Infective endocarditis in octogenarians. A retrospective study in a single, high-volume surgical centre.

BACKGROUND: Infective endocarditis (IE) is a severe disease associated with high morbidity and mortality. Little is known about the best management of elderly patients with IE. In these patients, surgery may be challenging. Our study aimed to describe IE's features in octogenarians and to identify the independent predictors of mortality, focusing on the prognostic impact of disability. METHODS: We retrospectively analyzed 551 consecutive patients admitted to a single surgical centre with a definite diagnosis of non-device-related infective endocarditis; of these, 97 (17.6%) were older than 80 years. RESULTS: In patients under eighty, males were mostly involved with a sex ratio exceeding 2:1. This ratio was inverted in older people, where the female gender represented 53.6% of the total. Enterococci (29.8 vs. 17.4%, p = 0.005) were significantly more frequent than in younger people. Comorbidities were more frequent in elderly patients; consequently, EuroSCORE II was higher (median ± IQR 16.4 ± 21.1 vs. 5.0 ± 10.3, p = 0.001). In octogenarians, IE was more frequently left-sided (97.9 vs. 89.8%, p = 0.011). Octogenarians were more often excluded from surgery despite indication (23.7 vs. 8.1%, p = 0.001) and had higher three-year mortality (45.3 vs. 30.6%, p = 0.005) than younger patients. In elderly patients, age did not independently predict mortality, while exclusion from surgery and a high grade of disability did. CONCLUSIONS: Octogenarians with IE have specific clinical and microbiological characteristics. Older patients are more often excluded from surgery, and the overall prognosis is poor. Age per se should not be a reason to deny surgery, while disability predicts futility.

Impact of septic cerebral embolism on prognosis and therapeutic strategies of infective endocarditis: a retrospective study in a surgical centre.

BACKGROUND: Infective endocarditis still has high mortality and invalidating complications, such as cerebral embolism. The best strategies to prevent and manage neurologic complications remain uncertain. This study aimed to identify predictors of cerebral septic embolism and evaluate the role of surgery in these patients in a real-world surgical centre. METHODS: We retrospectively analyzed 551 consecutive patients admitted to our department with a definite diagnosis of non-device-related infective endocarditis; of these, 126 (23%) presented a neurologic complication. RESULTS: Cerebral embolism was significantly more frequent in patients with large vegetations (p = 0.004), mitral valve infection (p = 0.001), and Staphylococcus aureus infection (p = 0.025). At multivariable analysis, only vegetation length was an independent predictor of cerebral embolism (HR per unit 1.057, 95% CI 1.025-1.091, p 0.001), with a best predictive threshold of 10 mm at ROC curve analysis (AUC 0.54, p = 0.001). Patients with neurologic complications were more often excluded from surgery despite an indication to it (16% vs 8%, p = 0.001). If eligible, they were treated within two weeks from diagnosis in similar proportions as patients without cerebral embolism with a similar survival rate. Predictors of mortality were hemorrhagic lesions (p = 0.018), a GCS < 14 (p = 0.001) or a severe degree of disability (p = 0.001) at presentation. The latter was the only independent predictor of mortality at multivariable analysis (HR 2.3, 95% CI 1.43-3.80, p = 0.001). CONCLUSIONS: The present study highlights the prognostic value of functional presentation and the safety of cardiac surgery, when feasible, in patients with cerebral septic embolism.

Double-valve infective endocarditis: clinical features and prognostic impact-a retrospective study in a surgical centre.

Most cases of infective endocarditis (IE) involve a single valve, and little is known concerning IE that simultaneously affects two valves. The involvement of more than one valve may imply more severe and extensive cardiac lesions. In these patients, surgery may be challenging. We aimed to determine the clinical characteristics, the therapeutic strategy, and the prognostic impact of double-valve IE (DVIE). We retrospectively included in the analysis that 440 consecutive patients with definite active IE in a single surgical centre. DVIE occurred in 75 of the total enrolled 440 patients (17%) and involved mostly the combination of mitral and aortic valves (N = 63, 84%). Most patients had double-native IE (N = 45, 60%). Staphylococci were less frequent in patients with double-valve than single-valve IE (SVIE). The proportion of patients undergoing valve repair among those treated surgically was higher for patients with DVIE than for SVIE (p < 0.03). Valve repair of at least one valve was associated with non-significant better survival than double replacement. DVIE was associated with higher all-cause mortality than SVIE (p < 0.013) and a higher relapse rate (p = 0.023). DVIE was not associated with a higher risk of composite non-fatal adverse events. DVIE represents a considerable proportion of overall cases of IE, mainly involving aortic and mitral valves, with a jet lesion on the mitral valve; Staphylococcus is significantly less frequent than in SVIE; DVIE is independently associated with higher mortality and relapse rate; finally, mitral valve repair is feasible in a considerable proportion of surgical cases.

