Ribociclib and palbociclib-induced erythema multiforme: a case report.

Cyclin-dependent kinase 4/6 inhibitors (CKIs), ribociclib, palbocilb and abemaciclib, have been approved in combination with endocrine therapy for the treatment of hormone receptor-positive and human epidermal growth factor 2-negative advanced or metastatic breast cancer. Severe dermatological adverse events are rare with these agents; however, they require direct recognition and management in order not to become life-threatening. Erythema multiforme (EM) belongs to a dermatopathic spectrum that includes immune-mediated, widespread hypersensitivity reaction, which occurs with varying degrees of severity and affects the skin and/or the mucosa. We hereby present a case of ribociclib- and palbociclib-related EM. We sought to report this case given the implication of two agents from the same drug class in EM onset. We also aim to emphasize the breadth of mechanisms of actions of CKIs, with an impingement in the immune system as well, and the importance of promptly identifying and handling such skin toxicities.

Renal function and mortality in patients with atrial fibrillation.

AIM: The aim of this study is to examine the association of the presence of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) values with mortality in patients with atrial fibrillation. METHODS: This posthoc analysis of a randomized controlled trial consisted of hospitalized patients with atrial fibrillation who were followed up for a median of 2.7 years after discharge. Kaplan-Meier curves, multivariate Cox-regression and spline curves were utilized to assess the association of CKD, CKD stages 2-5 according to the KDOQI guidelines, and the continuum of eGFR values with the primary outcome of all-cause death, and the secondary outcome of cardiovascular mortality. RESULTS: Out of 1064 hospitalized patients with atrial fibrillation, 465 (43.7%) had comorbid CKD. The presence of CKD was associated with an increased risk for both all-cause and cardiovascular mortality following hospitalization [adjusted hazard ratio (aHR): 1.60; 95% confidence intervals (95% CIs): 1.25-2.05 and aHR: 1.74; 95% CI: 1.30-2.33, respectively]. The aHRs for all-cause mortality in CKD stages 2-5, as compared with CKD stage 1 were 2.18, 2.62, 4.20 and 3.38, respectively (all P < 0.05). In spline curve analyses, eGFR values lower than 50 ml/min/1.73 m2 were independent predictors of higher all-cause and cardiovascular mortality. CONCLUSION: In recently hospitalized patients with atrial fibrillation, the presence of CKD was independently associated with decreased survival, which was significant across CKD stages 2-5, as compared with CKD stage 1. Values of eGFR lower than 50 ml/min/1.73 m2 were incrementally associated with worse prognosis.

Education level predicts mortality and morbidity in hospitalised patients with atrial fibrillation.

AIM: Education level has been long considered a life-quality modifier, but little is known about its relation to life expectancy in patients with cardiovascular disease. This study aims to assess possible correlations between education level and survival in patients with atrial fibrillation (AF). METHODS: This retrospective cohort study used data from a randomised trial of 1082 hospitalised patients with AF (mean age of 75 ± 11 years) who were followed up after discharge. Patients were divided into three groups based on their education level: i) none or primary (NPEL), ii) secondary (SEL), and iii) tertiary education level (TEL). Kaplan-Meier curves and multivariable-adjusted hazard ratios (aHRs) were used to compare survival rates between groups. The primary outcome was all-cause mortality. The composite secondary outcome was cardiovascular mortality or any hospitalisation. RESULTS: After a median 31-month follow-up period, 289 (41.9%) patients died in the NPEL group, 75 (31.1%) in the SEL group, and 29 (19.1%) in the TEL group. The aHRs for all-cause mortality were 0.42 (95% CI, 0.27 to 0.66; p < 0.001) for the TEL group compared with the NPEL group, 0.55 (95% CI, 0.33 to 0.93; p = 0.02) for the TEL group compared with the SEL group, and 0.68 (95% CI, 0.50 to 0.93; p = 0.01) for the SEL group compared with the NPEL group. The corresponding aHRs for the composite secondary outcome were 0.36 (95% CI, 0.23 to 0.52; p < 0.001), 0.49 (95% CI, 0.29 to 0.80; p < 0.001), and 0.67 (95% CI, 0.50 to 9.91; p = 0.01). CONCLUSION: Higher education levels were independently associated with fewer fatal and non-fatal outcomes in recently hospitalised patients with AF.

