Anthracycline-induced cardiotoxicity on regional myocardial work and left ventricular mechanical dispersion in adolescents and young adults in post-lymphoma remission.

BACKGROUND: Myocardial work (MW) is a new echocardiographic tool with a high sensitivity to detect early and subtle alterations of myocardial function. We aimed to evaluate the late effects of anthracyclines by assessing the global and segmental MW and intraventricular mechanical dispersion from speckle tracking echocardiography in childhood lymphoma survivors (CLS). METHODS: Thirty-one young adults including CLS and age-matched healthy controls were enrolled. All underwent echocardiography including an evaluation of left ventricular (LV) morphology and regional function. We assessed LV longitudinal (differentiating sub-endocardial and sub-epicardial layers), circumferential strains and twist, global and regional MW index (MWI). LV mechanical dispersion was assessed from the time dispersion of LV longitudinal strain, from myocardial wasted work (MWW) and myocardial work efficiency (MWE). RESULTS: The longitudinal strains both at the level of the sub-endocardium and sub-epicardium were reduced in CLS compared to controls. The global MWI was also decreased (1668 ± 266 vs 1870 ± 264%.mmHg in CLS patients and controls, respectively, p < 0.05), especially on the apical segments. An increase of LV intraventricular mechanical dispersion was observed in CLS. MWW and MWE remained unchanged compared to controls. CONCLUSION: Our results strongly support that cardiac remodeling is observed in CLS, characterized by a decrease in MW and an increase in LV mechanical dispersion. The apex is specifically altered, but its clinical significance remains uncertain. MW as a complement to strain seems interesting in cancer survivors to detect myocardial dysfunction at early stage and adapt their follow-up.

Fitness and metabolic response to exercise in young adult survivors of childhood lymphoma.

PURPOSE: Childhood lymphoma survivors (CLSs) are at high risk of reduced daily activity. This work studied metabolic substrate use and cardiorespiratory function in response to exercise in CLSs. METHODS: Twenty CLSs and 20 healthy adult controls matched for sex, age, and BMI took an incremental submaximal exercise test to determine fat/carbohydrate oxidation rates. Resting echocardiography and pulmonary functional tests were performed. Physical activity level, and blood metabolic and hormonal levels were measured. RESULTS: CLSs reported more physical activity than controls (6317 ± 3815 vs. 4268 ± 4354 MET-minutes/week, p = 0.013), had higher resting heart rate (83 ± 14 vs. 71 ± 13 bpm, p = 0.006), and showed altered global longitudinal strain (- 17.5 ± 2.1 vs. - 19.8 ± 1.6%, p = 0.003). We observed no difference in maximal fat oxidation between the groups, but it was reached at lower relative exercise intensities in CLSs (Fatmax 17.4 ± 6.0 vs. 20.1 ± 4.1 mL/kg, p = 0.021). At V̇O2 peak, CLSs developed lower relative exercise power (3.2 ± 0.9 vs. 4.0 ± 0.7 W/kg, p = 0.012). CONCLUSION: CLSs reported higher levels of physical activity but they attained maximal fat oxidation at lower relative oxygen uptake and applied lower relative power at V̇O2 peak. CLSs may thus have lower muscular efficiency, causing greater fatigability in response to exercise, possibly related to chemotherapy exposure during adolescence and childhood. Long-term follow-up is essential and regular physical activity needs to be sustained.

Long-term prognosis of patients treated by coronary sinus-based percutaneous annuloplasty: single centre experience.

