Long-term cardiac effects of modern treatment for Hodgkin's lymphoma.

BACKGROUND: Hodgkin's lymphoma (HL) is a hematological malignancy that affects both children and young adults. Traditional treatment is associated with a life-time prevalence of cardiac disease exceeding 50%. In the late 1990s protocols were modified to reduce cancer therapy-related adverse cardiac effects. This study aimed to assess the long-term impact of advances in treatment protocols on the cardiac health of HL survivors (HLS). METHODS: HLS (n = 246) treated between 1997 and 2007 with anthracycline-based chemotherapy in three centers in Norway were included. Of these, 132 (53%) had also received mediastinal radiotherapy. HLS were compared to controls (n = 58) recruited from the general population and matched for sex, age, smoking status, and heredity for coronary artery disease. All subjects underwent echocardiography, clinical assessment, and blood sampling. RESULTS: The HLS were 46 ± 9 years old and had been treated 17 ± 3 years before inclusion in the study. There was no significant difference between HLS and controls in ejection fraction (EF) (58%±5 vs. 59%±4, p = 0.08) or prevalence of heart failure. HLS treated with both anthracyclines and mediastinal radiotherapy (AC + MRT) had slightly worse left ventricular global longitudinal strain than controls (-19.3 ± 2.5% vs. -20.8 ± 2.0%, p < 0.001), but those treated with only anthracyclines did not. HLS treated with AC + MRT had a higher prevalence of valve disease than those treated only with anthracyclines (12% vs. 4%, p < 0.05). CONCLUSIONS: HLS treated with anthracyclines after the late 1990s have similar cardiac function and morphology as age-matched controls, apart from higher rates of valvular disease in those who also underwent mediastinal radiotherapy.

Distinguishing left ventricular hypertrophy from hypertrophic cardiomyopathy in adolescents: a longitudinal observation study.

AIMS: Echocardiographic characteristics to distinguish physiological left ventricular (LV) hypertrophy from pathology are warranted in early adolescent athletes. This study aimed to explore the phenotype, progression, and potential grey zone of LV hypertrophy during adolescence in athletes and hypertrophic cardiomyopathy (HCM) genotype-positive patients. METHODS AND RESULTS: In this longitudinal observation study, we compared seventy-six 12-year-old athletes with 55 age-matched and sex-matched HCM genotype-positive patients. Echocardiographic parameters were evaluated by using paediatric reference values (Z-scores). Hypertrophic cardiomyopathy genotype-positive patients were included if they had no or mild LV hypertrophy [maximum wall thickness <13 mm, Z-score <6 for interventricular septum diameter (ZIVSd), or posterior wall thickness]. We collected clinical data, including data on cardiac events. The mean follow-up-time was 3.2 ± 0.8 years. At baseline, LV hypertrophy was found in 28% of athletes and 21% of HCM genotype-positive patients (P = 0.42). Septum thickness values were similar (ZIVSd 1.4 ± 0.9 vs. 1.0 ± 1.3, P = 0.08) and increased only in HCM genotype-positive patients {ZIVSd progression rate -0.17 [standard error (SE) 0.05], P = 0.002 vs. 0.30 [SE 0.10], P = 0.001}. Left ventricular volume Z-scores (ZLVEDV) were greater in athletes [ZLVEDV 1.0 ± 0.6 vs. -0.1 ± 0.8, P < 0.001; ZLVEDV progression rate -0.05 (SE 0.04), P = 0.21 vs. -0.06 (SE 0.04), P = 0.12]. Cardiac arrest occurred in two HCM genotype-positive patients (ages 13 and 14), with ZIVSd 8.2-11.5. CONCLUSION: Left ventricular hypertrophy was found in a similar proportion in early adolescence but progressed only in HCM genotype-positive patients. A potential grey zone of LV hypertrophy ranged from a septum thickness Z-score of 2.0 to 3.3. Left ventricular volumes remained larger in athletes. Evaluating the progression of wall thickness and volume may help clinicians distinguish physiological LV hypertrophy from early HCM.

It is important to distinguish exercise-induced cardiac left ventricular (LV) hypertrophy from hypertrophic cardiomyopathy (HCM), because athletes with HCM may have an increased risk of sudden cardiac death. Limited data are available on this distinction in adolescent athletes. Therefore, we performed a longitudinal observation study comparing the development of LV hypertrophy during adolescence in athletes and HCM genotype­positive patients. In early adolescence, LV hypertrophy was found in a similar proportion of athletes and HCM genotype­positive patients, with a potential grey zone ranging from a septum thickness Z-score of 2.0 to 3.3. After 3 years of follow-up, LV hypertrophy had progressed only in HCM genotype­positive patients, while athletes had larger LV volumes throughout the study period.Evaluation of LV volume and septum thickness progression may assist clinicians in distinguishing exercise-induced LV hypertrophy from early HCM disease in adolescents.