Rhythm control versus rate control in patients with atrial fibrillation and heart failure across the left ventricular ejection fraction spectrum.

BACKGROUND: Rhythm control and rate control are both employed commonly in patients with atrial fibrillation (AF) and heart failure (HF), but limited real-world data exist on them. We aimed to compare outcomes between these two strategies across the left ventricular ejection fraction (LVEF) spectrum. MATERIALS AND METHODS: This retrospective cohort study used data from the randomized MISOAC-AF trial, including from patients with AF and coexistent HF who were hospitalized and followed up after discharge. At baseline, the patients were classified into pharmaceutical (or electrical cardioversion) rhythm control strategy or rate control treatment (b-blocker, digoxin, calcium channel blockers) groups. The primary outcome was all-cause mortality. Kaplan-Meier curves and multivariable-adjusted Cox regression were utilized to compare the two strategies. Spline curve models were used to demonstrate the results across the LVEF stratified spectrum. RESULTS: In total, 199 AF patients with HF were studied (mean age, 77 years). At discharge, 73 (36.7%) patients received rhythm control and 126 (63.3%) rate control treatment. After a median follow-up period of 31 months, 26 (35.6%) patients in the rhythm-control group died, as compared to 43 (33.3%) in the rate-control group (aHR: 1.29; 95% CI: 0.78-2.14; p = 0.31). The spline curves also revealed no difference in all-cause mortality favoring either strategy in any HF subtype across the nominally classified LVEF. CONCLUSION: The use of a pharmacological rhythm-control strategy was not associated with a survival advantage compared to the rate control strategy in recently hospitalized patients with AF and comorbid HF. More randomized trials and large studies are needed in the future to explore these results in each subgroup of HF patients.

Associations of Atrial Fibrillation Patterns With Mortality and Cardiovascular Events: Implications of the MISOAC-AF Trial.

AIM: This retrospective cohort study aimed to evaluate the prognostic implications of the distinct atrial fibrillation (AF) temporal patterns: first diagnosed, paroxysmal, and persistent or permanent AF. METHODS: In this post hoc analysis of the MISOAC-AF trial (NCT02941978), a total of 1052 patients with AF (median age 76 years), discharged from the cardiology ward between 2015 and 2018, were analyzed. Kaplan-Meier and Cox-regression analyses were performed to compare the primary outcome of all-cause mortality, the secondary outcomes of stroke, major bleeding and the composite outcome of cardiovascular (CV) mortality or hospitalization among AF patterns. RESULTS: Of patients, 121 (11.2%) had first diagnosed, 356 (33%) paroxysmal, and 575 (53.2%) persistent or permanent AF. During a median follow-up of 31 months (interquartile range 10 to 52 months), 37.3% of patients died. Compared with paroxysmal AF, patients with persistent or permanent AF had higher mortality rates (adjusted hazard ratio (aHR), 1.37; 95% confidence interval [CI], 1.08-1.74, P = .009), but similar CV mortality or hospitalization rates (aHR, 1.09; 95% CI, 0.91-1.31, P = .35). Compared with first diagnosed AF, patients with persistent or permanent AF had similar mortality (aHR, 1.26; 95% CI, 0.87-1.82, P = .24), but higher CV mortality or hospitalization rates (aHR, 1.35; 95% CI, 1.01-1.8, P = .04). Stroke and major bleeding events did not differ across AF patterns (all P > .05). CONCLUSIONS: In conclusion, in recently hospitalized patients with comorbid AF, the presence of persistent or permanent AF was associated with a higher incidence of mortality and morbidity compared with paroxysmal and first diagnosed AF.

