Clinical Congestive Heart Failure Research Articles

Succeeding in Medicare’s newest bundled payment program: Results from teaching hospitals

BackgroundIn 2018, Medicare implemented a successor to its Bundled Payments for Care Improvement (BPCI) program, BPCI Advanced, with stricter participation rules and new financial incentives to reduce spending. MethodsUsing claims-based episode data from thirteen participants, we compared spending and utilization in the first fifteen months of the new program (October 2018 to December 2019) to hospital- and episode-specific target prices, with a deep dive into clinical correlates for the most commonly-selected clinical episodes, sepsis and congestive heart failure. ResultsTwelve out of thirteen participants in a collaborative of teaching hospitals achieved shared savings for both Medicare and their own institution. Aggregate hospital shared savings were 5.8% of benchmark prices across 6,131 patients in 16 clinical episodes (p<0.001), appreciably higher than the reference savings rates reported after the first period of Medicare’s predecessor BPCI program. Differences in shared savings across hospitals for sepsis and congestive heart failure correlated with reductions in patients’ use of post-acute care, including reductions in skilled nursing facility, readmission, and home health rates. Evidence is presented showing reductions in patient utilization for cost-intensive post-acute settings accompanied increases in the proportion of patients exclusively utilizing non-institutional care after discharge from an anchor stay or procedure. ConclusionsThese findings provide an example of the fulfillment of a core promise of bundled payments to uncover new opportunities for reduced spending. Level of evidenceNon-random cohort of hospitals.

Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: ASCO Guideline Update.

To update evidence-based guideline recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 545 articles. Outcomes of interest included efficacy and safety. Of the 545 publications identified and reviewed, 14 were identified to form the evidentiary basis for the guideline recommendations. HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and trastuzumab deruxtecan for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations. There is a lack of head-to-head trials; therefore, there is insufficient evidence to recommend one regimen over another. The patient and the clinician should discuss differences in treatment schedule, route, toxicities, etc during the decision-making process. Options include regimens with tucatinib, trastuzumab emtansine, trastuzumab deruxtecan (if either not previously administered), neratinib, lapatinib, chemotherapy, margetuximab, hormonal therapy, and abemaciclib plus trastuzumab plus fulvestrant, and may offer pertuzumab if the patient has not previously received it. Optimal duration of chemotherapy is at least 4-6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive or progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone.Additional information is available at www.asco.org/breast-cancer-guidelines.

Evaluation of prognostic value of lung ultrasound in st-segment elevation myocardial infarction killip i

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Societat Catalana de Cardiologia (SCC) Sociedad Española de Cardiología (SEC) Introduction About 80-90% of patients admitted for ST-segment elevation myocardial infarction (STEMI) present with no signs of heart failure at admission. Heart failure at admission is one of the most relevant prognostic factors in STEMI, whereas incidence and prognostic significance of HF developed during hospitalization is unclear. B-lines in lung ultrasound (LUS) provide useful diagnostic and prognostic information in heart failure patients with the potential to stratify the risk of complications in patients presenting with STEMI KKI. Purpose To assess the capacity of the lung ultrasound to predict heart failure developing or death during hospitalization in patients admitted for STEMI KKI Methods This is a prospective observational multicenter study. Consecutive patients admitted for STEMI KKI in four tertiary hospitals were included, exclusion criteria were patients with cardiac arrest at presentation, severe lung disease or hemodialysis. The LUS was carried out by an independent operator blinded to clinical data in the first 24 hours after admission. We counted B-lines using 8-scan site LUS protocol and divided patients in two groups : wet lung group (3 or more B-lines in at least one zone) and dry lung (no positive zone). The primary endpoint was a composite of clinical congestive heart failure, cardiogenic shock, or mortality during the index hospitalization. Results From June 2020 to November 2021, 221 patients STEMI KKI patients were included. Fifty-four patients (25,4%) had a wet lung according to the LUS. Seventeen patients (7,7%) presented the primary outcome (all of them developed congestive heart failure, 1 of them cardiogenic shock and 2 of them died during hospitalization). Fourteen in 54 wet-lung patients (25,9%) presented the primary outcome whereas only 3 in 167 (1,7%) of the dry-lung patients [relative risk of 14,4 (IC 95% 4,3-48,3)]. Patients who develop the primary outcome had no differences in NTproBNP at admission but had higher NTproBNP peak, higher troponin T peak, lower left ventricular ejection fraction and longer length of stay. Conclusions In patients admitted with STEMI KKI, presenting 3 or more B-lines at least at one lung zone in the LUS at first 24 hours after admission was strongly associated with worse prognosis during hospitalization. LUS allows a better risk classification of patients and may potentially discriminate those with potential risk of complications during hospitalization from those with an excellent prognosis who can benefit from early discharge.

