Immediate evaluation of global longitudinal strain at initiation of trastuzumab treatment in breast cancer patients.

BACKGROUND: Global longitudinal strain (GLS) is recommended to detect subclinical changes preceding reduced left ventricular ejection fraction (LVEF) in trastuzumab related cardiotoxicity. Since the possibility to detect signs of acute myocardial deterioration at treatment initiation is not clarified, the objective of this study was to assess changes in GLS and biomarkers within the first 2 weeks of trastuzumab treatment. METHODS: In a prospective cohort study, 45 patients with non-metastatic breast cancer (age 54, LVEF 62.8%, GLS -19.9%, 40% hypertension) scheduled for trastuzumab treatment were included. Echocardiography and measurement of troponin and NT-proBrain-Natriuretic-Peptide were conducted before initiation of trastuzumab, at days 3, 7, and 14 and after 3, 6, and 9 months. RESULTS: A significant deterioration in LVEF from 62.8% (SD±3.6) to 58.4% (SD±4.1) (p < 0.0001), GLS from -19.9 (SD±2.1) to -18.1 (SD±2.5) (p = 0.004), s' (p < 0.0001), e' septal (p = 0.008), and s' RV (p < 0.0001) occurred at 9 months and was preceded by significant changes in these parameters within the first 14 days. After 14 days, 12 patients (27%) had a ≥10% deterioration in GLS, which was associated with significantly lower LVEF at 55.2% (SD±4.1) at 9 months compared to patients with < 10% early deterioration in GLS (LVEF = 59.5% (SD±3.5) (p = 0.001)). No difference in plasma concentrations of biomarkers was observed between the two groups. CONCLUSION: In this study deteriorations in key echocardiographic parameters within normal limits were detected during the first 2 weeks of trastuzumab treatment, and an early ≥10% deterioration in GLS was associated with a lower LVEF at 9 months.

Association between speckle tracking echocardiography and pressure-volume loops during cardiogenic shock development.

BACKGROUND: The relationship between speckle tracking assessed global longitudinal strain (GLS) and Doppler-based echocardiography with basic physiological markers of cardiac function derived from pressure-volume loops is poorly elucidated. OBJECTIVE: We aimed to describe the association between LS and Doppler-based echocardiography and direct measurements of central haemodynamic parameters from conductance catheter-based pressure-volume loops in an animal model with increasing left ventricular (LV) dysfunction. METHODS: 12 Danish landrace female pigs (75-80 kg) were used. All instrumentations were performed percutaneously, including the conductance catheter in the LV. Progressive LV dysfunction was induced by embolisation through the left main coronary artery with microspheres every 3 min until a >50% reduction in cardiac output (CO) or mixed venous saturation (SvO2), compared with baseline, or SvO2 <30%. Echocardiography was performed at baseline and 90 s after each injection. RESULTS: With progressive LV dysfunction, mean CO decreased from 5.6±0.9 L/min to 2.1±0.9 L/min, and mean SvO2 deteriorated from 61.1±7.9% to 35.3±6.1%. Mean LS and LV outflow tract velocity time integral (LVOT VTI) declined from -13.8±3.0% to -6.1±2.0% and 16.9±2.6 cm to 7.8±1.8 cm, respectively. LS and LVOT VTI showed the strongest correlation to stroke work in unadjusted linear regression (r2=0.53 and r2=0.49, respectively). LS correlated significantly with stroke volume, end-systolic elastance, systolic blood pressure, ventriculo-arterial coupling and arterial elastance. CONCLUSION: In an animal model of acute progressive LV dysfunction, echocardiographic and conductance catheter-based measurements changed significantly. LS and LVOT VTI displayed the earliest and the largest alterations with increased myocardial damage and both correlated strongest with stroke work.

Cardiovascular morbidity and all-cause mortality in patients with retinal vein occlusion: a Danish nationwide cohort study.

