Obstructive and restrictive pulmonary dysfunction in long-term lymphoma survivors after high-dose therapy with autologous stem cell transplantation.

BACKGROUND: Obstructive and restrictive dysfunction in long-term lymphoma survivors (LSs) after high-dose therapy with autologous stem-cell transplantation (HDT-ASCT) has not been addressed systematically previously. MATERIAL AND METHODS: LSs treated in Norway 1987-2008 with HDT-ASCT who performed spirometry, measurement of static lung volumes and echocardiography 2012-2014 at either Oslo or St. Olavs University Hospitals was eligible. Smoking data were recorded by questionnaire. Treatment data were collected from medical records or hospital databases. Factors associated with obstructive and restrictive impairments (dichotomous outcomes) were examined by Poisson regression. Linear regression with the margins post-estimation command was used to derive adjusted mean values of forced expiratory volume in 1 s (FEV1). We used the normative reference data recommended by the European Respiratory Society for calculating percent predicted values. RESULTS: A total of 226 LSs were studied, of whom 11.5 and 5.8% had obstructive and restrictive impairment, respectively. For women and men, mean FEV1 was 2.31 and 3.34 l corresponding to 11.4%- and 11.1%-points below that predicted from norms, respectively. In multivariable regression analyses, cumulative doxorubicin dose (400-775 mg/m2) and current smoking were associated with increased risk of obstructive impairment, and chest RT (>13-66 Gy) was associated with increased risk of restrictive impairment. Currently smoking LSs within the highest doxorubicin category (400-775 mg/m2), had the lowest adjusted mean FEV1. CONCLUSIONS: Despite intensive cancer treatment, our analysis showed modest reductions in obstructive parameters among long-term LSs after HDT-ASCT compared to normative reference data. To limit obstructive impairments in LSs after HDT-ASCT, we suggest that targeted smoking-cessation advice is directed towards patients who have received high cumulative doses of doxorubicin.

Cardiorespiratory fitness in long-term lymphoma survivors after high-dose chemotherapy with autologous stem cell transplantation.

BACKGROUND: Cardiorespiratory fitness as measured by peak oxygen consumption (VO2peak) is a strong predictor of longevity and may be compromised by anticancer therapy, inactivity, and smoking. We compared VO2peak among lymphoma survivors (LSs) with reference data from healthy sedentary subjects, after a 10.2-year (mean) follow-up post high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT). We further examined the association between VO2peak and treatment, physical activity, smoking, pulmonary, and cardiac function. METHODS: Lymphoma survivors treated with HDT-ASCT in Norway 1987-2008 were eligible. VO2peak was assessed by cardiopulmonary exercise testing. Pulmonary function testing and echocardiography were also conducted. Data on treatment, physical activity, and smoking were collected from hospital records and questionnaires. VO2peak was compared with age-sex predicted reference data. Linear regression was used to associate clinical factors with VO2peak cross-sectionally. RESULTS: A total of 194 LSs without heart failure were studied. Mean VO2peak was 4.5% and 7.7% below norms in females and males, respectively. Twenty-two percent had impaired (<80% predicted) VO2peak. Decreasing VO2peak was associated with impaired diffusion capacity and current smoking, while physical activity level and VO2peak were positively associated. CONCLUSION: We suggest increased attention towards physical activity counseling and smoking cessation advice to preserve cardiorespiratory fitness in LSs after HDT-ASCT. Patients with impaired diffusion capacity may benefit from subsequent monitoring to detect pulmonary vascular diseases.

Cardiac response to early conversion from calcineurin inhibitor to everolimus in renal transplant recipients--a three-yr serial echocardiographic substudy of the randomized controlled CENTRAL trial.