Impaired Left Ventricular Ejection Fraction Induces “Very Early Pre-Diagnostic” Hemopoietic Modifications in Myeloid Leukemia Patients

Background: There is strong association between clonal hematopoiesis of undetermined prognosis (CHIP) and coronary artery disease (CAD) development. Indeed, ischemic heart disease is a leading cause of congestive heart failure (CHF) in western society. CH induces not only enhanced risk for myeloid malignancies, but also significant cardiovascular morbidity in elderly patients (pt). Pt with impaired ejection fraction (EF) and clinical manifestation of heart failure frequently initiates systemic pro-inflammatory state [SPS] characterized by interleukin-6 (IL6) and tumor necrosis factor alpha (TNF-α) upregulation. Previous studies suggest that such an inflammatory state is capable of sustaining and/or accelerating hemopoietic clonal selection/dominance. How these CHF induced inflammatory changes affect “peripheral blood cell count composition' in pt with suspected CHIP is unknown. However, modifications in peripheral blood count data ”months before hemopoietic malignancy diagnosis“ may inform association between clonal dynamics and hemopoietic output under CHF stress. The primary objective of our study was to investigate effect of heart failure in ”pre- AML diagnosis“ peripheral blood count data to detect ”early“ hemopoietic modifications induced by CHF. Methods: After IRB approval, AML pt diagnosed with and without CHF were selected for analysis. Given possible differential inflammatory effect between pt exhibiting CHF with and with low EF, we analyzed peripheral blood cell count in pt with ”echocardiographically confirmed“ EF <> 50% and those pt with and without clinically documented CHF [cdCHF]. Descriptive statistics was performed for categorical and continues variable with Chi-square and t-test. SAS software was used for analysis. Results: 27/152 (17.7%) and 125/152 (82.2%) pt developed or not EF <50%. Median age was 71.1 years (y) v 61.2 y, in pt with and without EF<50%, p=<0.0001. Aging was negatively correlated with EF, [R= -0.25, p=0.001]. Median age was 73 y v 61 y, for pt with and without cdCHF, p=0.001. 100% and 82% of pt were male among those with and without EF <50%. In pt who had or did not have EF <55% Favorable (fav), Intermediate (Int) and unfavorable (unfav) ELN-2017 subgroups were 3.23% vs 13.6%; 42% vs 46%; and 55% vs 40%, p=0.07. To address our main hypothesis that CHF induces ”early pre-diagnostic AML' hemopoietic modifications, CBC data at 6 and 12 months (m) before AML onset in pt with and without EF<50% v those with and without cdCHF was extracted. At 12 m prior AML diagnosis, EF<> 50% detected differential expression for WBC [p=0.07], Hemoglobin [p=0.002], platelets [p=0.05] and absolute lymphocyte count (ALC) [p=0.006] [Fig 1, panel A, C, I, K]. Similarly, EF <>50% at 6 m prior AML diagnosis detected differential expression for platelets [p=0.01], ALC [p=0.04] [Fig 1, panel D, J, L]. In contrast, cdCHF detected only differential hemoglobin at 12 m [p=0.01]. Conclusions: CHF induces quantitative count defects 6 and 12 m before AML diagnosis. Changes are characterized by WBC, hemoglobin, platelets and ALC decline that are directly correlated with objective left ventricular EF impairment, but not with only clinical CHF. Our study adds body of evidence to support the role of CHF with low EF as “hemopoietic cell extrinsic stressor'. CHF associated with low EF seems to be prerequisite for hemopoietic stress in hosts with already initiated clonal hematopoiesis. Our findings have important experimental implications, especially for studies that seek to understand how cell extrinsic stressors facilitate clonal progression. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Lung ultrasound can predict heart failure developing and mortality during hospitalization in ST-segment elevation myocardial infarction

Abstract Introduction About 10% of patients admitted for ST-segment elevation myocardial infarction (STEMI) present with signs of heart failure at admission. Heart failure developed during hospitalization and mortality are uncommon complications in patients admitted for STEMI with no signs of heart failure at admission (Killip-Kimball class I, KKI). Most of these patients have a good prognosis during hospitalization. B-lines in lung ultrasound (LUS) provide useful diagnostic and prognostic information in heart failure patients with the potential to stratify the risk of complications in patients presenting with STEMI KKI. Purpose To evaluate the predictive value of the LUS to develop heart failure and death during hospitalization in patients admitted with STEMI KKI. Methods This is a prospective observational multicenter study. Consecutive patients admitted for STEMI KKI in two tertiary hospitals were included. Exclusion criteria were patients with cardiac arrest at presentation, severe lung disease or hemodialysis. The LUS was carried out by an independent operator blinded to clinical data in the first 24 hours after admission. We counted B-lines using 8-scan site LUS protocol and divided patients in two groups: wet lung group (3 or more B-lines in at least one zone) and dry lung (no positive zone). The primary endpoint was a composite of clinical congestive heart failure, cardiogenic shock or mortality during the index hospitalization. Results From June 2020 to February 2021, 135 patients STEMI KKI patients were included. Twenty-nine patients (21,5%) had a wet lung according to the LUS. Ten patients (7,4%) presented the primary outcome (all of them developed heart failure, 1 of them cardiogenic shock and 2 of them died during hospitalization). Eight in 29 wet-lung patients (27,6%) presented the primary outcome whereas only 2 in 106 (1,9%) of the dry-lung patients [relative risk of 14,6 (IC 95% 3,3–65,1)]. Patients who develop the primary outcome had no differences in NTproBNP at admission but had higher NTproBNP peak, higher troponin T peak, lower left ventricular ejection fraction and longer length of stay (Figure 1). Conclusions In patients admitted with STEMI KKI, presenting 3 or more B-lines at least at one lung zone in the LUS at first 24 hours after admission was strongly associated with worse prognosis during hospitalization. LUS allows a better risk classification of patients and may potentially discriminate those with potential risk of complications during hospitalization from those with an excellent prognosis who can benefit from early discharge. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 2020 grant for training and research of the Association of Ischemic Heart Disease and Critical Cardiological Care, Spanish Society of Cardiology Figure 1. Baseline data in event/no event groupsFigure 2. Wet lung/dry lung groups events graphic

Pulmonary, cardiac and renal distribution of ACE2, furin, TMPRSS2 and ADAM17 in rats with heart failure: Potential implication for COVID-19 disease.