Indications for percutaneous left atrial appendage occlusion in hospitalized patients with atrial fibrillation.

AIMS: Percutaneous left atrial appendage occlusion (LAAO) is an alternative nonpharmacological therapeutic option for stroke prevention in patients with NVAF. However, no data exist on potential LAAO candidates' prevalence among 'real-world' NVAF patients. This study aimed to investigate the indications for LAAO in hospitalized patients with comorbid nonvalvular atrial fibrillation (NVAF). METHODS: This is a post-hoc analysis of the MISOAC-AF (Motivational Interviewing to Support OAC-AF, ClinicalTrials.gov: NCT02941978), randomized controlled trial, which enrolled NVAF patients hospitalized for any reason in a tertiary cardiology department. In this analysis, patients with a history of major bleeding or stroke under OAC therapy were considered to have a strong indication for LAAO. RESULTS: A total of 980 patients with NVAF were studied (mean age 73.9 ±â€Š10.9 years, 54.7% men). Prior major bleeding occurred in 134 (13.7%) patients (intracranial bleeding in 1%, upper and lower gastrointestinal bleeding in 6.4 and 8.9%, respectively). A total of 58 (5.9%) patients experienced an embolic stroke while being treated using OAC. Overall, either of these events was prevalent in 173 (17.7%) patients, denoting a strong indication for LAAO. CONCLUSION: Almost one out of six patients hospitalized with comorbid NVAF may be considered eligible for percutaneous LAAO for stroke prevention.Trial Identification: NCT02941978, https://clinicaltrials.gov/ct2/show/NCT02941978.

Oral anticoagulation patterns and prognosis in octogenarian patients with atrial fibrillation.

The relationship between oral anticoagulants (OACs) and prognosis in elderly patients with atrial fibrillation (AF) has not been adequately explored. In this retrospective cohort study, we identified subjects aged over 80 from a database of 1140 AF patients discharged from the cardiology ward of a single tertiary center between 2015 and 2018. We examined the OAC treatment of octogenarian patients at discharge [VKA (vitamin K antagonist), NOAC (non-vitamin K antagonist oral anticoagulant), no OAC treatment]. We analyzed follow-up data of patients on OAC at discharge. The primary endpoint was all-cause death. The secondary endpoint was the incidence of stroke and major bleeding. The association of NOAC versus VKA treatment with these endpoints was assessed with multivariable Cox regression, using the VKA group as reference. A total of 330 octogenarian patients with AF were included with a mean (± SD) age of 83.9 ± 3.5 years. At discharge, 53.3% received a NOAC, 30% a VKA, and 16.7% no OAC. Patients on OAC were followed-up over a median of 2.6-years . The adjusted risk of all-cause death was not different in the NOAC group, compared with the VKA group (hazard ratio [HR], 0.72; 95% confidence intervals [CI] 0.50-1.03; P = 0.07). The risk of stroke or major bleeding was not different either (all P > 0.05). In conclusion, in this cohort of post-discharge octogenarian patients with AF, the risk for all-cause death was similar in NOAC versus VKA users, after adjustment for baseline covariates. No differences in stroke and major bleeding events among these treatment groups were revealed.

Predictive Role of Platelet-Associated Indices on Admission and Discharge in the Long-Term Prognosis of Acute Coronary Syndrome Patients.

Our study aimed to investigate the association between platelet indices and their in-hospital change and long-term prognosis in acute coronary syndrome (ACS). Data from a randomized controlled trial (NCT02927808) recruiting ACS patients were analyzed (survival analysis). The examined variables were platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) on admission and discharge, as well as their alteration during hospitalization. The primary endpoint was major adverse cardiac events (MACE) (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke or hospitalization for unstable angina) and all-cause mortality, while secondary endpoints were all-cause hospitalization and bleeding events. The study included 252 patients with a follow-up of 39 (28-45) months. In the univariate analysis, MACE was associated with discharge PC [hazard ratio (HR) 2.20, 95% confidence interval (CI) 1.10-4.40], discharge MPV (HR 0.48, 95% CI 0.25-0.94), and in-hospital PC difference (HR 0.25, 95% CI 0.13-0.51). In the multivariable analysis, only in-hospital PC decrease correlated with lower MACE incidence (adjusted HR .27, 95% CI 0.14-0.54) and lower all-cause hospitalization risk (adjusted HR 0.36, 95% CI 0.19-0.68). PC reduction during hospitalization for ACS is an independent predictor of better prognosis.