BACKGROUND: In transplant recipients, calcineurin inhibitors (CNIs) are associated with adverse cardiac effects while mTOR inhibitors have been reported to be beneficial. We performed a randomized controlled trial (RCT) in de novo renal transplant recipients examining cardiac responses of everolimus vs. CNI. METHODS: This was a substudy of the three-yr CENTRAL study, an RCT on safety and efficacy of early (week 7 post-engraftment) conversion from cyclosporine A (CsA) to everolimus vs. continued CsA. Thirty-nine recipients [median age 64 yr, (range 31-81)] completed echocardiographic evaluations at baseline, one, and three yr. RESULTS: After three yr, there was no difference between groups in left ventricle (LV) diastolic function, LV systolic function, LV morphology, and blood pressure response. We observed a relevant decrease in LV mass (CsA; 9.6%, p = 0.008, vs. everolimus; 7.0% reduction, p = 0.15), stabilized LV diastolic function, and a trend toward lower systolic blood pressure with 6 mmHg decrease in both arms (CsA, p = 0.08; everolimus, p = 0.14). Diastolic blood pressure was significantly reduced (8 mmHg decrease, p = 0.002) only in everolimus patients. CONCLUSIONS: After three-yr follow-up, no clinically relevant effect on cardiac function of an early conversion from CsA to an everolimus-based immunosuppressive regimen was detected in de novo renal transplant recipients.

Effects of high-intensity interval training on cardiac remodelling, function and coronary microcirculation in de novo heart transplant patients: a substudy of the HITTS randomised controlled trial.

Objectives: High-intensity interval training (HIT) improves peak oxygen consumption (VO2peak) in de novo heart transplant (HTx) recipients. It remains unclear whether this improvement early after HTx is solely dependent on peripheral adaptations, or due to a linked chain of central and peripheral adaptations. The objective of this study was to determine whether HIT results in structural and functional adaptations in the cardiovascular system. Methods: Eighty-one de novo HTx recipients were randomly assigned to participate in either 9 months of supervised HIT or standard care exercise-based rehabilitation. Cardiac function was assessed by echocardiogram and the coronary microcirculation with the index of microcirculatory resistance (IMR) at baseline and 12 months after HTx. Results: Cardiac function as assessed by global longitudinal strain was significantly better in the HIT group than in the standard care group (16.3±1.2% vs 15.6±2.2%, respectively, treatment effect = -1.1% (95% CI -2.0% to -0.2%), p=0.02), as was the end-diastolic volume (128.5±20.8 mL vs 123.4±15.5 mL, respectively, treatment effect=4.9 mL (95% CI 0.5 to 9.2 mL), p=0.03). There was a non-significant tendency for IMR to indicate improved microcirculatory function (13.8±8.0 vs 16.8±12.0, respectively, treatment effect = -4.3 (95% CI -9.1 to 0.6), p=0.08). Conclusion: When initiated early after HTx, HIT leads to both structural and functional cardiovascular adaptations. Trial registration number: NCT01796379.

Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3-Year Results of the SUCCOUR Trial.

BACKGROUND: Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction and guide initiation of cardioprotection (CPT). OBJECTIVES: In this study, the authors sought to determine whether echocardiography GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care at 3 years. METHODS: In this international multicenter prospective randomized controlled trial, patients were enrolled from 28 international sites. All patients treated with anthracyclines with another risk factor for heart failure were randomly allocated to GLS-guided (>12% relative reduction in GLS) or ejection fraction (EF)-guided (>10% absolute reduction of EF to <55%) CPT. The primary end point was the change in 3-dimensional (3D) EF (ΔEF) from baseline to 3 years. RESULTS: Among 331 patients enrolled, 255 (77%, age 54 ± 12 years, 95% women) completed 3-year follow-up (123 in the EF-guided group and 132 in the GLS-guided group). Most had breast cancer (n = 236; 93%), and anthracycline followed by trastuzumab was the most common chemotherapy regimen (84%). Although 67 (26%) had hypertension and 32 (13%) had diabetes mellitus, left ventricular function was normal at baseline (EF: 59% ± 6%, GLS: 20.7% ± 2.3%). CPT was administered in 18 patients (14.6%) in the EF-guided group and 41 (31%) in the GLS-guided group (P = 0.03). Most patients showed recovery in EF and GLS after chemotherapy; 3-year ΔEF was -0.03% ± 7.9% in the EF-guided group and -0.02% ± 6.5% in the GLS-guided (P = 0.99) group; respective 3-year EFs were 58% ± 6% and 59% ± 5% (P = 0.06). At 3 years, 17 patients (5%) had cancer therapeutics-related cardiac dysfunction (11 in the EF-guided group and 6 in the GLS guided group; P = 0.16); 1 patient in each group was admitted for heart failure. CONCLUSIONS: Among patients taking potentially cardiotoxic chemotherapy for cancer, the 3-year data showed improvement of LV dysfunction compared with 1 year, with no difference in ΔEF between GLS- and EF-guided CPT. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).

