Giulia Russo

Trastuzumab adjuvant chemotherapy and cardiotoxicity in real-world women with breast cancer.

BACKGROUNDnAdjuvant trastuzumab therapy improves survival of human epidermal growth factor receptor 2 (HER2)-positive women with early breast cancer (EBC). A careful monitoring of cardiac function is needed due to potential trastuzumab cardiotoxicity (Tcardiotox). To date, the incidence, timing, and phenotype of patients with Tcardiotox in clinical practice are not well known.nnnMETHODS AND RESULTSnA total of 499 consecutive HER2-positive women (mean age 55 ± 11 years) with EBC treated with trastuzumab between January 2008 and June 2009 at 10 Italian institutions were followed for 1 year. We evaluated incidence, time of occurrence, and clinical features associated with Tcardiotox. Left ventricular ejection fraction (LVEF) was evaluated by echocardiography at baseline and at 3, 6, 9, and 12 months during trastuzumab therapy. Tcardiotox was recognized in 133 patients (27%): 102 (20%) showed asymptomatic reduction in LVEF of >10% but ≤20% (grade 1 Tcardiotox); 15 (3%) had asymptomatic decline of LVEF of >20% or <50% (grade 2); and 16 (3%) had symptomatic heart failure (grade 3). Trastuzumab was discontinued due to cardiotoxicity in 24 patients (5%) and restarted in 13 after LVEF recovery. Forty-one percent of Tcardiotox cases occurred within the first 3 months of follow-up, most prevalently in older patients with higher creatinine levels and in patients pretreated with doxorubicin and radiotherapy.nnnCONCLUSIONSnIn clinical practice, Tcardiotox is frequent in HER2-positive women with EBC and occurs in the first 3 months of therapy. Cardiac dysfunction is mild and asymptomatic in the majority of patients. The interruption of treatment is a rare event which occurs, however, in a significantly higher percentage than reported in randomized clinical trials.

Role of renal function on the development of cardiotoxicity associated with trastuzumab-based adjuvant chemotherapy for early breast cancer

Anthracyclines, taxanes and trastuzumab are used for therapy in early breast cancer (EBC) overexpressing Human Epidermal Growth Factor 2 (HER2+). These drugs, considered alone, do not present potential nephrotoxicity. However, renal dysfunction (RD) may increase the myocardial sensibility to the insult of these chemotherapies used in combination. The aim of the study is to assess the role of RD on the development of cardiotoxicity associated with trastuzumab-based adjuvant therapy (aTrastC) for EBC. Clinical and echocardiographic data of 499 women with ERB2+ EBC were analyzed. At 12-month evaluation, any symptoms of heart failure or decrease in left ventricular ejection fraction (LVEF) were recorded. Patients who had cardiotoxicity (nxa0=xa0130, 26xa0%) were older (57xa0±xa011 vs. 55xa0±xa011xa0years; pxa0=xa00.03), had lower glomerular filtration rate (GFR) (76xa0±xa015 vs. 83xa0±xa019xa0ml/min/1.73xa0m2; pxa0=xa00.003), higher LVEF (69xa0±xa06 vs. 63xa0±xa05xa0%; pxa0<xa00.001) and received more frequent doses of doxorubicin (18 vs. 9xa0%; pxa0=xa00.01) than those who did not. In patients with GFR 60–90 and <60xa0ml/min/1.73xa0m2, the 1-year event rate of cardiotoxicity was 25 and 38xa0%, respectively. ROC analysis showed that the best cut-off point of GFR for predicting cardiotoxicity was 78xa0ml/min/1.73xa0m2 (AUCxa0=xa00.66, [95xa0% CI 0.57–0.74]). Multiple logistic regression revealed that GRF <78xa0ml/min/1.73xa0m2 was the strongest predictor of cardiotoxicity (OR 3.32 [CIxa0=xa01.30–8.65]), independent of doxorubicin treatment and left ventricular ejection fraction. A reduced renal function represents a condition of higher risk of developing cardiotoxicity at 12-month follow-up in patients with HER2 + EBC treated with aTrastC.

The 30-day metric in acute heart failure revisited: data from IN-HF Outcome, an Italian nationwide cardiology registry.

