Reversible Cardiotoxicity Associated with Carfilzomib Use in Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2126-2126 ◽  
Author(s):  
Tania Jain ◽  
Hemalatha Narayanasamy ◽  
Joseph Mikhael ◽  
Craig B. Reeder ◽  
P. Leif Bergsagel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Cardiac Dysfunction ◽  
Research Funding ◽  
Systolic Dysfunction ◽  
Effective Therapy ◽  
Calcium Isotopes ◽  
History Of ◽  
Initial Drop

Abstract Background: Proteasome inhibition with carfilzomib (CFZ) has shown to be effective therapy in relapsed refractory multiple myeloma (MM).1 Cardiac toxicity induced by CFZ has been reported in a small subset of patients treated in phase 3 clinical trials, including congestive heart failure (CHF) in approximately 2-5% of patients. The natural history or reversibility of cardiac dysfunction with CFZ has not been fully reported. The myocardium constantly contracts in adults and thus, adequate protein metabolism may be essential; and hence, effective proteasome degradation may pose a risk for contractility. Methods and results: We identified 12 patients, who received CFZ at Mayo Clinic in Arizona, and had a drop in ejection fraction (EF) attributable to the use of CFZ. Medical records were reviewed for baseline cardiovascular (CV) risk factors, CV disease reversibility and mortality resulting from CFZ induced cardiac dysfunction. Patients who had a drop in EF attributed to other causes, were not included in this count. The median age at the time of initiation of therapy with CFZ was 62.5 years (range, 55-70 years), median body mass index was 27.65 (range, 21 - 40), with 4 (33%) patients being obese and 6 (50%) in the overweight range. Two (17%) patients had history of coronary artery disease while 9 (75%) had hypertension, and were on medical treatment prior to CFZ initiation. Six (46%) patients had a previous history of CHF. Two of these had symptomatic systolic dysfunction, however at the time of CFZ initiation, EF had improved. The other 4 with prior CHF had sub-normal EFs noted on echocardiograms done prior to initiation of CFZ (median EF of these 4 was 49%). Overall, baseline EF was available for 10 out of these 12 patients and median EF at baseline was 55% (range, 45 - 67%). Other risk factors predisposing to cardiac dysfunction were smoking in 1 patient and history of radiation to the chest in 2 (17%) patients. No patient had received cardiotoxic dose of anthracyclines prior to starting CFZ. Myeloma therapies: All patients had received multiple lines of therapy for MM (median 4, range, 2-7). Ten (83%) patients had previous received bortezomib and 10 (83%) had received autologous stem cell transplant. Cardiac events and CFZ use: Median duration of CFZ therapy received prior to documented systolic dysfunction was 4 months (range, 0.5 - 20 months), with 3 episodes happening with less than one month of total CFZ therapy. Five out of the 12 (42%) patients had previously discontinued CFZ for other reasons when the systolic dysfunction was noted. However they were included since CHF occurred shortly after treatment (median of 2 months, range, 0.5 - 3). The median drop in EF was 22% (range, 9 - 45%). Recovery/ outcomes: Follow-up echocardiograms were available in 8 patients and all of these showed some improvement in EF (table 1). Median improvement in EF noted by the time of last follow up was 16% (range, 7-30%). Median best EF noted after the initial drop was 48% (range, 35 - 67%). Two patients never discontinued CFZ and EF improved spontaneously, to 67% and 64% respectively, after an initial drop. Another patient was rechallenged with CFZ due to progression of MM, 8 months after initial discontinuation, and did not have recurrence of systolic dysfunction. No patients succumbed to CHF. Six (50%) out of these 12 patients had died by the time of last follow-up. Cause of death was progressive MM in 4 (67%) and sepsis secondary to immunosuppression resulting from chemotherapy in 2 (33%). Conclusions: Our data, although with limited number of patients, suggests using caution when treating patients who have underlying cardiac risk factors with CFZ. Nevertheless, the cardiotoxicity was mostly reversible, with the minimal EF after recovery of 35%. In the setting of a life threatening malignancy, the impact and reversibility of cardiotoxicity needs to be understood so as not to prevent the utilization of otherwise effective therapy such as CFZ. Larger studies are needed to confirm these findings. References: 1. Stewart et al. Carfilzomib, Lenalidomide and Dexamethasone for relapsed multiple myeloma. NEJM 2015;372:142-52. Disclosures Mikhael: Celgene: Research Funding; Abbvie: Research Funding; Sanofi: Research Funding; Onyx: Research Funding. Reeder:Novartis, Millennium, BMS and Celgene: Research Funding. Bergsagel:Amgen, BMS, Novartis, Incyte: Consultancy; Novartis: Research Funding. Fonseca:Millennium, a Takeda Company: Consultancy; Sanofi: Consultancy; AMGEN: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Millennium, a Takeda Company: Consultancy; Novartis: Consultancy; AMGEN: Consultancy; Janssen: Consultancy; Janssen: Consultancy; BMS: Consultancy; Millennium, a Takeda Company: Consultancy; Bayer: Consultancy; Millennium, a Takeda Company: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Celgene: Consultancy; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; AMGEN: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Celgene: Consultancy; BMS: Consultancy; Bayer: Consultancy; Novartis: Consultancy; Sanofi: Consultancy; AMGEN: Consultancy.

scholarly journals Incidence, Management and Outcomes of Arterial and Venous Thromboembolism after Chimeric Antigen Receptor Modified T Cells for B-Cell Lymphoma and Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-7
Author(s):  
Anna L. Parks ◽  
Swetha Kambhampati ◽  
Bita Fakhri ◽  
Charalambos Andreadis ◽  
Lissa Gray ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
T Cells ◽  
Venous Thromboembolism ◽  
B Cell ◽  
Research Funding ◽  
Vte Prophylaxis ◽  
Therapeutic Anticoagulation ◽  
Car T ◽  
History Of

