Elisavet Kaldara

Long-term outcomes of primary systemic light chain (AL) amyloidosis in patients treated upfront with bortezomib or lenalidomide and the importance of risk adapted strategies

Bortezomib and lenalidomide are increasingly used in patients with AL amyloidosis, but long term data on their use as primary therapy in AL amyloidosis are lacking while early mortality remains significant. Thus, we analyzed the long term outcomes of 85 consecutive unselected patients, which received primary therapy with bortezomib or lenalidomide and we prospectively evaluated a risk adapted strategy based on bortezomib/dexamethasone to reduce early mortality. Twenty‐six patients received full‐dose bortezomib/dexamethasone, 36 patients lenalidomide with oral cyclophosphamide and low‐dose dexamethasone and 23 patients received bortezomib/dexamethasone at a dose and schedule adjusted to the risk of early death. On intent to treat, 67% of patients achieved a hematologic response (24% hemCRs) and 34% an organ response; both were more frequent with bortezomib. An early death occurred in 20%: in 36% of those treated with full‐dose bortezomib/dexamethasone, in 22% of lenalidomide‐treated patients but only in 4.5% of patients treated with risk‐adapted bortezomib/dexamethasone. Activity of full vs. adjusted dose bortezomib/dexamethasone was similar; twice weekly vs. weekly administration of bortezomib also had similar activity. After a median follow up of 57 months, median survival is 47 months and is similar for patients treated with bortezomib vs. lenalidomide‐based regimens. However, risk adjusted‐bortezomib/dexamethasone was associated with improved 1‐year survival vs. full‐dose bortezomib/dexamethasone or lenalidomide‐based therapy (81% vs. 56% vs. 53%, respectively). In conclusion, risk‐adapted bortezomib/dexamethasone may reduce early mortality and preserve activity while long term follow up indicates that remissions obtained with lenalidomide or bortezomib may be durable, even without consolidation with alkylators.Am. J. Hematol. 90:E60–E65, 2015.

Neuroticism personality trait is associated with Quality of Life in patients with Chronic Heart Failure

AIM To evaluate Quality of life (QoL) in chronic heart failure (CHF) in relation to Neuroticism personality trait and CHF severity. METHODS Thirty six consecutive, outpatients with Chronic Heart Failure (6 females and 30 males, mean age: 54 ± 12 years), with a left ventricular ejection fraction ≤ 45% at optimal medical treatment at the time of inclusion, were asked to answer the Kansas City Cardiomyopathy Questionnaire (KCCQ) for Quality of Life assessment and the NEO Five-Factor Personality Inventory for personality assessment. All patients underwent a symptom limited cardiopulmonary exercise testing on a cycle-ergometer, in order to access CHF severity. A multivariate linear regression analysis using simultaneous entry of predictors was performed to examine which of the CHF variables and of the personality variables were correlated independently to QoL scores in the two summary scales of the KCCQ, namely the Overall Summary Scale and the Clinical Summary Scale. RESULTS The Neuroticism personality trait score had a significant inverse correlation with the Clinical Summary Score and Overall Summary Score of the KCCQ (r = -0.621, P < 0.05 and r = -0.543, P < 0.001, respectively). KCCQ summary scales did not show significant correlations with the personality traits of Extraversion, Openness, Conscientiousness and Agreeableness. Multivariate linear regression analysis using simultaneous entry of predictors was also conducted to determine the best linear combination of statistically significant univariate predictors such as Neuroticism, VE/VCO2 slope and VO2 peak, for predicting KCCQ Clinical Summary Score. The results show Neuroticism (β = -0.37, P < 0.05), VE/VCO2 slope (β = -0.31, P < 0.05) and VO2 peak (β = 0.37, P < 0.05) to be independent predictors of QoL. In multivariate regression analysis Neuroticism (b = -0.37, P < 0.05), the slope of ventilatory equivalent for carbon dioxide output during exercise, (VE/VCO2 slope) (b = -0.31, P < 0.05) and peak oxygen uptake (VO2 peak), (b = 0.37, P < 0.05) were independent predictors of QoL (adjusted R2 = 0.64; F = 18.89, P < 0.001). CONCLUSION Neuroticism is independently associated with QoL in CHF. QoL in CHF is not only determined by disease severity but also by the Neuroticism personality trait.

The challenge of treating congestion in advanced heart failure

Volume overload is a common manifestation of heart failure decompensation. Interaction between impaired renal and heart function constitutes an important pathophysiologic mechanism that leads to congestion. In addition to improving symptoms and volume status, reduction of rehospitalization rates, maintenance of renal function and improvement of survival are all important goals of every therapeutic strategy. Currently, the use of diuretics, vasodilators, inotropes and ultrafiltration, together with investigational agents such as oral vasopressin antagonists and adenosine A1-receptor antagonists, constitute the main therapeutic options for the congested heart failure patient.

HIGH FUROSEMIDE DOSE IS AN INDEPENDENT RISK FACTOR FOR MORTALITY IN PATIENTS WITH CHRONIC HEART FAILURE

Diuretics relieve congestion in HF patients but activate the renin-angiotensin-aldosterone system (RAAS). High furosemide doses have been correlated with higher mortality; it is not clear whether higher diuretic doses represent a marker of disease severity or an independent prognostic factor. We

THE ROLE OF INTRAAORTIC BALLOON PUMP AS A BRIDGE TO DECISION FOR PATIENTS WITH ADVANCED STAGE HEART FAILURE DUE TO IDIOPATHIC DILATED CARDIOMYOPATHY

Despite maximal therapy, patients with advanced heart failure frequently experience continuous deterioration, while end organ dysfunction precludes long term mechanical support (LVAD) or transplantation. We examined the role of long term IABP support in unstable patients with idiopathic dilated