Congestive heart failure (CHF) is often associated with kidney and pulmonary dysfunction. Activation of the renin‐angiotensin‐aldosterone system (RAAS) contributes to avid sodium retention, cardiac hypertrophy and oedema formation, including lung congestion. While the status of the classic components of RAAS such as renin, angiotensin converting enzyme (ACE), angiotensin II (Ang II) and angiotensin II receptor AT‐1 is well studied in CHF, the expression of angiotensin converting enzyme‐2 (ACE2), a key enzyme of angiotensin 1‐7 (Ang 1‐7) generation in the pulmonary, cardiac and renal systems has not been studied thoroughly in this clinical setting. This issue is of a special interest as Ang 1‐7 counterbalance the vasoconstrictory, pro‐inflammatory and pro‐proliferative actions of Ang II. Furthermore, CHF predisposes to COVID‐19 disease severity, while ACE2 also serves as the binding domain of SARS‐CoV‐2 in human host‐cells, and acts in concert with furin, an important enzyme in the synthesis of BNP in CHF, in permeating viral functionality along TMPRSST2. ADAM17 governs ACE2 shedding from cell membranes. Therefore, the present study was designed to investigate the expression of ACE2, furin, TMPRSS2 and ADAM17 in the lung, heart and kidneys of rats with CHF to understand the exaggerated susceptibility of clinical CHF to COVID‐19 disease. Heart failure was induced in male Sprague Dawley rats by the creation of a surgical aorto‐caval fistula. Sham‐operated rats served as controls. One week after surgery, the animals were subdivided into compensated and decompensated CHF according to urinary sodium excretion. Both groups and their controls were sacrificed, and their hearts, lungs and kidneys were harvested for assessment of tissue remodelling and ACE2, furin, TMPRSS2 and ADAM17 immunoreactivity, expression and immunohistochemical staining. ACE2 immunoreactivity and mRNA levels increased in pulmonary, cardiac and renal tissues of compensated, but not in decompensated CHF. Furin immunoreactivity was increased in both compensated and decompensated CHF in the pulmonary, cardiac tissues and renal cortex but not in the medulla. Interestingly, both the expression and abundance of pulmonary, cardiac and renal TMPRSS2 decreased in CHF in correlation with the severity of the disease. Pulmonary, cardiac and renal ADAM17 mRNA levels were also downregulated in decompensated CHF. Circulating furin levels increased in proportion to CHF severity, whereas plasma ACE2 remained unchanged. In summary, ACE2 and furin are overexpressed in the pulmonary, cardiac and renal tissues of compensated and to a lesser extent of decompensated CHF as compared with their sham controls. The increased expression of the ACE2 in heart failure may serve as a compensatory mechanism, counterbalancing the over‐activity of the deleterious isoform, ACE. Downregulated ADAM17 might enhance membranal ACE2 in COVID‐19 disease, whereas the suppression of TMPRSS2 in CHF argues against its involvement in the exaggerated susceptibility of CHF patients to SARS‐CoV2.

Etiological aspects of congestive heart failure in hospital university Ibn Rochd (about 3412 patients)

Congestive heart failure (CHF) is a major and growing health problem around the world. In Africa, heart failure seems to be attributable mostly to systolic dysfunction and occurs as a major complication of high blood pressure. As a contribution to decreasing mortality of acute myocardial infarction and better treatment of high blood pressure as well as congestive heart failure the number of patients in heart failure have increased substantially. In contrast to the Framingham Study, nowadays coronary artery disease is the most prevalent etiology of congestive heart failure followed by hypertensive heart disease. The main objective of the study is to relate the principle causes leading to heart failure in our department. It is a transversal retrospective study conducted between May 2006 and June 2019 including all patients beyond the age of 14 with congestive heart failure followed-up in the therapeutic unit of heart failure of our department. The data were collected on Excel and analyzed using SPSS 2.0 software. We studied cardiovascular risk factors prevalence and causes repartition among these patients. The mean age was 64,92 ± 12,95 years, sex ratio H/F was 1,7, the prevalence of hypertension was 38,9%, 30,4% were diabetic, 31,9% were smokers, 9,9% were dyslipidemic. The leading cause of CHF among our patients was ischemic heart disease (76,81%), 13,47% dilated cardiomyopathy, 4,83% valvular heart disease, 2,38% cardiac toxicity, 0,9% of heart failure with preserved ejection fraction, 0,4% peripartum cardiomyopathy, 0,3% arrhythmia–induced cardiomyopathy. Our data show a high incidence of ischemic heart disease. Despite advances in our therapies for ischemic heart disease and hypertension, CHF remains a common and highly lethal condition. There is accumulating evidence that treatment of hypertension and ischemic heart disease can decrease the incidence of clinical CHF, related morbidity and mortality.