Unplanned readmissions early after a discharge from acute heart failure hospitalization are common and have become a reimbursement benchmark and marker of hospital quality. However, the competing risk of short‐term post‐discharge mortality is substantial.

Role of hypertension on new onset congestive heart failure in patients receiving trastuzumab therapy for breast cancer

Background Adjuvant trastuzumab therapy improves survival of Human Epidermal growth factor receptor 2 (HER2)-positive women with early breast cancer (EBC). Trastuzumab-induced cardiotoxicity is not uncommon. In the setting of community patients, the incidence, timing and phenotype of new onset congestive heart failure (CHF) is unknown. Methods Forty hundred and ninety nine consecutive HER2-positive women (mean age 55u200a±u200a11) with EBC treated with trastuzumab between January 2008 and June 2009 at 10 Italian institutions were followed-up for 1 year. We evaluated incidence, time of occurrence, clinical features associated with CHF. Left ventricular ejection fraction (LVEF) was evaluated by echocardiography at baseline and 3, 6, 9and 12 months during trastuzumab therapy. Results CHF occurred in 16 patients (3.2%), who were older, more hypertensive and with a higher degree of hypertension in comparison with patients who did not have CHF. All CHF patients had a significant reduction in LVEF with a mean peak of −12 points % detected at 3-month follow-up. CHF occurred in seven patients (44%) within 3-month follow-up, in four patients (25%) between 3–6 months, in three patients (19%) between 6–9 months and in two patients (12%) between 9 and 12 months. Trastuzumab was discontinued in 10 of 16 patients and re-started in five after LVEF recovery and clinical improvement. New onset CHF was predicted by the presence of hypertension [OR 2.9 (CI 1.1–7.9]). Conclusion New onset CHF occurs seldom in HER2-positive women with EBC, prevalently in the first 6 months of therapy. CHF is associated with a significant reduction in LVEF and is predicted by a history of hypertension.

Clinical implications of the CKD epidemiology collaboration (CKD-EPI) equation compared with the modification of diet in renal disease (MDRD) study equation for the estimation of renal dysfunction in patients with cardiovascular disease

AbstractThe CKD-EPI equation is more accurate than the MDRD equation in the general population. We performed this study to establish whether chronic kidney disease (CKD) is commonly recognized by clinicians and whether the CKD-EPI equation improves prognosis estimation in patients with chronic cardiovascular disease (CVD). We analyzed data on 12394 CVD patients consecutively examined at the Cardiovascular Center of Trieste (Italy) between November 2009 and October 2013. The outcomes were all-cause death and a composite outcome of death/hospitalization for CV events (D+cvH). CKD-EPI formula reclassified 1786 (14.4xa0%) patients between KDIGO categories compared to the MDRD: 2.3xa0% (nxa0=xa0280) placed in a lower risk and 12.1xa0% (nxa0=xa01506) into a higher risk group. CKD, defined as eGFR-CKD-EPI formula <60xa0ml/min, was present in 3083 patients (24.9xa0%) but not recognized by clinicians in 1946 (63.1xa0% of patients with CKD). The lack of recognition of CKD was inversely proportional to the KDIGO class for both equations. There were 986 deaths and 2726 D+cvH during 24xa0months follow-up. The incidence of death and D+cvH was about twice as high in patients with unrecognized CKD than in those with normal renal function (31xa0% vs. 17.1xa0%, aHR: 1.35, 95xa0% CI: 1.15 to 1.60), even in those patients with eGFR-MDRD >60 but eGFR-CKD-EPI formula <60 (31.1xa0% vs 17.1xa0%, pxa0<xa00.001). CKD-EPI equation provides more accurate risk stratification than MDRD equation in patients with CVD. CKD was unrecognized in nearly two-thirds of these patients but clinical outcomes were similar in those for patients with recognized CKD.n

Prevalence and factors related to inappropriately high left ventricular mass in patients with rheumatoid arthritis without overt cardiac disease