Introduction: Chimeric antigen receptor modified T Cell (CAR-T) therapy is a rapidly developing treatment for patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). Although this population is at high risk for thrombosis, there are few data about rates of venous thromboembolism (VTE) and arterial thromboembolism (ATE) with CAR-T. Additionally, treatment with anticoagulation is complicated because of the prevalence of thrombocytopenia following CAR-T. Our goal was to determine the incidence, associated risk factors, management and outcomes of VTE and ATE in the 60 days following CAR-T therapy. Methods: We performed a single-center, retrospective cohort study of all patients who received inpatient CAR-T cells at UCSF Medical Center between January 2018 and May 2020 for R/R NHL or MM as standard-of-care or on a clinical trial. The outcomes of incident VTE and ATE were identified by ICD-10 codes and medical record review. Patient characteristics, pre-existing thrombosis risk factors, laboratory results, medications, and major or clinically relevant non-major bleeding or recurrent thrombotic complications were obtained through chart review. We used descriptive statistics to delineate risk factors, incidence, management and outcomes of thrombotic events. Results: Ninety-one patients who underwent CAR-T therapy were included in the analysis, 37 with NHL and 54 with MM. For NHL, mean age was 63 (range 38-82), and 41% were women. For MM, mean age was 62 (range 33-77), and 50% were women. Patients with NHL were treated with either investigational or Federal Drug Administration-approved CD19-directed therapies, and patients with MM were treated with a variety of investigational B-cell maturation antigen-directed (BCMA) therapies. For thrombotic risk factors, 13% of patients with NHL had a history of VTE, 3% had a history of ATE, 27% had a BMI ≥30, 59% had a recent procedure including central venous catheter (CVC) placement, 14% had an intensive care unit (ICU) stay, and 22% had an infectious complication in the 30 days pre- or post-CAR-T. Forty-one percent of patients with NHL had neurotoxicity of any grade, and 59% had CRS of any grade. At 30 days, 57% had a complete response, 41% had a partial response, 3% had stable disease. For MM, 6% of patients had a pre-existing history of VTE, 2% had a history of ATE, 19% had a BMI ≥30, 96% had a recent procedure, 11% had an ICU stay and 19% had an infection. Seventeen percent had neurotoxicity, and 85% had CRS. Thirty-two percent of patients with NHL and 48% with MM received pharmacologic VTE prophylaxis while undergoing CAR-T. For those who did not receive VTE prophylaxis, thrombocytopenia was the reason for holding prophylaxis, which occurred in 51% and 50% of NHL and MM patients, respectively. In the 60 days post-CAR-T, 4 (11%) patients with NHL were diagnosed with VTE-3 pulmonary embolism (PE) and 1 lower extremity deep vein thrombosis (DVT) associated with a previously placed inferior vena cava filter. Four (7%) patients with MM were diagnosed with VTE-1 PE and 3 upper extremity DVTs associated with CVCs. Five out of these 8 (63%) patients had symptomatic VTE, while the remainder were incidental on PETCT. Mean time from CAR-T infusion to VTE diagnosis was 20 days (range 6-39 days). There were no documented ATEs. Six out of 8 (75%) were treated with therapeutic anticoagulation. Of those who were anticoagulated, 4 patients received direct oral anticoagulants and 2 received low-molecular-weight-heparin. Duration was 3 months in 3 patients, 11 days in 1, 150 days in 1, and indefinitely in 1 with atrial fibrillation. Among all 8 patients with VTE, there were no bleeding events or recurrent thromboses regardless of whether or not they received anticoagulation. Discussion: In this cohort of patients with R/R NHL or MM who received either CD19- or BCMA-directed therapies, almost 1 in 10 developed VTE in the 60 days post-CAR-T. This occurred in the context of a high prevalence of risk factors for thrombosis and low rates of pharmacologic prophylaxis. Among those who developed VTE, the majority were treated with therapeutic anticoagulation for at least 3 months, without documented bleeding or recurrent VTE. Our findings provide crucial information on a common complication that can inform patients, clinicians and researchers and should be expanded upon in larger, prospective studies to identify optimal preventive and therapeutic strategies. Disclosures Fakhri: University of California San Francisco: Current Employment. Andreadis:Jazz Pharmaceuticals: Honoraria; Karyopharm: Honoraria; Incyte: Consultancy; Merck: Research Funding; Gilead/Kite: Consultancy; Novartis: Research Funding; BMS/Celgene/Juno: Honoraria, Research Funding; Genentech: Consultancy, Current equity holder in publicly-traded company. Wong:Janssen: Research Funding; Amgen: Consultancy; Roche: Research Funding; Fortis: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; GSK: Research Funding. Shah:BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy.

scholarly journals Risk Factors of Thrombosis in Adults with Primary Immune Thrombocytopenia. a French Nationwide Cohort Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3745-3745
Author(s):  
Guillaume Moulis ◽  
Bérangère Baricault ◽  
Charlotta Ekstrand ◽  
Margaux Lafaurie ◽  
Christian Fynbo Christiansen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Additional Risk Factor ◽  
Discharge Diagnosis ◽  
Additional Risk ◽  
Icd 10 ◽  
History Of

