off, the 2-year survival was higher both in patients with moderate AS (96.3 vs. 70%, P = 0.02) and those with severe AS (92.9 vs. 80.9%, P = 0.005). However when dichotomized according to flow/gradient patterns, the association was only statistically significant in the subgroup of patients with NF/HG. By multivariable cox regression analysis, A4-C LS <|13.75| remained independently associated with overall mortality (hazard ratio: 1.8; P = 0.045). Conclusion: A4-C LS is independently associated with death in patients with AS and preserved LVEF, however the flow/gradient pattern should also be considered as an important parameter. The management of these patients may use A4-C LS as a new parameter of evaluation of LV function and prognosis.