Objectives: Due to the chronic inflammatory status, specific neuro-hormones and progression of arterial stiffness, patients with rheumatoid arthritis (RA) are exposed to the development of excessive left ventricular mass disproportionate to the need to compensate left ventricular load. This condition, named inappropriately high left ventricular mass (iLVM), is associated with unfavorable prognosis in patients with hypertension, aortic stenosis or diabetes. In this study, we assessed prevalence and factors associated with iLVM in a large cohort of patients with RA and tested the hypothesis that RA per se is a condition related to iLVM. Methods: We prospectively analyzed 235 RA patients without overt cardiac disease recruited between January and December 2014, who were compared with 235 controls matched for age, sex, BMI, prevalence of hypertension and diabetes. iLVM was defined as measured/predicted LVM ratio above 123%. LVM was predicted in each individual by using a simple equation considering height, sex and left ventricular work. Results: iLVM was detected in 150 RA patients (64%) and in 30 controls (15%; Pu200a<u200a0.001). In patients with RA, the variables independently associated with iLVM emerged by multivariate logistic regression analysis were left ventricular systolic dysfunction measured as mid-wall shortening and concentric left ventricular geometry. Considering both groups of patients with RA and matched controls, RA was the strongest variable related to iLVM (odds ratio 3.37, 95% confidence interval 1.37–8.31, Pu200a=u200a0.008). Conclusions: Two-thirds of patients with RA without overt cardiac disease have iLVM, which is associated with left ventricular systolic dysfunction and concentric geometry. RA per se is a condition closely related to iLVM.

Reasons why patients suffering from chronic heart failure at very high risk for death survive

BACKGROUNDnAn accurate prognostic stratification is essential for optimizing the clinical management and treatment decision-making of patients with chronic heart failure (HF). Among the best available models, we used the Cardiac and Comorbid Conditions HF (3C-HF) Score, to predict all-cause mortality in patients with CHF.nnnMETHODSnwe selected and characterized the subgroup of patients at very high risk with the worst mid-term prognosis belonging to the highest decile of 3C-HF score with the aim to assess predictors of survival in subjects with an expected probability of 1-year mortality near to 45%.nnnMETHODS AND RESULTSnWe recruited 1777 consecutive chronic HF patients at 3 Italian Cardiology Units. Median age was 76 ± 10 years, 43% were female, and 32% had preserved ejection fraction. Subjects belonging to the highest decile of 3C-HF score were 246 (13.8% of total population). During a median follow-up of 21 [12-40] months, 110 of these patients (45%) survived and 136 (55%) died. The variables that contributed to survival prediction emerged by Cox regression multivariate analysis were the lower degree of renal dysfunction and higher body mass index.nnnCONCLUSIONSnThe prognostic stratification of chronic HF patients allows in daily practice to select patients at different risk for death and identify prognosticators of survival in outliers at very high risk of death. The reasons why these patients outlive the matching part of subjects who expectedly die are related to the maintenance of a satisfactory renal function and body mass index.

Il raggiungimento dei target raccomandati di profilo lipidico in una popolazione con cardiopatia ischemica cronica: dalle linee guida al mondo reale

BACKGROUND: It is known that less than half of patients with coronary heart disease reaches the target of LDL cholesterol (LDL-C) <100 mg/dl. According to the latest international guidelines, this target has been lowered to <70 mg/dl in very high-risk patients. METHODS: From November 1, 2009 to December 31, 2012, 4953 patients with coronary heart disease were enrolled in the Cardiovascular Registry of Trieste (Italy). We assessed clinical data, LDL-C levels, statin prescription and medium-term outcome in patients with coronary heart disease. RESULTS: At first clinical evaluation, LDL-C values were available for only 61.5% of patients. The target level of LDL-C <70 mg/dl was reached in 17% of cases and LDL-C <100 mg/dl in 53%. Patients with lower LDL-C levels were more frequently males, with higher cardiovascular risk profile, more comorbidity and more frequent polypharmacy. LDL-C levels influenced statin prescription: in patients with LDL-C ≥ 100 mg/dl, cardiologists started or modified the dosage of statin therapy twice more than in patients with LDL-C <100 mg/dl, even if only in less than 20% of cases. Patients with LDL-C <100 mg/dl in statin therapy had better prognosis, whereas patients with low LDL-C levels without statin therapy had the worst prognosis. Other prognostic factors in this population with LDL-C <100 mg/dl were age, presence of heart failure, comorbidities (evaluated with Charlson index) and polypharmacy. CONCLUSIONS: In our population of outpatients with coronary heart disease, the target of LDL-C <100 mg/dl was reached in 53% of cases. LDL-C levels influenced statin prescription and modification of dosages. The medium-term outcome is closely influenced by the achievement of target LDL-C levels and statin prescription.

