Very early detection of low dose anti-cancer therapy-related cardiotoxicity in lymphoma patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y.W Liu ◽  
H.Y Chang ◽  
C.H Lee ◽  
W.C Tsai ◽  
P.Y Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cancer Therapy ◽  
Cardiac Dysfunction ◽  
Systolic Dysfunction ◽  
Multivariable Analysis ◽  
Cardiopulmonary Exercise Test ◽  
Left Ventricular ◽  
Funding Source ◽  
Anti Cancer ◽  
All Cause Mortality

Abstract Background and purpose Left ventricular (LV) global peak systolic longitudinal strain (GLS) by speckle-tracking echocardiography is a sensitive modality for the detection of subclinical LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving anti-cancer therapy remains unknown. Methods We prospectively enrolled 74 patients (57.9±17.0 years old, 57% male) with lymphoma who underwent echocardiography prior to chemotherapy, post 3rd and 6th cycle and 1 year after chemotherapy. Cancer therapy-related cardiac dysfunction (CTRCD) is defined as the reduction of absolute GLS value from baseline of ≥15%. All the eligible patients underwent a cardiopulmonary exercise test (CPET) upon completion of 3 cycles of anti-cancer therapy. The primary outcome was defined as a composite of all-cause mortality and heart failure events. Results Among 36 (49%) patients with CTRCD, LV GLS was significantly decreased after the 3rd cycle of chemotherapy (20.1±2.6% vs. 17.5±2.3%, p<0.001). In the multivariable analysis, male sex and anemia (hemoglobin <11 g/dL) were found to be independent risk factors of CTRCD. Objectively, patients with CTRCD had lower minute oxygen consumption/kg (VO2/kg) and lower VO2/kg value at anaerobic threshold in the CPET. The incidence of the primary composite outcome was higher in the CTRCD group than in the non-CTRCD group (hazard ratio 3.21; 95% CI, 1.04–9.97; p=0.03). Conclusion LV GLS is capable of detecting early cardiac dysfunction in lymphoma patients receiving anti-cancer therapy. Patients with CTRCD not only had a reduced exercise capacity but also a higher risk of all-cause mortality and heart failure events. Change of LVEF and GLS after cancer Tx Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Ministry of Science and Technology (MOST), Taiwan

scholarly journals Subtle cardiac dysfunction in lymphoma patients receiving low to moderate dose chemotherapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hsien-Yuan Chang ◽  
Chun-Hui Lee ◽  
Po-Lan Su ◽  
Sin-Syue Li ◽  
Ming-Yueh Chen ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Exercise Capacity ◽  
Cardiac Dysfunction ◽  
Primary Outcome ◽  
Early Stage ◽  
Systolic Dysfunction ◽  
Anticancer Therapy ◽  
Cardiopulmonary Exercise Test ◽  
Left Ventricular ◽  
Relative Reduction

AbstractLeft ventricular (LV) global peak systolic longitudinal strain (GLS) is a sensitive measurement for detecting subtle LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving cancer therapy remains unknown. We prospectively enrolled 74 lymphoma patients (57.9 ± 17.0 years old, 57% male). We performed echocardiographic studies after the 3rd and 6th cycles and 1 year after chemotherapy and a cardiopulmonary exercise test upon completion of 3 cycles of anticancer therapy. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥ 15% relative reduction in GLS value from baseline. The primary outcome was a composite of all-cause mortality and heart failure events. Thirty-six patients (49%) had CTRCD (LV GLS: baseline vs. after 3rd cycle of therapy: 20.1 ± 2.6 vs. 17.5 ± 2.3%, p < 0.001). CTRCD was detected after the 3rd cycle of anticancer therapy. CTRCD patients had impaired exercise capacity (minute oxygen consumption/kg, CTRCD vs. CTRCD (-): 13.9 ± 3.1 vs. 17.0 ± 3.9 ml/kg/min, p = 0.02). More primary outcome events occurred in the CTRCD group (hazard ratio 3.21; 95% confidence interval 1.04–9.97; p = 0.03). LV GLS could detect subtle but clinically significant cardiac dysfunction in lymphoma patients in the early stage of anticancer therapy. CTRCD may be associated with not only a reduced exercise capacity but also a worse prognosis.

