scholarly journals Prospective, Comprehensive Cardiac Assessment in Patients Receiving BTK Inhibitor Therapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4301-4301
Author(s):  
Chloe Pek Sang Tang ◽  
Andre La Gerche ◽  
Julie McMullen ◽  
Erin Howden ◽  
Sasanka M. Handunnetti ◽  
...  
Keyword(s):  
Cardiac Mri ◽  
Left Atrial ◽  
Research Funding ◽  
Cardiopulmonary Exercise Testing ◽  
Vo2 Max ◽  
Ventricular Ejection Fraction ◽  
Holter Monitor ◽  
Cardiopulmonary Exercise ◽  
Cardiac Assessment

The development of Bruton Kinase Inhibitors (BTKi) has been a major advance in the treatment of chronic lymphocytic leukaemia and related B cell malignancies, but atrial fibrillation (AF) and sudden cardiac deaths are emerging as unique side effects of BTKi. The pathophysiology of cardiac side effects in BTKi treated patients is not known, and an excess of cardiac diseases is not exhibited in the congenital BTK deficiency population. Our group has previously shown in cell models that ibrutinib inhibits the phosphoinositide 3-kinase (PI3K)-AKT pathway in the heart, providing a potential explanation for cardiotoxicity. The PI3K pathway is the major cardioprotective mechanism in the heart under stress conditions, and mice with cardiomyopathy and reduced PI3K can display AF, ventricular arrhythmias and develop severe cardiomyopathy. Concerningly, given the above information, cardiac surveillance has not been routinely incorporated in BTKi trials. We therefore sought to prospectively and systemically assess cardiac function and rhythm in patients commencing BTKi therapy. Method: This is a prospective, multicentre study with the aim of conducting comprehensive cardiac assessment of patients commencing BTKi. This assessment involved 2 domains: 1) detection of subclinical arrhythmias by performing baseline and 3 month follow-up Holter Monitor testing, 2) quantification of subclinical structural changes including dynamic atrial and ventricular contractile function using transthoracic echocardiogram (TTE) and exercise cardiac magnetic resonance imaging (MRI) at baseline and 3 months. The primary outcome assessed was significant reduction in left atrial(LA) volume as a measure of ibrutinib-induced myocardial dysfunction. A 12.5% difference in LA volume is clinically meaningful given that it has been associated with greater AF risk in predisposed individuals. A sample size of 40 provides adequate power of 0.8, α = 0.05 for detecting a 12.5% increase in LA volume from an expected baseline of -18±3. Secondary outcomes measured were: 1) Reduction in ventricular ejection fraction during exercise cardiac MRI, 2) reduction in VO2 max on cardiopulmonary exercise testing. Results: A total number of 40 patients with median age of 68 years were recruited over median follow-up of 12 months (Table 1). 6/40 patients demonstrated significant reduction in left atrial volume at 3 month follow-up. They were not clinically symptomatic and did not have co-existing history of AF. Functional testing with VO2 max on cardiopulmonary exercise testing showed significant reduction in VO2 max in 8/40 patients. There were no significant reduction in ventricular ejection fraction during exercise cardiac MRI. 1/40 patients developed symptomatic AF 257 days after commencing ibrutinib and symptoms were controlled with a beta blocker. He had normal baseline TTE but was found to have enlargement of LA volume during follow-up. One patient with Waldenstrom Macroglobulinameia with normal baseline cardiac testing died from presumed ventricular tachycardia 3 months after commencing trial drug, before reassessment could be conducted. Overall, our data indicated that despite thorough cardiac surveillance, no significant cardiac abnormalities were detected at 3 month follow-up. Conclusion: This prospective and comprehensive cardiac study demonstrated no significant evidence of functional, structural or rhythm abnormalities at 3 month follow-up of patients commencing BTKiinhibitor, as assessed by Holter monitor, exercise cardiac MRI, cardiopulmonary testing and transthoracic echocardiography. Longer follow-up and additional electrophysiological studies may be required to further delineate the cause of BTKi induced cardiotoxicity. Disclosures McMullen: CLL Global Research Funding: Research Funding. Handunnetti:Gilead: Honoraria; Abbvie: Other: Travel Grant. Tam:Abbvie, Janssen: Research Funding; Abbvie, Janssen, Beigene, Roche, Novartis: Honoraria.