Abstract Background: Immune thrombocytopenia (ITP) is associated with an increased risk of venous and arterial thrombosis (VT and AT, respectively) as compared with the general population. However, the impact of thrombosis risk factors and of ITP treatments, particularly of thrombopoietin-receptor agonists (TPORAs), is not well known in the routine clinical practice. Aim: The objective of this cohort study was to assess the risk factors of VT and AT in adults with primary ITP, including ITP treatments. Methods: The population was the cohort of all incident primary ITP adults in France during 2009-2015 built within the national health insurance database (French Adult Immune Thrombocytopenia - FAITH - cohort; NCT03429660). Incident ITP patients were identified using a validated algorithm combining drug exposures and diagnosis codes according to the international classification of diseases, version 10 (ICD-10). Risks of first hospitalization with a validated primary discharge diagnosis code of VT and AT (coded with the ICD-10) were assessed separately. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Variables included in multivariable models were: age, sex, history of AT and of VT, diabetes, cardiovascular disease, chronic kidney disease, chronic liver disease, cancer; exposures to antihypertensive, lipid-lowering, antiplatelet, anticoagulant drugs and ITP treatments including splenectomy were modeled as time-dependent variables. Results: The cohort included 7225 adult patient with incident primary ITP: 3807 (52.7%) were ≥60 year-old, 3199 (44.3%) were males, 692 (9.6%) had a history of cardiovascular disease, 937 (13.0%) had diabetes. During the follow-up, 5737 (79.4%) were exposed to corticosteroids, 3364 (46.6%) to intravenous immunoglobulin (IVIg), 995 (13.8%) to TPORAs, and 755 (10.4%) were splenectomized. During the follow-up (23 852 patient-years in total; mean follow-up: 39.5 months), 174 patients had a hospitalization with a primary discharge diagnosis of VT and 333 of AT, leading to incidences of 7.4 (95% CI: 6.4-8.6) and 14.4 (95% CI:12.9-16.0)/1000 patient-years, respectively. In multivariable Cox models, the most important risk factors for VT were higher age (≥60 years vs. <40 years: HR: 2.22, 95% CI: 1.39-3.53), a history of VT (HR: 4.38, 95% CI: 1.07-18.02), splenectomy (HR: 3.22, 95% CI: 2.06-3.03), exposure to IVIg (HR: 2.30, 95% CI: 1.41-3.75), corticosteroids (HR: 3.29, 95% CI: 2.39-4.53) and TPORAs (HR: 3.16, 95% CI: 2.04-4.88). All classical baseline cardiovascular risk factors listed above as covariables were associated with the risk of AT. The HRs for AT were 0.97 (95% CI: 0.59-1.61) for splenectomy, 1.05 (95% CI: 0.80-1.40) for corticosteroids, 2.35 (95%CI: 1.58-3.50) for IVIg, 1.25 (95%CI: 0.46-3.37) for danazol and 1.31 (95%CI: 0.84-2.06) for TPORAs. It is of note that among the 25 patients who had a VT while treated by TPORA, 18 (72.0%) were>50 year-old, 14 (56.0%) were women, 6 (24.0%) were splenectomized, 9 (36.0%) were concomitantly exposed to corticosteroids and 3 (12.0%) to IVIg; only 3 women aged<50 years had no additional risk factor. Among the 21 patients who had an AT while treated by TPORA, 18 (85.7%) were>50 year-old, 15 (71.4%) were men, 8 (38.1%) were splenectomized, 5 (23.8%) were concomitantly exposed to corticosteroids and one to IVIg; only one 48-year-old man had no additional risk factor for AT. Conclusions: Baseline risk factors for VT and AT were highly associated with VT and AT occurrence in adults with primary ITP. Splenectomy, corticosteroids, IVIg and TPORAs were risk factors for VT. Most patients who had a thrombosis while treated by TPORA had additional risk factors. These findings help choosing a tailored treatment strategy for a given patient depending on his/her risk profile for VT and AT. Disclosures Christiansen: Amgen: Research Funding. Bahmanyar:Amgen: Research Funding.

scholarly journals Analyzing Risk of Infection with Anti-CD38 Monoclonal Antibody Therapy for Patients with Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 49-49
Author(s):  
Augustine Hong ◽  
Augusta Eduafo ◽  
Hannah Schmikla ◽  
George Brown ◽  
Gayathri Ravi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Research Funding ◽  
Advisory Board ◽  
Risk Of Infection ◽  
Factors Associated ◽  
History Of ◽  
Grade 3 ◽  
Line Of Therapy ◽  
Significant Factors