scholarly journals Layer-specific strain in patients with heart failure using cardiovascular magnetic resonance: not all layers are the same

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Lingyu Xu ◽  
◽  
Joseph J. Pagano ◽  
Mark J. Haykowksy ◽  
Justin A. Ezekowitz ◽  
...  
Keyword(s):  
Heart Failure ◽  
At Risk ◽  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Ejection Fraction ◽  
Systolic Dysfunction ◽  
Multivariable Analysis ◽  
Left Ventricular ◽  
All Cause Mortality ◽  
The Difference

Abstract Background Global longitudinal strain (GLS), most commonly measured at the endocardium, has been shown to be superior to left ventricular (LV) ejection fraction (LVEF) for the identification of systolic dysfunction and prediction of outcomes in heart failure (HF). We hypothesized that strains measured at different myocardial layers (endocardium = ENDO, epicardium = EPI, average = AVE) will have distinct diagnostic and predictive performance for patients with HF. Methods Layer-specific GLS, layer-specific global circumferential strain (GCS) and global radial strain (GRS) were evaluated by cardiovascular magnetic resonance imaging (CMR) feature tracking in the Alberta HEART study. A total of 453 subjects consisted of healthy controls (controls, n = 77), at-risk for HF (at-risk, n = 143), HF with preserved ejection fraction (HFpEF, n = 87), HF with mid-range ejection fraction (HFmrEF, n = 88) and HF with reduced ejection fraction (HFrEF, n = 58). For outcomes analysis, CMR-derived imaging parameters were adjusted with a base model that included age and N-terminal prohormone of b-type natriuretic peptide (NT-proBNP) to test their independent association with 5-year all-cause mortality. Results GLS_EPI distinguished all groups with preserved LVEF (controls − 16.5 ± 2.4% vs. at-risk − 15.5 ± 2.7% vs. HFpEF − 14.1 ± 3.0%, p < 0.001) while GLS_ENDO and all GCS (all layers) were similar among these groups. GRS was reduced in HFpEF (41.1 ± 13.8% versus 48.9 ± 10.7% in controls, p < 0.001) and the difference between GLS_EPI and GLS_ENDO were significantly larger in HFpEF as compared to controls. Within the preserved LVEF groups, reduced GRS and GLS_EPI were significantly associated with increased LV mass (LVM) and LVM/LV end-diastolic volume EDV (concentricity). In multivariable analysis, only GLS_AVE and GRS predicted 5-year all-cause mortality (all ps < 0.05), with the strongest association with 5-year all-cause mortality by Akaike Information Criterion analysis and significant incremental value for outcomes prediction beyond LVEF or GLS_ENDO by the likelihood ratio test. Conclusion Global strains measured on endocardium, epicardium or averaged across the wall thickness are not equivalent for the identification of systolic dysfunction or outcomes prediction in HF. The endocardium-specific strains were shown to have poorest all-around performance. GLS_AVE and GRS were the only CMR parameters to be significantly associated with 5-year all-cause mortality in multivariable analysis. GLS_EPI and GRS, as well as the difference in endocardial and epicardial strains, were sensitive to systolic dysfunction among HF patients with normal LVEF (> 55%), in whom lower strains were associated with increased concentricity.

Novel rehabilitation program after left ventricular assist device (LVAD) implantation improves functional tests and reduces levels of prognostic heart failure biomarkers

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Chwyczko ◽  
L Zalucka ◽  
E Smolis-Bak ◽  
I Kowalik ◽  
E Noszczak ◽  
...  
Keyword(s):  
Heart Failure ◽  
Exercise Test ◽  
Cardiopulmonary Exercise Test ◽  
Rehabilitation Program ◽  
Left Ventricular ◽  
Prognostic Biomarkers ◽  
Funding Source ◽  
Walking Test ◽  
Cardiopulmonary Exercise ◽  
Galectin 3