Carfilzomib-induced thrombotic microangiopathy. A case report.

INTRODUCTION: Drug-induced thrombotic microangiopathy (DITMA) is an acquired condition resulting from exposure to a drug that induces the formation of platelet-rich thrombi in small arterioles or capillaries secondary to drug-dependent antibodies or direct tissue toxicity. Carfilzomib is a selective proteasome inhibitor approved to treat selected patients with Multiple Myeloma (MM). It is one of the drugs with the strongest evidence for a causal association with non-antibody-mediated DITMA. CASE REPORT: A 75-year-old man presented to the emergency department for the outbreak of vomit, asthenia, oliguria and dark stool emission. He was recently diagnosed with multiple myeloma, treated with lenalidomide, dexamethasone and carfilzomib. Laboratory exams were significant for microangiopathic haemolytic anaemia, thrombocytopenia and new-onset renal failure. ADAMTS-13 levels were in range, and no infectious signs were found both in blood nor in stool test. MANAGEMENT & OUTCOME: A carfilzomib induced thrombotic microangiopathy was soon suspected. Thus, since daily haemodialysis and supportive care did not seem to get a fast enough recovery, the patient was treated with eculizumab with a good general outcome. DISCUSSION: Drug-induced thrombotic microangiopathy is a rare and often life-threatening acquired condition whose diagnosis can be challenging and whose therapy is not always limited to supportive treatment and drug avoidance. Carfilzomib, along with other proteasome inhibitors, is one of the described potential drugs which can trigger such a manifestation.

Infective endocarditis in intravenous drug abusers: clinical challenges emerging from a single-centre experience.

BACKGROUND: Intravenous drug abuse (IDA) is a known risk factor for infective endocarditis (IE) and is associated with frequent relapses, but its prognostic impact is still debated. The potential futility of surgery in this population is a further issue under discussion. We aimed to describe the clinical characteristics, the therapeutic strategy, and the prognosis associated with IDA in IE. METHODS: We retrospectively analysed 440 patients admitted to a single surgical centre for definite active IE from January 2012 to December 2020. RESULTS: Patients reporting IDA (N = 54; 12.2%) were significantly younger (p < 0.001) and presented fewer comorbidities (p < 0.001). IDA was associated with a higher proportion of relapses (27.8 vs. 3.3%, p < 0.001) and, at multivariable analysis, was an independent predictor of long-term mortality (HR 2.3, 95%CI 1.1-4.7, p = 0.015). We did not register multiple relapses in non-IDA patients. Among IDA patients, we observed 1 relapse after discharge in 9 patients, 2 relapses in 5 patients and 3 relapses in 1 patient. In IDA patients, neither clinical and laboratory variables nor the occurrence of even multiple relapses emerged as indicators of an adverse risk-benefit ratio of surgery in patients with surgical indication. CONCLUSIONS: IE secondary to IDA affects younger patients than those with IE not associated with IDA. Probably due to this difference, IE secondary to IDA is not associated with significantly higher mortality, whereas the negative, long-term prognostic impact of IDA emerges in multivariate analysis. Considering the good prognosis of patients with uncomplicated IE treated medically, surgery should be reserved to patients with a strict- guidelines-based indication. However, since there are no clear predictors of an unfavourable risk-benefit ratio of surgery in patients with surgical indication, all patients with a complicated IE should be operated, irrespective of a history of IDA.

Predictors of mortality and adverse events in patients with infective endocarditis: a retrospective real world study in a surgical centre.

