Polycythemia Vera and Heart Failure: Association and Outcomes- a Propensity Matched Analysis in Hospitalized Patients

Abstract Polycythemia Vera (PV) is a rare chronic myeloproliferative disorder (MPN), a hematopoietic stem cell-derived malignancy that is characterized by clonal proliferation of myeloid cells with variable degrees of morphologic maturity. PV is distinguished from other MPNs by the presence of an elevated red blood cell mass (ie, erythrocytosis), and is associated with an increased risk for thromboembolic events, leukemic transformation, and/or myelofibrosis. This translates to sludging of blood flow due to hyperviscosity. Patients with PV have increased risk of both arterial and venous thrombosis as well as hemorrhage. Acute coronary syndrome and cardiac thrombotic events are well known complications of PV, however there is insufficient data on PV associated with heart failure (HF) and its repercussions. Through this study we aim to determine baseline characteristics of PV patients with and without HF and its impact on morbidity, mortality and overall hospital length of stay. We identified all hospitalized adult patients with PV from the National Inpatient Sample Database between January 2016 to December 2018 using ICD-10-CM codes, and divided them into groups with and without heart failure. We compared patient's baseline characteristics, associated comorbidities, mortality, length of stay and hospitalization costs among PV patients with and without HF. Propensity-score 1:1 matching for age, sex, race, and co-morbidities was performed among both groups. SAS 9.4 software was used for statistical analysis. Out of 61265 patients hospitalized with PV, 16900(27.6%) patients were found to have HF. The patients in HF group were noted to have higher mean age (74.7±12.3 vs 69±14.3 years), and higher prevalence of comorbidities such as diabetes mellitus (27.5 vs 20.4%), coronary artery disease (47.2 vs 22.4%), peripheral vascular disease (12.1 vs 9.9%), chronic pulmonary obstructive disease (33.9 vs 20.6%), Renal failure (20.2 vs 9.4%) and obesity (13.6 vs 10.5%). In terms of propensity matched outcomes, the group with PV and coexisting HF had higher inpatient mortality (5.9 vs 3.6%), higher total length of stay (6.5 ± 7.3 vs 5.2 ± 5.3 days), and higher total hospitalization cost (18081 ± 27506 vs 14529 ± 18412 $) (p<0.001). Our study noted that almost 27.6% of hospitalized PV patients had concurrent HF. We observed that presence of HF in patients with PV significantly increased mortality, hospitalization costs and total length of stay. Despite major advances in Heart failure (HF) treatment strategies, morbidity and mortality remains high. With regard to the etiology, there are different causes of HF, and their recognition can be crucial for treatment optimization. With mounting epidemiological evidence of association and fatal outcomes, our study also shines light on a significant knowledge gap in the field of MPN such as PV and concurrent HF, and warrants further studies to better delineate pathogenesis and early diagnostic and treatment strategies specifically curated for PV associated HF. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Polycythemia Vera and Cardiac Arrhythmias: Association and Outcomes- a Propensity Matched Analysis in Hospitalized Patients

Blood ◽

10.1182/blood-2021-149947 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4644-4644

Author(s):

Shivani Dalal ◽

Krunalkumar Patel ◽

Akash Patel ◽

Daniel Tran ◽

Thanh Nguyen ◽

...

Keyword(s):