Serum markers of cardiac complications in a systemic sclerosis cohort.

Primary cardiac involvement is one of the leading causes of mortality in systemic sclerosis (SSc), but little is known regarding circulating biomarkers for cardiac SSc. Here, we aimed to investigate potential associations between cardiac SSc and candidate serum markers. Serum samples from patients of the Oslo University SSc cohort and 100 healthy controls were screened against two custom-made candidate marker panels containing molecules deemed relevant for cardiopulmonary and/or fibrotic diseases. Left (LV) and right ventricular (RV) dysfunction was assessed by protocol echocardiography, performed within three years from serum sampling. Patients suspected of pulmonary hypertension underwent right heart catheterization. Vital status at study end was available for all patients. Descriptive analyses, logistic and Cox regressions were conducted to assess associations between cardiac SSc and candidate serum markers. The 371 patients presented an average age of 57.2 (± 13.9) years. Female sex (84%) and limited cutaneous SSc (73%) were predominant. Association between LV diastolic dysfunction and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (OR 0.41, 95% CI 0.21-0.78, p = 0.007) was identified. LV systolic dysfunction defined by global longitudinal strain was associated with angiopoietin 2 (ANGPT2) (OR 3.42, 95% CI 1.52-7.71, p = 0.003) and osteopontin (OPN) (OR 1.95, 95% CI 1.08-3.52, p = 0.026). RV systolic dysfunction, measured by tricuspid annular plane systolic excursion, was associated to markers of LV dysfunction (ANGPT2, OPN, and TRAIL) (OR 1.67, 95% CI 1.11-2.50, p = 0.014, OR 1.86, 95% CI 1.25-2.77, p = 0.002, OR 0.32, 95% CI 0.15-0.66, p = 0.002, respectively) and endostatin (OR 1.86, 95% CI 1.22-2.84, p = 0.004). In conclusion, ANGPT2, OPN and TRAIL seem to be circulating biomarkers associated with both LV and RV dysfunction in SSc.

Incremental Value of Myocardial Work over Global Longitudinal Strain in the Surveillance for Cancer-Treatment-Related Cardiac Dysfunction: A Case-Control Study.

The load dependence of global longitudinal strain (GLS) means that changes in systolic blood pressure (BP) between visits may confound the diagnosis of cancer-treatment-related cardiac dysfunction (CTRCD). We sought to determine whether the estimation of myocardial work, which incorporates SBP, could overcome this limitation. In this case-control study, 44 asymptomatic patients at risk of CTRCD underwent echocardiography at baseline and after oncologic treatment. CTRCD was defined on the basis of the change in the ejection fraction. Those with CTRCD were divided into subsets with and without a follow-up SBP increment >20 mmHg (CTRCD+BP+ and CTRCD+BP-), and matched with patients without CTRCD (CTRCD-BP+ and CTRCD-BP-). The work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were assessed in addition to the GLS. The largest increases in the GWI and GCW at follow-up were found in CTRCD-BP+ patients. The CTRCD+BP- patients demonstrated significantly larger decreases in GWI and GCW than their CTRCD+BP+ and CTRCD-BP- peers. ROC analysis for the discrimination of LV functional changes in response to increased afterload in the absence of cardiotoxicity revealed higher AUCs for GCW (AUC = 0.97) and GWI (AUC = 0.93) than GLS (AUC = 0.73), GWW (AUC = 0.51), or GWE (AUC = 0.63, all p-values < 0.001). GCW (OR: 1.021; 95% CI: 1.001-1.042; p < 0.04) was the only feature independently associated with CTRCD-BP+. Myocardial work is superior to GLS in the serial assessments in patients receiving cardiotoxic chemotherapy. The impairment of GLS in the presence of an increase in GWI and GCW indicates the impact of elevated afterload on LV performance in the absence of actual myocardial impairment.

[A man with persisting fever, night sweats and high sedimentation rate]. / En mann med vedvarende feber, nattesvette og høy senkningsreaksjon.