PURPOSE: Mortality in infective endocarditis (IE) is still high, and the long term prognosis remains uncertain. This study aimed to identify predictors of long-term mortality for any cause, adverse event rate, relapse rate, valvular and ventricular dysfunction at follow-up, in a real-world surgical centre. METHODS: We retrospectively analyzed 363 consecutive episodes of IE (123 women, 34%) admitted to our department with a definite diagnosis of non-device-related IE. Median follow-up duration was 2.9 years. Primary endpoints were predictors of mortality, recurrent endocarditis, and major non-fatal adverse events (hospitalization for any cardiovascular cause, pace-maker implantation, new onset of atrial fibrillation, sternal dehiscence), and ventricular and valvular dysfunction at follow-up. RESULTS: Multivariate analysis independent predictors of mortality showed age (HR per unit 1.031, p < 0.003), drug abuse (HR 3.5, p < 0.002), EUROSCORE II (HR per unit 1.017, p < 0.0006) and double valve infection (HR 2.3, p < 0.001) to be independent predictors of mortality, while streptococcal infection remained associated with a better prognosis (HR 0.5, p < 0.04). Major non-fatal adverse events were associated with age (HR 1.4, p < 0.022). New episodes of infection were correlated with S aureus infection (HR 4.8, p < 0.001), right-sided endocarditis (HR 7.4, p < 0.001), spondylodiscitis (HR 6.8, p < 0.004) and intravenous drug abuse (HR 10.3, p < 0.001). After multivariate analysis, only drug abuse was an independent predictor of new episodes of endocarditis (HR 8.5, p < 0.001). Echocardiographic follow-up, available in 95 cases, showed a worsening of left ventricular systolic function (p < 0.007); severe valvular dysfunction at follow-up was reported only in 4 patients, all of them had mitral IE (p < 0.03). CONCLUSIONS: The present study highlights some clinical, readily available factors that can be useful to stratify the prognosis of patients with IE.

Endocarditis with spondylodiscitis: clinical characteristics and prognosis.

BACKGROUND: The association of infective endocarditis (IE) with spondylodiscitis (SD) was first reported in 1965, but few data are available about this issue. This study aimed to evaluate the prevalence of SD in patients with IE, and to determine the clinical features and the prognostic impact of this association. METHODS: We retrospectively analysed 363 consecutive patients admitted to our Department with non-device-related IE. Radiologically confirmed SD was revealed in 29 patients (8%). Long-term follow-up (average: 3 years) was obtained by structured telephone interviews; in 95 cases (13 of whom had been affected by SD), follow-up echocardiographic evaluation was also available. RESULTS: At univariable analysis, the combination of IE with SD was associated with male gender (p = 0.017), diabetes (p = 0.028), drug abuse (p = 0.009), Streptococcus Viridans (p = 0.009) and Enterococcus (p = 0.015) infections. At multivariable analysis, all these factors independently correlated with presence of SD in patients with IE. Mortality was similar in patients with and without SD. IE relapses at 3 years were associated with the presence of SD (p = 0.003), Staphylococcus aureus infection (p < 0.001), and drug abuse (p < 0.001) but, at multivariable analysis, only drug abuse was an independent predictor of IE relapses (p < 0.001; HR 6.8, 95% CI 1.6-29). At echocardiographic follow-up, SD was not associated with worsening left ventricular systolic function or valvular dysfunction. CONCLUSIONS: The association of IE with SD is not rare. Hence, patients with IE should be screened for metastatic infection of the vertebral column, especially if they have risk factors for it. However, SD does not appear to worsen the prognosis of patients with IE, either in-hospital or long-term.

Echocardiographic Abnormalities in Adults With Anorexia Nervosa.

Anorexia nervosa (AN) is a psychiatric disorder that may lead to cardiac complications. The objective of this study was to evaluate global and regional longitudinal strain changes in patients affected by AN as an early marker of myocardial damage. We prospectively enrolled 48 consecutive patients with AN and 44 age-matched and gender-matched healthy controls. In all subjects, we performed echocardiography, including global longitudinal strain (GLS) measurement. A subset of 33 patients with AN had further echocardiographic examinations during the follow-up. Compared with healthy controls, patients with AN had a greater prevalence of pericardial effusion (9 of 48 vs 0 of 44, p = 0.003), a smaller left ventricular mass (63 ± 15 vs 99 ± 30 g, p < 0.001), a lower absolute value of GLS (-18.9 ± 2.8 vs -20.2 ± 1.8%, p = 0.010) and of basal LS (-15.4 ± 6.0 vs -19.4 ± 2.6%, p < 0.001). The bull's eye mapping showed a plot pattern with blue basal areas in 18 of 48 patients with AN versus 1 of 44 controls (p < 0.001). During the follow-up, of 13 patients with blue areas in the first bull's eye mapping, 11 recovered completely, and of 20 patients with a red bull's eye at the first examination, none presented blue areas at the second one. In conclusion, GLS is significantly altered in patients with AN, and a basal blue pattern on bull's eye mapping identifies more severe cases. These changes seem to be reversible.

