Plasma proteome profiling of cardiotoxicity in patients with diffuse large B-cell lymphoma.

BACKGROUND: Cardiovascular toxicity is a notorious complication of doxorubicin (DXR) therapy for diffuse large B-cell lymphoma (DLBCL). Although surveillance of well-known biological markers for cardiovascular disease (CVD) as NTproBNP and Troponins may be helpful, there are no established markers to monitor for evolving CVD during treatment. New possibilities have arisen with the emergence of newer techniques allowing for analysis of plasma proteins that can be associated with cardiovascular disease. Proximity Extension Assay is one of them. OBJECTIVES: We aimed to illustrate the incidence of CVD in DLBCL patients treated with DXR and to establish whether there are plasma proteins associated with pre-existing or emerging CVD. METHODS: In 95 patients, 182 different proteins from OLINK panels, NTproBNP, Troponin I and CRP were assessed prior to, during and after treatment. For comparison, samples from controls were analyzed. RESULTS: In the DLBCL cohort, 33.3% had pre-treatment CVD compared to 5.0% in the controls and 23.2% developed new CVD. Of the 32.6% who died during follow up, CVD was the cause in 4 patients. Spondin-1 (SPON-1) correlated to pre-treatment CVD (1.22 fold change, 95% CI 1.10-1.35, p = 0.00025, q = 0.045). Interleukin-1 receptor type 1 (IL-1RT1) was associated to emerging CVD (1.24 fold change, 95% CI 1.10-1.39, p = 0.00044, q = 0.082). CONCLUSION: We observed a higher prevalence of CVD in DLBCL patients compared to controls prior to DXR therapy. Two proteins, SPON-1 and IL-1RT1, were related to pre-existing and emerging CVD in DXR treated patients. If confirmed in larger cohorts, IL-1RT1 may emerge as a reliable biomarker for unfolding CVD in DLBCL.

Right ventricular mechanics and contractility after aortic valve replacement surgery: a randomised study comparing minimally invasive versus conventional approach.

Objective: Minimally invasive aortic valve replacementsurgery (MIAVR) is an alternative surgical technique to conventional aortic valve replacement surgery (AVR) in selected patients. The randomised study Cardiac Function after Minimally Invasive Aortic Valve Implantation (CMILE) showed that right ventricular (RV) longitudinal function was reduced after both MIAVR and AVR, but the reduction was more pronounced following AVR. However, postoperative global RV function was equally impaired in both groups. The purpose of this study was to explore alterations in RV mechanics and contractility following MIAVR as compared with AVR. Methods: A predefined post hoc analysis of CMILE consisting of 40 patients with severe aortic valve stenosis who were eligible for isolated surgical aortic valve replacement were randomised to MIAVR or AVR. RV function was assessed by echocardiography prior to surgery and 40 days post-surgery. Results: Comparing preoperative to postoperative values, RV longitudinal strain rate was preserved following MIAVR (-1.5±0.5 vs -1.5±0.4 1/s, p=0.84) but declined following AVR (-1.7±0.3 vs -1.4±0.3 1/s, p<0.01). RV longitudinal strain reduced following AVR (-27.4±2.9% vs -18.8%±4.7%, p<0.001) and MIAVR (-26.5±5.3% vs -20.7%±4.5%, p<0.01). Peak systolic velocity of the lateral tricuspid annulus reduced by 36.6% in the AVR group (9.3±2.1 vs 5.9±1.5 cm/s, p<0.01) and 18.8% in the MIAVR group (10.1±2.9 vs 8.2±1.4 cm/s, p<0.01) when comparing preoperative values with postoperative values. Conclusions: RV contractility was preserved following MIAVR but was deteriorated following AVR. RV longitudinal function reduced substantially following AVR. A decline in RV longitudinal function was also observed following MIAVR, however, to a much lesser extent.

Improved right ventricular index of myocardial performance in the assessment of right ventricular function after coronary artery bypass grafting.

