Valvulitis: a new echocardiographic criterion for the diagnosis of bioprosthetic aortic valve infective endocarditis.

INTRODUCTION AND OBJECTIVES: Diffuse homogeneous hypoechoic leaflet thickening, with a wavy leaflet motion documented by transesophageal echocardiography (TEE), has been described in some cases of prosthetic valve endocarditis (PVE) involving aortic bioprosthesis (AoBio-PVE). This echocardiographic finding has been termed valvulitis. We aimed to estimate the prevalence of valvulitis, precisely describe its echocardiographic characteristics, and determine their clinical significance in patients with AoBio-PVE. METHODS: From 2011 to 2022, 388 consecutive patients with infective endocarditis (IE) admitted to a tertiary care hospital were prospectively included in a multipurpose database. For this study, all patients with AoBio-PVE (n=86) were selected, and their TEE images were thoroughly evaluated by 3 independent cardiologists to identify all cases of valvulitis. RESULTS: The prevalence of isolated valvulitis was 12.8%, and 20.9% of patients had valvulitis accompanied by other classic echocardiographic findings of IE. A total of 9 out of 11 patients with isolated valvulitis had significant valve stenosis, whereas significant aortic valve regurgitation was documented in only 1 patient. Compared with the other patients with AoBio-PVE, cardiac surgery was less frequently performed in patients with isolated valvulitis (27.3% vs 62.7%, P=.017). In 4 out of 5 patients with valve stenosis who did not undergo surgery but underwent follow-up TEE, valve gradients significantly improved with appropriate antibiotic therapy. CONCLUSIONS: Valvulitis can be the only echocardiographic finding in infected AoBio and needs to be identified by imaging specialists for early diagnosis. However, this entity is a diagnostic challenge and additional imaging techniques might be required to confirm the diagnosis. Larger series are needed.

Non-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value.

Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. This study reports mechanistic insights into the electromechanical remodeling process associated with AF progression and further demonstrates its prognostic value in the clinic. In pigs, sequential electromechanical assessment during AF progression shows a progressive decrease in mechanical activity and early dissociation from its electrical counterpart. Atrial tissue samples from animals with AF reveal an abnormal increase in cardiomyocytes death and alterations in calcium handling proteins. High-throughput quantitative proteomics and immunoblotting analyses at different stages of AF progression identify downregulation of contractile proteins and progressive increase in atrial fibrosis. Moreover, advanced optical mapping techniques, applied to whole heart preparations during AF, demonstrate that AF-related remodeling decreases the frequency threshold for dissociation between transmembrane voltage signals and intracellular calcium transients compared to healthy controls. Single cell simulations of human atrial cardiomyocytes also confirm the experimental results. In patients, non-invasive assessment of the atrial electromechanical relationship further demonstrate that atrial electromechanical dissociation is an early prognostic indicator for acute and long-term rhythm control.

Humoral response to heterologous prime-booster vaccination in heart transplant recipients aged 18-70 years primed with a viral vector SARS-CoV-2 vaccine.

Solid organ transplant recipients have demonstrated a blunted immune response to standard 2-dose vaccination against SARS-CoV-2. This study sought to determine the humoral response to heterologous booster vaccination (viral vector vaccine dose 1 and 2 + mRNA booster). Heart transplant recipients, aged 18 to 70 years of age who initially received two doses of the viral vector ChAdOx1 nCoV-19 vaccine followed by a BNT162b2 mRNA booster were recruited. A detectable antibody response in the absence of prior SARS-CoV-2 was the primary outcome measured. This was defined as an anti-spike titre of ≥0.8 U/mL on the Elecsys anti-SARS-CoV-2 S immunoassay. A total of 80 heart transplant patients (mean age 49 ± 13 years, 28% female) were included. Blood samples were drawn at a median of 30 (IQR 28-33) days after the BNT162b2 mRNA booster. The frequency of a detectable antibody response increased from 37.5% (n = 30) after dose 2 to 56% (n = 45) post dose 3 (p < 0.001). A non-detectable antibody response was significantly more common in recipients with a shorter time interval from transplantation (p < 0.001), lower likelihood of cardiac allograft vasculopathy (p = 0.003) and in those prescribed a triple versus dual immunosuppressant regime (p = 0.009) and a tacrolimus versus cyclosporine basedregimen (p = 0.007). Despite heterologous prime-booster vaccination 44% of this vulnerable population ultimately continue to have no detectable antibodies.

