Systolic myocardial function measured by echocardiographic speckle-tracking and peak oxygen consumption in pediatric childhood cancer survivors-a PACCS study.

Background: Cancer therapy-related cardiotoxicity is a major cause of cardiovascular morbidity in childhood cancer survivors. The aims of this study were to investigate systolic myocardial function and its association to cardiorespiratory fitness in pediatric childhood cancer survivors. Methods: In this sub-study of the international study "Physical Activity and fitness in Childhood Cancer Survivors" (PACCS), echocardiographic measures of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were measured in 128 childhood cancer survivors aged 9-18 years and in 23 age- and sex-matched controls. Cardiorespiratory fitness was measured as peak oxygen consumption achieved on treadmill and correlated to myocardial function. Results: Mean LV-GLS was reduced in the childhood cancer survivors compared to the controls, -19.7% [95% confidence interval (CI) -20.1% to -19.3%] vs. -21.3% (95% CI: -22.2% to -20.3%) (p = 0.004), however, mainly within normal range. Only 13% of the childhood cancer survivors had reduced LV longitudinal strain z-score. Mean RV-LS was similar in the childhood cancer survivors and the controls, -23.2% (95% CI: -23.7% to -22.6%) vs. -23.3% (95% CI: -24.6% to -22.0%) (p = 0.8). In the childhood cancer survivors, lower myocardial function was associated with lower peak oxygen consumption [correlation coefficient (r) = -0.3 for LV-GLS]. Higher doses of anthracyclines (r = 0.5 for LV-GLS and 0.2 for RV-LS) and increasing time after treatment (r = 0.3 for LV-GLS and 0.2 for RV-LS) were associated with lower myocardial function. Conclusions: Left ventricular function, but not right ventricular function, was reduced in pediatric childhood cancer survivors compared to controls, and a lower left ventricular myocardial function was associated with lower peak oxygen consumption. Furthermore, higher anthracycline doses and increasing time after treatment were associated with lower myocardial function, implying that long-term follow-up is important in this population at risk.

Effectiveness, safety, and patient reported outcomes of a planned investment procedure in higher-risk chronic total occlusion percutaneous coronary intervention: Rationale and design of the invest-CTO study.

BACKGROUND: The anatomical complexity of a chronic total occlusion (CTO) correlates with procedural failure and complication rates. CTO modification after unsuccessful crossing has been associated with subsequent higher technical success rates, but complication rates remain high with this approach. While successful CTO percutaneous coronary intervention (PCI) has been associated with improved angina and quality of life (QOL) this has not been demonstrated in anatomically high-risk CTOs. Whether a planned CTO modification procedure, hereafter named Investment procedure, could improve patient outcomes has never been investigated. STUDY DESIGN: Invest-CTO is a prospective, single-arm, international, multicenter study, evaluating the effectiveness and safety of a planned investment procedure, with a subsequent completion CTO PCI (at 8-12 weeks), in anatomically high-risk CTOs. We will enroll 200 patients with CTOs defined as high-risk according to our Invest CTO criteria at centers in Norway and United Kingdom. Patients with aorto-ostial lesions, occlusion within a previous stent, or a prior attempt at target vessel CTO PCI within 6 months will be excluded. The co-primary endpoints are cumulative procedural success (%) after both procedures, and a composite safety endpoint at 30 days after completion CTO PCI. Patient reported outcomes (PROs), treatment satisfaction, and clinical endpoints will be reported. CONCLUSION: This study will prospectively evaluate the effectiveness and safety of a planned two staged PCI procedure in the treatment of high-risk CTOs and may have the potential to change current clinical practice.

Myocardial function including estimates of myocardial work in young adults born very preterm or with extremely low birthweight - a cohort study.