Correction: Effects of Aerobic Exercise on Cardiorespiratory Fitness, Cardiovascular Risk Factors, and Patient-Reported Outcomes in Long-Term Breast Cancer Survivors: Protocol for a Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/45244.].

Effects of Aerobic Exercise on Cardiorespiratory Fitness, Cardiovascular Risk Factors, and Patient-Reported Outcomes in Long-Term Breast Cancer Survivors: Protocol for a Randomized Controlled Trial.

BACKGROUND: Anthracycline-based chemotherapy has been mainstay of adjuvant breast cancer therapy for decades. Although effective, anthracyclines place long-term breast cancer survivors at risk of late effects, such as reduced cardiorespiratory fitness and increased risk of cardiovascular disease. Previous research has shown beneficial effects of exercise training on cardiorespiratory fitness, but the effects of exercise on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes in long-term survivors are less clear. Whether previous exposure to breast cancer therapy modulates the effects of exercise is also unknown. OBJECTIVE: The primary aim of the CAUSE (Cardiovascular Survivors Exercise) trial is to examine the effect of aerobic exercise on cardiorespiratory fitness in anthracycline-treated long-term breast cancer survivors. Secondary aims are to examine effects of exercise training on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes, and to compare baseline values and effects of exercise training between similar-aged women with and those without prior breast cancer. A third aim is to examine the 24-month postintervention effects of aerobic exercise on primary and secondary outcomes. METHODS: The CAUSE trial is a 2-armed randomized controlled trial, where 140 long-term breast cancer survivors, 8-12 years post diagnosis, are assigned to a 5-month nonlinear aerobic exercise program with 3 weekly sessions or to standard care. Seventy similar-aged women with no history of cancer will undergo the same exercise program. Cardiorespiratory fitness measured as peak oxygen consumption (VO2peak), limiting factors for VO2peak (eg, cardiac function, pulmonary function, hemoglobin mass, blood volume, and skeletal muscle characteristics), cardiovascular risk factors (eg, hypertension, diabetes, dyslipidemia, obesity, physical activity level, and smoking status), and patient-reported outcomes (eg, body image, fatigue, mental health, and health-related quality of life) will be assessed at baseline, post intervention, and 24 months post intervention. RESULTS: A total of 209 patients were included from October 2020 to August 2022, and postintervention assessments were completed in January 2023. The 24-month follow-up will be completed in February 2025. CONCLUSIONS: The findings from the CAUSE trial will provide novel scientific understanding of the potential benefits of exercise training in long-term breast cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT04307407; https://clinicaltrials.gov/ct2/show/NCT04307407. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45244.

Young athlete's growing heart: sex differences in cardiac adaptation to exercise training during adolescence.

BACKGROUND: Athlete's heart is a condition of exercise-induced cardiac remodelling. Adult male endurance athletes more often remodel beyond reference values. The impact of sex on remodelling through adolescence remains unclear. Paediatric reference values do not account for patient sex or exercise history. We aimed to study the effect of sex on cardiac remodelling throughout adolescence. METHODS: We recruited 76 male (M) and female (F) 12-year-old cross-country skiers in a longitudinal cohort study. Echocardiography was performed and analysed according to guidelines at age 12 (48 M, 28 F), 15 (34 M, 14 F) and 18 (23 M, 11 F). Repeated echocardiographic measurements were analysed by linear mixed model regression. RESULTS: Males displayed greater indexed left ventricular end-diastolic volumes (LV EDVi) from age 12 (M 81±7 vs F 76±7, mL/m², p≤0.01), and progressed further until follow-up at age 18 (M 2.3±9.7 vs F -3.9±4.5 ΔmL/m², p≤0.01). LV EDVi remained above adult upper reference values in both groups. Males increased LV Mass Index from age 12 to 18 (M 33±27 vs F 4±19, Δg/m², p≤0.01). Males displayed LV mass above paediatric reference values at ages 15 and 18. A subset of males (35%) and females (25%) displayed wall thickness above paediatric reference values at age 12. Cardiac function was normal. There was no sex difference in exercise hours. CONCLUSION: Sex-related differences in athlete's heart were evident from age 12, and progressed throughout adolescence. Remodelling beyond reference values was more frequent than previously reported, particularly affecting males. Age, sex and exercise history may assist clinicians in distinguishing exercise-induced remodelling from pathology in adolescents.