Remote Ischemic Conditioning in Patients with Acute Coronary Syndromes: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.

ObjectiveTo evaluate the efficacy of remote ischemic conditioning (RIC) as compared to no conditioning on clinical endpoints in acute coronary syndromes (ACS) patients undergoing percutaneous coronary intervention (PCI).DesignSystematic review of randomized clinical trials (RCTs).Material and MethodsLiterature was searched up to September 13, 2019, and we identified a total of 13 RCTs. The efficacy of RIC on incidence of clinical events during follow-up was quantified by the rate ratio (RR) with its 95% confidence interval (CI), and we used fixed and random effects models to synthetize the results. Small-study effect was evaluated, and controlled for by the trim-and-fill method. Heterogeneity between studies was examined by subgroup and meta-regression analyses. The risk of false-positive results in meta-analysis was evaluated by trial sequential analysis (TSA).ResultsPooled analysis of 13 trials (7183 patients) showed that RIC compared to no conditioning revealed a non-significant risk reduction on endpoint mortality (RR=0.81, 95% CI: 0.56–1.17) during a median follow-up time of 1 year (range: 0.08–3.8) with low heterogeneity (I2=16%). Controlling for small-study effect showed no efficacy of RIC (adjusted RR: 1.03, 95% CI: 0.66–1.59). Pooled effect of RIC on the incidence of myocardial infarction (MI) from 11 trials (6996 patients) was non-significant too (RR=0.85, 95% CI: 0.62–1.18), with no observed heterogeneity (I2=0%) or small-study effect. A similar lack of efficacy was found in endpoint congestive heart failure (CHF) from 6 trials including 6098 patients (RR=0.71, 95% CI: 0.44–1.15), with moderate heterogeneity (I2=30%). TSAs showed that the pooled estimates from the cumulative meta-analyses were true negative with adequate power.ConclusionEvidence from this updated systematic review demonstrates no beneficial effect of RIC on the incidence of clinical endpoint mortality, MI and CHF during a median follow-up of 1 year in ACS patients undergoing PCI.

P4434The first report of significantly improvement of NT-proBNP level in rheumatoid arthritis patients treated with tofacitinib during 12-month follow-up

Abstract Objectives To prospectively investigate the effect of tofacitinib (TOFA), the first oral reversible inhibitor of JAK approved for RA treatment, on the levels of NT-proBNP, as a predictor of congestive heart failure (CHF) in patients (pt) with active RA. Methods Twenty six RA pt (median age 54 [40; 62] years, 81% female, disease duration 44 [24; 63,0] month (m), moderate to high activity (SDAI–27 (22; 35)), positive for ACCP (73%)/RF (77%), who were non-responders to methotrexate (MTX) at least 15 mg/week and other synthetic DMARDs) free of clinical overt cardiovascular disease were treated with TOFA and followed for 12 m. TOFA therapy was started in all pt in dose 5 mg BID per os with dose escalation to 10 mg BID in 8 (31%) pt. TOFA used in combination with MTX in 24 (92%) pt, leflunomide in 1 (4%). Low-dose oral corticosteroids (&lt;10 mg/day prednisone or equivalent) were received by 9 (35%) pt. Remission was achieved in 38,5% (SDAI). Cardiovascular risk factors (CVRF) and the NT-proBNP levels were measured at baseline and after 12m. At baseline the most of pt had multiple CVRF and subclinical organ damage. Cardioprotective therapy received 16 (57%) pt (beta-AB–7, ARA/ACE inhibitors–11, statins–11, dihydropyridine CCB-7). Twenty controls matched for CVRF were included for comparison of normal NT-proBNP levels. Results The NT-proBNP level was significantly higher in RA pt than in the control group (median 62.2 (26.9–101.7) pg/mL vs 44.0 (34.0–54.3) pg/mL, p&lt;0.05). At baseline NT-proBNP level was higher in female than in male (p=0,019). All 3 (11,5%) RA pt with a NT-proBNP level over 125 pg/mL were asymptomatic and exhibited normal echocardiography. Median SDAI were significantly reduced following TOFA treatment (from 26.8 to 4.7, p&lt;0.001, respectively). During follow-up, no RA pt exhibited a cardiovascular event or CHF. NT-proBNP levels decreased by 63% over the 12-m of TOFA treatment (from 62.16 pg/mL to 14.8 pg/mL, p=0.011). The incidence rate of arterial hypertention (58% vs 65%), overweight (62% vs 62%), abdominal obesity (58% vs 62%), smokers (27% vs 27%), menopausal status (52% vs 52%), DM type 2 (7% vs 7%), mSCORE≥5% (23% vs 27%), subclinical carotid atherosclerosis (58% vs 58%) did not change significantly. An increase in body mass index (BMI) was observed from 26.5 [22.9; 29.0] to 26.9 [24.0; 30.1], p&lt;0.001 and in HDL level from 1.37 [1.06; 1.87] to 1.90 [1.29; 2.16], p&lt;0.01. The percentage change in the NT-proBNP level significantly correlated with the percentage change in the BMI (r=0,6, p=0,007), SDAI (r=0.51, p=0.009). Changes in NT-proBNP levels in RA pt with remission was greater than that observed in pt who didn't achieve remission (−87% vs −26%, p=0,005). The percentage change in the NT-proBNP level was not correlated with the percentage change in other CVRF. Conclusion TOFA decreased the NT-proBNP level in patients with RA without clinical overt cardiovascular disease and CHF. TOFA may have a cardioprotective effect in those with active RA.

Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: ASCO Clinical Practice Guideline Update.

Purpose To update evidence-based guideline recommendations for practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer to 2018. Methods An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 622 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events. Results Of the 622 publications identified and reviewed, no additional evidence was identified that would warrant a change to the 2014 recommendations. Recommendations HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and trastuzumab emtansine for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and may offer pertuzumab if the patient has not previously received it. Optimal duration of chemotherapy is at least 4 to 6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive/progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone. Additional information is available at www.asco.org/breast-cancer-guidelines .

HEART FAILURE OUTCOMES AND PREDICTORS OF SUBCLINICAL ATRIAL FIBRILLATION PROGRESSION

Long-term monitoring with implanted cardiac devices can detect asymptomatic, subclinical atrial fibrillation (SCAF). We hypothesized that progression from shorter to longer SCAF episodes would be associated with a higher risk of congestive heart failure (CHF), one of the leading causes of AF-related morbidity and mortality. Subjects in the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) were ≥65 years, had a history of hypertension, no known prior clinical AF, and had an implanted pacemaker or defibrillator. Among participants whose longest episode of SCAF was between >6 minutes and 24 hours during the first 12 months after enrollment (N=415), we evaluated the relationship between subsequent development of SCAF >24 hours or clinical AF and CHF hospitalization using time-dependent Cox proportional-hazards models. Over a mean follow-up of 2 years, 65 patients (15.7%) progressed to SCAF >24 hours or clinical AF (incidence rate 8.8%/year). The rate of CHF hospitalization among patients with versus without SCAF progression was 8.9 and 2.5%/year, respectively. SCAF progression was independently associated with CHF hospitalization in multivariable models (HR 4.58, 95%-CI 1.64 – 12.8, p=0.004). Similar results were observed after exclusion of patients with prior history of CHF (7.06, 95%-CI 1.82-27.3, p=0.005); when examining progression in patients with SCAF between >6 minutes and 12 hours in the first year (HR 7.73, 95%-CI 2.52-23.8, p < 0.001); and when defining SCAF progression as >24 hours only (HR 3.68, 95%-CI 1.27-10.7, p=0.016). Older age (HR 1.59, 95%-CI 1.05-2.39 per 10 year increment), increasing body mass index (HR 1.83, 95%-CI 1.14-2.94 per 10 kg/m2 increment) and longer SCAF duration within the first year of enrollment (HR 1.13, 95%-CI 1.09-1.17 per 1 hour increment) were independent predictors of SCAF progression. In this prospective cohort of older, hypertensive patients with an implanted pacemaker or defibrillator, SCAF progression was a strong and independent predictor of CHF hospitalization.

Involvement of Cytokines in the Pathogenesis of Salt and Water Imbalance in Congestive Heart Failure.

Congestive heart failure (CHF) has become a major medical problem in the western world with high morbidity and mortality rates. CHF adversely affects several systems, mainly the kidneys and the lungs. While the involvement of the renin–angiotensin–aldosterone system and the sympathetic nervous system in the progression of cardiovascular, pulmonary, and renal dysfunction in experimental and clinical CHF is well established, the importance of pro-inflammatory mediators in the pathogenesis of this clinical setting is still evolving. In this context, CHF is associated with overexpression of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1, and IL-6, which are activated in response to environmental injury. This family of cytokines has been implicated in the deterioration of CHF, where it plays an important role in initiating and integrating homeostatic responses both at the myocardium and circulatory levels. We and others showed that angiotensin II decreased the ability of the lungs to clear edema and enhanced the fibrosis process via phosphorylation of the mitogen-activated protein kinases p38 and p42/44, which are generally involved in cellular responses to pro-inflammatory cytokines. Literature data also indicate the involvement of these effectors in modulating ion channel activity. It has been reported that in heart failure due to mitral stenosis; there were varying degrees of vascular and other associated parenchymal changes such as edema and fibrosis. In this review, we will discuss the effects of cytokines and other inflammatory mediators on the kidneys and the lungs in heart failure; especially their role in renal and alveolar ion channels activity and fluid balance.

Retrospective study of efficacy and safety of neoadjuvant docetaxel, carboplatin, and trastuzumab in HER2-positive locally advanced and oligometastatic breast cancer: An Indian experience.

