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.

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.

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.

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.

Geometry as a Confounder When Assessing Ventricular Systolic Function: Comparison Between Ejection Fraction and Strain.

BACKGROUND: Preserved left ventricular (LV) ejection fraction (EF) and reduced myocardial strain are reported in patients with hypertrophic cardiomyopathy, ischemic heart disease, diabetes mellitus, and more. OBJECTIVES: The authors performed a combined mathematical and echocardiographic study to understand the inconsistencies between EF and strains. METHODS: An analytical equation showing the relationship between EF and the 4 parameters, global longitudinal strain (GLS), global circumferential strain (GCS), wall thickness, and short-axis diameter, was derived from an elliptical LV model. The equation was validated by measuring the 4 parameters by echocardiography in 100 subjects with EF ranging from 16% to 72% and comparing model-predicted EF with measured EF. The effect of the different parameters on EF was explored in the model and compared with findings in the patients. RESULTS: Calculated EF had very good agreement with measured EF (r = 0.95). The model showed that GCS contributes more than twice as much to EF than GLS. A significant reduction of GLS could be compensated by a small increase of GCS or wall thickness or reduced diameter. The model further demonstrated how EF can be maintained in ventricles with increased wall thickness or reduced diameter, despite reductions in both longitudinal and circumferential shortening. This was consistent with similar EF in 20 control subjects and 20 hypertrophic cardiomyopathy patients with increased wall thickness and reductions in both circumferential and longitudinal shortening (all p < 0.01). CONCLUSIONS: Reduced deformation despite preserved EF can be explained through geometric factors. Due to geometric confounders, strain better reflects systolic function in patients with preserved EF.

Focused cardiac ultrasound by unselected residents-the challenges.

BACKGROUND: Focus Cardiac Ultrasound (FoCUS) performed by internal medicine residents on call with 2 h of training can provide a means for ruling out cardiac disease, but with poor sensitivity. The purpose of the present study was to evaluate diagnostic usefulness as well as diagnostic accuracy of FoCUS following 4 h of training. METHODS: All residents on call were given a 4-h training course with an additional one-hour training course after 6 months. They were asked to provide a pre- and post-FoCUS diagnosis, with the final diagnosis at discharge as reference. RESULTS: During a 7 month period 113 FoCUS examinations were reported; after 53 were excluded this left 60 for evaluation with a standard echocardiogram performed on average 11.5 h after FoCUS. Examinations were performed on the basis of chest pain and dyspnoea/edema. The best sensitivity was found in terms of the detection of reduced left ventricular (LV) ejection fraction (EF) (92%), LV dilatation (85%) and pericardial effusion (100%). High values were noted for negative predictive values, although false positives were seen. A kappa > 0.6 was observed for reduced LVEF, right ventricular area fraction and dilatation of LV and left atrium. In 48% of patients pre- and post-FoCUS diagnoses were identical and concordant with the final diagnosis. Importantly, in 30% examinations FoCUS correctly changed the pre-FoCUS diagnosis. CONCLUSIONS: A FoCUS protocol with a 4-h training program gained clinical usefulness in one third of examinations. False positive findings represented the major challenge.

Left ventricular dysfunction is related to the presence and extent of a septal flash in patients with right ventricular pacing.

Aims: Septal flash (SF), a marker of left ventricular (LV) dyssynchrony in the presence of a left bundle branch block (LBBB), has been shown to predict improved ventricular function and outcome when corrected with cardiac resynchronization therapy. We hypothesized that a SF is present in patients receiving right ventricular (RV) pacing and its presence and extent could predict the development of LV dysfunction and remodelling. Methods and Results: Seventy-four consecutive patients receiving conventional RV pacing (>6 months, >85% paced) were studied with two-dimensional (2D) echocardiography. Indications for pacing were sinus-node dysfunction and atrioventricular conduction disorders. The presence of a SF was determined on stepwise advanced 2D echocardiographic views and confirmed using greyscale M-mode. Septal flash excursion was quantified by the amplitude of the early inward motion, measured from QRS onset to maximal inward motion. Fifty-seven (of 74; 77%) patients receiving RV pacing had a detectable SF. Patients with a SF had lower LV ejection fraction (EF) (52 ± 10 vs. 60 ± 4%, P < 0.001) and greater indexed end-systolic volume (33 ± 16 vs. 23 ± 5 mL/m2, P < 0.001). Receiver operating characteristic analysis demonstrated that a SF of 3.5 mm was the optimal cut-off value (area under the curve = 0.95) to identify reduced LV function (EF < 50%) with a sensitivity of 91% and a specificity of 90%. Conclusion: A SF was present in a majority of patients receiving conventional RV pacing and its magnitude was related to LV dysfunction and adverse remodelling. Given the similarities observed in LBBB and pacemaker-induced dyssynchrony, SF magnitude might be a predictor for the development of LV dysfunction and adverse remodelling in patients receiving conventional RV pacing.

Strain echocardiographic assessment of left atrial function predicts recurrence of atrial fibrillation.