BACKGROUND: Preterm birth and low birthweight have been associated with increased risk of heart failure and cardiovascular disease in young adulthood. However, results from clinical studies of myocardial function are not consistent. Echocardiographic strain analyses allow detection of early stages of cardiac dysfunction, and non-invasive estimates of myocardial work can provide additional information on cardiac function. We aimed to evaluate left ventricular (LV) myocardial function including measures of myocardial work in young adults born very preterm (gestational age < 29 weeks) or with extremely low birthweight (< 1000 g) (PB/ELBW), compared with term-born age- and sex matched controls. METHODS: 63 PB/ELBW and 64 controls born in Norway in the periods 1982-1985, 1991-1992, and 1999-2000 were examined with echocardiography. LV ejection fraction (EF) and LV global longitudinal strain (GLS) were measured. Myocardial work was estimated from LV pressure-strain loops after determination of GLS and construction of a LV pressure curve. Diastolic function was evaluated by determination of the presence or absence of elevated LV filling pressure, including measures of left atrial longitudinal strain. RESULTS: The PB/ELBW with mean birthweight 945 (standard deviation (SD) 217) grams, mean gestational age 27 (SD 2) weeks, and mean age 27 (SD 6) years had LV systolic function mainly within normal range. Only 6% had EF < 50% or impaired GLS >-16%, but 22% had borderline impaired GLS between - 16% and - 18%. Mean GLS in PB/ELBW (-19.4% (95% confidence interval (CI) -20.0, -18.9)) was impaired compared to controls (-20.6% (95% CI -21.1, -20.1)), p = 0.003. Lower birthweight was associated to more impaired GLS (Pearson correlation coefficient - 0.2). Means of EF, measures of diastolic function including left atrial reservoir strain, global constructive and wasted work, global work index and global work efficiency was similar in PB/ELBW and controls. CONCLUSION: The young adults born very preterm or with extremely low birthweight had impaired LV-GLS compared to controls, although systolic function mainly within normal range. Lower birthweight was associated with more impaired LV-GLS. These findings could indicate an elevated lifetime risk of developing heart failure in preterm born individuals. Measures of diastolic function and myocardial work were similar compared to controls.

Vascular Endothelial Function Assessed by Flow-Mediated Vasodilatation in Young Adults Born Very Preterm or With Extremely Low Birthweight: A Regional Cohort Study.

Background: Preterm birth and low birthweight have been associated with increased risk of cardiovascular disease in young adults. Endothelial dysfunction is established as an early marker for development of atherosclerotic cardiovascular disease. Previous studies of endothelial function in young adults born very preterm or with extremely low birthweight have, however, shown diverging results. Objective: We aimed to evaluate the risk of cardiovascular disease as measured by vascular endothelial function in young adults born very preterm (<29 weeks of gestation) or with extremely low birthweight (<1,000 g), compared with term-born controls. Methods: This study included 50 young adults born very preterm or with extremely low birthweight and 49 term-born controls born in Norway in the periods 1982-1985, 1991-1992, and 1999-2000 at mean age 28 (±6) years. The endothelial function was assessed by ultrasound measured flow-mediated dilatation (FMD) of the right brachial artery. The arterial diameter was measured at baseline, after release of 5 min of occlusion, and after sublingual administration of nitroglycerine. FMD was reported as absolute and percentage diameter change from baseline and relative to nitroglycerine-induced dilatation. Results: The participants were mainly normal weight non-smokers, without hypertension, diabetes, or established cardiovascular disease. The cases and controls had mean blood pressure 112/71 (SD 12/9) and 112/69 (SD 11/8) mmHg, body mass index 24.0 (SD 4.2) and 24.4 (SD 4.5) kg/m2, and HbA1c 32.7 (SD 2.5) and 33.0 (SD 2.6) mmol/mol, respectively. For both groups, 4 (8%) were smokers. Mean FMD for the adults born very preterm or with extremely low birthweight was 0.17 mm (95% CI 0.14, 0.21) vs. 0.24 mm (95% CI 0.20, 0.28) for the controls (p = 0.01), corresponding to a percentage increase of 5.4% (95% CI 4.2, 6.6) and 7.6% (95% CI 6.2, 8.9), respectively (p = 0.02). The FMD relative to maximal nitroglycerine-induced dilatation was 20% and 31%, respectively (p = 0.001). Conclusions: Young adults born very preterm or with extremely low birthweight have significantly lower FMD compared with the term-born controls suggesting an increased risk of cardiovascular disease.