Risk Factors ◽

Length Of Stay ◽

Polycythemia Vera ◽

Cardiac Arrhythmias ◽

Conflicts Of Interest ◽

Cell Mass ◽

Hospitalized Patients ◽

Hospital Length Of Stay ◽

Hospitalization Costs ◽

Baseline Characteristics

Abstract Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN), which is characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. PV is distinguished clinically from the other MPNs by the presence of an elevated red blood cell mass, and are commonly noted to have persistent leukocytosis and thrombocytosis. Pruritus, hypertension, vasomotor symptoms like erythromelalgia, thrombosis and bleeding events are well known clinical features of PV, however there is insufficient data on PV and associated cardiac arrhythmias and its repercussions. Through this study we aim to determine baseline characteristics of PV patients with and without arrhythmias and its impact on morbidity, mortality and overall hospital length of stay. We identified all adult hospitalized patients with PV, during the time frame of January 2016 to December 2018, and divided them into groups with and without cardiac arrhythmias using ICD-10-CM Codes from National Inpatient sample Database. We compared patient's baseline characteristics, associated comorbidities, mortality, length of stay and hospitalization costs among PV patients with and without documented arrhythmias. Propensity-score matching for age, sex, income, and co-morbidities were performed among both groups. SAS 9.4 software was used for statistical analysis. We analyzed a total of 61265 patients. Out of this cohort, 20165 (32.9%) patients were found to have cardiac arrhythmias. The group with cardiac arrhythmias were noted to have a higher mean age (75.6±11.6 vs 68.2±14.4 yrs), were predominantly males (57.4 vs 42.6%), and had higher prevalence of associated comorbidities such as congestive heart failure (16.7 vs 8.3%), coronary artery disease (40.1 vs 23.9%), peripheral vascular disease (11.8 vs 9.9%), chronic obstructive lung disease (25.7 vs 23.9%), renal failure (15.5 vs 10.9%), and coagulopathy (7.2 vs 6.2%). In terms of propensity matched outcomes, the group with PV and associated arrhythmias had higher inpatient mortality (5.8 vs 3.2%), longer length of stay (6.4±7.7 vs 5.2±5.3 days) and higher total hospitalization costs (18744±28815 vs 13870±16527 $). Amongst arrhythmias, atrial fibrillation was noted to be the most common arrhythmia (77.6%), followed by atrial flutter (8.2%), ventricular tachycardia (6.6%) and supraventricular tachycardia (6.4%).(p<0.001). Our study suggests that presence of arrhythmias in patients with PV significantly increases the hospital mortality, total cost and length of stay. Both PV and Arrhythmias are independent risk factors for thrombosis which increases morbidity and mortality outcomes in the patients. We identified a high incidence of atrial arrhythmias among patients with PV. The patients were older, cumulating more cardiovascular risk factors inducing more thrombotic events mainly in arteries, and have a higher incidence of death. PV presents the physician with a significant therapeutic challenge, where the physician has to carefully reflect and act on treating the strong thrombophilic state of PV and arrhythmias with careful caution to prevent bleeding catastrophes. With mounting epidemiological evidence of association and fatal outcomes, our study also shines light on a significant knowledge gap in the field of MPN such as PV and concurrent cardiac arrhythmias and warrants further studies to better delineate pathogenesis and early diagnostic and treatment strategies specifically curated for PV associated arrhythmias. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Adverse Outcome Prediction of Iron Deficiency in Patients with Acute Coronary Syndrome

Biomolecules ◽

10.3390/biom8030060 ◽

2018 ◽

Vol 8 (3) ◽

pp. 60 ◽

Cited By ~ 10

Author(s):

Tanja Zeller ◽

Christoph Waldeyer ◽

Francisco Ojeda ◽

Renate Schnabel ◽

Sarina Schäfer ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Acute Coronary Syndrome ◽