AIMS: This study aims to report long-term mortality, echocardiographic, and clinical outcomes of patients receiving treatment for functional mitral regurgitation (FMR) with the Carillon device. METHODS AND RESULTS: This was a single centre analysis of prospectively collected data from patients treated with the Carillon Mitral Contour System for symptomatic congestive heart failure despite guideline-directed medical therapy, who were included from a single centre from the TITAN II study. All patients presented with New York Heart Association (NYHA) class 2 or greater symptoms, grade 2+ to 4+ FMR, left ventricular enlargement, and reduced ejection fraction. Surviving patients were evaluated for long-term follow-up post-procedure, averaging 6.9 years. Fifteen (15) patients (mean age 72 years, 60% male, 100% NYHA class III or IV, 50% MR grade 3+ or 4+) were treated with the Carillon device. The Kaplan-Meier mortality rate was 40% at 6 years of follow-up. Long-term survival through 6 years was associated with echocardiographic improvement in mitral regurgitation (change in effective regurgitant orifice area in survivors versus non-survivors from baseline to 1 year follow-up, -9.0 ± 5.6 vs. -1.7 ± 1.5, P = 0.02) and clinical status at 12 months (difference in NYHA at 1 year follow-up between survivors versus non-survivors, P = 0. 05) which was sustained throughout follow-up. All patients at 6 year follow-up had ≤2+ MR, with 6 of 7 having 0-1+ MR. Left ventricular end-diastolic volume was reduced from 154.0 ± 65.7 mL at baseline to 104.5 ± 59.2 mL at 6 year follow-up, P = 0.03 in survivors with both measurements. CONCLUSIONS: Among patients with congestive heart failure treated with the Carillon device, long-term survival is associated with favourable 1 year and sustained improvements in mitral regurgitation, left ventricular volume, ejection fraction, and clinical status.

Is there benefit in optimising heart failure treatment in over-80 year-old patients? (HF-80 study): study protocol for a randomized controlled trial.

BACKGROUND: An aging population and better management of various heart diseases explain the exponential growth in incidence and prevalence of chronic heart failure, with poor prognosis and heavy health costs. Medical management is codified in international guidelines. The management of heart failure in over-80 year-old patients follows these guidelines, but no clinical trials have been able to confirm benefit. Moreover, registries show down-prescription of heart failure treatments in the elderly and over-80s. METHODS/DESIGN: We present the design of the HF-80 ("Is there benefit in optimising heart failure treatment in over-80 year-old patients?") study, which is a prospective randomised open-label clinical trial with blinded end-points, designed to evaluate the effect of optimising management by adhering to guidelines in over-80 year-old heart failure patients. Patients over 80 years of age admitted with acute heart failure will be included. The primary endpoint is to assess quality of life at 6 months on the Minnesota questionnaire. The secondary endpoints are to assess the effect of optimised management on quality of life, mortality, readmission for acute heart failure, cardiac fibrosis and economic data at 12 months. 80 patients will be included, divided into 2 groups: group A, with usual heart failure management by general practitioners; and group B, with optimised management based on international guidelines. DISCUSSION: It is necessary to assess the benefit of guidelines in over-80 year-old heart failure patients because of the fragility of this population and the elevated risk of iatrogenic complications. TRIAL REGISTRATION: Clinical trials.gov number: NCT01437371.

Global longitudinal strain as a major predictor of cardiac events in patients with depressed left ventricular function: a multicenter study.

BACKGROUND: The risk stratification of patients with left ventricular (LV) dysfunction can be performed using echocardiographic parameters such as the ejection fraction (EF). Recently, new technologies based on deformation measurements have been shown to identify early myocardial dysfunction before EF decrease. Consequently, tools such as two-dimensional strain have been incorporated into echocardiographic systems, allowing for fast, reliable, and reproducible calculation of longitudinal components of LV systolic deformation. The hypothesis in this study was that as a more sensitive marker of LV dysfunction, longitudinal strain would allow for the risk stratification of patients with heart failure. METHODS: This multicenter study included 147 patients with heart failure with LV EFs ≤ 45% (mean age, 64 ± 14 years; 74% men; mean LV EF, 29.9 ± 8.9%). Conventional echocardiographic parameters as well as global and segmental longitudinal strain were measured and compared with these values in a control population. Patients were monitored for cardiac events, defined as a composite criterion, over 12 months. RESULTS: Clinical events were observed in 20% of patients during the 12-month follow-up period. On receiver operating characteristic curve analysis, global longitudinal strain had the highest prognostic value (area under the curve, 0.83) and the highest combination of sensitivity (73%) and specificity (83%), using a cutoff value of -7%. CONCLUSION: Strain assessment is highly feasible and reliable in patients with LV dysfunction and allows for cardiovascular risk stratification in patients with heart failure with greater accuracy than LV EF.