Accuracy of 18F-FDG PET/CT in patients with the suspicion of cardiac implantable electronic device infections.

BACKGROUND: Utility of 18F-FDG PET/CT in diagnosing infective endocarditis (IE) associated with cardiac implantable electronic devices (CIEDs) is not well established. Current ESC guidelines recommend the use of FDG-PET imaging in patients with CIEDs and positive blood cultures, but the number of studies evaluating the diagnostic performance of FDG-PET imaging in these patients remain limited. Our objective was to assess the diagnostic yield of 18F-FDG PET/CT in patients with suspected CIED infections, differentiating between pocket infection (PI) and lead infection (CIED-IE). METHODS AND RESULTS: From 2013 to 2018, all patients (n = 63) admitted to a hospital with suspected CIED infection were prospectively recruited, undergoing a diagnostic work-up including a PET/CT. Explanted devices and material from the pocket were cultured. 14 cases corresponded to isolated PI and 13 were categorized as CIED-IE. Considering radionuclide uptake in the intracardiac portion of the lead, sensitivity and specificity of PET/CT for CIED-IE were 38.5% and 98.0%, respectively. Positive (19.2) and negative (0.6) likelihood ratio values, suggest that a positive PET/CT is much more probable to correspond to a patient with CIED-IE, whereas it is not possible to exclude this diagnosis when negative. For PI, sensitivity and specificity were 72.2% and 95.6%, respectively. CONCLUSIONS: The yield of 18F-FDG PET/CT for suspected CIED infections differs depending on the site of infection. Due to very high specificity but poor sensitivity, negative studies must be interpreted with caution if the suspicion of CIED-IE is high.

The SADDEN DEATH Study: Results from a Pilot Study in Non-ICU COVID-19 Spanish Patients.

Introduction: The worldwide pandemic, coronavirus disease 2019 (COVID-19) is a novel infection with serious clinical manifestations, including death. Our aim is to describe the first non-ICU Spanish deceased series with COVID-19, comparing specifically between unexpected and expected deaths. Methods: In this single-centre study, all deceased inpatients with laboratory-confirmed COVID-19 who had died from March 4 to April 16, 2020 were consecutively included. Demographic, clinical, treatment, and laboratory data, were analyzed and compared between groups. Factors associated with unexpected death were identified by multivariable logistic regression methods. Results: In total, 324 deceased patients were included. Median age was 82 years (IQR 76-87); 55.9% males. The most common cardiovascular risk factors were hypertension (78.4%), hyperlipidemia (57.7%), and diabetes (34.3%). Other common comorbidities were chronic kidney disease (40.1%), chronic pulmonary disease (30.3%), active cancer (13%), and immunosuppression (13%). The Confusion, BUN, Respiratory Rate, Systolic BP and age ≥65 (CURB-65) score at admission was >2 in 40.7% of patients. During hospitalization, 77.8% of patients received antivirals, 43.3% systemic corticosteroids, and 22.2% full anticoagulation. The rate of bacterial co-infection was 5.5%, and 105 (32.4%) patients had an increased level of troponin I. The median time from initiation of therapy to death was 5 days (IQR 3.0-8.0). In 45 patients (13.9%), the death was exclusively attributed to COVID-19, and in 254 patients (78.4%), both COVID-19 and the clinical status before admission contributed to death. Progressive respiratory failure was the most frequent cause of death (92.0%). Twenty-five patients (7.7%) had an unexpected death. Factors independently associated with unexpected death were male sex, chronic kidney disease, insulin-treated diabetes, and functional independence. Conclusions: This case series provides in-depth characterization of hospitalized non-ICU COVID-19 patients who died in Madrid. Male sex, insulin-treated diabetes, chronic kidney disease, and independency for activities of daily living are predictors of unexpected death.

Infective endocarditis in patients with aortic grafts.