BACKGROUND: Fever of unknown origin and high sedimentation rate are common clinical problems. MATERIAL AND METHODS: A middle-aged man with fever of unknown origin, night sweats and high sedimentation rate was referred to our hospital for investigation. RESULTS AND INTERPRETATION: The patient was suspected to have mononucleosis or reactivation of infectious mononucleosis because of mild anaemia and thrombocytopenia, a weakly positive IgM antibody test for Epstein-Barr virus and monocytosis (in peripheral blood). Because monocytosis, elevated sedimentation rate and fever persisted, bone marrow smears were prepared and biopsies taken.The third biopsy showed that morphology was consistent with chronic myelomonocytic leukemia (CMML), which was confirmed by two later biopsies. However, a malignant cell population (consisting of blasts in peripheral blood) was only found in one of several flow cytometry assessments of peripheral blood and bone marrow aspirate and cytogenetic analyses of bone marrow cells were normal. The patient's clinical situation has been stable for some years and treatment has not been necessary.

Systolic Dysfunction in Systemic Sclerosis: Prevalence and Prognostic Implications.

OBJECTIVE: Primary cardiac involvement is presumed to account for a substantial part of disease-related mortality in systemic sclerosis (SSc). Still, there are knowledge gaps on the evolution and total burden of systolic dysfunction in SSc. Here we evaluated prospective left ventricular (LV) and right ventricular (RV) systolic function in an unselected SSc cohort and assessed the burden of systolic dysfunction on mortality. METHODS: From the Oslo University Hospital cohort, 277 SSc patients were included from 2003-2016 and compared with healthy controls. Serial echocardiographies were reevaluated in order to detect change in systolic function. Right heart catheterization was performed on patients suspected of pulmonary hypertension. Descriptive and regression analyses were conducted. RESULTS: At baseline, LV systolic dysfunction by ejection fraction less than 50%, or a global longitudinal strain greater than -17.0%, was found in 12% and 24%, respectively. RV systolic dysfunction measured by tricuspid annular plane systolic excursion (TAPSE) less than 17 mm was evident in 10%. Follow-up echocardiography was performed after a median of 3.3 years (interquartile range [IQR] 1.5-5.6). At follow-up, LV systolic function remained stable, whereas RV function evaluated by TAPSE deteriorated (mean 23.1 to 21.7 mm, P = 0.005) equaling a 15% prevalence of RV systolic dysfunction. RV systolic function predicted mortality in multivariable models (hazard ratio 0.41, 95% confidence interval [CI] 0.19-0.90, P value 0.027), whereas LV systolic function lost predictive significance when adjusted for TAPSE. CONCLUSION: In this unselected and prospective study, systolic dysfunction of the LV and RV was a frequent complication of SSc. LV systolic function remained stable across the observation period, whereas RV function deteriorated and predicted mortality.

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.

Left Ventricular Diastolic Dysfunction Predicts Mortality in Patients With Systemic Sclerosis.

BACKGROUND: Primary cardiac affection is common and is a major cause of death in systemic sclerosis (SSc), but there are knowledge gaps regarding the effect of cardiac dysfunction on mortality. OBJECTIVES: The purpose of this study was to evaluate diastolic function in a large, unselected SSc cohort and assess the effect of diastolic dysfunction (DD) on mortality. METHODS: SSc patients followed prospectively at the Oslo University Hospital from 2003 to 2016 with available echocardiographies and matched control subjects were included. DD was assessed by echocardiography according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Pulmonary hypertension (PH) was diagnosed by right heart catheterization. Vital status was available for all patients. Cox regression analyses with hazards ratios (HRs) were conducted. RESULTS: Diastolic function was assessed in 275 SSc patients at baseline and in 186 patients at follow-up. At baseline, 46 of the 275 SSc patients (17%) were diagnosed with DD and 195 (71%) had normal diastolic function. After a median follow-up of 3.4 years (interquartile range: 1.6 to 6.2 years), the proportion of DD increased from 17% to 29%. During follow-up, 57% of patients with DD at baseline died, compared with 13% of patients with normal diastolic function. At baseline, 86 patients had performed right heart catheterization, and 43 were diagnosed with PH; of these 60% deceased. In multivariable Cox regression analyses, DD was a stronger predictor of death (HR: 3.7; 95% CI: 1.69 to 8.14; c-index 0.89) than PH (HR: 2.0; 95% CI: 1.1 to 3.9; c-index 0.84). CONCLUSIONS: DD is frequent in SSc, and the presence of DD is associated with high mortality. DD exceeds PH with respect to predicting mortality.