Cardiac troponin T and NT-proBNP for detecting myocardial ischemia in suspected chronic coronary syndrome.

BACKGROUND: Elevated N-terminal pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) are associated with poor outcome in patients with chronic coronary syndrome (CCS). The performance of these biomarkers in diagnosing ischemia, and their association with myocardial hypoperfusion and hypokinesis is unclear. METHODS: Patients with suspected CCS (history of angina, estimated cardiovascular risk >15% or a positive stress test) were included in the prospective, multi-center DOPPLER-CIP study. Patients underwent Single Positron Emission Computed Tomography for assessment of ischemia and NT-proBNP and cTnT were measured in venous blood samples. RESULTS: We included 430 patients (25% female) aged 64 ± 8 years. Reversible hypoperfusion and hypokinesis were present in 139 (32%) and 89 (21%), respectively. Concentrations of NT-proBNP and cTnT correlated moderately (rho = 0.50, p < 0.001). NT-proBNP and cTnT concentrations (median [IQR]) were higher in patients with versus without reversible ischemia: 150 (73-294) versus 87 (44-192) ng/L and 10 (6-13) versus 7 (4-11) ng/L, respectively (p < 0.001 for both), and the associations persisted after adjusting for possible confounders. The C-statistics to discriminate ischemia ranged from 63%-73%, were comparable for cTnT and NT-proBNP, and higher for hypokinesis than hypoperfusion, and both were superior to exercise electrocardiography and stress echocardiography. Very low concentrations (≤5 ng/L cTnT and ≤ 60 ng/L NT-proBNP) ruled out reversible hypokinesis with negative predictive value >90%. CONCLUSION: cTnT and NT-proBNP are associated with irreversible and reversible ischemia in patients with suspected CCS, particularly hypokinesis. The diagnostic performance was comparable between the biomarkers, and very low concentrations may reliably rule out ischemia.

Sex differences in disease progression and arrhythmic risk in patients with arrhythmogenic cardiomyopathy.

AIMS: We aimed to assess sex-specific phenotypes and disease progression, and their relation to exercise, in arrhythmogenic cardiomyopathy (AC) patients. METHODS AND RESULTS: In this longitudinal cohort study, we included consecutive patients with AC from a referral centre. We performed echocardiography at baseline and repeatedly during follow-up. Patients' exercise dose at inclusion was expressed as metabolic equivalents of task (MET)-h/week. Ventricular arrhythmia (VA) was defined as aborted cardiac arrest, sustained ventricular tachycardia, or appropriate therapy by implantable cardioverter-defibrillator. We included 190 AC patients (45% female, 51% probands, age 41 ± 17 years). Ventricular arrhythmia had occurred at inclusion or occurred during follow-up in 85 patients (33% of females vs. 55% of males, P = 0.002). Exercise doses were higher in males compared with females [25 (interquartile range, IQR 14-51) vs. 12 (IQR 7-22) MET-h/week, P < 0.001]. Male sex was a marker of proband status [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4-5.0, P = 0.003] and a marker of VA (OR 2.6, 95% CI 1.4-5.0, P = 0.003), but not when adjusted for exercise dose and age (adjusted OR 1.8, 95% CI 0.9-3.6, P = 0.12 and 1.5, 95% CI 0.7-3.1, P = 0.30, by 5 MET-h/week increments). In all, 167 (88%) patients had ≥2 echocardiographic examinations during 6.9 (IQR 4.7-9.8) years of follow-up. We observed no sex differences in deterioration of right or left ventricular dimensions and functions. CONCLUSION: Male AC patients were more often probands and had higher prevalence of VA than female patients, but not when adjusting for exercise dose. Importantly, disease progression was similar between male and female patients.

From talented child to elite athlete: The development of cardiac morphology and function in a cohort of endurance athletes from age 12 to 18.