Iron Deficiency ◽

Cardiovascular Mortality ◽

Adverse Outcome ◽

Smoking Status ◽

Coronary Syndrome ◽

Iron Deficient ◽

Increased Risk

Acute myocardial infarction remains a leading cause of morbidity and mortality. While iron deficient heart failure patients are at increased risk of future cardiovascular events and see improvement with intravenous supplementation, the clinical relevance of iron deficiency in acute coronary syndrome remains unclear. We aimed to evaluate the prognostic value of iron deficiency in the acute coronary syndrome (ACS). Levels of ferritin, iron, and transferrin were measured at baseline in 836 patients with ACS. A total of 29.1% was categorized as iron deficient. The prevalence of iron deficiency was clearly higher in women (42.8%), and in patients with anemia (42.5%). During a median follow-up of 4.0 years, 111 subjects (13.3%) experienced non-fatal myocardial infarction (MI) and cardiovascular mortality as combined endpoint. Iron deficiency strongly predicted non-fatal MI and cardiovascular mortality with a hazard ratio (HR) of 1.52 (95% confidence interval (CI) 1.03-2.26; p = 0.037) adjusted for age, sex, hypertension, smoking status, diabetes, hyperlipidemia, body-mass-index (BMI) This association remained significant (HR 1.73 (95% CI 1.07–2.81; p = 0.026)) after an additional adjustment for surrogates of cardiac function and heart failure severity (N-terminal pro B-type natriuretic peptide, NT-proBNP), for the size of myocardial necrosis (troponin), and for anemia (hemoglobin). Survival analyses for cardiovascular mortality and MI provided further evidence for the prognostic relevance of iron deficiency (HR 1.50 (95% CI 1.02–2.20)). Our data showed that iron deficiency is strongly associated with adverse outcome in acute coronary syndrome.

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Galectin-3 is Associated with Cardiovascular Events in Post-Acute Coronary Syndrome Patients with Type-2 Diabetes

Journal of Clinical Medicine ◽

10.3390/jcm9041105 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1105 ◽

Cited By ~ 2

Author(s):

Ana Lorenzo-Almorós ◽

Ana Pello ◽

Álvaro Aceña ◽

Juan Martínez-Milla ◽

Óscar González-Lorenzo ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Plasma Levels ◽

Cardiovascular Events ◽

Primary Outcome ◽

Coronary Syndrome ◽

Increased Risk ◽

Galectin 3 ◽

Secondary Outcomes

Introduction: Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. Methods: We followed 964 patients with coronary artery disease (CAD), assessing plasma levels of galectin-3, monocyte chemoattractant protein-1 (MCP-1), and N-terminal fragment of brain natriuretic peptide (NT-proBNP) at baseline. The secondary outcomes were acute ischemia and heart failure or death. The primary outcome was the combination of the secondary outcomes. Results. Two hundred thirty-two patients had T2DM. Patients with T2DM showed higher MCP-1 (144 (113–195) vs. 133 (105–173) pg/mL, p = 0.006) and galectin-3 (8.3 (6.5–10.5) vs. 7.8 (5.9–9.8) ng/mL, p = 0.049) levels as compared to patients without diabetes. Median follow-up was 5.39 years (2.81–6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients (Hazard ratio (HR) 1.57 (1.07–2.30); p = 0.022), along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in nondiabetic patients (HR 1.21 (1.04–1.42); p = 0.017 and HR 1.23 (1.05–1.44); p = 0.012, respectively), along with male sex and age. Galectin-3 was also the only biomarker associated with the development of acute ischemic events and heart failure or death in T2DM patients, while, in nondiabetics, MCP-1 and NT-proBNP, respectively, were related to these events. Conclusion: In CAD patients, galectin-3 plasma levels are associated with cardiovascular events in patients with T2DM, and MCP-1 and NT-proBNP in those without T2DM.

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P4151Changes in incidence and risk factors for heart failure over a 21-year follow-up period in two cohorts of middle aged men born 30 years apart

European Heart Journal ◽

10.1093/eurheartj/ehz745.0723 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

C Ergatoudes ◽

P.-O Hansson ◽

K Svardsudd ◽

A Rosengren ◽

E Thunstrom ◽

...