BACKGROUND: Infective endocarditis (IE) in patients with a valve-tube ascending aortic graft (AAG) is a rare entity with a challenging diagnosis and treatment. This study describes the clinical features, diagnosis and outcome of these patients. METHODS: Between 1996 and 2019, 1654 episodes of IE were recruited in 3 centres, of which 37 patients (2.2%) had prosthetic aortic valve and AAG-IE (21 composite valve graft, 16 supracoronary graft) and conformed our study group. RESULTS: Patients with aortic grafts were predominantly male (91.9%) and the mean age was 67.7 years. Staphylococci were the most frequently isolated microorganisms (32%). Viridans group streptococci were only isolated in patients with composite valve graft. TEE was positive in 89.2%. PET/CT was positive in all 15 patients in whom it was performed. Surgical treatment was performed in 62.2% of patients. In-hospital mortality was 16.2%. Heart failure and the type of infected graft (supracoronary aortic graft) were associated with mortality. Mortality among operated patients was 21.7%. Interestingly, 14 patients received antibiotic therapy alone, and only one died. Mortality was lower among patients with a composite valve graft compared to those with a supracoronary graft (4.8% vs 31.3%; p = 0.03). CONCLUSIONS: In patients with AAG and prosthetic aortic valve IE, mortality is not higher than in other patients with prosthetic IE. Multimodality imaging plays an important role in the diagnosis and management of these patients. Heart failure and the type of surgery were risk factors associated with in-hospital mortality. Although surgical treatment is usually recommended, a conservative management might be a valid alternative treatment in selected patients.

Contemporary epidemiology and outcomes in recurrent infective endocarditis.

OBJECTIVE: Recurrent infective endocarditis (IE) is a major complication of patients surviving a first episode of IE. This study sought to analyse the current state of recurrent IE in a large contemporary cohort. METHODS: 1335 consecutive episodes of IE were recruited prospectively in three tertiary care centres in Spain between 1996 and 2015. Episodes were categorised into group I (n=1227), first-IE episode and group II (n=108), recurrent IE (8.1%). After excluding six patients, due to lack of relevant data, group II was subdivided into IIa (n=87), reinfection (different microorganism), and IIb (n=15), relapse (same microorganism within 6 months of the initial episode). RESULTS: The cumulative burden and incidence of recurrence was slightly lower in the second decade of the study (2006-2015) (7.17 vs 4.10 events/100 survivors and 7.51% vs 3.82, respectively). Patients with reinfections, compared with group I, were significantly younger, had a higher frequency of HIV infection, were more commonly intravenous drug users (IVDU) and prosthetic valve carriers, had less embolic complications and cardiac surgery, with similar in-hospital mortality. IVDU was found to be an independent predictor of reinfection (HR 3.92, 95% CI 1.86 to 8.28).In the relapse IE group, prosthetic valve endocarditis (PVE) and periannular complications were more common. Among patients treated medically, those with PVE had a higher relapse incidence (4.82% vs 0.43% in native valve IE, p=0.018). Staphylococcus aureus and PVE were independent predictors of relapse (HR 3.14, 95% CI 1.11 to 8.86 and 3.19, 95% CI 1.13 to 9.00, respectively) and in-hospital-mortality was similar to group I. Three-year all-cause mortality was similar in recurrent episodes compared with single episodes. CONCLUSION: Recurrent IE remains a frequent late complication. IVDU was associated with a fourfold increase in the risk of reinfection. PVE treated medically and infections caused by S. aureus increased the risk of relapse. In-hospital and long-term mortality was comparable among groups.

IgG4-aortitis among thoracic aortic aneurysms.

OBJECTIVE: The incidence of aortitis in patients with thoracic aortic diseases is not well established. The aim of this study was to analyse the frequency and clinical course of patients with aortitis in a surgical series. METHODS: 320 consecutive patients with ascending aorta/aortic arch aneurysm or acute aortic syndrome who underwent surgery from 2012 to 2017 in a single tertiary referral hospital were retrospectively reviewed. Epidemiological data, clinical course and variables related to diagnosis, treatment and follow-up were collected from patients with histologically proven aortitis. RESULTS: From 320 examined aortic samples, 279 (87.2%) thoracic aneurysms and 41 acute aortic syndromes (12.8%), 9 (2.8%) were aortitis: 3 cases of Takayasu's arteritis, 3 of IgG4-related aortitis, 2 of giant cell, and 1 classified as idiopathic. Median age at surgery was 53.4 (51-69.2) years and six cases were female. Seven patients presented with non-specific symptoms and the diagnosis was made at pathology. Surgery was elective in eight patients and emergent in one case of IgG4-related aortitis. 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) was performed for disease extension study and as a monitoring technique during the follow-up of five patients, with just one case performed presurgically. All the patients with IgG4-related disease showed extrathoracic aortic involvement. There were no deaths, neither in-hospital nor during the 1.7 years of median follow-up. CONCLUSIONS: In surgically treated thoracic aorta pathology, the frequency of aortitis is low; IgG4-related disease is among the most common aetiologies with a frequency similar to other types of aortitis, such as Takayasu's and giant cell arteritis, and clinical manifestations are non-specific making presurgical diagnosis difficult. 18F-FDG PET/CT allows a better assessment of disease extension and therapeutic response. Surgery can be successfully performed and corticosteroid therapy ensures a good mid-term follow-up.