BACKGROUND: Adult athletes undergo cardiac adaptions in what is known as the "athlete's heart". Cardiac adaptations in young athletes have not been described in longitudinal studies but have previously been believed to be uniform in nature. METHODS: Seventy-six cross-country skiers were assessed at age 12. Forty-eight (63%) completed the first follow-up at age 15 and 36 (47%) the second follow-up at age 18. Comprehensive exercise data were collected. Echocardiography with three-dimensional measurements and cardiopulmonary exercise testing were performed at all time points. The cohort was divided into active and former endurance athletes, with an eight hours of weekly endurance exercise cut-off at age 18. RESULTS: The athletes underwent eccentric remodelling between ages 12 and 15, and concentric remodelling between ages 15 and 18. At age 18, the active endurance athletes had greater increases in inter-ventricular wall thickness (1.8 ± 1.4 Δmm vs 0.6 ± 1.0 Δmm, p < 0.05), left ventricular (LV) posterior wall thickness (1.6 ± 1.2 Δmm vs 0.8 ± 0.8 Δmm, p < 0.05), LV mass (63 ± 30 Δg vs 27 ± 21 Δg, p < 0.01), right ventricular (RV) end-diastolic area (3.4 ± 4.0 Δcm2 vs 0.6 ± 3.5Δ cm2, p < 0.05), RV end-systolic area (1.0 ± 2.3 Δcm2 vs -0.9 ± 2.0 Δcm2, p < 0.05) and left atrial volume (24 ± 21 ΔmL vs 6±10 ΔmL, p < 0.05) and had greater indexed maximal oxygen uptake (66.3 ± 7.4 mL/min/kg vs 57.1 ± 8.2 mL/min/kg, p < 0.01). There was no significant difference for LV volumes. CONCLUSION: This study finds a shift in the development of the young athlete's heart. Between ages 12 and 15, the active endurance athletes underwent eccentric remodelling. This dynamic switched to concentric remodelling between ages 15 and 18.

The cardiac impact of cisplatin-based chemotherapy in survivors of testicular cancer: a 30-year follow-up.

AIMS: Cisplatin-based chemotherapy (CBCT) is essential in the treatment of metastatic testicular cancer (TC) but has been associated with long-term risk of cardiovascular morbidity and mortality. Furthermore, cisplatin can be detected in the body decades after treatment. We aimed to evaluate the long-term impact of CBCT on cardiac function and morphology in TC survivors 30 years after treatment. METHODS AND RESULTS: TC survivors treated with CBCT (1980-94) were recruited from the longitudinal Norwegian Cancer Study in Testicular Cancer Survivors and compared with a control group matched for sex, age, smoking status, and heredity for coronary artery disease. All participants underwent laboratory tests, blood pressure measurement, and 2D and 3D echocardiography including 2D speckle-tracking strain analyses. Ninety-four TC survivors, on average 60 ± 9 years old, received a median cumulative cisplatin dose of 780 mg (IQR 600-800). Compared with controls, TC survivors more frequently used anti-hypertensive (55% vs. 24%, P < 0.001) and lipid-lowering medication (44% vs. 18%, P < 0.001). TC survivors had worse diastolic function parameters with higher E/e'-ratio (9.8 ± 3.2 vs. 7.7 ± 2.5, P < 0.001), longer mitral deceleration time (221 ± 69 vs. 196 ± 57ms, P < 0.01), and higher maximal tricuspid regurgitation velocity (25 ± 7 vs. 21 ± 4 m/s, P = 0.001). The groups did not differ in left or right ventricular systolic function, prevalence of arrhythmias, or valvular heart disease. Cumulative cisplatin dose did not correlate with cardiac parameters. CONCLUSION: No signs of overt or subclinical reduction in systolic function were identified. Long-term cardiovascular adverse effects three decades after CBCT may be limited to metabolic dysfunction and worse diastolic function in TC survivors.

Clinical validation of three cardiovascular magnetic resonance techniques to measure strain and torsion in patients with suspected coronary artery disease.

BACKGROUND: Several cardiovascular magnetic resonance (CMR) techniques can measure myocardial strain and torsion with high accuracy. The purpose of this study was to compare displacement encoding with stimulated echoes (DENSE), tagging and feature tracking (FT) for measuring circumferential and radial myocardial strain and myocardial torsion in order to assess myocardial function and infarct scar burden both at a global and at a segmental level. METHOD: 116 patients with a high likelihood of coronary artery disease (European SCORE > 15%) underwent CMR examination including cine images, tagging, DENSE and late gadolinium enhancement (LGE) in the short axis direction. In total, 97 patients had signs of myocardial disease and 19 had no abnormalities in terms of left ventricular (LV) wall mass index, LV ejection fraction, wall motion, LGE or a history of myocardial infarction. Thirty-four patients had myocardial infarct scar with a transmural LGE extent (transmurality) that exceeded 50% of the wall thickness in at least one segment. Global circumferential strain (GCS) and global radial strain (GRS) was analyzed using FT of cine loops, deformation of tag lines or DENSE displacement. RESULTS: DENSE and tagging both showed high sensitivity (82% and 71%) at a specificity of 80% for the detection of segments with > 50% LGE transmurality, and receiver operating characteristics (ROC) analysis showed significantly higher area under the curve-values (AUC) for DENSE (0.87) than for tagging (0.83, p < 0.001) and FT (0.66, p = 0.003). GCS correlated with global LGE when determined with DENSE (r = 0.41), tagging (r = 0.37) and FT (r = 0.15). GRS had a low but significant negative correlation with LGE; DENSE r = - 0.10, FT r = - 0.07 and tagging r = - 0.16. Torsion from DENSE and tagging had a weak correlation (- 0.20 and - 0.22 respectively) with global LGE. CONCLUSION: Circumferential strain from DENSE detected segments with > 50% scar with a higher AUC than strain determined from tagging and FT at a segmental level. GCS and torsion computed from DENSE and tagging showed similar correlation with global scar size, while when computed from FT, the correlation was lower.