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Antihypertensive Medication ◽

Piecewise Linear ◽

Risk Profile ◽

Middle Aged ◽

Glucose Levels ◽

Increased Risk ◽

Baseline Characteristics

Abstract Background Several characteristics or conditions are associated with increased risk for heart failure (HF). In recent years we have witnessed gradually improved cardiovascular prevention and treatment. However, how the risk profile of HF has changed during the last decades remains inadequately studied. Purpose To compare risk factors for heart failure in two generations of middle-aged men from the general population born 30 years apart. Methods Two cohorts of randomly selected men born in 1913 (n=855) and in 1943 (n=798) and resident in Gothenburg, Sweden were first examined at 50 years of age in 1963 and 1993, respectively, and followed longitudinally over 21 years until age 71. Data about medical history, concomitant diseases and general health were collected by questionnaires, repeated medical examinations and review of individual medical records. The outcome was defined as hospitalization with HF as a discharge diagnosis or HF reported on the death certificate. Cox-regression analysis was used to examine the impact of baseline characteristics and time-updated atrial fibrillation (AF), ischemic heart disease (IHD) and diabetes mellitus (DM) on the outcome. Furthermore the incidence of HF overall between the two cohorts was also compared. Significance was defined as p<0.05 for all two-sided tests, except for interaction terms where p<0.10 was applied. Results During a 21-year follow up, 80 men born in 1913 (9.4%) and 36 men born in 1943 (4.6%) developed HF. Men born in 1943 had a 52% lower risk for HF (adjusted HR 0.48 95% CI 0.29–0.77 p=0.003) compared to men born in 1913. Baseline characteristics associated with higher HF risk in both cohorts were higher body mass index (BMI) and the use of antihypertensive medication. Higher heart rate was associated with an increased risk only in men born 1913 whereas higher systolic blood pressure (SBP), smoking, higher glucose levels and higher total cholesterol levels were associated with higher risk in men born 1943. Onset of AF, IHD or DM was associated with higher HF risk in both cohorts. Multivariable models using stepwise regression showed that AF, IHD, higher BMI (continuous variable), use of antihypertensive medication and higher heart rate (piecewise linear) were independent predictors for HF in men born in 1913 whereas AF, higher glucose levels, IHD and higher SBP (piecewise linear) in men born in 1943. Finally, interaction analyses showed that in comparison with those born in 1913, the relative importance as risk factors for HF among those born in 1943 has decreased for AF whereas it has increased for systolic blood pressure and cholesterol. Of note, impact of IHD as risk factor decreased numerically, and that of physical activity increased, but for both without reaching statistical significance. Cox proportional hazard analysis Conclusions The incidence of HF in middle aged men living in Gothenburg has decreased during the last decades, and in the meantime risk profile for incident HF has also changed.

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Cardiac Biomarkers in the Emergency Department: The Role of Soluble ST2 (sST2) in Acute Heart Failure and Acute Coronary Syndrome—There is Meat on the Bone

Journal of Clinical Medicine ◽

10.3390/jcm8020270 ◽

2019 ◽

Vol 8 (2) ◽

pp. 270 ◽

Cited By ~ 8

Author(s):

Aneta Aleksova ◽

Alessia Paldino ◽

Antonio Beltrami ◽

Laura Padoan ◽

Massimo Iacoviello ◽

...

Keyword(s):

Heart Failure ◽

Emergency Department ◽

Acute Heart Failure ◽

Ventricular Remodeling ◽

Left Ventricular ◽

Cardiac Biomarkers ◽

Soluble St2 ◽

Coronary Syndrome ◽

Clinical Scenarios ◽

Increased Risk

Soluble ST2 (sST2) has recently emerged as a promising biomarker in the field of acute cardiovascular diseases. Several clinical studies have demonstrated a significant link between sST2 values and patients’ outcome. Further, it has been found that higher levels of sST2 are associated with an increased risk of adverse left ventricular remodeling. Therefore, sST2 could represent a useful tool that could help the risk stratification and diagnostic and therapeutic work-up of patients admitted to an emergency department. With this review, based on recent literature, we have built sST2-assisted flowcharts applicable to three very common clinical scenarios of the emergency department: Acute heart failure, type 1, and type 2 acute myocardial infarction. In particular, we combined sST2 levels together with clinical and instrumental evaluation in order to offer a practical tool for emergency medicine physicians.

