Infective endocarditis presentations during the COVID-19 pandemic: have they paid an untold toll?

Background: COVID-19 caused restrictions and re-allocation of medical resources among all healthcare services. During the peak of the pandemic, several unrelated-yet critical-conditions had silently taken their toll. Infective endocarditis (IE), owing to its non-specific clinical presentation, may have been largely mislabeled as COVID-19 in a number of cases. Results: This retrospective observational study reviewed all IE presentations at an IE unit in a university hospital during the peak of COVID-19. Patient characteristics, courses, and outcomes were compared with historical controls from our IE database published before the COVID era. We identified 30 IE cases [Group A] during the COVID-19 peak in our region (June 2021 to June 2022), with a 25% decrease compared to the usual annual rate. This is in contrast to the expected surge during the pandemic. Compared with group B (398 published IE cases from our database), group A had significantly longer symptoms-to-presentation intervals (60 [31-92] vs. 28 [14-72] days, p = 0.01). Male sex dominated both groups, but group A had significantly less pre-existing structural heart disease. Despite the more liberal use of empirical antibiotics in the COVID-era, group-A had lower rates of culture-negative IE. Compared to group B, group A demonstrated a better response to medical therapy, fewer arterial embolizations, fewer indications for surgery, and fewer overall complications, except for increased acute kidney injury. This can be explained by the abundant use of non-steroidal anti-inflammatory drugs. The data analysis strongly suggests that there might have been a natural selection or selection bias of IE patients with favorable profiles to survive the pandemic to the appropriate diagnosis. Conclusions: The diagnosis of IE and commencing the appropriate workup were significantly undermined during the COVID-19 pandemic. The inexplicable decline in IE referral rate and the favorable outcomes witnessed during the pandemic strongly suggest a referral bias and natural selection of those who survived the pandemic to the appropriate IE diagnosis.

Infective endocarditis in adult patients with congenital heart disease.

BACKGROUND: Congenital Heart Disease (CHD) predisposes to Infective Endocarditis (IE), but data about characterization and prognosis of IE in CHD patients is scarce. METHODS: The ESC-EORP-EURO-ENDO study is a prospective international study in IE patients (n = 3111). In this pre-specified analysis, adult CHD patients (n = 365, 11.7%) are described and compared with patients without CHD (n = 2746) in terms of baseline characteristics and mortality. RESULTS: CHD patients (73% men, age 44.8 ± 16.6 years) were younger and had fewer comorbidities. Of the CHD patients, 14% had a dental procedure before hospitalization versus 7% in non-CHD patients (p < 0.001) and more often had positive blood cultures for Streptococcus viridans (16.4% vs 8.8%, p < 0.001). As in non-CHD patients, IE most often affected the left-sided valves. For CHD patients, in-hospital mortality was 9.0% vs 18.1% in non-CHD patients (p < 0.001), and also, during the entire follow-up of 700 days, survival was more favorable (log-rank p < 0.0001), even after adjustment for age, gender and major comorbidities (Hazard Ratio (HR) 0.68; 95%CI 0.50-0.92). Within the CHD population, multivariable Cox regression revealed the following effects (HR and [95% CI]) on mortality: fistula (HR 6.97 [3.36-14.47]), cerebral embolus (HR 4.64 [2.08-10.35]), renal insufficiency (HR 3.44 [1.48-8.02]), Staphylococcus aureus as causative agent (HR 2.06 [1.11-3.81]) and failure to undertake surgery when indicated (HR 5.93 [3.15-11.18]). CONCLUSIONS: CHD patients with IE have a better outcome in terms of all-cause mortality. The observed high incidence of dental procedures prior to IE warrants further studies about the current use, need and efficacy of antibiotic prophylaxis in CHD patients.

Efficacy and speed of conversion of recent onset atrial fibrillation using oral propafenone versus parenteral amiodarone: A randomized controlled comparative study.

