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.

Bispectral index and suppression ratio after cardiac arrest: are they useful as bedside tools for rational treatment escalation plans?

INTRODUCTION AND OBJECTIVES: Myocardial dysfunction contributes to early mortality (24-72 hours) among survivors of a cardiac arrest (CA). The benefits of mechanical support in refractory shock should be balanced against the patient's potential for neurological recovery. To date, these early treatment decisions have been taken based on limited information leading mainly to undertreatment. Therefore, there is a need for early, reliable, accessible, and simple tools that offer information on the possibilities of neurological improvement. METHODS: We collected data from bispectral index (BIS) and suppression ratio (SR) monitoring of adult comatose survivors of CA managed with targeted temperature management (TTM). Neurological status was assessed according to the Cerebral Performance Category (CPC) scale. RESULTS: We included 340 patients. At the first full neurological evaluation, 211 patients (62.1%) achieved good outcome or CPC 1-2. Mean BIS values were significantly higher and median SR lower in patients with CPC 1-2. An average BIS> 26 during first 12 hours of TTM predicted good outcome with 89.5% sensitivity and 75.8% specificity (AUC of 0.869), while average SR values> 24 during the first 12 hours of TTM predicted poor outcome (CPC 3-5) with 91.5% sensitivity and 81.8% specificity (AUC, 0.906). Hourly BIS and SR values exhibited good predictive performance (AUC> 0.85), as soon as hour 2 for SR and hour 4 for BIS. CONCLUSIONS: BIS/SR are associated with patients' potential for neurological recovery after CA. This finding could help to create awareness of the possibility of a better outcome in patients who might otherwise be wrongly considered as nonviable and to establish personalized treatment escalation plans.

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.

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.

Anomalous Origin of Left Coronary Artery with Intramural Aortic Course Causing Symptoms in a Teenaged Athlete.

Anomalous origin of the left coronary artery from the opposite sinus of Valsalva with an intramural aortic course is a rare congenital anomaly with a poor prognosis. We report the case of a 14-year-old soccer player who briefly lost consciousness while sprinting. He had exertional chest pain, syncope, ischemic changes on his electrocardiogram, and elevated cardiac troponin levels. Computed tomographic angiograms showed an anomalous origin of the left coronary artery from the right sinus of Valsalva and a course through the aortic wall toward the left coronary sinus. A surgically created neo-ostium in the left coronary sinus relieved the patient's ischemia, and he resumed playing soccer after cardiac rehabilitation.

Predictive model of in-hospital mortality in left-sided infective endocarditis.

INTRODUCTION AND OBJECTIVES: Infective endocarditis (IE) is a complex disease with high in-hospital mortality. Prognostic assessment is essential to select the most appropriate therapeutic approach; however, international IE guidelines do not provide objective assessment of the individual risk in each patient. We aimed to design a predictive model of in-hospital mortality in left-sided IE combining the prognostic variables proposed by the European guidelines. METHODS: Two prospective cohorts of consecutive patients with left-sided IE were used. Cohort 1 (n=1002) was randomized in a 2:1 ratio to obtain 2 samples: an adjustment sample to derive the model (n=688), and a validation sample for internal validation (n=314). Cohort 2 (n=133) was used for external validation. RESULTS: The model included age, prosthetic valve IE, comorbidities, heart failure, renal failure, septic shock, Staphylococcus aureus, fungi, periannular complications, ventricular dysfunction, and vegetations as independent predictors of in-hospital mortality. The model showed good discrimination (area under the ROC curve=0.855; 95%CI, 0.825-0.885) and calibration (P value in Hosmer-Lemeshow test=0.409), which were ratified in the internal (area under the ROC curve=0.823; 95%CI, 0.774-0.873) and external validations (area under the ROC curve=0.753; 95%CI, 0.659-0.847). For the internal validation sample (observed mortality: 29.9%) the model predicted an in-hospital mortality of 30.7% (95%CI, 27.7-33.7), and for the external validation cohort (observed mortality: 27.1%) the value was 26.4% (95%CI, 22.2-30.5). CONCLUSIONS: A predictive model of in-hospital mortality in left-sided IE based on the prognostic variables proposed by the European Society of Cardiology IE guidelines has high discriminatory ability.