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.

Cardiovascular Parameters to 2 years After Kidney Transplantation Following Early Switch to Everolimus Without Calcineurin Inhibitor Therapy: An Analysis of the Randomized ELEVATE Study.

BACKGROUND: Mammalian target of rapamycin inhibitors may confer cardioprotective advantages, but clinical data are limited. METHODS: In the open-label ELEVATE trial, kidney transplant patients were randomized at 10 to 14 weeks after transplant to convert from calcineurin inhibitor (CNI) to everolimus or remain on standard CNI therapy. Prespecified end points included left ventricular mass index and, in a subpopulation of patients, arterial stiffness as measured by pulse wave velocity. RESULTS: The mean change in left ventricular mass index from randomization was similar with everolimus versus CNI (month 24, -4.37 g/m versus -5.26 g/m; mean difference, 0.89 [p = 0.392]). At month 24, left ventricular hypertrophy was present in 41.7% versus 37.7% of everolimus and CNI patients, respectively. Mean pulse wave velocity remained stable with both everolimus (mean change from randomization to month 12, -0.24 m/s; month 24, -0.03 m/s) and CNI (month 12, 0.11 m/s; month 24, 0.16 m/s). The change in mean ambulatory nighttime blood pressure from randomization showed a benefit for diastolic pressure at month 12 (P = 0.039) but not at month 24. Major adverse cardiac events occurred in 1.1% and 4.2% of everolimus-treated and CNI-treated patients, respectively, by month 12 (P = 0.018) and 2.3% (8/353) and 4.5% by month 24 (P = 0.145). CONCLUSIONS: Overall, these data do not suggest a clinically relevant effect on cardiac end points after early conversion from CNI to a CNI-free everolimus-based regimen.

Impaired Right Ventricular Function in Long-Term Lymphoma Survivors.

BACKGROUND: Cardiotoxicity from anthracyclines or cardiac radiation therapy is detrimental to left ventricular (LV) function. However, the long-term effects on right ventricular (RV) performance are largely unknown. The aim of this study was to investigate the long-term impact of cardiotoxic treatment on RV function among adult cancer survivors. METHODS: Adult lymphoma survivors (LSs) who underwent autologous hematopoietic stem cell transplantation in Norway from 1987 to 2008 were invited to undergo cardiovascular evaluation by echocardiography and cardiopulmonary exercise testing. In total, 274 LSs participated. The mean age was 56 ± 12 years, and the mean follow-up time since lymphoma diagnosis was 13 ± 6 years. Echocardiographic parameters were compared with those of age- and gender-matched control subjects from an existing large Norwegian database. RV systolic dysfunction was indicated by two or more abnormal RV systolic parameters according to current recommendations. LV systolic dysfunction was indicated by LV global longitudinal strain > -17%. RESULTS: All parameters of RV systolic function were impaired in LSs compared with control subjects (P < .01 for all). The most pronounced difference was observed for tricuspid annular plane systolic excursion: 22.9 ± 4.1 versus 27.1 ± 4.2 mm. Greater cardiotoxic treatment burden was associated with larger RV functional impairment. Tricuspid annular plane systolic excursion correlated with peak oxygen consumption (r = 0.23, P = .001). RV systolic performance was associated with LV systolic function (r = 0.49, P < .001 for tricuspid annular plane systolic excursion vs LV global longitudinal strain), but a greater proportion of patients had LV dysfunction (30.8%) compared with RV dysfunction (6.2%) (P < .001). CONCLUSIONS: RV systolic function was impaired in LSs. The association between RV and LV function indicates a global, long-term cardiotoxic effect. However, RV dysfunction was less prevalent than LV dysfunction.