BACKGROUND: Atrial fibrillation is the most commonly encountered arrhythmia. Several antiarrhythmic agents are effective in restoring and maintaining sinus rhythm. AIM OF THE WORK: To compare the efficacy and rapidity of conversion of recent onset atrial fibrillation using oral propafenone versus intravenous infusion of amiodarone. METHODS: The study included 200 patients with recent onset atrial fibrillation. Patients were equally divided into 2 groups; group A where intravenous infusion amiodarone was given and group B where oral propafenone was administrated. The effectiveness and the time needed for conversion of atrial fibrillation to sinus rhythm were compared in both groups. RESULTS: The success of conversion of atrial fibrillation to sinus rhythm was 83% in group A and 85% in group B, p-value = 0.699. The time elapsed from drug administration till conversion of atrial fibrillation was 9.07 ± 5.04 hours in group A versus 3.9 ± 1.54 hours in group B, p-value = 0.001. In both groups, patients who showed failed conversion had a significantly larger left atrial diameter and a significantly higher high sensitivity C-reactive protein (hsCRP) level. CONCLUSION: Oral propafenone was faster than parenteral amiodarone in the conversion of recent onset atrial fibrillation to sinus rhythm. Patients with failed conversion had a bigger left atrial diameter and a higher hsCRP when compared to patients with successful conversion.

Cancer and Infective Endocarditis: Characteristics and Prognostic Impact.

Background: The interplay between cancer and IE has become of increasing interest. This study sought to assess the prevalence, baseline characteristics, management, and outcomes of IE cancer patients in the ESC EORP EURO-ENDO registry. Methods: Three thousand and eighty-five patients with IE were identified based on the ESC 2015 criteria. Three hundred and fifty-nine (11.6%) IE cancer patients were compared to 2,726 (88.4%) cancer-free IE patients. Results: In cancer patients, IE was mostly community-acquired (74.8%). The most frequently identified microorganisms were S. aureus (25.4%) and Enterococci (23.8%). The most frequent complications were acute renal failure (25.9%), embolic events (21.7%) and congestive heart failure (18.1%). Theoretical indication for cardiac surgery was not significantly different between groups (65.5 vs. 69.8%, P = 0.091), but was effectively less performed when indicated in IE patients with cancer (65.5 vs. 75.0%, P = 0.002). Compared to cancer-free IE patients, in-hospital and 1-year mortality occurred in 23.4 vs. 16.1%, P = 0.006, and 18.0 vs. 10.2%; P < 0.001, respectively. In IE cancer patients, predictors of mortality by multivariate analysis were creatinine > 2 mg/dL, congestive heart failure and unperformed cardiac surgery (when indicated). Conclusions: Cancer in IE patients is common and associated with a worse outcome. This large, observational cohort provides new insights concerning the contemporary profile, management, and clinical outcomes of IE cancer patients across a wide range of countries.

Impact of Cardiac Computed Tomographic Angiography on Diagnostic and Therapeutic Decisions in Patients with Suspected Prosthetic Heart Valve Dysfunction.

INTRODUCTION: Computed Tomography (CT) scan is a helpful tool to assess the coronary arteries and the great vessels. However, its routine use in the assessment of patients with suspected prosthetic valve dysfunction (PVD) has not been studied thoroughly. OBJECTIVE: To determine the impact of routine cardiac computed tomography angiography (CCTA) on diagnostic and therapeutic decisions in patients with suspected PVD. METHODS AND RESULTS: This was a prospective cohort study that was conducted on 50 consecutive patients with suspected PVD who underwent both 64-slice ECG-gated CT and transesophageal echocardiography (TEE). The gold standard was the intraoperative findings. Surgery was performed in forty-six patients. ECG-gated CT showed findings that were not detected by TEE in sixteen patients (32%) namely aortic root abscess, aortic pseudoaneurysm, paravalvular leakage (PVL), sclero-calcific disruption of sutures as cause of PVL, mechanical prosthesis occluder malfunction, an underlying thrombus as cause of malfunction and finally presence of aortic dissection. Furthermore, CTA findings dictated treatment changes in fourteen patients (28%). CONCLUSION: This study demonstrates that ECG-gated CTA has a complementary role to TEE in patients with suspected PVD. CCTA is more accurate in diagnosis of periannular complications (Aortic root abscess and Pseudo-aneurysm) and in delineating their anatomical relation to surrounding cardiac structures. Therefore CCTA can have important role in deciding and planning the method of correction whether surgical or percutaneous and has to be considered after TEE in patients with a high suspicion on PVD.