Monoclonal antibodies targeting CD38 are emerging as a mainstay of therapy for Multiple Myeloma (MM) in the relapse setting as well as upfront. These antibodies not only target CD38 on myeloma cells inducing anti-tumor pleiotropic effects, they also influence normal CD38-expressing cells, including normal plasma cells, natural killer cells and immunosuppressive regulatory cells (van de Donk et al , 2018). These cells play a key role in innate as well as humoral immunity and provide protection against a variety of infectious insults; hence, their depletion in MM patients (pts) can be expected to have deleterious immunological effects due to the dismantling of an effective immune responses in a population already strained by dysfunctional immunity. While it has been previously shown that NK cells decline with exposure to daratumumab (DARA) (Casneuf et al , 2017), its clinical impact on the incidence of infection has yet to be elucidated because clinical trials have shown conflicting results, while POLLUX and CASTOR trials showed generally similar rates of grade 3 or 4 infections (28·3% vs. 22·8% and 21·4% vs. 19·0%, respectively, the ALCYONE trial, reported that grade 3-4 infections were higher in the DARA arm (23·1% vs. 14·7%). Here, we aim to explore the impact of different risk factors on infection during DARA therapy. Methods: We retrospectively reviewed patient records who received DARA-containing regimens for MM between Jan 2016 and Jan 2020. The history of infection, prior therapies, rate of infection during therapy with DARA, hospitalizations, baseline and nadir absolute counts of lymphocyte, monocyte and neutrophil population were extracted. Pts who had less than 1 month of DARA were excluded. Survival was measured from time of DARA start. Survival distribution was estimated using Kaplan-Meier methods and differences of OS, PFS between groups was examined by Wilcoxon test. The effect of treatment on OS and PFS was estimated using a Cox model after controlling for the effects of different variables. Results: Of 123 pts reviewed, median line of therapy was 3 (range: 0-9). Median time from diagnosis was 52 months (range: 0- 232 months). 43 pts (35%) were Black and 77 (63%) Caucasian. Median age was 70 (range 34-94 y/o). 86 (70%) were IgG, 24 were IgA (20%) and 10 light chain myeloma (10%). 24 (20%) had stage I, 37 (30%) had stage II and 61 (50%) had ISS stage III. 66 (53%) pts had transplant as prior therapy and the rest did not undergo transplant. 29 (24%) pts had DARA as a single agent, 66 (53%) in combination with IMiDs and 28 (23%) pts in combination with PI. Median duration of therapy was 133 days (range 30-1245 days). Median ANC 1243 /ml (range: 420-1120). Median ALC 710 /mL (170-8020). Median AMC was 455 /mL (0-2300). 31 pts had history of prior infections and the rest did not. 39 pts had infection during DARA. Overall, there were 125 hospital admission encounters for whole cohort occurred in 36% of cases, more than half of them (55%) were attributable to an infectious process. Bacterial pathogens accounted for the majority of infection. Pts with infection during DARA therapy had statistically significant nadir ALC (median 560 /ml) compared to pts without any infection. The univariate analysis showed age, history of infection, nadir ALC less than 600/ml and number of prior line of therapy as significant factors associated with infection rate during DARA therapy. Multivariate analysis after controlling for these factors shows only Low nadir ALC less than 600 /ml, hazard ratio (HR): 2.15, 95% confidence interval (CI): 1.19-3.76, and history of infection, HR: 1.87, 95% CI: 1.11-2.92, stands out as statistically significant factor. The whole cohort were divided based on ALC&lt;600 during the therapy or history of previous infection; the group with none of these two risk factors was assigned as low risk, the group with either of those as intermediate risk and the pts with both risk factor were characterized as high-risk group (Figure-1). Conclusion: Here we showed that infections is frequent among MM pts treated with DARA-containing regimen and assessed risk factors associated infection during DARA therapy. Dropping ALC and history of prior infection are significant factors associated with higher risk of infection during DARA therapy. These finding suggests vigilance for, and identification of risk factor are warranted for treating MM patient with DARA. The risk model is warranted to be examined in a prospective study. Disclosures de Lima: Pfizer: Other: Personal fees, advisory board, Research Funding; BMS: Other: Personal Fees, advisory board; Incyte: Other: Personal Fees, advisory board; Kadmon: Other: Personal Fees, Advisory board; Celgene: Research Funding. Malek:Cumberland: Research Funding; Takeda: Other: Advisory board , Speakers Bureau; Bluespark: Research Funding; Sanofi: Other: Advisory board; Clegene: Other: Advisory board , Speakers Bureau; Amgen: Honoraria; Medpacto: Research Funding; Janssen: Other: Advisory board, Speakers Bureau.

Incidence, Risk Factors and Outcome of Late Onset Noninfectious Pulmonary Complications after Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective Cohort Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4562-4562
Author(s):  
Anne Bergeron ◽  
Sylvie Chevret ◽  
Regis Peffault De La Tour ◽  
Karine Chagnon ◽  
Cedric De Bazelaire ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Research Funding ◽  
Late Onset ◽  
Cox Model ◽  
Pulmonary Complications ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
History Of

Abstract Introduction: Late onset noninfectious pulmonary complications (LONIPCs) occurring beyond the third month following allogeneic hematopoietic stem cell transplantation (HSCT) are various and are associated with a poor outcome. Bronchiolitis obliterans (BO) is the most frequent LONIPC. Available epidemiological data are conflicting and exclusively come from retrospective studies. Methods: We conducted a prospective observational cohort study where all consecutive patients who were scheduled to receive an allogeneic HSCT between January, 31, 2006 and December, 31, 2008 at the university-teaching Saint Louis Hospital (Paris, France) were prospectively screened for inclusion in the study. Those allogeneic HSCT recipients surviving at day 100 were included in the cohort. They were followed-up for at least three years after HSCT. Clinical outcomes were the 3-year incidence and mortality of LONIPC, and the identification of early risk factors for LONIPC and specifically BO. This study is registered with ClinicalTrials.gov, number NCT 01219972. Results: 198 patients were included after a median of 101 [IQR: 99-106] days following HSCT, from a total of 243 screened patients. The actual median follow up of the 198 included patients was 72.3 months [IQR: 15.2-88.5]. 68 patients died within the first 36 months resulting in a 3-year overall survival after inclusion of 65.4% (95%CI: 59.1-72.4%). Fifty five episodes of LONIPC were diagnosed in 43 patients. These 55 LONIPC were diagnosed as BO (n=22), interstitial lung disease (n=12), and others. Ten patients had more than one LONIPC during the follow-up. At 36 months after inclusion, the estimated cumulative incidence of LONIPC was 19.8% (95%CI: 14.2-25.3%). The 36 months cumulative incidence of BOS was 10.7%, (95%CI: 6.3-15.1%). 18 patients with a LONIPC died during the follow up with an estimated median survival of 78.5 months (95%CI: 20.0-not reached) after the diagnosis of LONIPC. The occurrence of LONIPC was associated with an increased hazard of death (HR=2.18, 95%CI= 1.14; 4.15; p= 0.0181). Based on a multivariable Cox model, a chest irradiation prior to HSCT, a history of pneumonia within the 100 days post HSCT and a low FEF 25-75 at day 100 were associated with the development of LONIPC. The use of PBSC was predictive for BOS based on a multivariable Cox model both after multiple imputation and on the complete cases whereas both a history of post transplantation pneumonia and bronchial abnormalities on CT scan at day 100 were also identified as predictive factors after multiple imputation and a 10% FEV1 decline from baseline to day 100 was a predictive factor for BOS on the complete cases. Conclusion: our data give clues to identify high-risk patients for developing LONIPC/BO. These patients should be targeted for close monitoring, and so offer earlier treatment of LONIPC or prophylactic treatment to improve the outcome. Funding: The study was supported by an institutional grant from the French Ministry of Health (CRC 04118). Disclosures Peffault De La Tour: PFIZER: Consultancy, Honoraria, Research Funding; ALEXION: Consultancy, Honoraria, Research Funding; NOVARTIS: Consultancy, Honoraria, Research Funding.