Prognostic implications of valvular heart disease in patients with non-valvular atrial fibrillation.

BACKGROUND: Valvular heart disease (VHD) in non-valvular atrial fibrillation (AF) is a puzzling clinical entity. The aim of this study was to evaluate the prognostic effect of significant VHD (sVHD) among patients with non-valvular AF. METHODS: This is a post-hoc analysis of the MISOAC-AF trial (NCT02941978). Consecutive inpatients with non-valvular AF who underwent echocardiography were included. sVHD was defined as the presence of at least moderate aortic stenosis (AS) or aortic/mitral/tricuspid regurgitation (AR/MR/TR). Cox regression analyses with covariate adjustments were used for outcome prediction. RESULTS: In total, 983 patients with non-valvular AF (median age 76 [14] years) were analyzed over a median follow-up period of 32 [20] months. sVHD was diagnosed in 575 (58.5%) AF patients. sVHD was associated with all-cause mortality (21.6%/yr vs. 6.5%/yr; adjusted HR [aHR] 1.55, 95% confidence interval [CI] 1.17-2.06; p = 0.02), cardiovascular mortality (16%/yr vs. 4%/yr; aHR 1.70, 95% CI 1.09-2.66; p = 0.02) and heart failure-hospitalization (5.8%/yr vs. 1.8%/yr; aHR 2.53, 95% CI 1.35-4.63; p = 0.02). The prognostic effect of sVHD was particularly evident in patients aged < 80 years and in those without history of heart failure (p for interaction < 0.05, in both subgroups). After multivariable adjustment, moderate/severe AS and TR were associated with mortality, while AS and MR with heart failure-hospitalization. CONCLUSION: Among patients with non-valvular AF, sVHD was highly prevalent and beared high prognostic value across a wide spectrum of clinical outcomes, especially in patients aged < 80 years or in the absence of heart failure. Predominantly AS, as well as MR and TR, were associated with worse prognosis.

Τhe association of heart failure across left ventricular ejection fraction with mortality in atrial fibrillation.

AIMS: The aim of this study is to investigate the prognostic implications of the presence of heart failure (HF) across the range of left ventricular ejection fraction (LVEF) in patients with comorbid atrial fibrillation (AF). METHODS AND RESULTS: We conducted a retrospective cohort study of 1063 patients (median age 76 years), discharged from the cardiology ward with a primary or secondary diagnosis of AF between 2015 and 2018. We used Cox proportional-hazards and spline models to examine the association of the presence of HF, across the range of LVEF, with the primary outcome of all-cause mortality. HF was documented in 52.9% of patients at baseline. During a median follow-up of 31 months (interquartile range 10 to 52 months), 37.3% of patients died. The presence of HF was associated with a significantly higher risk of mortality [adjusted hazard ratio (aHR) 2.17; 95% confidence interval (CI), 1.70 to 2.77; P < 0.001], which was evident across HF with reduced (aHR 3.03; 95% CI 2.41 to 4.52), mid-range (aHR 2.08; 95% CI 1.47 to 2.94), and preserved LVEF (aHR 1.94; 95% CI 1.47 to 2.55). Among patients with HF, the spline curve depicted a non-linear association between LVEF and the risk of death, in which there was a steep and progressive increase in mortality for every 5% reduction in LVEF below 25% (aHR 1.97, 95% CI 1.04 to 3.73, P = 0.04). CONCLUSIONS: In patients with AF who were discharged from the hospital, the presence of HF at baseline was independently associated with a twofold risk of death, which was significant across LVEF-classified HF subtypes. Among patients with AF and HF, the risk of death rose significantly as LVEF was reduced below 25%.