Blood volume expansion does not explain the increase in peak oxygen uptake induced by 10 weeks of endurance training.

PURPOSE: The endurance training (ET)-induced increases in peak oxygen uptake ([Formula: see text]O2peak) and cardiac output ([Formula: see text]peak) during upright cycling are reversed to pre-ET levels after removing the training-induced increase in blood volume (BV). We hypothesised that ET-induced improvements in [Formula: see text]O2peak and [Formula: see text]peak are preserved following phlebotomy of the BV gained with ET during supine but not during upright cycling. Arteriovenous O2 difference (a-[Formula: see text]O2diff; [Formula: see text]O2/[Formula: see text]), cardiac dimensions and muscle morphology were studied to assess their role for the [Formula: see text]O2peak improvement. METHODS: Twelve untrained subjects ([Formula: see text]O2peak: 44 ± 6 ml kg-1 min-1) completed 10 weeks of supervised ET (3 sessions/week). Echocardiography, muscle biopsies, haemoglobin mass (Hbmass) and BV were assessed pre- and post-ET. [Formula: see text]O2peak and [Formula: see text]peak during upright and supine cycling were measured pre-ET, post-ET and immediately after Hbmass was reversed to the individual pre-ET level by phlebotomy. RESULTS: ET increased the Hbmass (3.3 ± 2.9%; P = 0.005), BV (3.7 ± 5.6%; P = 0.044) and [Formula: see text]O2peak during upright and supine cycling (11 ± 6% and 10 ± 8%, respectively; P ≤ 0.003). After phlebotomy, improvements in [Formula: see text]O2peak compared with pre-ET were preserved in both postures (11 ± 4% and 11 ± 9%; P ≤ 0.005), as was [Formula: see text]peak (9 ± 14% and 9 ± 10%; P ≤ 0.081). The increased [Formula: see text]peak and a-[Formula: see text]O2diff accounted for 70% and 30% of the [Formula: see text]O2peak improvements, respectively. Markers of mitochondrial density (CS and COX-IV; P ≤ 0.007) and left ventricular mass (P = 0.027) increased. CONCLUSION: The ET-induced increase in [Formula: see text]O2peak was preserved despite removing the increases in Hbmass and BV by phlebotomy, independent of posture. [Formula: see text]O2peak increased primarily through elevated [Formula: see text]peak but also through a widened a-[Formula: see text]O2diff, potentially mediated by cardiac remodelling and mitochondrial biogenesis.

The developing athlete's heart: a cohort study in young athletes transitioning through adolescence.

BACKGROUND: Athlete's heart is a term used to describe physiological changes in the hearts of athletes, but its early development has not been described in longitudinal studies. This study aims to improve our understanding of the effects of endurance training on the developing heart. METHODS: Cardiac morphology and function in 48 cross-country skiers were assessed at age 12 years (12.1 ± 0.2 years) and then again at age 15 years (15.3 ± 0.3 years). Echocardiography was performed in all subjects including two-dimensional speckle-tracking strain echocardiography and three-dimensional echocardiography. All participants underwent cardiopulmonary exercise testing at both ages 12 and 15 years to assess maximal oxygen uptake and exercise capacity. RESULTS: Thirty-one (65%) were still active endurance athletes at age 15 years and 17 (35%) were not. The active endurance athletes had greater indexed maximal oxygen uptake (62 ± 8 vs. 57 ± 6 mL/kg/min, P < 0.05) at follow-up. There were no differences in cardiac morphology at baseline. At follow-up the active endurance athletes had greater three-dimensional indexed left ventricular end-diastolic (84 ± 11 mL/m2 vs. 79 ± 10 mL/m2, P < 0.05) and end-systolic volumes (36 ± 6 mL/m2 vs. 32 ± 3 mL/m2, P < 0.05). Relative wall thickness fell in the active endurance athletes, but not in those who had quit (-0.05 ΔmL/m2 vs. 0.00 mL/m2, P = 0.01). Four active endurance athletes had relative wall thickness above the upper reference values at baseline; all had normalised at follow-up. CONCLUSION: After an initial concentric remodelling in the pre-adolescent athletes, those who continued their endurance training developed eccentric changes with chamber dilatation and little change in wall thickness. Those who ceased endurance training maintained a comparable wall thickness, but did not develop chamber dilatation.