Abstract Background Rehabilitation after LVAD implantation is increasingly used. We developed the novel method of comprehensive rehabilitation starting directly after LVAD implantation. Study group 21 recent LVAD (15 Heart Mate III, 6 HeartWare) recipients (56.2±11.7 yrs, 100% men) were included to 5-week rehabilitation program, which included supervised endurance training on cycloergometer (5 times per week), resistance training, general fitness exercises with elements of equivalent and coordination exercises (every day). 6-minute walking test (6MWT), cardiopulmonary exercise test (CPET) and prognostic biomarkers: NT-proBNP, Galectin-3 and ST2 were investigated at the beginning and at the end of rehabilitation program. Results See Table 1. At the end of rehabilitation program, significant increase in 6MWT distance, maximum workload, peak VO2 and upward shift of anaerobic threshold in CPET were observed in all patients. Significant reductions of NTproBNP, ST2 and galectin-3 levels were observed. There were no major adverse events during rehabilitaton. Conclusions Comprehensive novel rehabilitation in LVAD recipients is safe and results in significant improvement of 6-minutes walking test distance and cardiopulmonary exercise test results. Moreover, this novel rehabilitation program reduces levels of prognostic biomarkers of heart failure: NT-proBNP, Galectin-3 and ST2. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Center for Research and Development - STRATEGMED II project

Prognostic value of global longitudinal layer specific strain for patients with heart failure with reduced ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Johnsen ◽  
M Sengeloev ◽  
P Joergensen ◽  
N Bruun ◽  
D Modin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Prognostic Value ◽  
Left Ventricular ◽  
Volume Index ◽  
Funding Source ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
All Cause Mortality ◽  
Echocardiographic Parameters

Abstract Background Novel echocardiographic software allows for layer-specific evaluation of myocardial deformation by 2-dimensional speckle tracking echocardiography. Endocardial, epicardial- and whole wall global longitudinal strain (GLS) may be superior to conventional echocardiographic parameters in predicting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF). Purpose The purpose of this study was to investigate the prognostic value of endocardial-, epicardial- and whole wall GLS in patients with HFrEF in relation to all-cause mortality. Methods We included and analyzed transthoracic echocardiographic examinations from 1,015 patients with HFrEF. The echocardiographic images were analyzed, and conventional and novel echocardiographic parameters were obtained. A p value in a 2-sided test &lt;0.05 was considered statistically significant. Cox proportional hazards regression models were constructed, and both univariable and multivariable hazard ratios (HRs) were calculated. Results During a median follow-up time of 40 months, 171 patients (16.8%) died. A lower endocardial (HR 1.17; 95% CI (1.11–1.23), per 1% decrease, p&lt;0.001), epicardial (HR 1.20; 95% CI (1.13–1.27), per 1% decrease, p&lt;0.001), and whole wall (HR 1.20; 95% CI (1.14–1.27), per 1% decrease, p&lt;0.001) GLS were all associated with higher risk of death (Figure 1). Both endocardial (HR 1.12; 95% CI (1.01–1.23), p=0.027), epicardial (HR 1.13; 95% CI (1.01–1.26), p=0.040) and whole wall (HR 1.13; 95% CI (1.01–1.27), p=0.030) GLS remained independent predictors of mortality in the multivariable models after adjusting for significant clinical parameters (age, sex, total cholesterol, mean arterial pressure, heart rate, ischemic cardiomyopathy, percutaneous transluminal coronary angioplasty and diabetes) and conventional echocardiographic parameters (left ventricular (LV) ejection fraction, LV mass index, left atrial volume index, deceleration time, E/e', E-velocity, E/A ratio and tricuspid annular plane systolic excursion). No other echocardiographic parameters remained an independent predictors after adjusting. Furthermore, endocardial, epicardial and whole wall GLS had the highest C-statistics of all the echocardiographic parameters. Conclusion Endocardial, epicardial and whole wall GLS are independent predictors of all-cause mortality in patients with HFrEF. Furthermore, endocardial, epicardial and whole wall GLS were superior prognosticators of all-cause mortality compared with all other echocardiographic parameters. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Herlev and Gentofte Hospital

scholarly journals Enhanced Inflammation is a Marker for Risk of Post-Infarct Ventricular Dysfunction and Heart Failure