Risk stratification in hf with mid-range LVEF: the role of cardiopulmonary exercise testing

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B.M.L Rocha ◽  
G.J Lopes Da Cunha ◽  
P.M.D Lopes ◽  
P.N Freitas ◽  
F Gama ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Exercise Testing ◽  
Primary Endpoint ◽  
Prognostic Significance ◽  
Cardiopulmonary Exercise Testing ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Cardiopulmonary Exercise

Abstract Background Cardiopulmonary exercise testing (CPET) is recommended in the evaluation of selected patients with Heart Failure (HF). Notwithstanding, its prognostic significance has mainly been ascertained in those with left ventricular ejection fraction (LVEF) <40% (i.e., HFrEF). The main goal of our study was to assess the role of CPET in risk stratification of HF with mid-range (40–49%) LVEF (i.e., HFmrEF) compared to HFrEF. Methods We conducted a single-center retrospective study of consecutive patients with HF and LVEF <50% who underwent CPET from 2003–2018. The primary composite endpoint of death, heart transplant or HF hospitalization was assessed. Results Overall, 404 HF patients (mean age 57±11 years, 78.2% male, 55.4% ischemic HF) were included, of whom 321 (79.5%) had HFrEF and 83 (20.5%) HFmrEF. Compared to the former, those with HFmrEF had a significantly higher mean peak oxygen uptake (pVO2) (20.2±6.1 vs 16.1±5.0 mL/kg/min; p<0.001), lower median minute ventilation/carbon dioxide production (VE/VCO2) [35.0 (IQR: 29.1–41.2) vs 39.0 (IQR: 32.0–47.0); p=0.002) and fewer patients with exercise oscillatory ventilation (EOV) (22.0 vs 46.3%; p<0.001). Over a median follow-up of 28.7 (IQR: 13.0–92.3) months, 117 (28.9%) patients died, 53 (13.1%) underwent heart transplantation, and 134 (33.2%) had at least one HF hospitalization. In both HFmrEF and HFrEF, pVO2 <12 mL/kg/min, VE/VCO2 >35 and EOV identified patients at higher risk for events (all p<0.05). In Cox regression multivariate analysis, pVO2 was predictive of the primary endpoint in both HFmrEF and HFrEF (HR per +1 mL/kg/min: 0.81; CI: 0.72–0.92; p=0.001; and HR per +1 mL/kg/min: 0.92; CI: 0.87–0.97; p=0.004), as was EOV (HR: 4.79; CI: 1.41–16.39; p=0.012; and HR: 2.15; CI: 1.51–3.07; p<0.001). VE/VCO2, on the other hand, was predictive of events in HFrEF but not in HFmrEF (HR per unit: 1.03; CI: 1.02–1.05; p<0.001; and HR per unit: 0.99; CI: 0.95–1.03; p=0.512, respectively). ROC curve analysis demonstrated that a pVO2 >16.7 and >15.8 mL/kg/min more accurately identified patients at lower risk for the primary endpoint (NPV: 91.2 and 60.5% for HFmrEF and HFrEF, respectively; both p<0.001). Conclusions CPET is a useful tool in HFmrEF. Both pVO2 and EOV independently predicted the primary endpoint in HFmrEF and HFrEF, contrasting with VE/VCO2, which remained predictive only in latter group. Our findings strengthen the prognostic role of CPET in HF with either reduced or mid-range LVEF. Funding Acknowledgement Type of funding source: None

P3656Fontan operation performed in adult patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Santos Monteiro ◽  
C Cruz Lamas ◽  
M C Terra Cola ◽  
A J Oliveira Monteiro ◽  
M Machado Melo ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Fontan Operation ◽  
Cardiopulmonary Exercise Testing ◽  
Adult Patients ◽  
Venous Blood Flow ◽  
Inhospital Mortality ◽  
Vo2 Max ◽  
Venae Cavae ◽  
The Mean

