ABSTRACT
Congestive heart failure and subclinical left ventricular systolic dysfunction (LVSD) affect long-term survivors of hematopoietic stem cell transplant (HSCT). Echocardiographic measurements of global longitudinal and circumferential strain have shown promise in identifying subclinical LVSD in cancer survivors. We analyzed echocardiograms in 95 children and young adults with malignancies or bone marrow failure syndromes performed before HSCT and 1-6 years after HSCT. We additionally measured the biomarkers soluble suppression of tumorigenicity-2 (sST-2) and cardiac troponin-I (cTn-I) in the same children through 49 days post HSCT. Ejection fraction (EF) after HSCT was unchanged from baseline (baseline: z-score -0.73 vs long-term follow up: -0.44, P=0.11). Global longitudinal strain was unchanged from baseline (-20.66 vs -20.74%, P=0.90) as was global circumferential strain (-24.3 vs -23.5%, P=0.32). Levels of sST-2 were elevated at all time points compared with baseline samples and cTn-I was elevated at days 14 and 28. Cardiac biomarkers at any time point did not correlate with long-term follow-up EF. In children and young adult survivors of HSCT, EF was unchanged in the first years after HSCT. Elevation in cardiac biomarkers occurring after HSCT suggest subclinical cardiac injury occurs in many patients and long-term monitoring for LVSD should continue.
Subject(s)
Heart Failure , Hematopoietic Stem Cell Transplantation , Stroke Volume , Survivors , Ventricular Dysfunction, Left , Adolescent , Adult , Anemia, Aplastic/blood , Anemia, Aplastic/physiopathology , Anemia, Aplastic/therapy , Bone Marrow Diseases/blood , Bone Marrow Diseases/physiopathology , Bone Marrow Diseases/therapy , Bone Marrow Failure Disorders , Child , Child, Preschool , Female , Follow-Up Studies , Heart Failure/blood , Heart Failure/physiopathology , Hemoglobinuria, Paroxysmal/blood , Hemoglobinuria, Paroxysmal/physiopathology , Hemoglobinuria, Paroxysmal/therapy , Humans , Infant , Interleukin-1 Receptor-Like 1 Protein/blood , Male , Neoplasms/blood , Neoplasms/physiopathology , Neoplasms/therapy , Troponin I/blood , Ventricular Dysfunction, Left/blood , Ventricular Dysfunction, Left/physiopathology , Young AdultABSTRACT
We hypothesized that subclinical cardiac injury in the peri-transplant period is more frequent than currently appreciated in children and young adults. We performed echocardiographic screening on 227 consecutive patients prior to hematopoietic stem cell transplantation (HSCT), and 7, 30 and 100 days after transplant. We measured cardiac biomarkers cardiac troponin-I (cTn-I), and soluble suppressor of tumorigenicity 2 (sST2) prior to transplant, during conditioning, and days +7, +14, +28 and +49 in 26 patients. We subsequently analyzed levels of cTn-I every 48-72 h in 15 consecutive children during conditioning. Thirty-two percent (73/227) of patients had a new abnormality on echocardiogram. New left ventricular systolic dysfunction (LVSD) occurred in 6.2% of subjects and new pericardial effusion in 27.3%. Eight of 227 (3.5%) patients underwent pericardial drain placement, and 5 (2.2%) received medical therapy for clinically occult LVSD. cTn-I was elevated in 53.0% of all samples and sST2 in 38.2%. At least one sample had a detectable cTn-I in 84.6% of patients and an elevated sST2 in 76.9%. Thirteen of fifteen patients monitored frequently during condition had elevation of cTn-I. Echocardiographic and biochemical abnormalities are frequent in the peri-HSCT period. Echocardiogram does not detect all subclinical cardiac injuries that may become clinically relevant over longer periods.
Subject(s)
Heart Injuries/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Adolescent , Adult , Biomarkers/blood , Child , Child, Preschool , Echocardiography , Female , Heart Injuries/diagnosis , Humans , Infant , Interleukin-1 Receptor-Like 1 Protein/blood , Male , Pericardial Effusion/etiology , Time Factors , Troponin I/blood , Ventricular Dysfunction, Left/etiology , Young AdultABSTRACT
Estimating prognosis in sickle cell anemia (SCA) assumes greater importance as intensive treatments, such as hematopoietic SCT (HSCT), are being tested. Here we estimate the mortality risk from the walk-PHaSST (Sildenafil Therapy for Pulmonary Hypertension and Sickle Cell Disease) trial of homozygous SCA patients with suspected pulmonary hypertension (19/468 deaths; 10 centers in the US and UK). Parallel investigations were also undertaken in the Cooperative Study of Sickle Cell Disease (CSCCD) and a contemporary urban sickle cell disease population (Case Western Reserve University-University Hospitals (CWRU-UH), Cleveland, OH, USA). One- and two-value positive predictive values for 2-year mortality (from study entry) are calculated using factors that include demographics, laboratory values and clinical evaluations. We define high-, intermediate-, and low-risk SCA as > 15%, 10-15% and < 10% 2-year mortality. In walk-PHaSST, no single factor qualifies as high-risk SCA, although several combinations of two factors (that is, both age > 35 years and history of chronic transfusion) do. Either elevated white blood cell count (> 13.5 × 10(3) cells/mcL, 7/70 deaths) or elevated Tricuspid Regurgitant Jet Velocity (⩾ 3.0 m/s, 8/67 deaths) was individually associated with intermediate-risk disease, as were many two-factor combinations. N-terminal pro-brain natriuretic peptide > 160 ng/L, lactate dehydrogenase > 600 IU/L, history of chronic transfusion, sepsis or age > 35 years are individually associated with low-risk SCA, as are many two-factor combinations. SCA risk was integrated with estimated donor type-associated risk from HSCT to form 'Traffic Light' eligibility criteria for clinical trials of HSCT. This method is adaptable to evolutions in clinical care.