scholarly journals Risk Factors Associated with Development of Extramedullary Disease in Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5596-5596
Author(s):  
Martin Stork ◽  
Sabina Sevcikova ◽  
Marta Krejci ◽  
Zdenek Adam ◽  
Viera Sandecka ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Board Of Directors ◽  
Research Funding ◽  
Poor Prognosis ◽  
First Line ◽  
Advisory Committees ◽  
Line Of Therapy

Abstract Background Multiple myeloma (MM) is the second most common hematological malignancy characterized by plasma cell (PC) infiltration of the bone marrow. Unfortunately, better imaging techniques convey multiple reports about increased incidence of the so-called extramedullary disease of MM (EM), an aggressive, mostly resistant entity with poor prognosis for patients. EM probably develops because of 'bone marrow escape' of PC subclone that migrates out of the BM infiltrating soft tissues losing dependence on the BM microenvironment, either partially or completely. There are two types of EM - primary, found at the time of MM diagnosis, and secondary, found at the time of MM relapse. However, there are very few reports about EM. Aims This study aims to analyze risk factors connected to EM development. Methods Data from the Registry of Monoclonal Gammopathies (RMG) were analyzed. The RMG represents a database for collection of clinical data concerning diagnosis, treatment and follow-up of Czech MM and other monoclonal gammopathies patients. In total, data of 4985 MM patients were collected into the RMG database between 2007 and June 2017. Our analysis compared patients who developed EM at initiation of first or higher line of therapy with patients without EM during at least 5-year-long follow-up (patients who died earlier included). Logistic regression analysis was used to assess the association of baseline characteristics at MM diagnosis with EM occurrence at first line and relapse, respectively. Results In total, 4985 MM patients data were collected into the RMG database between 2007 and 2017. Patients were treated with bortezomib, lenalidomide, thalidomide, pomalidomide, ixazomib and daratumumab. Regardless of treatment, EM patients responded worse than MM patients did to any form of treatment. While primary EM patients had similar PFS as MM patients, OS was significantly worse (48.7 vs 60.6 months, resp.). Secondary EM patients did even worse, with PFS 8.7 months and OS 23.8 months only. We found 543 MM patients (10.9%) who developed EM during the entire follow-up. Out of these EM patients, we found 309 patients who were diagnosed with primary EM at initiation of first line of therapy. At initiation of 2nd line of treatment, we found 111 secondary EM patients. At 3rd, 4th and 5th, we found 61, 39 and 23 EM patients, resp. Finally, 309 patients who developed EM at initiation of 1st line and 234 patients who developed EM at initiation of further treatments were compared to 2092 patients who did not develop EM during the entire course of the disease. Overall, occurrence of EM at 1st or higher lines of treatment was associated with younger age, male sex, low ISS, D-S substage A, low B2 microglobulin, low creatinine, high hemoglobin, elevated thrombocytes, other types of M-Ig than IgG and presence of bone lesions. For EM cases found only at initiation of 1st line (primary EM), we found association with high ECOG status, low LDH, low M-protein quantity and low % of plasma cells infiltration in the bone marrow. For EM cases found at MM relapse (secondary EM), we found association with high D-S stage, high LDH, high CRP, high Ca, del13q and gain1q. Conclusion EM remains an aggressive disease with poor prognosis regardless of use of novel drugs. Surprisingly, in our group of patients, most EM disease developed early in the course of the disease - more than 60% at first relapse. We analyzed risk factors connected to development of EM and found that LDH, hemoglobin, thrombocytes and M-Ig status were associated with EM development. We suggest that in such patients, PET/CT or whole body MRI should be performed regularly to ensure early detection of EM. Grant support: AZV 17-29343A. Disclosures Maisnar: BMS: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hajek:Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

scholarly journals High-Oxygen-Affinity Hemoglobinopathy-Associated Erythrocytosis: Clinical Outcomes and Impact of Therapy in 41 Cases

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1492-1492
Author(s):  
Naseema Gangat ◽  
Jennifer L Oliveira ◽  
James D Hoyer ◽  
Mrinal M. Patnaik ◽  
Animesh Pardanani ◽  
...  
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Research Funding ◽  
Oxygen Affinity ◽  
Aspirin Therapy ◽  
High Oxygen ◽  
History Of ◽  
High Oxygen Affinity ◽  
Systemic Anticoagulation