2020 ◽  
Vol 21 (3) ◽  
pp. 807 ◽  
Author(s):  
Iwona Świątkiewicz ◽  
Przemysław Magielski ◽  
Jacek Kubica ◽  
Adena Zadourian ◽  
Anthony N. DeMaria ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Multivariable Analysis ◽  
High Sensitivity ◽  
Left Ventricular ◽  
St Segment Elevation ◽  
Reactive Protein

Acute ST-segment elevation myocardial infarction (STEMI) activates inflammation that can contribute to left ventricular systolic dysfunction (LVSD) and heart failure (HF). The objective of this study was to examine whether high-sensitivity C-reactive protein (CRP) concentration is predictive of long-term post-infarct LVSD and HF. In 204 patients with a first STEMI, CRP was measured at hospital admission, 24 h (CRP24), discharge (CRPDC), and 1 month after discharge (CRP1M). LVSD at 6 months after discharge (LVSD6M) and hospitalization for HF in long-term multi-year follow-up were prospectively evaluated. LVSD6M occurred in 17.6% of patients. HF hospitalization within a median follow-up of 5.6 years occurred in 45.7% of patients with LVSD6M vs. 4.9% without LVSD6M (p < 0.0001). Compared to patients without LVSD6M, the patients with LVSD6M had higher CRP24 and CRPDC and persistent CRP1M ≥ 2 mg/L. CRP levels were also higher in patients in whom LVSD persisted at 6 months (51% of all patients who had LVSD at discharge upon index STEMI) vs. patients in whom LVSD resolved. In multivariable analysis, CRP24 ≥ 19.67 mg/L improved the prediction of LVSD6M with an increased odds ratio of 1.47 (p < 0.01). Patients with LVSD6M who developed HF had the highest CRP during index STEMI. Elevated CRP concentration during STEMI can serve as a synergistic marker for risk of long-term LVSD and HF.

scholarly journals Toxicity of cancer therapy: what the cardiologist needs to know about angiogenesis inhibitors

Heart ◽  
2018 ◽  
Vol 104 (24) ◽  
pp. 1995-2002 ◽  
Author(s):  
Stephen J H Dobbin ◽  
Alan C Cameron ◽  
Mark C Petrie ◽  
Robert J Jones ◽  
Rhian M Touyz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Cancer Therapy ◽  
Therapeutic Potential ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Blood Pressure Measurement ◽  
Left Ventricular ◽  
National Guidelines ◽  
Wide Range

Clinical outcomes for patients with a wide range of malignancies have improved substantially over the last two decades. Tyrosine kinase inhibitors (TKIs) are potent signalling cascade inhibitors and have been responsible for significant advances in cancer therapy. By inhibiting vascular endothelial growth factor receptor (VEGFR)-mediated tumour blood vessel growth, VEGFR-TKIs have become a mainstay of treatment for a number of solid malignancies. However, the incidence of VEGFR-TKI-associated cardiovascular toxicity is substantial and previously under-recognised. Almost all patients have an acute rise in blood pressure, and the majority develop hypertension. They are associated with the development of left ventricular systolic dysfunction (LVSD), heart failure and myocardial ischaemia and can have effects on myocardial repolarisation. Attention should be given to rigorous baseline assessment of patients prior to commencing VEGFR-TKIs, with careful consideration of baseline cardiovascular risk factors. Baseline blood pressure measurement, ECG and cardiac imaging should be performed routinely. Hypertension management currently follows national guidelines, but there may be a future role forendothelin-1 antagonism in the prevention or treatment of VEGFR-TKI-associated hypertension. VEGFR-TKI-associated LVSD appears to be independent of dose and is reversible. Patients who develop LVSD and heart failure should be managed with conventional heart failure therapies, but the role of prophylactic therapy is yet to be defined. Serial monitoring of left ventricular function and QT interval require better standardisation and coordinated care. Management of these complex patients requires collaborative, cardio-oncology care to allow the true therapeutic potential from cancer treatment while minimising competing cardiovascular effects.