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Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies

Thrombosis ◽

10.1155/2011/536062 ◽

2011 ◽

Vol 2011 ◽

pp. 1-16 ◽

Cited By ~ 43

Author(s):

Jonathan S. Bleeker ◽

William J. Hogan

Keyword(s):

Polycythemia Vera ◽

Essential Thrombocythemia ◽

Myeloproliferative Neoplasms ◽

Treatment Options ◽

Treatment Strategies ◽

Diagnostic Evaluation ◽

Diagnostic Process ◽

Special Focus ◽

Thrombotic Risk ◽

Increased Risk

Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera.

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miRNAs Expression Pattern in Essential Thrombocythemia and Polycythemia Vera Patients.

Blood ◽

10.1182/blood.v114.22.1912.1912 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1912-1912

Author(s):

Aina Pons ◽

Carlos Besses ◽

Luz Martínez-Avilés ◽

Alberto Alvarez-Larran ◽

Raquel Longaron ◽

...

Keyword(s):

Polycythemia Vera ◽

Expression Pattern ◽

Essential Thrombocythemia ◽

Mirna Expression ◽

Fold Change ◽

Differentially Expressed ◽

Hematopoietic Stem ◽

Mutational Status ◽

Increased Risk ◽

Normal Controls

Abstract Abstract 1912 Poster Board I-935 Background: Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are myeloproliferative neoplasms (MPN) arising from a multipotent hematopoietic stem cell characterized by an unregulated production of platelets, red cells and white cells alone or in combination, a tendency to clonal evolution and an increased risk of thrombohemorrhagic complications. MicroRNAs (miRNA) are negative regulators of genes involved in cellular proliferation, apoptosis and/or carcinogenesis. Aim: To analyze the expression pattern of miRNA between PV and ET patients and to find distinctive signatures in ET patients according to JAK2V617F and c-MPL mutational status. Material and Methods: Total RNA was extracted from peripheral blood granulocytes of 50 ET patients, 10 PV patients and 10 controls. Median age of patients was 57 years (range, 20-88); males 36%. The JAK2V617F mutation was present in 23 (46%) of 50 ET patients and in all PV patients. MPL mutations were present in 5 (18%) of 27 JAK2V617F negative cases (3 cases MPLW515L, 1 case MPLW515K and 1 case MPLS505N). miRNA expression was profiled in 384 miRNA via Taqman Low Density Array in ABI PRISM 7900. Expression data was normalized with RNU48 and relative quantification was calculated with the 2–σσCt method. The data were presented as log10 of relative quantity of target miRNA. Median of normal controls was used as calibrator for all samples. Data were analyzed by means of Significant Analysis of MicroArrays (SAM), Prediction Analysis of MicroArrays (PAM) and Class Comparison methods using BRB array tools version 3.7.0 and TIGR multiexperiment viewer version 4.3. Results: We found a general downregulation of miRNA in ET and PV patients respect to normal controls. A set of 29 miRNA allowed us to discriminate between ET and PV versus normal controls; three of these miRNA were up-regulated and 16 down-regulated in PV and ET vs. normal controls with a >2 fold change and p value <0.01. A distinctive signature of 79 miRNAs differentiated ET, PV and controls and a hierarchical clustering analysis defined miRNA expression profiles of the three particular groups. When we compared miRNA differentially expressed between PV and ET patients, we found nine miRNA, 4 up-regulated and 5 down-regulated in ET with respect to PV patients (p<0.01). Statistical comparisons between ET JAK2V617F-positive and ET JAK2V617F-negative cases showed a distinctive signature of 13 miRNA that allowed us to discriminate between the two groups. In addition, we also found in JAK2V617F cases 19 miRNA differentially expressed between MPL positive and MPL negative patients, with a >2 fold change and p<0.01. Finally, an increased expression of miR-142-5p correlated with JAK2V617F allele burden in ET patients Conclusions: Our study demonstrates that ET and PV can be defined by specific signatures of miRNA. In ET, some miRNA allow us to discriminate cases according to JAK2V617F mutational status and also between MPL-positive and MPL-negative JAK2V617F-negative patients. Research Funding: FIS EC07/90791 Disclosures: No relevant conflicts of interest to declare.