Axl expression is increased in early stages of left ventricular remodeling in an animal model with pressure-overload.

BACKGROUND: AXL is a receptor tyrosine kinase that has been related to kidney and vascular disorders. Heart failure patients with reduced ejection fraction have higher AXL in serum than controls. No information about Axl expression with HF progression is available. METHODS: Thoracic transverse aortic constriction (TAC) was successfully performed on male Wistar rats (n = 25) with different constriction levels. Controls underwent sham surgery (n = 12). Echocardiography measurements were performed 4-8 weeks after surgery. Collagen deposition was measured with picrosirius red staining. Axl mRNA levels in left ventricle (LV), left kidney (LK) and ascending aorta (aAo) and the LV expression of cardiac remodeling and fibrogenic factors were quantified with real-time PCR. AXL LV protein levels were quantified with western blot and localization was analyzed by immunohistochemistry. Soluble AXL levels in plasma were assayed with ELISA. RESULTS: Successful TAC rats were classified into LV hypertrophy (LVH) or heart failure (HF), modeling the progressive cardiac changes after pressure overload. Collagen deposition was increased only in the HF group. LV Axl mRNA levels were higher in LVH and HF than in Sham rats, and correlated with LVHi, and hypertrophic and fibrogenic mediators. However, no association was found with LV systolic function. AXL was expressed in LV myocytes and other cell types. Concentration of circulating sAXL in plasma was increased in the LVH group compared to Sham and HF rats. Axl mRNA levels were similar in all groups in the LK and aAo. CONCLUSIONS: Axl expression pattern suggests a role in the early progression of LV remodeling in HF but not in the later systolic dysfunction. The higher levels of circulating AXL found in HF patients most probably shed from the heart.

Should the septum be included in the assessment of right ventricular longitudinal strain? An ultrasound two-dimensional speckle-tracking stress study.

Right ventricular longitudinal strain (RVLS) by 2D speckle-tracking echocardiography (2D-STE) is a useful parameter for assessing systolic function. However, the exact method to perform it is not well defined as some authors evaluate only free wall (FW) segments while others include all six RV segments. To compare the assessment of RVLS at rest and during exercise by these two approaches. Echocardiography was performed on 80 healthy subjects at rest and during exercise. The analysis consisted of standard and 2D-STE assessment of RV global and segmental strain tracing only RVFW and also tracing all six RV segments. At rest, RVLS could be assessed in 78 (feasibility 97.5%) subjects by both methods. However, during exercise, RVLS by RVFW method was feasible in 67 (83.8%) as compared to 74 (92.5%) by RV6S approach. Both at rest and during exercise, RVLS values by the two methods showed excellent correlation (r = > 0.90). However, RVLS values assessed by RV6S were lower (absolute values) than those by RVFW approach (RV6S vs. RVFW; rest: - 27.0 ± 3.9 vs. - 9.5 ± 3.9, p < 0.001 and exercise: - 30.7 ± 5.2 vs. - 33.3 ± 5.1, p < 0.001). Furthermore, basal strain was higher and apical strain lower (absolute values) by RV6S approach. At rest, reproducibility for RVLS was excellent and similar for the two methods. However, during exercise, reproducibility for RVFW method was poorer, especially at the apex. The two currently described methods for RVLS assessment by 2D-STE demonstrated excellent agreement. However, the RV6S approach seemed to be more feasible and reproducible, particularly during exercise. Moreover, global and segmental strain values are different with both methods and should not be interchanged.

Left Ventricular Regional Wall Motion Abnormality is a Strong Predictor of Cardiotoxicity in Breast Cancer Patients Undergoing Chemotherapy / Alteração Contrátil Segmentar Ventricular Esquerda é Preditor Independente de Cardiotoxicidade em Pacientes com Câncer de Mama em Tratamento Quimioterápico