Epidemiology and general pathophysiological classification of heart failure

2020 ◽  
pp. 3390-3397
Author(s):  
Theresa A. McDonagh ◽  
Kaushik Guha
Keyword(s):  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Clinical Syndrome ◽  
Normal Left Ventricular ◽  
Patients With Heart Failure ◽  
Definition Of

Heart failure is a clinical syndrome caused by cardiac dysfunction, most commonly left ventricular systolic dysfunction. Patients with heart failure symptoms or signs and normal or near normal left ventricular function are often classified as having heart failure with preserved ejection fraction (HF-PEF), but there is no clear and generally accepted definition of this condition. Estimates of incidence and prevalence are heavily influenced by definition. Prevalence rises significantly with age, with a median age of first presentation in the mid-seventies. Longitudinal data suggests that the incidence of heart failure has remained fairly stable over the last few decades, but prevalence is increasing as more people survive cardiovascular disease earlier in life.

Relationship between regional left ventricular dysfunction and cancer-therapy-related cardiac dysfunction

Heart ◽  
2020 ◽  
Vol 106 (22) ◽  
pp. 1752-1758 ◽  
Author(s):  
Yoshihito Saijo ◽  
Kenya Kusunose ◽  
Yuichiro Okushi ◽  
Hirotsugu Yamada ◽  
Hiroaki Toba ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cardiac Dysfunction ◽  
Longitudinal Strain ◽  
Systolic Dysfunction ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Kaplan Meier ◽  
The Difference ◽  
Risk Of Cancer

ObjectiveThe aim of our study was to assess the association between risk of cancer-therapy-related cardiac dysfunction (CTRCD) after first follow-up and the difference in echocardiographic measures from baseline to follow-up.MethodsWe retrospectively enrolled 87 consecutive patients (58±14 years, 55 women) who received anthracycline and underwent echocardiographic examinations both before (baseline) and after initial anthracycline administration (first follow-up). We measured absolute values of global longitudinal strain (GLS), apical longitudinal strain (LS), mid-LS and basal-LS at baseline and first follow-up, and per cent changes (Δ) of these parameters were calculated. Among 61 patients who underwent further echocardiographic examinations (second follow-up, third follow-up, etc), we assessed the association between regional left ventricular (LV) systolic dysfunction from baseline to follow-up and development of CTRCD, defined as LV ejection fraction (LVEF) under 53% and more absolute decrease of 10% from baseline, after first follow-up.ResultsLVEF (65%±4% vs 63±4%, p=0.004), GLS (23.2%±2.6% vs 22.2±2.4%, p=0.005) and basal-LS (21.9%±2.5% vs 19.9±2.4%, p<0.001) at first follow-up significantly decreased compared with baseline. Among the 61 patients who had further follow-up echocardiographic examinations, 13% developed CTRCD. In the Cox-hazard model, worse Δbasal-LS was significantly associated with CTRCD. By Kaplan–Meier analysis, patients with Δbasal-LS decrease of more than the median value (−9.7%) had significantly worse event-free survival than those with a smaller decrease (p=0.015).ConclusionsBasal-LS significantly decreased prior to development of CTRCD, and worse basal-LS was associated with development of CTRCD in patients receiving anthracycline chemotherapy.

scholarly journals Clinical outcomes of chemotherapy-induced subclinical left ventricular systolic dysfunction among breast cancer patients detected using echocardiographic global longitudinal strain

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.G.G Manaloto ◽  
M.K Cruz-Tan ◽  
R.H Tiongco ◽  
R.M Jimenez ◽  
G.H Cornelio
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Longitudinal Strain ◽  
Systolic Dysfunction ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Breast Cancer Patients ◽  
All Cause Mortality