Abstract Background Approximately 100 high oxygen affinity (HOA) hemoglobin (Hgb) variants have been reported to date; review of the Mayo Clinic laboratory database (1974-2018) identified 80 distinct variants including 12 novel variants (60 β, 20 α). One-third of HOA Hgb variants result in secondary erythrocytosis, provoking concern regarding increased risk for thrombosis. Current management guidelines lack supporting evidence regarding the utilization of phlebotomy in such cases. We describe presenting features, treatment strategies and follow-up events involving 41 consecutive cases seen at our institution. Methods Study patients were recruited from our institutional laboratory and clinical Hgb variant database. Initial evaluation for Hgb variants was conducted by capillary electrophoresis and high-performance liquid chromatography. Additional testing which included mass spectrometry and isoelectric focusing was pursued as necessary. Since the majority of variants were difficult to identify by protein studies, DNA sequencing of HBB, or HBA1, HBA2 genes was performed for confirmation. Symptoms and thrombosis, both at presentation and during follow up, were recorded. Therapeutic interventions were based on physician discretion and mostly included phlebotomy and/or aspirin therapy; a careful response assessment was performed to determine the impact of each therapy on symptoms and/or thrombosis. Results A total of 41 patients with HOA Hgb variant-associated erythrocytosis (median age 39 years, range 1-81; 54% males) were seen at our institution between January 1973 and February 2020. The majority of the patients carried β-chain variants (n=34; 83%), common variants being Hgb Malmo (n=13), Olympia (n=4), San Diego (n=3), and Wood (n=2). Among the 7 patients with α-chain variants, Hgb Dallas was the most frequent (n=4). Presenting median values (range) for Hgb/Hct, serum erythropoietin and p50 were 18 g/dl/52.9%(16-21.9g/dl/48-66%) 10.4 mIU (4-36.3 mIU), and 20 mmHg (12-25 mmHg), respectively. Family history was documented in 34 patients, of which 24 (71%) reported one or more affected family members. Family history of thrombosis was documented in 7 patients (21%). CV risk factors were present in half of the patients; by contrast, history of thrombosis prior to or at diagnosis was documented in only two patients (5%). Of 23 pregnancies reported in 12 women, live birth rate was 78% (n=18); none of the fetal losses were attributed to erythrocytosis. Active therapies at the time of initial referral consisted of phlebotomy (n=12), aspirin (n=11) and systemic anticoagulation (n=1). At a median follow-up of 10 years (range; 0.04-44), 23 patients had reported one or more symptoms, attributed to hyper-viscosity, such as headaches, fatigue, and lightheadedness. Neither Hct level at diagnosis (p=0.32) nor phlebotomy (p=0.16; 75% patients on vs 52% not on phlebotomy) or aspirin therapy (p=0.75; 55% patients on vs 60% not on aspirin) appeared to influence the occurrence of symptoms. Phlebotomy relieved symptoms in 7 (42%) symptomatic patients; however, 7 (30%) of 23 patients on phlebotomy reported one or more adverse symptoms that were attributed to phlebotomy-induced iron deficiency. Ten patients (24%) experienced thrombosis prior to or following diagnosis: 6 arterial and 4 venous. Median age at thrombotic event was 51 years and median hematocrit 52%; active therapies at the time of event included phlebotomy in 5 patients, aspirin in 4, and systemic anticoagulation in 2. Hct level at diagnosis (p=0.10) or the time of event (p=0.67) did not correlate with occurrence of thrombosis. Additionally, the incidence of thrombosis was no different among patients receiving or not receiving phlebotomy (5/23(22%) vs 5/18(28%), respectively; p=0.66). The presence of CV risk factors was predictive of arterial events (p=0.002). Two of the 4 venous events developed in the context of concomitant thrombophilia. Eight patients (20%), median age 28 years, without CV risk factors, were observed without therapy for a median of 9.5 years (range; 0.4-21) and have not experienced any thrombosis to date. Conclusions We found no association between Hct level and either thrombotic or non-thrombotic symptoms in HOA hemoglobinopathy-associated erythrocytosis; furthermore, implementation of aggressive phlebotomy did not provide a clear benefit with respect to thrombosis risk reduction. Figure 1 Figure 1. Disclosures Patnaik: StemLine: Research Funding; Kura Oncology: Research Funding.

scholarly journals Renal Function and Risk of Arterial Thrombotic Events in Patients Positive for Lupus Anticoagulant

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 290-290
Author(s):  
Meaghan Colling ◽  
Florian Posch ◽  
Silvia Koder ◽  
Peter Quehenberger ◽  
Cihan Ay ◽  
...  
Keyword(s):  
Risk Factors ◽  
Renal Function ◽  
Lupus Anticoagulant ◽  
Research Funding ◽  
Prior History ◽  
Thromboembolic Events ◽  
Active Smoking ◽  
History Of ◽  
Prospective Risk

Abstract Background: Patients with lupus anticoagulant (LA) are at risk for arterial and venous thromboembolic events. Recent work suggests that LA positive patients who experience thrombotic events in different vascular beds constitute distinct subgroups. To risk stratify patients, further work is needed to better characterize predictors for thromboembolic events in these subgroups. Aims: The aim of this study was to identify baseline characteristics and laboratory parameters associated with the development of arterial or venous thrombotic events. Methods: Patients with at least 2 previous positive LA tests were serially monitored for thrombotic events within the prospective Vienna Lupus Anticoagulant and Thrombosis Study (LATS). Patients without clinical follow-up were excluded from this analysis. Statistical analysis was performed with RStudio (Version 1.1.442). Results: One-hundred-eighty-seven patients were followed (Table 1) for a median of 11.4 years and 1865 follow-up visits (median visit/patient=9). Fifty-seven prospective thrombotic events (TE), including 27 arterial thrombotic events (ATE) and 30 venous thrombotic events (VTE), were observed. This corresponded to 10-year prospective ATE, VTE and overall thrombosis incidences of 13.9% [95%CI: 8.3, 19.6], 18.8% [12.2, 25.4], and 32.0% [24.1, 39.8], respectively. (Figure 1). Thirty-seven of the 57 events occurred in patients with a prior history of thrombosis ("recurrent thrombosis"). In univariable competing risk analysis, age (subdistribution hazard ratio (SHR) = 1.02, 95% CI: 1.00-1.05, p=0.019), body mass index (BMI, 1.05, 1.00-1.11, p=0.042), history of ATE (3.14, 1.45-6.81, p=0.0038), active smoking (2.16, 1.00-4.62, p=0.049), diabetes (4.16, 1.47-11.8, p=0.0073), VKA use at baseline (0.42, 0.18-0.97, p=0.042), aCL IgM positivity (2.48, 1.05-5.83, p=0.038), aβ 2GPI IgM positivity (2.86, 1.18-6.93, p=0.020), mean platelet volume (1.17, 1.06- 1.30, p=0.0024), creatinine (3.76, 1.32- 10.7, p=0.013), and estimate glomerular filtration rate (eGFR, 0.98, 0.96-0.99, p=0.0011) were associated with prospective risk of ATE (Table 2). Conversely, the prospective risk of VTE was univariably associated only with prior history of VTE (3.26, 1.40-7.68, p=0.0061). After adjusting for traditional arterial thrombotic risk factors (age, sex, BMI, active smoking, diabetes,), history of ATE (SHR = 3.97, 95% CI: 1.71-9.025, p=0.0014), prior history of both ATE and VTE (3.87, 1.06-14.16, p=0.041), creatinine (3.93, 1.22-12.66, p=0.022), and eGFR (CKD-EPI, 0.96, 0.96-0.99, p=0.0037) remained independently associated with prospective risk of ATE (Table 2). In detail, the 10-year cumulative risk of ATE was 24.9% [95%CI: 8.8, 41.0], 15.0% [5.8, 24.2], and 6.7% [2.2, 13.8] in patients with a baseline eGFR less than 60 mL/min/1.73m 2, between 60 and 89 mL/min/1.73m 2, and greater than or equal to 90 mL/min/1.73m 2, respectively (Gray's test, p=0.019, Figure 2). Conclusion: Approximately 14% of patients persistently positive for LA experienced an ATE over 10 years. After adjusting for traditional arterial risk factors, decreased renal function was associated with an increased prospective risk of ATE. Notably, decreased renal function was not associated with development of VTE and the association with ATE was also independent of underlying SLE, LLD, or rheumatic disease (data not shown). Clinically, LA positive patients with decreased renal function may represent a subgroup that might benefit from more aggressive anti-thrombotic therapy or anti-thrombotic prophylaxis. Figure 1 Figure 1. Disclosures Pabinger: Bayer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Daiichi Sanchyo: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; NovoNordisk: Consultancy, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding.