Morphological characterization of vegetation by real-time three-dimensional transesophageal echocardiography in infective endocarditis: Prognostic impact.

PURPOSE: Vegetation size is a prognostic predictor in infective endocarditis (IE) and guides surgical management. The aim of this study was to evaluate the accuracy of real-time 3-dimensional transesophageal echocardiography (RT3DTEE) compared to 2DTEE in the diagnosis and characterization of vegetation, as well as its potential clinical impact. METHODS: Two hundred and three consecutive patients with IE were recruited (2009-2016) and retrospectively analyzed. Vegetation diameters and area from 68 patients were measured by 2DTEE and RT3DTEE at admission. The association between size and systemic embolisms was evaluated with logistic regression models. Differences in the discriminative power for the best dimensions' cutoff points were assessed by comparing the area under the ROC curves (AUC). RESULTS: Vegetation size and area were larger by RT3DTEE (P < 0.001) than by 2DTEE, and RT3DTEE was especially relevant in the characterization of nonfiliform vegetation, Morphology was strongly associated with friability, being sessile vegetation less likely to embolize, compared to filiform and raceme-shaped ones (15.4% vs 46% vs 50%). Major diameter by RT3DTEE had better embolic predictive performance than 2DTEE (AUC 0.76 [0.57-0.89] vs 0.71 [0.53-0.86]; P = 0.611). The best cutoff points associated with embolic events during the infection were 17 mm for RT3DTEE and 15 mm for 2DTEE. Based exclusively on vegetation size, the proportion of patients meeting a surgical indication according to current guidelines is higher using RT3DTEE. CONCLUSIONS: RT3DTEE allows a better characterization of IE vegetation than 2DTEE, what may have a clinical impact on surgical management and also prognostic due to a more accurate prediction of embolic risk.

Usefulness of positron emission tomography/computed tomography in patients with valve-tube graft infection.

OBJECTIVE: Infection of valved aortic grafts is a rare entity whose diagnosis remains challenging. Positron emission tomography (PET)/CT has become a criterion for the diagnosis of infective endocarditis (IE) in prosthetic valves, but its role on ascending aortic graft infections remains unclear. This study aims to assess the diagnostic value of PET/CT in patients with valved aortic graft infection. METHODS: 12 episodes with a valved aortic graft who had undergone a PET/CT due to suspicion of IE were prospectively included (group I) and compared with five controls free of infection who underwent PET/CT for other reasons (group II). Pathological uptake of 18F-fluorodeoxyglucose (FDG) and its pattern at the prosthetic valve and aortic graft were studied. RESULTS: Diagnosis of IE was confirmed in 9 out of 12 episodes of group I. 18F-FDG uptake was detectable in eight out of nine cases with a final diagnosis of IE. The most repeated pattern of uptake was homogeneous around the valve and heterogeneous around the tube. There was one false-negative study. Of the three patients in which IE was ruled out, there were two false positives and one true negative. In group II, there were three patients with a positive PET/CT study, two of them had active aortitis and the third was considered false positive. CONCLUSIONS: 18F-FDG PET/CT shows high sensitivity in the detection of infected aortic grafts. Thus, this technique should be considered in the diagnostic work-up of patients with suspicion of aortic graft infection. However, further validation of this approach is needed.

Respuesta al ECG de noviembre de 2017 / Response to ECG, November 2017

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ECG de noviembre de 2017 / ECG, November 2017

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