Different patterns of left ventricular enlargement and long-term prognosis after reperfused acute myocardial infarction.

BACKGROUND: Dilation of end-systolic and end-diastolic volumes (ESV, EDV) has been used to define left ventricular remodelling after acute myocardial infarction (MI), but the prognostic significance of different enlargement patterns has not been evaluated fully. AIM: To analyse the evolution of left ventricular volumes and parameters of global and regional contractility and their correlations with long-term prognosis in patients treated by angioplasty in the acute phase of MI. METHODS: Seventy-four patients (mean age 56+/-13 years; 77% men), treated successfully by angioplasty in the acute phase of MI, were included prospectively. Significant enlargement of left ventricular volumes was defined as a greater than 20% increase between acute phase and 6-month control, assessed by contrast ventriculography. Clinical follow-up was obtained for all patients at 82+/-19 months. RESULTS: Four groups were identified based on volume evolution: Group I (n=29, 39%; no volume enlargement); Group II (n=8, 11%; isolated EDV enlargement); Group III (n=10, 14%; isolated ESV enlargement); Group IV (n=27, 36%; ESV plus EDV enlargement). Global left ventricular ejection fraction increased in Groups I (p=0.001) and II (p=0.037), but decreased in Groups III (p=0.0002) and IV (p=0.019). The 6-year event-free survival rate was significantly (p=0.0039) better in Groups I and II (100%) than in Groups III and IV (80 and 78%, respectively). CONCLUSION: ESV enlargement in patients with reperfused acute MI impacts negatively on long-term prognosis, while isolated EDV enlargement does not.

Effect of thrombus aspiration on infarct size and left ventricular function in high-risk patients with acute myocardial infarction treated by percutaneous coronary intervention. Results of a prospective controlled pilot study.

BACKGROUND: Thrombus aspiration devices have been shown to improve reperfusion criteria and to reduce distal embolization in patients treated by percutaneous coronary interventions (PCI) in the acute phase of ST-elevation myocardial infarction (STEMI). There are, however, little data about their efficacy in the reduction of infarct size. METHODS: We sought to assess in a prospective randomized trial the impact of thrombus aspiration on infarct size and severity and on left ventricular function in high-risk patients with a first STEMI. The primary end point was scintigraphic infarct size, and secondary end points were infarct severity and regional and global left ventricular function. Forty-four patients with completely occluded (Thrombolysis in Myocardial Infarction flow 0-1) proximal segments of infarct-related artery were randomly assigned to thrombus aspiration group with the Export catheter (n = 20) (Medtronic, Inc, Minneapolis, MN) or PCI-only group. A rest Tc-99-mibi gated single-photon emission computed tomographic and contrast-enhanced magnetic resonance imaging were performed 6 +/- 2 days later. RESULTS: Infarct size was comparable in patients in the thrombus aspiration group and PCI-only group (30.6% +/- 15.8% vs 28.5% +/- 17.9% of the left ventricle, P = .7) as was infarct severity in infarct-related artery territory (55% +/- 12% vs 55% +/- 14%, P = .9). Transmurality score as assessed by magnetic resonance imaging was similar in both groups (2.03 +/- 1.05 vs 2.16 +/- 1.21, P = .7). There was no impact of thrombus aspiration on other secondary end points. CONCLUSION: In our study, thrombus aspiration with the Export catheter performed as adjunctive therapy in high-risk patients with total occlusion of the proximal part of major coronary arteries does not decrease infarct size or severity and has no effect on left ventricular regional and global function.