Gender differences in clinical features and complications of infective endocarditis: 11-year experience of a single institute in Egypt.

BACKGROUND: No data exists about the gender differences among patients with infective endocarditis (IE) in Egypt. The objective was to study possible gender differences in clinical profiles and outcomes of patients in the IE registry of a tertiary care center over 11 years. RESULTS: The IE registry included 398 patients with a median age of 30 years (interquartile range, 15 years); 61.1% were males. Males were significantly older than females. Malignancy and recent culprit procedures were more common in females while chronic liver disease and intravenous drug abuse (IVDU) were more in males. IE on top of structurally normal hearts was significantly more in males (25.6% vs 13.6%, p = 0.005) while rheumatic valvular disease was more common in females (46.3% vs 29.9%, p = 0.001). There was no difference in the duration of illness before presentation to our institution. The overall complication rate was high but significantly higher in females. However, there were no significant differences in the major complications: mortality, fulminant sepsis, renal failure requiring dialysis, heart failure class III-IV, or major cerebrovascular emboli. CONCLUSION: In this registry, IE occurred predominantly in males. Females were significantly younger at presentation. History of recent culprit procedures was more common in females while IVDU was more common in males who had a higher incidence of IE on structurally normal hearts. The overall complication rate was higher in women. IE management and its outcomes were similar in both genders.

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as independent predictors of outcome in infective endocarditis (IE).

BACKGROUND: Early and accurate risk assessment is an important clinical demand in patients with infective endocarditis (IE). The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are independent predictors of prognosis in many infectious and cardiovascular diseases. Very limited studies have been conducted to evaluate the prognostic role of these markers in IE. RESULTS: We analyzed clinical, laboratory, and echocardiographic data and outcomes throughout the whole period of hospitalization for a total of 142 consecutive patients with definitive IE. The overall in-hospital mortality was 21%. Major complications defined as central nervous system embolization, fulminant sepsis, acute heart failure, acute renal failure, and major artery embolization occurred in 38 (27%), 34 (24%), 32 (22.5%), 40 (28%), and 90 (63.4%) patients, respectively. The NLR, total leucocyte count (TLC), neutrophil percentage, creatinine, and C-reactive protein (CRP) level obtained upon admission were significantly higher in the mortality group [p ≤ 0.001, p = 0.008, p = 0.001, p = 0.004, and p = 0.036, respectively]. A higher NLR was significantly associated with fulminant sepsis and major arterial embolization [p = 0.001 and p = 0.028, respectively]. The receiver operating characteristic (ROC) curve of the NLR for predicting in-hospital mortality showed that an NLR > 8.085 had a 60% sensitivity and an 84.8% specificity for an association with in-hospital mortality [area under the curve = 0.729, 95% confidence interval (CI) 0.616-0.841; p = 0.001]. The ROC curve of the NLR for predicting severe sepsis showed that an NLR > 5.035 had a 71.8% sensitivity and a 68.5% specificity for predicting severe sepsis [area under the curve 0.685, 95% CI 0.582-0.733; p = 0.001]. The PLR showed no significant association with in-hospital mortality or in-hospital complications. CONCLUSION: A higher NLR, TLC, neutrophil percentage, creatinine level, and CRP level upon admission were associated with increased in-hospital mortality and morbidity in IE patients. Furthermore, a lower lymphocyte count/percentage and platelet count were strong indicators of in-hospital mortality among IE patients. Calculation of the NLR directly from a CBC upon admission may assist in early risk stratification of patients with IE.

Clinical features and outcomes of infective endocarditis in Egypt: an 11-year experience at a tertiary care facility.