The neoadjuvant chemotherapy in HER2-positive breast cancer consists of a chemotherapy backbone and HER2-directed therapy. The increase in cardiotoxicity by the use of trastuzumab with an anthracycline-based regimen has led to the use of nonanthracycline-based alternative regimens. The docetaxel, carboplatin, and trastuzumab (TCH) are one such regimen. The efficacy and toxicity of this regimen have not been widely studied in Indian patients. This retrospective study aims to evaluate the efficacy and toxicity of neoadjuvant TCH regimen in locally advanced and oligometastatic HER2-positive breast cancer in Indian patients. The hospital records between January 2014 and December 2016 were reviewed to identify patients with locally advanced and oligometastatic HER2-positive breast cancer treated with uniform 3-weekly neoadjuvant chemotherapy protocol-containing docetaxel (75 mg/m2), carboplatin (AUC = 6), and trastuzumab (8 mg/kg loading followed by 6 mg/kg) (TCH). The primary outcome was the pathologic complete response (pCR), which was defined as an absence of invasive and noninvasive cancer in breast or lymphnode. Thirty-two patients with mean age 46 years met our inclusion criteria, of these 24 patients had locally advanced breast cancer, and eight patients had oligometastatic breast cancer. 13 (40.6%) patients had hormone-positive breast cancer. The objective response rate as assessed clinically was 100%, and pCR rate was 36.3%. The patients with oligometastatic breast cancer also showed a good response to chemotherapy with three patients showing pCR and four patients showing resolution disease at metastatic sites. The patients experienced very few Grade III/IV toxicities, and no patient had clinical congestive heart failure. The TCH protocol is an efficacious neoadjuvant chemotherapy regimen for locally advanced and oligometastatic breast cancer and is safe and well tolerated in this population.

Cardiac Imaging in Heart Failure with Comorbidities.

: Imaging modalities stand at the frontiers for progress in congestive heart failure (CHF) screening, risk stratification and monitoring. Advancements in echocardiography (ECHO) and Magnetic Resonance Imaging (MRI) have allowed for improved tissue characterizations, cardiac motion analysis, and cardiac performance analysis under stress. Common cardiac comorbidities such as hypertension, metabolic syndromes and chronic renal failure contribute to cardiac remodeling, sharing similar pathophysiological mechanisms starting with interstitial changes, structural changes and finally clinical CHF. These imaging techniques can potentially detect changes earlier. Such information could have clinical benefits for screening, planning preventive therapies and risk stratifying patients. Imaging reports have often focused on traditional measures without factoring these novel parameters. This review is aimed at providing a synopsis on how we can use this information to assess and monitor improvements for CHF with comorbidities.

Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer: A Phase II Trial of the NSABP Foundation Research Group, FB-5

BackgroundThe purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC). Patients and MethodsPatients received every 3 week treatment with 4 cycles of EC (90/600 mg/m2) followed by 4 cycles of docetaxel (100 mg/m2). Targeted therapy with standard-dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year. Coprimary end points were (1) rate of cardiac events (CEs) in all patients defined as clinical congestive heart failure with a significant decrease in left ventricular ejection fraction or cardiac deaths; and (2) pathologic complete response (pCR) in breast and nodes in the neoadjuvant cohort. An independent cardiac review panel determined whether criteria for a CE were met. ResultsA total of 105 patients were accrued, 76 with LABC treated with neoadjuvant therapy and 29 with PS3BC treated with adjuvant therapy. Median follow-up was 59.2 months. Among 99 evaluable patients for cardiac safety, 4 (4%; 95% confidence interval [CI], 1.1%-10.0%) met CE criteria. The pCR percentage in LABC patients was 46% (95% CI, 34%-59%). Five-year recurrence-free survival (RFS) and overall survival (OS) for all patients was 79.9% and 90.8%, respectively. ConclusionThe regimen met predefined criteria for activity of interest with an acceptable rate of CEs. Although the pCR percentage was comparable with chemotherapy regimens with trastuzumab alone the high RFS and OS are of interest in these high-risk populations.

0476 : Clinical characteristics and predictors of mortality at six months of patients hospitalized for acute heart failure

Heart failure is known as a major cause of morbidity and mortality in developed countries. Few data are currently available on the demographic and clinical characteristics and prognosis of patients hospitalized for acute heart failure. To determine the clinical characteristics and predictors of 6- month mortality of patients admitted for acute heart failure. Retrospective Study on 234 patients hospitalized for acute heart failure. The demographic, clinical, echocardiographic and laboratory data were collected and tested by univariate and multi-variate studies to identify prognostic markers. The mean age was 65 ± 13.8 years, 65% were male. Hypertension was noted in 60.3% and 51.7% diabetes. 60.3% had a clinical congestive heart failure. The main causes of HF were ischemic heart disease (48.7%), Hypertension (21.4%) and dilated cardiomyopathy (14.5%). The precipitating factor most frequently noted was ischemic attack (35%) followed by pulmonary disease (20.5%). 97% of our patients had received transthoracic echocardiography, among them 46.6% had a normal ejection fraction and 17.2% had a severe left ventricular dysfunction. At the exit, the use of an inhibitor of the renin angiotensin system was observed in 86.8% and that of beta-blockers in 41.5% of patients. The mortality rate at 6 months was 11.2%. In multivariate analysis, independent predictors of mortality at 6 months were: QRS width > 130 ms, hyperglycemia on admission, higher HbA1C, worsening of renal function during the stay and non-use of beta-blockers to the output. The predictive prognostic factors for mortality in the medium and long ermes are still poorly studied. In our study, independent predictors of mortality at 6 months were: wide QRS > 130 ms, hyperglycemia on admission, a high A1C, worsening of renal function during the hospitalization and non-use of beta-blockers on exit. The author hereby declares no conflict of interest