Abstract Introduction Treatment of patients with univentricular physiology is based on a sequence of palliative surgeries which end with the Fontan operation, when all venous blood flow is diverted to the lungs, bypassing the heart. Most centers advise to complete this process around 4 years of age, and there are few data about the performance of the Fontan operation in adults. Purpose To describe the results of the Fontan surgery when performed in adult patients. Methods A retrospective review of patients submitted to the Fontan operation between 2014 and 2018, with data collection from charts, regarding their pre-operative state and follow up, including improvement in exercise capacity and hemoglobin levels. Results There were 12 patients submitted to the Fontan operation in the study period, with mean age 24±5 years, 8 female and 4 male. Two patients had no previous surgery, 2 only had bandage of the pulmonary artery, 7 had the Glenn surgery and 1 had the Damus and the Glenn surgery. Five patients had tricuspid atresia (TA) with valvular pulmonary stenosis (PS) or atresia, 1 patient had TA alone, 2 had TA with transposition of the great arteries, 1 patient had double inlet left ventricle (LV) with PS, 2 had double inlet LV with coarctation of the aorta, and 1 patient had hypoplastic right heart. One patient had suspected Noonan Syndrome. The patients who did not have Glenn surgery were submitted to connection of superior and inferior venae cavae with the pulmonary artery in the same procedure (4 patients). Seven patients had the fenestrated Fontan procedure. Six patients had a combined operation. Inhospital mortality was 0%. One patient died 4 months after the surgery due to bilateral subdural hematoma. The immediate post operative complications were tachyarrhythmia (2); important bleeding (2); pericardial effusion (4); pleural effusion (7); provisional pacemaker (1); junctional rhythmn (1); temporary hemodialysis (1); infection of the operative wound (1); fungal endocarditis (1); and mild stroke (1). The mean duration of hospitalization was 41.5±18.7 days. The length of hospital stay after surgery was 31.1±16.2 days. The exercise functional capacity improved in all patients. Before surgery there was 1 patient NYHA II that became NYHA I, 10 were NYHA III and became II or I, and 1 patient who was NYHA IV became II. The average oxygen saturation before surgery was 82% ± 8.2% and after was 91.7% ± 4.7%. The mean hemoglobin went from 17.8 g/dL to 13.9 g/dL. Eight patients performed cardiopulmonary exercise testing (CPX) before surgery, 1 patient was Weber B, 4 patients Weber C, 1 D and 1 E. Mean VO2 max was 11.7 ml/kg.min (± 3.69), and the mean slope was 71.8±35.0. Four patients performed CPX after surgery, mean VO2 max was 16.5±7.3, and mean slope was 39±16.6. Mean follow up was 20.3±17.7 months. Conclusions The Fontan operation is safe in adult patients and may still confer them significant benefits.

Abstract 16117: Nonresponders to Cardiac Rehabilitation and Outcomes

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Alban De Schutter ◽  
Carl Lavie ◽  
Eiman Jahangir ◽  
Arthur Menezes ◽  
Homeyar Dinshaw ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Cardiac Rehabilitation ◽  
Exercise Capacity ◽  
Poor Prognosis ◽  
Cardiopulmonary Exercise Testing ◽  
Significant Risk ◽  
Metabolic Equivalent ◽  
Cardiopulmonary Exercise ◽  
Before And After

Introduction: Studies of coronary heart disease (CHD) and cardiac rehabilitation (CR) have traditionally focused on increasing enrollment in CR. We examine here the prognosis of patients who enrolled and completed CR, but saw no significant improvement in exercise capacity [nonresponders (NR)]. Hypothesis: Nonresponders have a poor prognosis. Methods: 780 CHD patients who completed CR with cardiopulmonary exercise testing (CPX) before and after the intervention were divided according to improvement in exercise tolerance (ET; no change or decline vs improvement in metabolic equivalent). Mortality was tracked post CR for all patients; 1 to 161 months of follow-up (mean 6.4 years). Results: 243 (31%) subjects were NR. After adjustment for body mass index, age, gender, ejection fraction and baseline ET, lack of improvement in exercise capacity was associated with a statistically significant 55% increase in mortality (p=0.03; Figure 1). Higher age (OR 1.02; p 0.05) and baseline ET (OR 1.07; p 0.001) was significantly associated with being a NR, but depression, gender and ejection fraction were not significant risk factors. Conclusions: A substantial proportion of subjects referred to CR have no improvement in ET and comparatively demonstrate a poor prognosis. Further investigation into the identifying characteristics of this population is needed to examine if their prognosis can be altered.

scholarly journals Prospective long-term follow-up analysis of the cardiovascular system in marathon runners: study design of the Pro-MagIC study