BACKGROUND: Few data are available on the characteristics of infective endocarditis (IE) cases in Egypt. The aim of this work is to describe the characteristics and outcomes of IE patients and evaluate the temporal changes in IE diagnostic and therapeutic aspects over 11 years. RESULTS: The IE registry included 398 patients referred to the Endocarditis Unit of a tertiary care facility with the diagnosis of possible or definite IE. Patients were recruited over two periods; period 1 (n = 237, 59.5%) from February 2005 to December 2011 and period 2 (n = 161, 40.5%) from January 2012 to September 2016. An electronic database was constructed to include information on patients' clinical and microbiological characteristics as well as complications and mortality. The median age was 30 years and rheumatic valvular heart disease was the commonest underlying cardiac disease (34.7%). Healthcare-associated IE affected 185 patients (46.5%) and 275 patients (69.1%) had negative blood cultures. The most common complications were heart failure (n = 148, 37.2%), peripheral embolization (n = 133, 33.4%), and severe sepsis (n = 100, 25.1%). In-hospital mortality occurred in 108 patients (27.1%). Period 2 was characterized by a higher prevalence of injection drug use-associated IE (15.5% vs. 7.2%, p = 0.008), a higher staphylococcal IE (50.0% vs. 35.7%, p = 0.038), lower complications (31.1% vs. 45.1%, p = 0.005), and a lower in-hospital mortality (19.9% vs. 32.1%, p = 0.007). CONCLUSION: This Egyptian registry showed high rates of culture-negative IE, complications, and in-hospital mortality in a largely young population of patients. Improvements were noted in the rates of complications and mortality in the second half of the reporting period.

The ESC-EORP EURO-ENDO (European Infective Endocarditis) registry.

AIMS: The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) European Endocarditis (EURO-ENDO) registry aims to study the care and outcomes of patients diagnosed with infective endocarditis (IE) and compare findings with recommendations from the 2015 ESC Clinical Practice Guidelines for the management of IE and data from the 2001 Euro Heart Survey. METHODS AND RESULTS: Patients (n = 3116) aged over 18 years with a diagnosis of IE based on the ESC 2015 IE diagnostic criteria were prospectively identified between 1 January 2016 and 31 March 2018. Individual patient data were collected across 156 centres and 40 countries. The primary endpoint is all-cause mortality in hospital and at 1 year. Secondary endpoints are 1-year morbidity (all-cause hospitalization, any cardiac surgery, and IE relapse), the clinical, epidemiological, microbiological, and therapeutic characteristics of patients, the number and timing of non-invasive imaging techniques, and adherence to recommendations as stated in the 2015 ESC Clinical Practice Guidelines for the management of IE. CONCLUSION: EURO-ENDO is an international registry of care and outcomes of patients hospitalized with IE which will provide insights into the contemporary profile and management of patients with this challenging disease.

Correction: Aspergillus endocarditis: Diagnostic criteria and predictors of outcome, A retrospective cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0201459.].

Aspergillus endocarditis: Diagnostic criteria and predictors of outcome, A retrospective cohort study.