Echocardiographic evidence of right ventricular functional improvement after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) induces right ventricular (RV) adaptive changes but often results in RV failure and death. Balloon pulmonary angioplasty (BPA) is a treatment option in patients in whom pulmonary endarterectomy is contraindicated and in patients with residual pulmonary hypertension after pulmonary endarterectomy. We hypothesized that RV reverse remodeling and improved RV function would occur after BPA in patients with CTEPH. METHODS: In 26 patients with CTEPH (59 ± 12 years old; 11 men), echocardiography, cardiopulmonary exercise testing, blood samples, and right-sided cardiac catheterization were performed before and after 4 ± 2 BPA procedures. Echocardiography images were analyzed off-line with particular focus on RV function according to current recommendations. Differences from baseline to follow-up were analyzed by paired samples t tests. RESULTS: Significant improvements in hemodynamics, peak oxygen consumption, and levels of N-terminal pro-B-type natriuretic peptide were detected after BPA. All measures of RV function improved considerably, including fractional area change (+6%; p = 0.003), tricuspid annular plane systolic excursion (+3 mm; p < 0.001), and RV free wall peak strain (-4.4; p = 0.002). RV end-diastolic diameter, area, and free wall thickness decreased significantly, whereas left ventricular diameter and stroke volume increased. CONCLUSIONS: After BPA, a significant improvement in RV functional parameters could be observed by echocardiography, adding credibility to this form of treatment in patients with CTEPH.

Valvular Dysfunction in Lymphoma Survivors Treated With Autologous Stem Cell Transplantation: A National Cross-Sectional Study.

OBJECTIVES: This study assessed the prevalence and associated risk factors for valvular dysfunction (VD) observed in adult lymphoma survivors (LS) after autologous hematopoietic stem cell transplantation (auto-HCT), and to determine whether anthracycline-containing chemotherapy (ACCT) alone in these patients is associated with VD. BACKGROUND: The prevalence of and risk factors for VD in LS after auto-HCT is unknown. Anthracyclines may induce heart failure, but any association with VD is not well-defined. METHODS: This national cross-sectional study included all adult LS receiving auto-HCT from 1987 to 2008 in Norway. VD was defined by echocardiography as either more than mild regurgitation or any stenosis. Observations in LS were compared with a healthy age- and gender-matched (1:1) control group. RESULTS: In total, 274 LS (69% of all eligible) participated. Mean age was 56 ± 12 years, mean follow-up time after lymphoma diagnosis was 13 ± 6 years, and 62% of participants were males. Mean cumulative anthracycline dosage was 316 ± 111 mg/m(2), and 35% had received radiation therapy involving the heart (cardiac-RT). VD was observed in 22.3% of the LS. Severe VD was rare (n = 9; 3.3% of all LS) and mainly aortic stenosis (n = 7). We observed VD in 16.7% of LS treated with ACCT alone (n = 177), corresponding with a 3-fold increased VD risk (odds ratio: 2.9; 95% confidence interval: 1.5 to 5.8; p = 0.002) compared with controls. Furthermore, the presence of aortic valve degeneration was increased in the LS after ACCT alone compared with controls (13.0% vs. 2.9%; p < 0.001). Female sex, age >50 years at lymphoma diagnosis, ≥3 lines of chemotherapy before auto-HCT, and cardiac-RT >30 Gy were identified as independent risk factors for VD in the LS. CONCLUSIONS: In LS, ACCT alone was significantly associated with VD and related to valvular degeneration. Overall, predominantly moderate VD was prevalent in LS, and longer observation time is needed to clarify the clinical significance of this finding.

The impact of cisplatinum-based chemotherapy on ventricular function and cardiovascular risk factors in female survivors after malignant germ cell cancer.

AIMS: Among male cancer survivors, cisplatinum-based chemotherapy (CBCT) is associated with impaired left ventricle (LV) diastolic function, increased risk of metabolic syndrome, and increased cardiovascular morbidity and mortality. Comparable data in females are limited. The long-term effects of cisplatin on right ventricle (RV) function are unknown in both genders. We aimed to investigate the impact of CBCT on cardiovascular risk factors and cardiac function in female survivors after malignant ovarian germ cell tumour (MOGCT). METHODS AND RESULTS: This national cross-sectional follow-up study recruited MOGCT survivors, diagnosed from 1980-09 (n = 153). Seventy-four (48%) participated in out-patient visit, of whom 41 had received CBCT (62% of all CBCT): median age, 35 years (range, 18-64 years); median time since CBCT, 14 years (range, 5-31 years). Participants were categorized into high-CBCT (n = 19) and low-CBCT (n = 22) groups and compared with age-matched healthy females. All participants underwent laboratory tests and echocardiography to determine cardiac function. Compared with low-CBCT participants, the high-CBCT group showed significantly impaired RV function, as evaluated by tricuspid annular plane systolic excursion (22.6 ± 2.4 mm vs. 26.3 ± 3.6 mm; P < 0.001); RV S' (10.7 ± 1.9 cm/s vs. 12.4 ± 2.3 cm/s; P = 0.01); RV global longitudinal strain (-23.4 ± 2.4% vs. -25.7 ± 3.7%; P = 0.02), and tricuspid annular displacement (21 ± 2 mm vs. 24 ± 3 mm; P = 0.001). LV diastolic function was impaired in the high-CBCT group compared with controls. Patients and controls exhibited similar metabolic syndrome prevalences. CONCLUSIONS: Among long-term survivors of MOGCT, CBCT was associated with impaired RV function and LV diastolic function. Unlike men, women do not appear to have an elevated risk of metabolic syndrome after CBCT.