Embolic risk stratification and prognostic impact of early surgery in left-sided infective endocarditis.

BACKGROUND: In patients with left-sided infective endocarditis (IE) and heart failure associated with large vegetations, early surgery prevents embolic events. However, optimal timing of surgery for other indications is still unresolved particularly when the presence of large vegetations represents the sole indication. METHODS: We retrospectively analyzed 308 consecutive patients admitted to our department with definite left-sided IE. Of these patients, 243 (79%) underwent cardiac surgery (complicated IE), 34 patients with uncomplicated IE received medical treatment, 24 were not operated due to prohibitive general conditions and 7 refused surgery. Long-term follow-up was obtained by structured telephone interviews. RESULTS: During the 6-year follow-up (average 121.8 weeks ± 76), patients not operated because of general conditions or refusal had the worst prognosis, while outcome in operated patients for complicated IE was comparable to that of uncomplicated IE treated medically. Early (<2 weeks from diagnosis) surgery was associated with better survival compared to delayed surgery (HR 0.58, p = 0.23). Embolic events were detected at admission in 38% of cases; Staphylococcus Aureus etiology and vegetation size were independently associated with embolism (OR 2.4, p = 0.01; OR 1, p=0.008 respectively). CONCLUSIONS: Compared to uncomplicated medically-treated patients, complicated IE showed comparable survival when managed aggressively by surgical intervention, whereas a conservative approach was associated with an adverse prognosis. Staphylococcus Aureus infection and vegetation size were independent predictors of systemic embolism. Our data support aggressive surgical management of complicated IE patients and highlight the importance of etiological characterization in clinical decision-making.

Thrombophilic mutations in high-risk atrial fibrillation patients: high prevalence of prothrombin gene G20210A polymorphism and lack of correlation with thromboembolism.

Atrial fibrillation (AF) is a common arrhythmia that results in a high risk of cerebral and peripheral embolism. Factor V Leiden and factor II G20210A variant are two leading conditions for venous thrombosis. The aim of our study was to find out whether these two common prothrombotic mutations play a role in the occurrence of embolic events in AF patients. We investigated 336 non-valvular AF patients and 336 healthy control subjects. Factor II G20210A variant was found in 24/336 patients (7.14%) and in 11/336 of control subjects (3.3%). At a multivariate analysis, factor II G20210A variant was independently associated to AF (OR 2.4 95% CI 1.1-5.2; p<0.05). No significant difference was observed in the prevalence of factor V Leiden in the two groups investigated [6/304 (2.0%) in patients vs 13/336 (3.9%) in controls (p=0.24)]. AF patients were separately analyzed in relation to the occurrence or absence of a cerebral or peripheral embolic event (200 with and 136 without embolic event). The prevalence of the two mutations among AF patients with and without an embolic event was similar [factor II G20210A polymorphism (7% and 7.3% respectively) and factor V Leiden (1.2% and 2.9%, respectively)]. No differences were found in relation to the type of embolic event. Our results suggest a possible relationship between the presence of prothrombin gene variant and AF per se.

Prevalence, predictors and prognostic significance of microalbuminuria in acute cardiac patients: a single center experience.

The objective of this study was to prospectively assess the prevalence, predictors and prognostic significance of microalbuminuria in a large cohort of consecutive acute cardiac patients, admitted to an intensive cardiac care unit from 1 January 2008 to 30 June 2009. In 815 acute cardiac patients, microalbuminuria is detectable in 39.3%. Microalbuminuria shows a significant negative correlation with left ventricular ejection fraction (Spearman's ρ = -0.228; p < 0.001), while it is positively correlated with C-reactive protein (Spearman's ρ = 0.239; p < 0.001), NT-pro-BNP (Spearman's ρ = 0.306; p < 0.001) and glycemia (Spearman's ρ = 0.191; p < 0.001). Microalbuminuria is an independent predictor for in-hospital mortality (1 µg/min step) (OR 1.015; 95% CI 1.008-1.023; p < 0.001). In the acute phase of cardiac patients, microalbuminuria is a common finding, and it represents an independent predictor for early mortality. It is strictly linked to the inflammatory activation (as indicated by C-reactive protein) and to acute glucose values, thus suggesting that it may be part of the acute response to stress.