2020 ◽  
Vol 6 (1) ◽  
pp. e000786
Author(s):  
Julia Schoenfeld ◽  
Michael Johannes Schindler ◽  
Bernhard Haller ◽  
Stefan Holdenrieder ◽  
David Christopher Nieman ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Cardiopulmonary Exercise Testing ◽  
Strenuous Exercise ◽  
Ventricular Ejection Fraction ◽  
Cardiovascular Changes ◽  
Link Type ◽  
Wide Range ◽  
Exercise Induced

IntroductionProlonged strenuous exercise training may result in structural, functional and electrical cardiac remodelling, as well as vascular and myocardial injuries. However, the extent to which high-volume, intense exercise is associated with arrhythmias, myocardial fibrosis, coronary heart disease and pathological alterations of the vasculature remains unknown. In addition, there is no clear consensus on the clinical significance of these exercise-induced changes. Previous studies typically used cross-sectional designs and examined exercise-induced cardiovascular changes in small cohorts of athletes for up to 3–7 days of recovery. Long-term longitudinal studies investigating cardiovascular changes induced by prolonged strenuous exercise in large cohorts of athletes are needed to improve scientific understanding in this area.Methods and analysisIn this prospective observational monocenter study, 277 participants of the Beer, Marathon, Genetics, Inflammation and the Cardiovascular System (Be-MaGIC) study (ClinicalTrials.gov: NCT00933218) will be invited to participate in this 10-year follow-up study. A minimum target sample size of 130 participants will be included in the study. Participating athletes will be examined via the following: anthropometry, resting electrocardiography and echocardiography, blood sampling, retinal vessel diameters, carotid sonography and cardiopulmonary exercise testing, including exercise electrocardiography.DiscussionThis longitudinal study will provide comprehensive data on physiological changes in the cardiovascular system and the development of pathologies after a 10-year period of prolonged and strenuous endurance exercise. Since the participants will have engaged in a wide range of training loads and competitive race events, this study will provide useful risk factor determinants and training load cut-off values. The primary endpoint is the association between the exercise-induced increase in cardiac troponin during the Munich marathon 2009 and the decline in right ventricular ejection fraction over the next 10 years.Trial registration numberNCT04166903.

Carbon dioxide elimination pattern at cardiopulmonary exercise testing in patients with low ejection fraction value

2020 ◽  
Vol 29 (6) ◽  
pp. 647-653
Author(s):  
O. V. Kamenskaya ◽  
I. Yu. Loginova ◽  
A. M. Chernyavskiy ◽  
D. V. Doronin ◽  
V. V. Lomivorotov
Keyword(s):  
Carbon Dioxide ◽  
Ejection Fraction ◽  
Exercise Testing ◽  
Resting State ◽  
Cardiopulmonary Exercise Testing ◽  
Unfavorable Outcome ◽  
Cardiopulmonary Exercise ◽  
Low Ejection Fraction ◽  
Over Time

The objective of this study was to evaluate partial pressure of end tidal carbon dioxide (PetCO2) over time on exertion (E) and its predictive value in evaluation of risk of unfavorable outcome in patients with low ejection fraction (EF) value.Materials and Methods. Patients (n = 53) with pronounced chronic heart failure (CHF), included in heart transplantation waiting list, were enrolled in the prospective study. All patients underwent cardiopulmonary exercise testing (CPET). Mortality or INCOR left ventricle bypass system implantation according to vital indications within 1 year of follow-up were evaluated as an end-point.Results. Patients with CHF and low EF were characterized by low parameters of E tolerance and peak oxygen consumption (10.4 (9.6–11.7) ml/min/kg). The average PetCO2 level by group was 30.4 (28.3–33.0) mm Hg; in 32% of patients this value decreased or did not change in CPET compared with that in resting state. The significant relationship between increased risk of unfavorable outcome within 1 year of follow-up with low baseline PetCO2 value (odds ratio (OR) – 0.22 (0.05–0.87); p = 0.020) and absence of its increment in PE (OR – 0.16 (0.10–0.54); p = 0.009) was observed.Conclusion. The significant predictive factors of unfavorable outcome within 1 year of follow-up in patients with pronounced CHF and low EF include PetCO2 value in resting state, as well as PetCO2 change over time after E challenge.

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