Abstract Background: Chemotherapeutic agents of anthracyclines class and humanized monoclonal antibodies are effective treatments for breast cancer, however, they present a potential risk of cardiotoxicity. Several predictors have been recognized as predictors in the development of cardiac toxicity, and the evaluation of left ventricular segmental wall motion abnormalities (LVSWMA) has not been studied. Objective: To analyze prospectively the role of LVSWMA among echocardiographic parameters in the prediction of development of cardiotoxicity in breast cancer patients undergoing treatment with chemotherapy. Methods: Prospective cohort of patients diagnosed with breast cancer and in chemotherapy treatment with potential cardiotoxicity medications including doxorubicin and trastuzumab. Transthoracic echocardiograms including speckle tracking strain echocardiography were performed at standard times before, during and after the treatment to assess the presence (or lack thereof) of cardiotoxicity. Cardiotoxicity was defined by a 10% decrease in the left ventricular ejection fraction, on at least one echocardiogram. Multivariate logistic regression models were used to verify the predictors related to the occurrence of cardiotoxicity over time. Results: Of the 112 patients selected (mean age 51,3 ± 12,9 years), 18 participants (16.1%) had cardiotoxicity. In the multivariate analysis using the logistic regression model, those with LVWMA (OR = 6.25 [CI 95%: 1.03; 37.95], p < 0,05), LV systolic dimension (1.34 [CI 95%: 1.01; 1.79], p < 0,05) and global longitudinal strain by speckle tracking (1.48 [CI 95%: 1.02; 2.12], p < 0,05) were strongly associated with cardiotoxicity. Conclusion: In the present study, we showed that LVWMA, in addition to global longitudinal strains, were strong predictors of cardiotoxicity and could be useful in the risk stratification of these patients.

Resumo Fundamento: Os agentes quimioterápicos da classe das antraciclinas e dos anticorpos monoclonais humanizados são tratamentos eficazes para o câncer de mama, entretanto, apresentam alto risco de cardiotoxicidade. Diversos parâmetros têm sido reconhecidos como preditores no desenvolvimento de toxicidade cardíaca, sendo que a avaliação da alteração contrátil segmentar ventricular esquerda (ACSVE) ainda não foi estudada. Objetivo: Analisar a associação entre o surgimento de ACSVE e o desenvolvimento de cardiotoxicidade em pacientes com câncer de mama em tratamento com quimioterapia. Métodos: Coorte prospectiva de pacientes diagnosticados com câncer de mama e em tratamento quimioterápico com doxorrubicina e/ou trastuzumab. Foram realizados ecocardiogramas transtorácicos antes, durante e depois do tratamento para avaliar a presença ou não de cardiotoxicidade. A cardiotoxicidade foi definida por um decréscimo de 10% na fração de ejeção do ventrículo esquerdo, em pelo menos um ecocardiograma. Modelos de regressão logística multivariada foram utilizados para verificar os fatores preditores na ocorrência de cardiotoxicidade ao longo do tempo. Resultados: Dos 112 pacientes selecionados (idade média = 51,3 ± 12,9 anos), 18 (16,1%) apresentaram cardiotoxicidade. Na análise multivariada os pacientes com ACSVE (OR = 6,25 [IC 95%: 1,03; 37,95], p < 0,05), diâmetro sistólico do VE (OR = 1,34 [IC 95%:1,01; 1,79], p < 0,05) e strain longitudinal global pela técnica de speckle tracking (OR = 1,48 [IC 95%: 1,02; 2,12], p < 0,05) foram preditores significativos e independentes na predição de cardiotoxidade. Conclusão: Mostramos que ACSVE, bem como a redução do strain longitudinal global foram preditores independentes para cardiotoxicidade, podendo ser úteis na estratificação de risco destes pacientes.

Left Ventricular Regional Wall Motion Abnormality is a Strong Predictor of Cardiotoxicity in Breast Cancer Patients Undergoing Chemotherapy.

BACKGROUND: Chemotherapeutic agents of anthracyclines class and humanized monoclonal antibodies are effective treatments for breast cancer, however, they present a potential risk of cardiotoxicity. Several predictors have been recognized as predictors in the development of cardiac toxicity, and the evaluation of left ventricular segmental wall motion abnormalities (LVSWMA) has not been studied. OBJECTIVE: To analyze prospectively the role of LVSWMA among echocardiographic parameters in the prediction of development of cardiotoxicity in breast cancer patients undergoing treatment with chemotherapy. METHODS: Prospective cohort of patients diagnosed with breast cancer and in chemotherapy treatment with potential cardiotoxicity medications including doxorubicin and trastuzumab. Transthoracic echocardiograms including speckle tracking strain echocardiography were performed at standard times before, during and after the treatment to assess the presence (or lack thereof) of cardiotoxicity. Cardiotoxicity was defined by a 10% decrease in the left ventricular ejection fraction, on at least one echocardiogram. Multivariate logistic regression models were used to verify the predictors related to the occurrence of cardiotoxicity over time. RESULTS: Of the 112 patients selected (mean age 51,3 ± 12,9 years), 18 participants (16.1%) had cardiotoxicity. In the multivariate analysis using the logistic regression model, those with LVWMA (OR = 6.25 [CI 95%: 1.03; 37.95], p < 0,05), LV systolic dimension (1.34 [CI 95%: 1.01; 1.79], p < 0,05) and global longitudinal strain by speckle tracking (1.48 [CI 95%: 1.02; 2.12], p < 0,05) were strongly associated with cardiotoxicity. CONCLUSION: In the present study, we showed that LVWMA, in addition to global longitudinal strains, were strong predictors of cardiotoxicity and could be useful in the risk stratification of these patients.