Contemporary Outcome in Patients With Idiopathic Dilated Cardiomyopathy.

Outcome is better in patients with idiopathic dilated cardiomyopathy (IDC) than in ischemic heart failure (HF), but morbidity and mortality are nevertheless presumed to be substantial. Most data on the prognosis in IDC stem from research performed before the widespread use of current evidence-based treatment, including implantable devices. We report outcome data from a cohort of patients with IDC treated according to current HF guidelines and compare our results with previous figures: 102 consecutive patients referred to our tertiary care hospital with idiopathic IDC and a left ventricular ejection fraction <40% were included in a prospective cohort study. After extensive baseline work-up, follow-up was performed after 6 and 13 months. Vital status and heart transplantation were recorded. Over the first year of follow-up, the patients were on optimal pharmacological treatment, and 24 patients received implantable devices. Left ventricular ejection fraction increased from 26 ± 10% to 41 ± 11%, peak oxygen consumption increased from 19.5 ± 7.1 to 23.4 ± 7.8 ml/kg/min, and functional class improved substantially (all p values <0.001). After a median follow-up of 3.6 years, 4 patients were dead, and heart transplantation had been performed in 9 patients. According to our literature search, survival in patients with IDC has improved substantially over the last decades. In conclusion, patients with IDC have a better outcome than previously reported when treated according to current guidelines.

Cardiac Function in Adult Patients with Juvenile Idiopathic Arthritis.

OBJECTIVE: To compare cardiac function in adults with longterm juvenile idiopathic arthritis (JIA) with that of healthy controls, and to investigate the influence of inflammation, disease severity, and use of antirheumatic medication on cardiac function. METHODS: Eighty-five patients with JIA (median age 38.6 yrs) with active disease for at least 15 years were reexamined at a median of 29 years after disease onset and compared with 46 matched controls. Echocardiography, including tissue Doppler imaging and longitudinal peak-systolic global strain, was used to assess diastolic and systolic myocardial function, and 12-channel electrocardiography was performed. RESULTS: The interventricular septum was thicker in patients than controls (mean ± SD 0.8 ± 0.2 cm vs 0.7 ± 0.1 cm, p = 0.036). Diastolic function in patients was altered compared with controls characterized by lower mitral E wave deceleration time (165 ± 36 ms vs 180 ± 40 ms, p = 0.029), higher surrogate marker of left ventricular (LV) filling pressure (median lateral E/e' 5.3, interquartile range 4.6-6.3 vs 4.8, 3.9-5.7, p = 0.036), and larger left atrial area (16.4 ± 2.9 cm(2) vs 15.1 ± 2.8 cm(2), p = 0.015). Systolic and diastolic blood pressures were higher in patients (120 ± 15 mmHg vs 114 ± 9 mmHg, p = 0.021 and 76 ± 10 mmHg vs 71 ± 8 mmHg, p = 0.009, respectively). QT corrected interval was similar in patients and controls. High high-sensitivity C-reactive protein (CRP), polyarticular disease course, and extended joint affection at 29-year followup, as well as duration of active disease, cumulative erythrocyte sedimentation rate, and CRP, and prednisolone use were associated with higher lateral E/e'. CONCLUSION: Adult patients with JIA did not differ from controls in LV systolic function, but had mildly thicker interventricular septum and indications for higher LV filling pressure, and most in patients with a higher disease burden.