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Psychiatric Comorbidity and Greater Hospitalization Risk, Longer Length of Stay, and Higher Hospitalization Costs in Older Adults with Heart Failure

Journal of the American Geriatrics Society ◽

10.1111/j.1532-5415.2007.01368.x ◽

2007 ◽

Vol 55 (10) ◽

pp. 1585-1591 ◽

Cited By ~ 59

Author(s):

Steven L. Sayers ◽

Nancy Hanrahan ◽

Ann Kutney ◽

Sean P. Clarke ◽

Brendali F. Reis ◽

...

Keyword(s):

Heart Failure ◽

Older Adults ◽

Length Of Stay ◽

Psychiatric Comorbidity ◽

Hospitalization Costs

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Treatment-Related Infections and Risk Factors in Patients with Myeloproliferative Neoplasms Treated with Ruxolitinib

Blood ◽

10.1182/blood.v128.22.1930.1930 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1930-1930 ◽

Cited By ~ 1

Author(s):

Amber C King ◽

Meier Hsu ◽

Michael J. Mauro ◽

Raajit K. Rampal

Keyword(s):

Clinical Practice ◽

Herpes Simplex ◽

Polycythemia Vera ◽

Cumulative Incidence ◽

Competing Risk ◽

Cell Transplant ◽

Practice Setting ◽

Hematopoietic Stem ◽

Increased Risk ◽

Clinical Practice Setting

Abstract Ruxolitinib is an orally available JAK1/2 inhibitor FDA approved for the treatment of myelofibrosis and polycythemia vera. Evidence suggest the effect of ruxolitinib on IL-1, IL-6, and TNF-α, among other immune mediators, may predispose patients to both opportunistic and non-opportunistic infections. Identification of patients at risk for infection while on a JAK inhibitor may impact clinical management. Authors sought to determine the cumulative incidence of ruxolitinib-related infections in the clinical practice setting and evaluated patient factors in order to characterize the types, onset, and severity of infections. This IRB approved, single-center, retrospective study at Memorial Sloan Kettering Cancer Center included myeloproliferative neoplasm (MPN) patients treated with ruxolitinib who were ≥18 years of age between 12/1/11 and 12/31/15. Patients on ruxolitinib for less than seven days, receiving ruxolitinib therapy for a non-MPN diagnosis, or had a manifestation of acute leukemia were excluded. Patients who met inclusion criteria were censored at time of splenectomy and hematopoietic stem cell transplant. Patients were identified through electronic medical records and an internal pharmacy database. Cumulative incidence of treatment-related infection was estimated and association with factors was assessed using competing risk regression analysis. Death without an infection was considered a competing risk event. A total of 44 patients were included in this analysis. The median age of this cohort was 66.5 years, with a slightly predominant male population (57%). There were 19 (43%) primary and 19 (43%) secondary myelofibrosis patients, 4 (9%) with polycythemia vera, and 2 (5%) patients with an unclassifiable MPN. For myelofibrosis patients, according to the Dynamic International Prognostic Scoring System (DIPSS), 2 (5%) were low risk, 3 (7%) were intermediate-1, 16 (36%) were intermediate-2, and 7 (16%) were high; remaining patients did not have available DIPSS scores at the time of evaluation. The median number of prior lines of therapy was 1.5 (range 0-4); median total daily dose of ruxolitinib was 10 mg. A majority of patients (70%) were not on concomitant immunosuppressive therapy during ruxolitinib treatment or strong CYP3A4 inhibitors (95%) that may have increased exposure to ruxolitinib. A total of 20 documented infections were identified throughout the evaluation period; median follow-up among survivors was 16 months (range 3-51). Cumulative incidences of treatment related infection were 33% by year 1 and 56% by year 2 of ruxolitinib treatment. Of these infections, four were CTCAEv4.0 grade 1 (one asymptomatic upper respiratory tract infection (URI) occurred after discontinuation was censored), seven were grade 2, and eight were grade 3. One grade 5 infection, septic shock of unknown origin occurred. Only one opportunistic pulmonary tuberculosis infection occurred 13 months post ruxolitinib treatment. The remainder of infections varied, including URIs(n=9), pneumonia, diverticulitis, osteomyelitis, clostridium difficile, proctitis, catheter-associated UTI, dental abscess, herpes zoster activation of the skin, and oral herpes simplex reactivation (all n=1)). One patient required viral prophylaxis for recurrent herpes simplex infections. With the limited number of events, no factors were found to be significantly associated with increased risk of infection but a trend toward increased risk of ruxolitinib-related infection was observed with baseline renal impairment. (Table 1). Conclusion: This data suggests a higher incidence of ruxolitinib associated infections observed in clinical practice compared to rates described in trials of ruxolitinib therapy. This may be attributable to differences between populations in the COMFORT and RESPONSE trials and patients in the clinical practice setting. Generally, infections were non-life threatening and managed with appropriate supportive care. Plasma values of ruxolitinib metabolites increase as renal function declines, correlation of infection risk via increased metabolites exposure warrants further exploration. Routine antimicrobial prophylaxis for all patients receiving ruxolitinib therapy is likely not warranted. However larger studies are needed to confirm these observations. Figure Figure. Disclosures Mauro: Pfizer: Consultancy; Ariad: Consultancy; BMS: Consultancy; Novartis: Consultancy.