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.

Coexistence of Spontaneous Coronary Artery Dissection and Ascending Aortic Aneurysm.

Spontaneous coronary artery dissection is associated with several conditions and vascular disorders. We describe the management of 2 patients presenting with spontaneous coronary artery dissection and unruptured ascending aortic aneurysms. Coexistence of spontaneous coronary artery dissection with extracoronary vascular disorders should be considered by clinicians.

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.

ST-Elevation Myocardial Infarction in Patients ≤35 Years of Age.

ST-elevation myocardial infarction (STEMI) in very young patients is an uncommon entity but with significant clinical meaning for the patient. These individuals may have different risk profiles and prognosis. Few reports have described epidemiology, clinical features, and long-term outcomes of these patients in the era of percutaneous coronary intervention, particularly of those ≤35. This observational study evaluates the clinical characteristics of patients <35 years with STEMI between January 2004 and September 2016 in 3 different centers. We gathered data and follow-up from the prospective database of the interventional cardiology department, medical history, and phone interviews. Over a total of 3,883 STEMI, we retrieved 61 patients ≤35. They were mainly male (88%), smokers (80%), and overweight (67%). Twenty-six percent were drug consumers. Only 2 patients (3%) were free of conventional risk factors. In-hospital mortality was 5% (3 deaths). They were followed-up for 5.9 ± 4.2 years with a total survival of 96.6% (2 deaths). Major adverse cardiovascular events incidence at the end of follow-up was only 17.2% (10 patients). STEMI in the young is a rare condition. These patients have several modifiable predisposing factors, a low clinical risk profile, and excellent short- and long-term prognosis with state-of-the-art treatment.

Early surgery for acute-onset infective endocarditis.

OBJECTIVES: Acute onset of infective endocarditis has been previously linked to the development of septic shock and a worse prognosis. The purpose of this study was to analyse the clinical features and in-hospital evolution of patients with acute-onset endocarditis as well as the potential role of early surgery in the treatment of these patients. METHODS: From 1996 to 2014, 1053 consecutive patients with left-sided endocarditis were prospectively included. Patients were classified into 2 groups according to the clinical presentation: patients with acute-onset endocarditis (n = 491) and patients with non-acute endocarditis (n = 562). Acute-onset endocarditis was considered when the time between the appearance of symptoms and diagnosis was <15 days. RESULTS: At admission, acute renal failure, septic shock and cerebral embolism predominated among patients with acute-onset endocarditis. Staphylococcus aureus was more frequently isolated in patients with an acute onset (27.7% vs 7.8% P < 0.001). During hospitalization, patients with acute onset developed systemic embolism and septic shock more frequently. Death was much more common in this group (42.7 vs 30.1%, P < 0.001). Paravalvular complications, nosocomial infection, heart failure, S. aureus and septic shock were predictors of mortality. Acute-onset presentation of endocarditis was strongly associated with increased mortality. Among patients with acute-onset endocarditis, early surgery, performed within the first 2 days after diagnosis, was associated with a 64% of reduction in mortality. CONCLUSIONS: Patients with endocarditis and acute onset of symptoms are at high risk of septic in-hospital complications and mortality. Early surgery, performed within the first 2 days after diagnosis, plays a central role in the treatment of these patients.

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.

The Evolving Nature of Infective Endocarditis in Spain: A Population-Based Study (2003 to 2014).