scholarly journals Younger Age at Diagnosis Is Associated with an Increased Risk of Venous Thromboembolism in Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1223-1223 ◽  
Author(s):  
Aisling Barrett ◽  
John Quinn ◽  
Siobhan Glavey ◽  
Jeremy Sargent ◽  
Michelle Lavin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Logistic Regression ◽  
Venous Thromboembolism ◽  
Research Funding ◽  
P Value ◽  
Younger Age ◽  
Increased Risk ◽  
The Mean

Abstract Introduction Multiple Myeloma (MM) patients are at an approximately 9-fold increased risk of developing venous thromboembolism (VTE), with risk being highest in the first year following diagnosis1. VTE is associated with significant morbidity and negatively influences survival in MM2. Although the Khorana score has been shown to predict rate of thrombosis in solid tumors, the validity of this score in haematological malignancies has yet to be assessed. Given the elevated rates of VTE in these conditions, in particular MM, clinically relevant risk prediction scores are essential. Additionally, data from the MRC-XI trial indicates that standard thromboprophylaxis may not prevent VTEs in MM3. Therefore identification of risk factors for MM-VTE are required to improve our understanding of the pathophysiology of thrombosis and to develop risk-adapted clinical practice guidelines. Through interrogation of an extensive clinical database we sought to identify factors predictive for VTE in our MM population. Methods We performed a retrospective cohort study of all newly diagnosed MM patients at our centre from 2001-2017. Patient medical records were reviewed for clinical and laboratory data including FBC parameters, beta-2-microglobulin, paraprotein and serum free light chain on the day of diagnosis, to minimize steroid effect. All VTE events were recorded, along with MM treatment regimen and thromboprophylaxis at time of event. History of thrombosis was defined as occurring within 6 month prior to, or following a diagnosis of MM. Patients with MGUS or smoldering MM were excluded. Statistical analysis including logistic regression and cox proportional hazard modelling was performed using SPSS (IBM Analytics, USA). A comparison of mortality was also performed between age matched cases with VTE and controls without VTE. Results Over a period of 17 years, 266 patients were diagnosed with myeloma, of which 34 (12.7%) developed VTE following MM diagnosis or within the preceding six months. The mean age of the VTE cohort at MM diagnosis was younger than the mean age of the non-VTE cohort (62.5 years vs. 68.6 years). Pulmonary embolisms and deep vein thromboses were equally represented (44% and 56% respectively) and additional risk factors for thrombosis were present in 46% of patients, not related to MM therapy. Of the patients on immunomodulatory drugs or corticosteroids at time of VTE, all were receiving thromboprophylaxis with either low molecular weight heparin (LMWH) or aspirin at time of VTE. The mortality odds ratio was 3.3 (95% CI 2.4-4.5) in patients who developed VTE in comparison to age matched controls with MM. Younger age at MM diagnosis (<64 years) predicted for VTE occurrence in logistic regression univariate (p-value=0.002) and multivariate analysis (p=0.004). Higher white cell count (WCC) at MM diagnosis showed a trend toward significance in univariate analysis (p-value=0.06) and, in combination with age, demonstrated an area under the curve of 0.72 on ROC analysis for prediction of VTE. Interestingly, the increased risk of VTE in younger patients was not related to longer duration of MM exposure or longer follow up as there was no statistically significant difference in time to VTE between all age groups (median 9 months). Other parameters incorporated in the Khorana score, such as haemoglobin and platelet count did not increase the risk of VTE (p-value=0.57, and 0.25 respectively). Conclusions Our data confirms that VTE is associated with an increased mortality in MM patients and estimates the risk of death to be 3.3 fold higher in these patients. As recently reported in a large cohort of MM patients, younger age is associated with an increased risk of VTE development4, our data support this finding and excludes longer duration of MM, and follow-up time, as confounding variables. Importantly, our data confirms, in unselected "real world" patients the signal that is now apparent from analysis of VTE in the MRC-XI trial3, that thromboprophylaxis with LMWH or aspirin is suboptimal for VTE prevention. This may point to alternative thrombotic mechanisms in MM-VTE and further data in larger MM cohorts is needed to develop risk adapted strategies for prevention strategies for these patients. References Kristinsson SY et el, Blood. 2008 Nov 1;112(9):3582-6. Schoen MW et al. J Clin Oncol 36, 2018 (suppl; abstr 8051). Bradbury CA et al, Blood 2017 130:553. Sanfilippo KM et al. Blood 2016;128:4726. Disclosures Quinn: Janssen: Honoraria. Lavin:Shire: Honoraria, Research Funding, Speakers Bureau. O'Donnell:Baxter: Research Funding, Speakers Bureau; Octapharma: Speakers Bureau; CSL Behring: Consultancy; Daiichi Sankyo: Consultancy; Pfizer: Consultancy, Research Funding; Novo Nordisk: Research Funding, Speakers Bureau; Bayer: Research Funding, Speakers Bureau; Shire: Research Funding, Speakers Bureau; Leo Pharma: Speakers Bureau.