AIMS: We evaluated if a dispersed left atrial (LA) contraction pattern was related to atrial fibrillation (AF) in patients with normal left ventricular (LV) function, and normal or mildly enlarged left atrium. METHODS AND RESULTS: We included 61 patients with paroxysmal AF (PAF). Of these, 30 had not while 31 had recurrence of AF after radiofrequency ablation (RFA). Twenty healthy individuals were included for comparison. Echocardiography was performed in patients in sinus rhythm the day before RFA. LA volume was calculated. Peak negative longitudinal strain was assessed in 18 LA segments during atrial systole. Contraction duration in 18 LA segments was measured as the time from peak of the P wave on electrocardiogram to maximum myocardial shortening in each segment. The standard deviation of contraction durations was defined as LA mechanical dispersion (LA MD). LA size was rather preserved in patients with PAF (LA volume 25 ± 10 mL/m(2)). LA MD was more pronounced in patients with recurrence of AF after RFA compared with those without recurrence and controls (38 ± 14 ms vs. 30 ± 12 ms vs. 16 ± 8 ms, both P < 0.001). LA MD was a predictor of PAF [OR 7.84 (95%CI 2.15-28.7), P < 0.01, per 10 ms increase] adjusted for age, LA volume, e', and LA function. LA function by strain was reduced in both patients with and without recurrent AF after RFA compared with controls (-14 ± 4% vs. -16 ± 3% vs. -19 ± 2%, both P < 0.05). CONCLUSION: LA MD was pronounced, and LA deformation was reduced in patients with PAF with apparently normal LV structure and function, and normal or mildly enlarged LA. LA MD may be useful as a predictor of AF recurrence after RFA.

Brief group training of medical students in focused cardiac ultrasound may improve diagnostic accuracy of physical examination.

BACKGROUND: Physical examination and auscultation can be challenging for medical students. The aim of this study was to investigate whether a brief session of group training in focused cardiac ultrasound (FCU) with a pocket-sized device would allow medical students to improve their ability to detect clinically relevant cardiac lesions at the bedside. METHODS: Twenty-one medical students in their clinical curriculum completed 4 hours of FCU training in groups. The students examined patients referred for echocardiography with emphasis on auscultation, followed by FCU. Findings from physical examination and FCU were compared with those from standard echocardiography performed and analyzed by cardiologists. RESULTS: In total, 72 patients were included in the study, and 110 examinations were performed. With a stethoscope, sensitivity to detect clinically relevant (moderate or greater) valvular disease was 29% for mitral regurgitation, 33% for aortic regurgitation, and 67% for aortic stenosis. FCU improved sensitivity to detect mitral regurgitation (69%, P < .001). However, sensitivity to detect aortic regurgitation (43%) and aortic stenosis (70%) did not improve significantly. Specificity was ≥89% for all valvular diagnoses by both methods. For nonvalvular diagnoses, FCU's sensitivity to detect moderate or greater left ventricular dysfunction (90%) was excellent, detection of right ventricular dysfunction (79%) was good, while detection of dilated left atrium (53%), dilated right atrium (49%), pericardial effusion (40%), and dilated aortic root (25%) was less accurate. Specificity varied from 57% to 94%. CONCLUSIONS: After brief group training in FCU, medical students could detect mitral regurgitation significantly better compared with physical examination, whereas detection of aortic regurgitation and aortic stenosis did not improve. Left ventricular dysfunction was detected with high sensitivity. More extensive training is advised.

The diagnostic accuracy of pocket-size cardiac ultrasound performed by unselected residents with minimal training.

Pocket-size imaging devices may represent a tool for fast initial cardiac screening in the emergency setting. Pocket-size cardiac ultrasound (PCU) examinations performed by experienced echocardiographers yield acceptable diagnostic accuracy compared to standard echocardiogram (SE). However, the success of this method when used by unselected non-cardiologists remains unexplored. The current study studies the diagnostic accuracy of PCU when used by unselected internal medicine residents with minimal training. All residents were given a 2-hour introductory course in PCU (Vscan) and reported PCU results for up to 15 predefined cardiac landmarks. These were arbitrarily divided into 3 priority groups, such that left ventricle (LV) and pericardium were of first priority. Diagnostic accuracy [sensitivity/specificity and negative/positive predictive values (PPV/NPV)] and agreement were evaluated using a subsequent SE as reference. During a 9.2 months period a total of 303 patients were included in the study, the majority on the basis of presenting with chest pain or suspected heart failure. In the pooled LV and pericardial (1st priority) data, sensitivity/specificity/PPV/NPV were 61/92/70/89% respectively. Similar specificities and NPVs were observed for the 11 remaining indices, as were lower sensitivities and PPVs. The best PCU sensitivity (76%) was attained for the assessment of LV wall motion abnormalities. Overall agreement was k = 0.50. PCU examination performed by internal medicine residents with minimal training could provide a suitable means of ruling out cardiac pathology, as reflected in the high specificities and NPVs. It is not, however, a satisfactory tool for identifying patients with various cardiac disorders.