Prevalence of job-related distress and satisfaction in a nationwide cardiology setting: The IANUS - itAliaN cardiologists' Undetected distress Study.

Introduction and objectives Cardiologists’ work distress has been seldom studied. The ItAliaN cardiologists’ Undetected distress Study survey was designed to assess prevalence of work distress and satisfaction, and to gain insight into associations among these constructs and socio-demographics and job description. Methods We invited members of our national cardiological society (Associazione Nazionale Medici Cardiologi Ospedalieri) to participate in an anonymous, self-report, exclusively web-based survey, posted on the Associazione Nazionale Medici Cardiologi Ospedalieri website. ItAliaN cardiologists’ Undetected distress Study included socio-demographics, job description and a 15-item questionnaire on job-related distress and work satisfaction. Results Of 7393 invited cardiologists, 1064 completed the survey. Organizational problems and worries about medico-legal controversies were reported by 71% and 49% of participants, respectively; over one-third reported loss of enthusiasm, helplessness, work-life imbalance and lack of control over work. Conversely, 86% felt competent at work, 67% rewarded by the moral/human meaning of their work and 52% satisfied with their professional fulfilment. Factor analysis revealed a meaningful underlying structure including four factors: job strain, positive meaning, emotional fatigue and relational difficulties. Relational difficulties were more frequent in cardiologists working in primary-level than in secondary and tertiary care hospitals (Pu200a=u200a0.017 and Pu200a=u200a0.013, respectively). Interventional cardiologists reported higher positive meaning than those in the clinical inpatients area and outpatient diagnostic settings (Pu200a=u200a0.007 and Pu200a=u200a0.025, respectively) and lower emotional fatigue than subjects in the clinical inpatients area (Pu200a=u200a0.0005). Conclusion Cardiologists’ work distress should be interpreted integrating job-related negative aspects with a reappraisal of protective personal and relational resources, which should be fostered to promote physicians’ wellbeing at the individual, collective and organizational levels.

Echocardiographic markers of inducible myocardial ischemia at baseline evaluation preparatory to exercise stress echocardiography

BackgroundTissue Doppler Imaging (TDI) is a sensible and feasible method to detect longitudinal left ventricular (LV) systolic dysfunction (LVSD) in patients with diabetes mellitus, hypertension or ischemic heart disease. In this study, we hypothesized that longitudinal LVSD assessed by TDI predicted inducible myocardial ischemia independently of other echocardiographic variables (assessed as coexisting potential markers) in patients at increased cardiovascular (CV) risk.MethodsTwo hundred one patients at high CV risk defined according to the ESC Guidelines 2012 underwent exercise stress echocardiography (ExSEcho) for primary prevention. Echocardiographic parameters were measured at rest and peak exercise.ResultsExSEcho classified 168 (83.6xa0%) patients as non-ischemic and 33 (16,4xa0%) as ischemic. Baseline clinical characteristics were similar between the groups, but ischemic had higher blood pressure, received more frequently beta-blockers and antiplatelet agents than non-ischemic patients. The former had greater LV size, lower relative wall thickness and higher left atrial systolic force (LASF) than the latter. LV systolic longitudinal function (measure as peak S’) was significantly lower in ischemic than non-ischemic patients (8.7u2009±u20092.1 vs 9.7u2009±u20092.7xa0cm/sec, pu2009=u20090.001). The factors independently related to myocardial ischemia at multivariate logistic analysis were: lower peak S’, higher LV circumferential end-systolic stress and LASF.ConclusionsIn asymptomatic patients at increased risk for adverse CV events baseline longitudinal LVSD together with higher LV circumferential end-systolic stress and LASF were the factors associated with myocardial ischemia induced by ExSEcho. The assessment of these factors at standard echocardiography might help the physicians for improving the risk stratification among these patients for ExSEcho.