Abstract P6-03-09: Genetic polymorphism and correlation with treatment induced cardiotoxicity and prognosis in HER2 amplified early breast cancer patients

Abstract Introduction: Small studies have indicated a possible correlation between a HER2 gene polymorphism at codon 655 and trastuzumab-associated cardiotoxicity. Association between a synonymous coding variant rs7853758 within the SLC28A3 gene and anthracycline induced cardiotoxicity has also been reported. This study aimed to validate these correlations and assess for any relationship with prognosis. Methods: Genomic DNA was isolated from 666 patients enrolled in a large trial of adjuvant chemotherapy in HER2 amplified early breast cancer (BCIRG 006). Genotyping was conducted using Sequenom MassARRAY System for HER2 G-&amp;gt;A polymorphism at amino acid codon 655 (rs1136201) and variant rs7853758 (L461L) within the SLC28A3 gene. Results: Of the 666 patients analyzed, 216 patients were treated with anthracycline based therapy, 226 with trastuzumab based therapy, and 224 with regimens containing both an anthracycline and trastuzumab. Compared with the overall results of the BCIRG006 study (N=3,222), in the subset of patients genotyped in this analysis, a less robust improvement in disease free survival (DFS) was observed for the trastuzumab arms than control arm (HR, 0.821). When stratified for prognostic features, the hazard ratio in favor of trastuzumab was consistent with that of the overall study (HR, 0.674). Samples from 662 patients were successfully genotyped for rs1136201. Of these, 424 (64%) were AA, 30 (4.5%) were GG, 208 (31%) were AG genotype. Samples from 665 patients were successfully genotyped for rs7853758. Of these, 19 (3%) were AA, 475 (71%) were GG, and 171 (26%) were AG genotype. There was no correlation seen between mean left ventricular ejection fraction (LVEF) and HER2 genotype at codon 655 in patients treated with trastuzumab. Of patients tested for the HER2 polymorphism, cardiac dysfunction [defined as &amp;gt; 10% decline in LVEF or clinical congestive heart failure (CHF)] developed in 16% of patients with AA, 17% of patients with GG and 20% of patients with AG. There was also no correlation between mean LVEF and variant rs7853758 in patients treated with anthracyclines. The percentage of patients who developed cardiac dysfunction was 13%, 17% and 21% in AA, GG, and AG genotypes respectively. No correlation between disease free survival and any of the genotypes was seen. Conclusion: In the largest analysis to date to evaluate for relationship between cardiac toxicity and HER2 polymorphism, we did not find a correlation with rs1136201 HER2 polymorphism and trastuzumab induced cardiac toxicity. Our study also did not show a correlation between variant rs7853758 (L461L) and anthracycline induced cardiotoxicity. Neither polymorphism correlated with prognosis. Citation Format: Peddi PF, Hurvitz SA, Fasching PA, Wang L, Cunningham J, Weinshilboum RM, Liu D, Quinaux E, Fourmanoir H, Robert NJ, Valero V, Crown J, Falkson C, Brufsky A, Pienkowski T, Eiermann W, Martin M, Bee V, Slamon DJ. Genetic polymorphism and correlation with treatment induced cardiotoxicity and prognosis in HER2 amplified early breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-03-09.

Abstract 9998: Prognosis of Low Normal Left Ventricular Ejection Fraction in an Asymptomatic Population -based Adult Cohort. MESA

Introduction: A reduced left ventricular ejection fraction (LVEF) is associated with adverse cardiovascular events; however, the optimal threshold for a “normal” LVEF is uncertain. In general a LVEF ≥ 55% is considered “normal” by guidelines, with a low normal designation for LVEF 50-55%. We assess the prognosis of participants with low normal LVEF (LN-EF) in the Multi Ethnic Study of Atherosclerosis. All participants were asymptomatic and had no known clinical CVD at baseline. Methods: 4669 out of 5004 had LVEF of ≥ 50% assessed using cardiac MRI (SSFP), had no significant valvular disease (- VD), did not have MI during follow up (-MI), had complete data and included in analysis. 475/4669(10.2%) had LN-EF. Cox proportional hazard and cubic spline analyses were used to assess the association of low normal LVEF and 10 years of adjudicated incident congestive heart failure(CHF) and all- cause mortality adjusting for age gender and race( model 1) and model 2: model 1 + DM, smoking, SBP, BP meds, BMI, creatinine, LDL, family history and educational status. Model 3: model 2 + LV mass. Results: Age averaged 61± 10yrs, 46% were men, 35% had BP meds, 8% T2DM. After 10.2 years of follow up, 112 developed CHF and 425 died. 87/112 CHF events had LVEF available at diagnosis [45 had a LVEF≥ 50%-HFPEF and 42 had LVEF&lt;50%-HFREF]. Table 1 shows our results.. Using LVEF of 55% as reference the risk of CHF in individuals with LVEF≥ 50% is non- linear (Figure 1). Conclusion: In asymptomatic population based adults -VD, -MI, LN-EF is prevalent(10.2%) and is an independent predictor of future clinical CHF. LN-EF is not associated with mortality. Future CHF prevention measures should also focus on individuals with LN-EF.