BACKGROUND: Little information exists regarding population-based epidemiological changes in infective endocarditis (IE) in Europe. OBJECTIVES: This study sought to analyze temporal trends in IE in Spain from 2003 to 2014. METHODS: This retrospective, population-based, temporal trend study analyzed the incidence, epidemiological and clinical characteristics, and outcome of all patients discharged from hospitals included in the Spanish National Health System with a diagnosis of IE, from January 2003 to December 2014. RESULTS: Overall, 16,867 episodes of IE were identified during the study period, 66.3% in men. The rate of IE significantly increased, from 2.72 in 2003 to 3.49 per 100,000 person-years in 2014, and this rise was higher among older adults. The most frequent microorganisms were staphylococci (28.7%), followed by streptococci (20.4%) and enterococci (13.1%). Twenty-three percent of patients underwent cardiac surgery. The in-hospital mortality rate was 20.4%. Throughout the study period, the proportion of patients with previously known heart valve disease and diabetes mellitus significantly increased, whereas the prevalence of intravenous drug use decreased. Regarding microorganisms, Staphylococcus aureus and streptococci slightly declined, whereas coagulase-negative staphylococci and enterococci consistently increased over the years. In-hospital complications and cardiac surgery rates significantly increased across the years. The risk-adjusted in-hospital mortality rate diminished (0.2% per year) during the study period. CONCLUSIONS: The incidence of IE episodes significantly increased over the decade of the study period, particularly among older adults. Relevant changes in clinical and microbiological profile included older patients with more comorbidity and a rise in enterococci and coagulase-negative staphylococcal infections. Adjusted mortality rates slightly declined over the study period.

Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway.

Phenotypic modulation (PM) of vascular smooth muscle cells (VSMCs) is central to the process of intimal hyperplasia which constitutes a common pathological lesion in occlusive vascular diseases. Changes in the functional expression of Kv1.5 and Kv1.3 currents upon PM in mice VSMCs have been found to contribute to cell migration and proliferation. Using human VSMCs from vessels in which unwanted remodeling is a relevant clinical complication, we explored the contribution of the Kv1.5 to Kv1.3 switch to PM. Changes in the expression and the functional contribution of Kv1.3 and Kv1.5 channels were studied in contractile and proliferating VSMCs obtained from human donors. Both a Kv1.5 to Kv1.3 switch upon PM and an anti-proliferative effect of Kv1.3 blockers on PDGF-induced proliferation were observed in all vascular beds studied. When investigating the signaling pathways modulated by the blockade of Kv1.3 channels, we found that anti-proliferative effects of Kv1.3 blockers on human coronary artery VSMCs were occluded by selective inhibition of MEK/ERK and PLCγ signaling pathways, but were unaffected upon blockade of PI3K/mTOR pathway. The temporal course of the anti-proliferative effects of Kv1.3 blockers indicates that they have a role in the late signaling events essential for the mitogenic response to growth factors. These findings establish the involvement of Kv1.3 channels in the PM of human VSMCs. Moreover, as current therapies to prevent restenosis rely on mTOR blockers, our results provide the basis for the development of novel, more specific therapies.

Kv1.3 channels can modulate cell proliferation during phenotypic switch by an ion-flux independent mechanism.

OBJECTIVE: Phenotypic modulation of vascular smooth muscle cells has been associated with a decreased expression of all voltage-dependent potassium channel (Kv)1 channel encoding genes but Kcna3 (which encodes Kv1.3 channels). In fact, upregulation of Kv1.3 currents seems to be important to modulate proliferation of mice femoral vascular smooth muscle cells in culture. This study was designed to explore if these changes in Kv1 expression pattern constituted a landmark of phenotypic modulation across vascular beds and to investigate the mechanisms involved in the proproliferative function of Kv1.3 channels. METHODS AND RESULTS: Changes in Kv1.3 and Kv1.5 channel expression were reproduced in mesenteric and aortic vascular smooth muscle cells, and their correlate with protein expression was electrophysiologicaly confirmed using selective blockers. Heterologous expression of Kv1.3 and Kv1.5 channels in HEK cells has opposite effects on the proliferation rate. The proproliferative effect of Kv1.3 channels was reproduced by "poreless" mutants but disappeared when voltage-dependence of gating was suppressed. CONCLUSIONS: These findings suggest that the signaling cascade linking Kv1.3 functional expression to cell proliferation is activated by the voltage-dependent conformational change of the channels without needing ion conduction. Additionally, the conserved upregulation of Kv1.3 on phenotypic modulation in several vascular beds makes this channel a good target to control unwanted vascular remodeling.