Abstract Background Echocardiographic global longitudinal strain (GLS) detects early subclinical left ventricular (LV) systolic dysfunction, before the occurrence of a decreased LV ejection fraction. However, our local data is lacking to determine its impact to clinical outcomes. Purpose The study aimed to determine the clinical outcomes of breast cancer patients who developed subclinical LV systolic dysfunction as determined by an abnormal GLS post-chemotherapy. Methods This retrospective cohort study included 99 breast cancer patients who underwent anthracycline and/or HER-2 receptor inhibitor chemotherapy from January 1, 2016 to December 31, 2018 in a single tertiary hospital. Clinical outcomes of all-cause mortality and overt heart failure were compared between those with normal and abnormal GLS post-chemotherapy. Results The prevalence of subclinical LV systolic dysfunction was 18%, wherein 28% of them had subsequent overt heart failure, and 33% expired. Abnormal GLS occurred at a mean 3.5 months (range 1–8 months) after initiation of chemotherapy and at 8 months (range 6–10 months) after the entire chemotherapy sessions. Development into heart failure was observed at a mean of 6.7 months (range 4–12 months) after occurrence of abnormal GLS. Hypertension and age &gt;56 years were determined to be risk factors. Beta-blockers, ACE inhibitors and statins seemed to be non-protective in our cohort. Abnormalities in GLS were observed at a mean dose of 260 mg/m2 of epirubicin, lower than the dose described as high risk in the literature (600 mg/m2 for epirubicin). In trastuzumab, abnormal GLS occurred as early as 1 month after initiation. LVEF had no significant change within 2 months (p=0.56), but was significantly lower within 12 months post-chemotherapy (p=0.005). All-cause mortality was 3-fold higher (RR=3.00; p=0.02), and the risk to develop heart failure was 4 times higher (RR=4.74; p=0.008) in those with abnormal GLS. Conclusion The development of abnormal GLS post-chemotherapy was associated with subsequent development of overt heart failure and increased all-cause mortality. Abnormal GLS occurred at lower doses of epirubicin and as early as 1 month after initiating trastuzumab. We recommend echo surveillance with GLS monitoring beginning &gt;250 mg/m2 with anthracycline (and after 1–2 months of Trastuzumab), and to repeat at 1–2 months and 9–12 months post-chemotherapy. Funding Acknowledgement Type of funding source: None

scholarly journals Chronic heart failure in younger patients: temporal trends in clinical characteristics, treatment and outcomes over two decades in a nationwide cardiology registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Iacoviello ◽  
M Marini ◽  
M Gori ◽  
L Gonzini ◽  
M Benvenuto ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Clinical Characteristics ◽  
Temporal Trends ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
All Cause Mortality ◽  
Over Time

Abstract Aim of the study We analyzed the temporal trends in characteristics, therapy and outcomes over two decades of younger chronic heart failure (CHF) patients enrolled in our nationwide registry. Methods Among the 14823 CHF patients enrolled in the registry since January 1999 through May 2018, 5465 (37%) were aged&lt;65 years (78% men, 54+9 years, left ventricular ejection fraction (LVEF) 36+11%). Patients were divided into 3 cohorts according with the recruitment epoch: 1999–2005; 2006–2011; 2012–2018. We analyzed trends over time of clinical characteristics, therapy, one-year all-cause mortality, all-cause mortality and/or all-cause hospitalization, all-cause mortality and/or CV hospitalization, and all-cause mortality and/or HF hospitalization. Results From 1999 to 2018 the proportion of patients &lt;65 years declined: 42% in first (2288/5404), 37% in second (1464/3971), 31% in third period (1713/5448). As shown in the Table, the proportion of women, diabetes, ischemic etiology and renin-angiotensin system inhibitor prescription did not change significantly among the three enrollment epochs, whereas preserved LVEF phenotype and prevalence of its driving risk factors increased. The proportion of guideline-recommended drug & device therapies significantly rose over time. All-cause mortality at 1-year follow-up decreased significantly across the 3 epochs studied (Figure). Conclusions During 20 years, the clinical characteristics, the implementation of recommended treatments and prognosis of patients &lt;65 years enrolled in a nationwide cardiology registry have deeply changed. These modifications reflect the evolution of cardiovascular risk factors and improved management strategies of CV disease. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Fondazione per il Tuo cuore – HCF onlus

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