Cardiac Troponin T Concentrations, Reversible Myocardial Ischemia, and Indices of Left Ventricular Remodeling in Patients with Suspected Stable Angina Pectoris: a DOPPLER-CIP Substudy.

BACKGROUND: Cardiac troponin T concentrations measured with high-sensitivity assays (hs-cTnT) provide important prognostic information for patients with stable coronary artery disease (CAD). However, whether hs-cTnT concentrations mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia in this population is not known. METHODS: We measured hs-cTnT concentrations in 619 subjects with suspected stable CAD in a prospectively designed multicenter study. We identified associations with indices of LV remodeling, as assessed by cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed by single positron emission computed tomography. RESULTS: Median hs-cTnT concentration was 7.8 ng/L (interquartile range, 4.8-11.6 ng/L), and 111 patients (18%) had hs-cTnT concentrations above the upper reference limit (>14 ng/L). Patients with hs-cTnT >14 ng/L had increased LV mass (144 ± 40 g vs 116 ± 34 g; P < 0.001) and volume (179 ± 80 mL vs 158 ± 44 mL; P = 0.006), lower LV ejection fraction (LVEF) (59 ± 14 vs 62 ± 11; P = 0.006) and global longitudinal strain (14.1 ± 3.4% vs 16.9 ± 3.2%; P < 0.001), and more reversible perfusion defects (P = 0.001) and reversible wall motion abnormalities (P = 0.008). Age (P = 0.009), estimated glomerular filtration rate (P = 0.01), LV mass (P = 0.003), LVEF (P = 0.03), and evidence of reversible myocardial ischemia (P = 0.004 for perfusion defects and P = 0.02 for LV wall motion) were all associated with increasing hs-cTnT concentrations in multivariate analysis. We found analogous results when using the revised US upper reference limit of 19 ng/L. CONCLUSIONS: hs-cTnT concentrations reflect both LV mass and reversible myocardial ischemia in patients with suspected stable CAD.

Morphological changes and myocardial function assessed by traditional and novel echocardiographic methods in preadolescent athlete's heart.

Background Athlete's heart is a term used to describe the morphological and functional changes in the hearts of athletes. Recent studies suggest that these changes may occur even in preadolescent athletes. This study aims to improve our understanding of the changes occurring in the preadolescent athlete's heart. Design and methods Cardiac morphology and function in 76 preadolescent cross-country skiers (aged 12.1 ± 0.2 years) were compared with 25 age-matched non-competing preadolescents. Echocardiography was performed in all subjects, including 2D speckle-tracking strain echocardiography and 3D echocardiography. All participants underwent cardiopulmonary exercise testing to assess oxygen uptake and exercise capacity. Results Athletes had greater indexed VO2 max (62 ± 7 vs. 44 ± 5 mL/kg per min, p < 0.001), indexed left ventricular end-diastolic volume (79 ± 7 vs. 68 ± 7 mL/m2, p < 0.001), left ventricular mass (69 ± 12 vs. 57 ± 13 g/m2, p < 0.001), indexed right ventricular basal diameter (28.3 ± 3.0 vs. 25.4 ± 3.5 mm/m2, p < 0.001) and right atrial area (10.6 ± 1.4 vs. 9.7 ± 1.2 cm2/m2, p < 0.01). There was no difference in left ventricular ejection fraction, global longitudinal strain, and global circumferential strain and right ventricular fractional area change between the groups. Controls had higher right ventricular global longitudinal strain (-28.1 ± 3.5 vs. -31.1 ± 3.3%, p < 0.01). VO2 max was highly correlated to left ventricular end-diastolic volume ( r = 0.76, p < 0.001). Conclusion Athletes had greater left ventricular mass and greater left and right ventricular chamber dimensions compared with controls, while left ventricular function did not differ. Interestingly, right ventricular deformation was significantly lower compared with controls. This supports the notion that there is physiological, adaptive remodelling in preadolescent athlete's heart.