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Blood pressure variability and risk of heart failure in ACCORD and the VADT

10.2337/figshare.12059250.v1 ◽

2020 ◽

Author(s):

Daniel S. Nuyujukian ◽

Juraj Koska ◽

Gideon Bahn ◽

Peter D. Reaven ◽

Jin J. Zhou ◽

...

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Risk Factor ◽

Blood Pressure Variability ◽

Treatment Strategies ◽

Risk Factor Management ◽

Increased Risk ◽

Blood Pressure Treatment

Objective: Although blood pressure variability is increasingly appreciated as a risk factor for cardiovascular disease, its relationship with heart failure is less clear. We examined the relationship between blood pressure variability and risk of heart failure (HF) in two cohorts of type 2 diabetes participating in trials of glucose and/or other risk factor management. Research Design and Methods: Data were drawn from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Veterans Affairs Diabetes Trial (VADT). Coefficient of variation (CV) and average real variability (ARV) were calculated for systolic (SBP) and diastolic blood pressure (DBP) along with maximum and cumulative mean SBP and DBP during both trials. Results: In ACCORD, CV and ARV of SBP and DBP were associated with increased risk of HF, even after adjusting for other risk factors and mean blood pressure (e.g., CV-SBP: HR=1.15, p = 0.01; CV-DBP: HR=1.18, p = 0.003). In the VADT, DBP variability was associated with increased risk of HF (ARV-DBP: HR=1.16, p = 0.001; CV-DBP: HR=1.09, p = 0.04). Further, in ACCORD, those with progressively lower baseline blood pressure demonstrated a stepwise increase in risk of HF with higher CV-SBP, ARV-SBP, and CV-DBP. Effects of blood pressure variability were related to dips, not elevations, in blood pressure. Conclusions: Blood pressure variability is associated with HF risk in individuals with type 2 diabetes, possibly a consequence of periods of ischemia during diastole. These results may have implications for optimizing blood pressure treatment strategies in those with type 2 diabetes.

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