Abstract WP244: Applicability of the Compass Trial Criteria Among Stable Outpatients With Established Atherothrombotic Disease or Major Risk Factors

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Carlos Cantu-Brito ◽  
Erwin Chiquete ◽  
Jose L Ruiz-Sandoval ◽  
Fernando Flores-Silva
Keyword(s):  
Risk Factors ◽  
Cerebrovascular Disease ◽  
Selection Criteria ◽  
Vascular Risk Factors ◽  
Cox Proportional Hazards Model ◽  
Vascular Risk ◽  
Similar Frequency ◽  
History Of ◽  
Atherothrombotic Disease

Background and Purpose: The objective of this study were to describe the proportion of patients eligible for the COMPASS trial among stable outpatients with either established atherothrombotic disease or major vascular risk factors, and to analyze 6-month incident stroke risk according vascular risk factors at baseline. Methods: We prospectively recruited 5,101 stable outpatients in 172 sites, within the Mexican INDAGA cohort study. Inclusion criteria were age >18 years and established atherothrombotic disease [history of either acute coronary syndromes (ACS), acute ischemic stroke (AIS)/transient ischemic attack (TIA) or peripheral artery disease (PAD)] or major vascular risk factors (age <55 years plus ≥2 major vascular risk factors, or age ≥55 years plus ≥1 vascular risk factors). Among these patients, we applied the selection criteria of the COMPASS trial for analysis, dividing the population in no COMPASS criteria met and COMPASS criteria met, and this last group subdivided among patients with previous AIS/TIA and without this antecedent, in order to stratify the risk for stroke during 6-month follow-up (incident AIS/TIA). Results: Among 5,101 stable outpatients with either established atherothrombotic disease (n=2,827) or major vascular risk factors (n=2,274), a total of 1,927 (37.8%) met COMPASS trial criteria: 1,054 (54.7%) with established cerebrovascular disease (past history of AIS/TIA) and 873 (45.3%) without. During 6-month follow-up, there were 89 incident AIS/TIA (39 AIS and 54 TIA): 1.7% among the whole population and 2.2% among the COMPASS subgroup. AIS/TIA occurred in a similar frequency among the COMPASS subgroup with established cerebrovascular disease (1.6%) and COMPASS without cerebrovascular disease (0.9%) (P=0.18). After a Cox-proportional hazards model, independent predictors of incident AIS/TIA were age ≥65 years (HR: 1.99, 95% CI: 1.29-3.07) and established cerebrovascular disease at baseline (HR: 1.61, 95% CI: 1.02-2.53). Conclusions: The majority of stable outpatients at vascular risk met COMPASS selection criteria and could be good candidates for low-dose rivaroxaban in addition to aspirin. Short-term predictors of AIS/TIA were old age and history of cerebrovascular disease

Abstract 12153: Impact of a Hybrid Nurse-Led Intervention for the Prevention of Progressive Cardiac Dysfunction in High Risk Individuals: Results From a Pragmatic, Randomized Trial (the NIL-CHF Study)

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Simon Stewart ◽  
Melinda Carrington ◽  
Yih Kai Chan ◽  
Garry Jennings ◽  
Chiew Wong ◽  
...  
Keyword(s):  
High Risk ◽  
Cardiac Function ◽  
Diastolic Dysfunction ◽  
Cardiac Dysfunction ◽  
Systolic Dysfunction ◽  
Cardiac Abnormality ◽  
Coronary Syndrome ◽  
History Of ◽  
Hybrid Program

Background: The natural history of chronic heart failure (CHF) is characterized by initial cardiac insult and/or stressors over time that leaves affected individuals at high risk for progressive cardiac dysfunction and eventual development of the syndrome. Methods: Of a total of 624 subjects at high risk of developing CHF randomized into the NIL-CHF Study comparing a hybrid program of home and clinic-based follow-up (NIL-CHF group) to Standard Care, 454 (73%) underwent serial echocardiography at 1 month post index cardiac hospitalization and at 3 years. At both time points (nil signs/symptoms of CHF at baseline), these were blindly classified as follows: 1) no cardiac abnormality, 2) systolic dysfunction/HFrEF - LVEF ≤ 45% ), 3) diastolic dysfunction/HFpEF as defined by any moderate diastolic dysfunction (with pseudonormalization pattern) or E/E prime ratio ≥ 15, 4) combination of 2 & 3 and 5) other cardiac abnormality (including LVH). Pre-specified criteria were used to determine - i) no change, ii) improvement or iii) deterioration in cardiac function from baseline to 3 years. Results: Mean age was 66±11 years, 71% were male, 70% were hospitalized with an acute coronary syndrome and 62% and 26%, respectively, were being treated for hypertension and diabetes. At baseline 25.2% vs. 28.4% (p=ns), 15.1% vs. 9.1% (p<0.05), 35.1% vs. 32.4% (p=ns) and 34.3% vs. 39.6% had normal cardiac function, HFrEF, HFpEF (13% both HFrEF and HFpEF overall) and LVH (the predominant “other” cardiac abnormality), respectively. At 3 years the proportion of subjects with reversal of pre-existing HFrEF or HFpEF was lower in the NIL-CHF group (23% vs. 16%; p=0.063). Moreover, significantly more NIL-CHF subjects demonstrated any form of cardiac recovery/reversal on echocardiography (39% vs. 25%, p=0.011, 95% CI 1.35, 95% CI 1.04, 1.76). They also demonstrated significantly greater regression to normal LV structure (36% vs. 25%; p=0.047) among those with LVH at baseline. Conclusions: These pre-specified analyses (secondary endpoint) of the recently completed NIL-CHF Study suggests a cardio-protective effect conferred by a long-term, nurse-led, home and clinic-based intervention targeting hospitalized individuals at high risk for developing CHF.

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