Diastolic function as an early marker for systolic dysfunction and all-cause mortality among cancer patients.

BACKGROUND: Increased survival among active cancer patients exposes a wide range of side effects, including cardiotoxicity, manifested by systolic dysfunction and associated with morbidity and mortality. Early diagnosis of subclinical function changes and cardiac damage is essential in the management of these patients. Diastolic dysfunction is considered common among cancer patients; however, its effect on systolic dysfunction or mortality is still unknown. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, enrolling and prospectively following all patients evaluated in the cardio-oncology clinic in the Tel Aviv Sourasky Medical Center. All patients underwent echocardiographic examinations including evaluation of diastolic parameters and global longitudinal strain (GLS). Systolic dysfunction was defined as either an absolute reduction >10% in left ventricular ejection fraction to a value below 53% or GLS relative reduction >10% between the 1st and 3rd echocardiography examinations. RESULTS: Overall, 190 active cancer patients were included, with a mean age of 58 ± 15 years and a female predominance (78%). During a median follow-up of 243 days (interquartile ranges [IQR]: 164-401 days), 62 (33%) patients developed systolic dysfunction. Over a median follow-up of 789 days (IQR: 521-968 days), 29 (15%) patients died. There were no significant differences in baseline cardiac risk factors between the groups. Using multivariate analysis, E/e' lateral and e' lateral emerged as significantly associated with systolic dysfunction development and all-cause mortality (P = .015). CONCLUSION: Among active cancer patients, evaluation of diastolic function may provide an early marker for the development of systolic dysfunction, as well as all-cause mortality.

Diastolic strain time as predictor for systolic dysfunction among patients with active breast cancer.

BACKGROUND: Although diastolic dysfunction is common among patients treated with cancer therapy, no clear evidence has been shown that it predicts systolic dysfunction. This study evaluated the correlation of diastolic strain time (Dst) with the routine echocardiography diastolic parameters and estimated its role in the early detection of cardiotoxicity among patients with active breast cancer. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling all adult patients referred to the cardio-oncology clinic. All patients with breast cancer, planned for Doxorubicin therapy, were included. Echocardiography, including global longitudinal systolic strain (GLS) and Dst, was assessed at baseline before chemotherapy (T1), during Doxorubicin therapy (T2) and after the completion of Doxorubicin therapy (T3). Cardiotoxicity was determined by GLS relative reduction of ≥15%. Dst was assessed as the time measured (ms) of the myocardium lengthening during diastole. RESULTS: Among 69 patients, 67 (97.1%) were females with a mean age of 52 ± 13 years. Dst was significantly associated with the routine diastolic parameters. Significant GLS reduction was observed in 10 (20%) patients at T3. Both in a univariate and a multivariate analyses, the change in Ds basal time from T1 to T2 emerged to be significantly associated with GLS reduction at T3 (P < .04). CONCLUSIONS: Among breast cancer patients, Dst showed high correlation to the routine diastolic echocardiography parameters. Change in Ds basal time emerged associated with clinically significant systolic dysfunction as measured by GLS reduction.

Longitudinal diastolic strain slope as an early sign for systolic dysfunction among patients with active cancer.

BACKGROUND: Diastolic dysfunction is a common finding in patients receiving cancer therapy. This study evaluated the correlation of diastolic strain slope (Dss) with routine echocardiography diastolic parameters and its role in early detection of systolic dysfunction and cardiovascular (CV) mortality within this population. METHODS: Data were collected from the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling adult patient receiving cancer therapy. All patients performed at least three echocardiography exams (T1, T2, T3), including left ventricle Global Longitudinal Strain (LV GLS) and Dss. Systolic dysfunction was determined by either LV GLS relative reduction of ≥ 15% or LV ejection fraction reduction > 10% to < 53%. Dss was assessed as the early lengthening rate, measured by the diastolic slope (delta%/sec). RESULTS: Among 144 patients, 114 (79.2%) were female with a mean age of 57.31 ± 14.3 years. Dss was significantly correlated with e' average. Mid segment Dss change between T1 and T2 showed significant association to systolic dysfunction development (Odds Ratio (OR) = 1.04 [1.01,1.06]. p = 0.036). In multivariate prediction, Dss increase was a significant predictor for the development of systolic dysfunction (OR = 1.06 [1.03,1.1], P < 0.001).An 8% increase in Dss between T1 and T2 was associated with a trend in increased CV mortality (HR = 3.4 [0.77,15.4], p = 0.085). CONCLUSIONS: This study is the first to use the novel measurement of Dss in patients treated with cancer therapies and to show significant correlation between routine diastolic dysfunction parameters and Dss. Changes in the mid segment were found to have significant independent early predictive value for systolic dysfunction development in univariate and multivariate analyses.

Quantitative assessment of effective regurgitant orifice: impact on risk stratification, and cut-off for severe and torrential tricuspid regurgitation grade.

AIMS: Asses the added value of quantitative evaluation of tricuspid regurgitation (TR), the proper cut-off value for severe TR and 'torrential TR' based on outcome data. The added value of quantitative evaluation of TR, and the cut-off values associated with increased mortality are unknown. METHODS AND RESULTS: In patients with all-cause TR assessed both qualitatively and quantitatively by proximal iso-velocity surface area method, long-term and 1-year outcome analysis was conducted. Thresholds for excess mortality were assessed using spline curves, receiver-operating characteristic curves, and minimum P-value analysis. The study involved 676 patients with all-cause TR (age 73.9 ± 14 years, male 45%, ejection fraction 52.9 ± 14%). Effective regurgitant orifice (ERO) was strongly associated with decreased survival in unadjusted [hazard ratio (HR) 2.38 (1.79-3.01), P < 0.0001 per 0.1 cm2 increment] and adjusted [2.6 (1.25-5.0), P = 0.01] analyses. Quantitative grading was superior to qualitative grading in prediction of outcome (P < 0.01). The optimal cut-off value for the best separation in survival between groups of patients with severe vs. lesser degree of TR was 0.35 cm2 [P < 0.0001, HR =2.0 (1.5-2.7)]. ERO negatively impacted survival, even when including only the subgroup of patients with severe TR [HR 1.5 (1.01-2.3); P = 0.04]. The optimal threshold corresponding for the best separation for survival between groups of patients with severe vs. 'torrential' TR was 0.7 cm2 [P = 0.005, HR =2.6 (1.2-5.1)]. CONCLUSION: TR can be severe and even 'torrential' and is associated with excess mortality. Quantitative assessment of TR by ERO measurement is a powerful independent predictor of outcome, superior to standard qualitative assessment. The optimal cut-off above which mortality is increased is 0.35 cm2, similar albeit slightly lower than suggested in recent guidelines. Torrential TR >0.7 cm2 is associated with poorer survival compared to patients with severe TR (ERO > 0.4 cm2 and <0.7 cm2).