OBJECTIVES: Decreased right ventricular (RV) longitudinal function following coronary artery bypass grafting (CABG), as assessed by tricuspid annular systolic excursion (TAPSE) and RV peak systolic velocity (RVS') is a known condition. We aimed to explore the feasibility of the right ventricular index of myocardial performance (RIMP) in the assessment of RV function after CABG at rest and during peak dobutamine stress echocardiography (DSE). METHODS: Forty-two patients indicated for CABG were included in this study. Coronary angiography, DSE and exercise bicycle test were performed within 6 weeks before and 3 months after CABG. The RIMP, RVS' and TAPSE at the lateral tricuspid annulus were also assessed. The results were presented as mean ± standard deviation. RESULTS: The RIMP improved after CABG both at rest (0.45 ± 0.11 before vs 0.38 ± 0.08 after CABG, P = 0.013) and during DSE (0.75 ± 0.23 vs 0.49 ± 0.14, P < 0.001). TAPSE declined significantly when comparing the values from before CABG to after CABG both at rest (23.9 ± 4.46 vs 14.6 ± 3.67, P < 0.001) and during DSE (20.9 ± 4.16 vs 11.9 ± 3.60, P < 0.001). RVS' also decreased after CABG both at rest (11.9 ± 2.40 vs 8.5 ± 1.93, P < 0.001) and during DSE (15.6 ± 4.30 vs 10.5 ± 3.21, P < 0.001). On the other hand, exercise capacity improved after CABG compared with baseline (128.4 ± 40.12 W vs 142.1 ± 46.73 W, P = 0.014). CONCLUSIONS: RIMP improved after CABG both at rest and during DSE. The reduction in TAPSE and RVS' after CABG indicate reduced regional mechanical RV function along the long axis rather than reduced global RV function.

Feasibility of myocardial performance index for evaluation of left ventricular function during dobutamine stress echocardiography before and after coronary artery bypass grafting.

AIMS: Myocardial performance index (MPI) is a measure of combined systolic and diastolic myocardial function. In patients with coronary artery disease (CAD) an increase in MPI is consistent with myocardial dysfunction. The objectives of this study were to characterize the changes in MPI after coronary artery bypass graft (CABG) at rest and at peak dobutamine stress echocardiography (DSE). METHODS AND RESULTS: Thirty-six patients diagnosed with CAD and accepted for CABG were studied by standard echocardiography and DSE 1 month prior and 3 month after CABG. The MPI was calculated using pulsed-wave tissue Doppler imaging (PW-TDI) of the left ventricular (LV) wall-motion velocity. At baseline, ejection fraction (EF; 42.7 ± 8%) and wall-motion score index (WMSI; 1.1 ± 0.2) were impaired at rest as well as at peak DSE (EF; 49.2 ± 9 and WMSI 1.4 ± 0.2). MPI was prolonged both at rest (0.61 ± 0.13) and at peak DSE (0.78 ± 0.16). After CABG, EF and WMSI did not improve at rest (43.7 ± 8% and 1.1 ± 0.2, respectively). On the other hand, MPI improved substantially both at rest (0.45 ± 0.08; P < 0.001) and at peak DSE (0.56 ± 0.1; P < 0.001). At peak DSE an improvement of EF (54.2 ± 9; P < 0.05) and WMSI (1.1 ± 0.16; P < 0.001) was seen as well. CONCLUSION: Myocardial performance index shows significant improvement after CABG in patients with CAD both at rest and peak DSE and appears to be a sensitive measure of myocardial function.

The relationship between the plasma concentration of irbesartan and the antihypertensive response is disclosed by an angiotensin II type 1 receptor polymorphism: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs. Atenolol (SILVHIA) Trial.

BACKGROUND: The aim of this study was to investigate the effect of the plasma concentration of irbesartan, a specific angiotensin II type 1 receptor (AT1R) antagonist, and the blood pressure response in relation to AT1R gene polymorphisms. METHODS: Plasma irbesartan was analyzed in 42 patients with mild-to-moderate hypertension and left ventricular hypertrophy from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs. Atenolol (SILVHIA) trial, who were treated with irbesartan as monotherapy for 12 weeks. Blood pressure and irbesartan concentration were measured at trough, i.e., 24 +/- 3 h after the last dose. Five AT1R gene polymorphisms were analyzed by minisequencing. RESULTS: Neither the plasma concentration of irbesartan, nor any of the AT1R polymorphisms were associated with the blood pressure response to irbesartan treatment. However, the interaction term between the plasma concentration of irbesartan and the AT1R C5245T polymorphism was related to the reduction in systolic blood pressure after 12 weeks of treatment (P = 0.025). Furthermore, the plasma concentration of irbesartan was related to the change in systolic blood pressure in individuals homozygous for the AT1R 5245 T allele (r = -0.56, P = 0.030), but not for other genotypes. CONCLUSIONS: There was an association between plasma concentrations of irbesartan and the blood pressure response for hypertensive patients with AT1R 5245 TT. Because of the small sample size, this study needs to be viewed as hypothesis generating. This is the first study, to our knowledge, indicating that the concentration-response relationship of an antihypertensive drug may be genotype dependent.