BACKGROUND: Fungal Endocarditis (FE), a relatively rare disease, has a high rate of mortality and is associated with multiple morbidities. Aspergillus endocarditis (AE) is severe form of FE. Incidence of AE has increased and is expected to rise due to an increased frequency of invasive procedures, cardiac devices and prosthetic valves together with increased use of immune system suppressors. AE lacks most of the clinical criteria used to diagnose infective endocarditis (IE), where blood culture is almost always negative, and fever may be absent. Diagnosis is usually late and in many cases is made post-mortem. Late or mistaken diagnosis of AE contribute to delayed and incorrect management of patients. In the current study we aimed to describe the clinical, laboratory and imaging characteristics of AE, to identify predictors of early diagnosis of this serious infection. METHODS: Patients with definite/possible IE, as diagnosed by the Kasr Al-Ainy IE Working Group from February 2005 through June 2016, were reviewed in this study. We compared the demographic, clinical, laboratory and imaging criteria of AE patients to non-fungal IE patients. RESULTS: This study included 374 patients with IE in which FE accounted for 43 cases. Aspergillus was the most common fungus (31 patients; 8.3%) in the patient group. Lack of fever and acute limb ischemia at presentation were significantly associated with AE (p < 0.001, p = 0.014, respectively). Health care associated endocarditis (HAE) and prosthetic valve endocarditis (PVE) were the only significant risk factors associated with AE (p < 0.001 for each). Mitral, non-valvular, and aortotomy site vegetations, as well as aortic abscess/pseudoaneurysm, were significantly associated with AE (p = 0.022, p = 0.004, p < 0.001, and p < 0.001, respectively). Through multivariate regression analysis, HAE, PVE, aortic abscess/pseudoaneurysm, and lack of fever were strongly linked to AE. The probability of an IE patient having AE with HAE, PVE, and aortic abscess/pseudoaneurysm, but no fever, was 0.92. In contrast, the probability of an IE patient having AE with fever, native valve IE, but no health-care associated IE and no abscess/pseudoaneurysm, was 0.003. Severe sepsis and mortality in the Aspergillus group were higher as compared to the non-fungal group (p = 0.098 and 0.097, respectively). Thirteen AE patients died during hospitalization. PVE, the use of single versus dual antifungal agents, severe heart failure, and severe sepsis were significant predictors of mortality (p = 0.008, 0.012, 0.003, and 0.01, respectively). CONCLUSION: To our knowledge, this is the first study to address diagnostic criteria for AE. Through multivariate regression analysis, absence of fever, HAE, PVE, and aortic abscess/pseudoaneurysm were strong predictors of AE. Use of these criteria my lead to earlier diagnoses of AE. Early treatment of AE patients with voriconazole in combination with other antifungal agents may be possible based on the previously mentioned criteria, which may facilitate better patient outcomes.

Correction: Aspergillus endocarditis: Diagnostic criteria and predictors of outcome, A retrospective cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0201459.].

Impact of routine cerebral CT angiography on treatment decisions in infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is commonly complicated by cerebral embolization and hemorrhage secondary to intracranial mycotic aneurysms (ICMAs). These complications are associated with poor outcome and may require diagnostic and therapeutic plans to be modified. However, routine screening by brain CT and CT angiography (CTA) is not standard practice. We aimed to study the impact of routine cerebral CTA on treatment decisions for patients with IE. METHODS: From July 2007 to December 2012, we prospectively recruited 81 consecutive patients with definite left-sided IE according to modified Duke's criteria. All patients had routine brain CTA conducted within one week of admission. All patients with ICMA underwent four-vessel conventional angiography. Invasive treatment was performed for ruptured aneurysms, aneurysms ≥ 5 mm, and persistent aneurysms despite appropriate therapy. Surgical clipping was performed for leaking aneurysms if not amenable to intervention. RESULTS: The mean age was 30.43 ± 8.8 years and 60.5% were males. Staph aureus was the most common organism (32.3%). Among the patients, 37% had underlying rheumatic heart disease, 26% had prosthetic valves, 23.5% developed IE on top of a structurally normal heart and 8.6% had underlying congenital heart disease. Brain CT/CTA revealed that 51 patients had evidence of cerebral embolization, of them 17 were clinically silent. Twenty-six patients (32%) had ICMA, of whom 15 were clinically silent. Among the patients with ICMAs, 11 underwent endovascular treatment and 2 underwent neurovascular surgery. The brain CTA findings prompted different treatment choices in 21 patients (25.6%). The choices were aneurysm treatment before cardiac surgery rather than at follow-up, valve replacement by biological valve instead of mechanical valve, and withholding anticoagulation in patients with prosthetic valve endocarditis for fear of aneurysm rupture. CONCLUSIONS: Routine brain CT/CTA resulted in changes in the treatment plan in a significant proportion of patients with IE, even those without clinically evident neurological disease. Routine brain CT/CTA may be indicated in all hospitalized patients with IE.