Prognostic significance of diabetes mellitus in patients with atrial fibrillation.

BACKGROUND: There are limited data on the association of diabetes mellitus (DM) and levels of glycated hemoglobin (HbA1c) with outcomes in patients with atrial fibrillation (AF). METHODS: This retrospective cohort study included patients who were recently hospitalized with a primary or secondary diagnosis of AF from December 2015 through June 2018. Kaplan-Meier curves and Cox-regression adjusted hazard ratios (aHR) were calculated for the primary outcome of all-cause mortality and for the secondary outcomes of cardiovascular (CV) mortality and the composite outcome of CV death or hospitalization. Competing-risk regression analyses were performed to calculate the cumulative risk of stroke, major bleeding, AF- or HF-hospitalizations adjusted for the competing risk of all-cause death. Spline curve models were fitted to investigate associations of HbA1c values and mortality among patients with AF and DM. RESULTS: In total 1109 AF patients were included, of whom 373 (33.6%) had DM. During a median follow-up of 2.6 years, 414 (37.3%) patients died. The presence of DM was associated with a higher risk of all-cause mortality (aHR = 1.40 95% confidence intervals [CI] 1.11-1.75), CV mortality (aHR = 1.39, 95% CI 1.07-1.81), sudden cardiac death (aHR = 1.73, 95% CI 1.19-2.52), stroke (aHR = 1.87, 95% CI 1.01-3.45) and the composite outcome of hospitalization or CV death (aHR = 1.27, 95% CI 1.06-1.53). In AF patients with comorbid DM, the spline curves showed a positive linear association between HbA1c levels and outcomes, with values 7.6-8.2% being independent predictors of increased all-cause mortality, and values < 6.2% predicting significantly decreased all-cause and CV mortality. CONCLUSIONS: The presence of DM on top of AF was associated with substantially increased risk for all-cause or CV mortality, sudden cardiac death and excess morbidity. HbA1c levels lower than 6.2% were independently related to better survival rates suggesting that optimal DM control could be associated with better clinical outcomes in AF patients with DM.

A novel prognostic tool to predict mortality in patients with atrial fibrillation: The BASIC-AF risk score.

BACKGROUND: This study sought to develop and validate a risk score to predict mortality in patients with atrial fibrillation (AF) after a hospitalization for cardiac reasons. METHODS: The new risk score was derived from a prospective cohort of hospitalized patients with concurrent AF. The outcome measures were all-cause and cardiovascular mortality. Random forest was used for variable selection. A risk points model with predictor variables was developed by weighted Cox regression coefficients and was internally validated by bootstrapping. RESULTS: In total, 1130 patients with AF were included. During a median follow-up of 2 years, 346 (30.6%) patients died and 250 patients had a cardiovascular cause of death. N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin-T were the most important predictors of mortality, followed by indexed left atrial volume, history and type of heart failure, age, history of diabetes mellitus, and intraventricular conduction delay, all forming the BASIC-AF risk score (Biomarkers, Age, ultraSound, Intraventricular conduction delay, and Clinical history). The score had good discrimination for all-cause (c-index = 0.85 and 95% CI 0.82-0.88) and cardiovascular death (c-index = 0.84 and 95% CI 0.81-0.87). The predicted probability of mortality varied more than 50-fold across deciles and adjusted well to observed mortality rates. A decision curve analysis revealed a significant net benefit of using the BASIC-AF risk score to predict the risk of death, when compared with other existing risk schemes. CONCLUSIONS: We developed and internally validated a well-performing novel risk score for predicting death in patients with AF. The BASIC-AF risk score included routinely assessed parameters, selected through machine-learning algorithms, and may assist in tailored risk stratification and management of these patients.