BACKGROUND/AIMS: Associations between retinal vein occlusion (RVO) and subsequent cardiovascular disease (CVD) or mortality have not been evaluated in a recent cohort, after novel therapeutic options have increased referrals for treatment of the condition. We aimed to evaluate overall and subtype-stratified risk of CVD and all-cause mortality following RVO and assess any alterations after the introduction of angiostatic therapy in Denmark in 2011. METHODS: This nationwide, registry-based cohort study from 1998 to 2018 evaluated 4 194 781 individuals. Hazard ratios (HRs) were reported for RVO as an overall measure and subclassified as branch and central RVO. RESULTS: Patients with RVO (n=15 665) were median 71.8 years old at the time of exposure and 50.7% were women. RVO associated with incident CVD (adjusted HR 1.13, 95% CI 1.09 to 1.17) but not mortality (adjusted HR 1.00, 95% CI 0.97 to 1.03). Almost similar risks of CVD were found for patients with branch and central RVO (adjusted HRs 1.14, 95% CI 1.03 to 1.25, and 1.12, 95% CI 1.00 to 1.25, respectively), but only patients with central RVO exhibited increased mortality (adjusted HR 1.12, 95% CI 1.04 to 1.21). Risk of CVD, especially non-ischaemic, was higher for patients diagnosed after 2011 (adjusted HRs 1.24, 95% CI 1.15 to 1.33 vs 1.06, 95% CI 1.01 to 1.12). CONCLUSION: In a cohort of the Danish population aged 40 years or more, patients with RVO had a 13% increased risk of incident CVD compared with unexposed individuals. Risk of CVD was increased after 2011, when intravitreal angiostatic treatment was introduced and referral practices altered.

Unloading using Impella CP during profound cardiogenic shock caused by left ventricular failure in a large animal model: impact on the right ventricle.

BACKGROUND AND AIM: This study aimed to assess right ventricular (RV) function during cardiogenic shock due to acute left ventricular (LV) failure, including during LV unloading with Impella CP and an added moderate dose of norepinephrine. METHODS: Cardiogenic shock was induced by injecting microspheres in the left main coronary artery in 18 adult Danish Landrace pigs. Conductance catheters were placed in both ventricles and pressure-volume loops were recorded simultaneously. RESULTS: Cardiogenic shock due to LV failure also impaired RV performance, which was partially restored during haemodynamic support with Impella CP, as demonstrated by changes in the ventriculo-arterial coupling (Ea/Ees ratio) (baseline (median [Q1;Q3]) 1.2 [1.1;1.6]), cardiogenic shock (3.0 [2.4;4.5]), Impella CP (2.1 [1.3;2.7]) (pBaseline vs CS < 0.0001, pCS vs Impella = 0.001)). Impella CP support also improved RV stroke work (SW) (cardiogenic shock 333 [263;530] vs Impella CP (830 [717;1121]) (p < 0.001). Moderate norepinephrine infusion concomitant with Impella CP further improved RV SW (Impella CP (818 [751;1065]) vs Impella CP+moderate norepinephrine (1231 [1142;1335]) (p = 0.01)) but at the expense of an increase in LV SW (Impella CP (858 [555;1392]) vs Impella CP+moderate norepinephrine (2101 [1024;2613]) (p = 0.04)). CONCLUSIONS: The Impella CP provided efficient LV unloading, improved RV function, and end-organ perfusion. Moderate doses of norepinephrine during Impella support further improved RV function, but at the expense of an increase in SW of the failing LV.

Empagliflozin in heart failure patients with reduced ejection fraction: a randomized clinical trial (Empire HF).

BACKGROUND: Data from recent cardiovascular outcome trials in patients with type 2 diabetes (T2D) suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors can prevent development of heart failure (HF) and prolong life in patients without HF. Ongoing event-driven trials are investigating whether the same effect is present in patients with well-defined HF. The mechanism behind the effect of SGLT2 inhibitors in patients with T2D and the potential effect in patients with overt HF is presently unknown. METHODS: This is a randomized, double-blinded, placebo-controlled, parallel group, clinical trial including HF patients with reduced left ventricular ejection fraction (HFrEF) with an ejection fraction ≤ 40% on optimal therapy recruited from specialized HF clinics in Denmark. The primary aim is to investigate the effect of the SGLT2 inhibitor empagliflozin on N-terminal pro-brain natriuretic peptide (NT-proBNP). Secondary endpoints include cardiac biomarkers, function and hemodynamics, metabolic and renal parameters, daily activity level, and quality of life. Patients are assigned 1:1 to 90 days treatment with empagliflozin 10 mg daily or placebo. Patients with T2D are required to be on recommended doses of anti-glycemic therapy with a hemoglobin A1c (HbA1c) of 6.5-10.0% (48-86 mmol/mol). To show a between-group difference in the change of NT-proBNP of 30%, a total of 189 patients will be included. DISCUSSION: The Empire HF trial will elucidate the effects and modes of action of empagliflozin in HFrEF patients with and without T2D and provide important mechanistic data which will complement ongoing event-driven trials. TRIAL REGISTRATION: Clinicaltrialsregister.eu, EudraCT Number 2017-001341-27 . Registered on 29 May 2017. ClinicalTrials.gov, NCT03198585 . Registered on 26 June 2017.