Adult Transfusion-Dependent Thalassemia Patients in 2014: A Single Center Cross-Sectional Analysis of Health Outcomes

Introduction: Adults with transfusion-dependent thalassemia syndromes are living into adulthood as a result of safer transfusion therapies and iron chelation. However, these patients continue to require regular care for co-morbidities from iron overload, liver failure, bone disease, transfusion-acquired viral infections, and cardiac disease. The purpose of this study was to provide a cross-sectional descriptive analysis of thalassemia patients by age groups.Methods: A retrospective review of electronic medical records was carried out from patients with transfusion-dependent (>8 transfusions per year) thalassemia major or thalassemia intermedia at the Weill Cornell Comprehensive Thalassemia Center. Information on demographics, diagnosis, severity, chelation therapy, and co-morbidities was collected. Iron overload was assessed by calculating average ferritin measurements over 12 months as well as liver iron content (LIC) and cardiac iron content measured by T2*-weighted MRI. Systemic inflammation was measured by serum markers (interleukin 6 and total complement activity; CH50).Results: Our study population consisted of 65 patients (median age = 36.8, range 16-63). 41 female patients and 24 male patients were identified. The majority of patients (n = 49) had thalassemia major, thirteen patients had thalassemia intermedia (TI), one patient had hemoglobin Lepore, one patient had alpha thalassemia major, and one patient had Hemoglobin E/beta thalassemia.98% of patients (n = 64) were on chelation therapy; 64% (n = 41) were using deferasirox, 20% (n = 11) were using deferiprone and desferoxamine in combination, and 14% (n = 9) were using deferiprone. Two patients were using desferoxamine alone, and one patient was using deferasirox and desferoxamine in combination. The median CH50 was 103 % activity (range 0-182) with a median average ferritin of 1128ng/ml (range 251-7956). The median LIC was 2.821 mg/g dry weight (range 0.5 – 135), and median cardiac iron content was 34 msec (range 7-50 msec).In total, there were 26 patients with Hepatitis C (40%), 2 patients (3%) with Hepatitis B, no cases of HIV, and 2 cases of malignancy. 13 patients (20%) had a history of clinical congestive heart failure and 6 patients (9.4%) had pulmonary hypertension. Seven patients (10.8%) had insulin dependent diabetes mellitus. There were no cases of hypertension, myocardial infarction, or coronary artery disease.Patients were subdivided into 5 groups by age: < 20, 20-30, 31-40, 41-50, and > 50 years of age. The mean average ferritin values were significantly decreased with increasing age (p = 0.001), accompanied by a significant decrease in LIC (p < 0.0001). Age was not associated with cardiac iron T2 (p = 0.14). The prevalence of Hepatitis C and pulmonary hypertension was significantly greater with increasing age (p < 0.0001 and p = 0.009, respectively). Diabetes showed a non-significant trend towards greater prevalence with increasing age (p = 0.08). There were no significant differences in inflammatory markers between the different age groups (p = 0.28 for IL-6 and p = 0.31 for CH50).Conclusion: Transfusion-dependent thalassemia populations now spend the majority of their lives as adults. Oral chelation strategies are preferred by most patients. Adults over 40 are more likely to have HCV infection, diabetes, pulmonary HTN. Even in patients over 40, coronary artery disease, hypertension, and malignancy were rare. More research is needed to establish chronic disease epidemiology in adults with transfusion-dependent thalassemia. DisclosuresNo relevant conflicts of interest to declare.

Abstract 12978: Incident Atrial Fibrillation is Similar in Blacks and Whites With Congestive Heart Failure

Introduction: Clinical studies have demonstrated that blacks have a lower prevalence and incidence of atrial fibrillation (AF) compared with whites. Given the strong biologic associations between AF and congestive heart failure (CHF), we hypothesized that the racial disparity for incident AF is attenuated in CHF patients. Methods: The University of Pennsylvania Atrial Fibrillation Free-Congestive Heart Failure (PAFF-CHF) Cohort is a large, multi-hospital retrospective cohort of individuals with clinical CHF and without AF at index visit. Baseline demographic and clinical parameters were obtained, and medical records were queried for incident outcomes. The primary outcome was incident AF, which was defined as a clinical or ECG diagnosis of AF on any follow up encounter. Results: Of 5,131 patients in PAFF-CHF, there were 2,037 blacks (40%) and 3,094 whites (60%). Median follow up time was 4.5 years (1.8, 5.9), with blacks having significantly longer follow up (4.7 v 4.2 yr, p &lt; 0.001). During this follow-up, 851 subjects (16%) developed AF, with rates of 5.1 per 100 person years in whites and 4.9 per 100 person years in blacks (p = 0.8). Time independent risk factors for developing AF included male gender (OR 1.42 [95% CI 1.22 - 1.65], p &lt; 0.001); LBBB on index ECG (1.32 [1.01 - 1.72], p = 0.04); and black race (OR 1.31 [1.13 - 1.52], p &lt; 0.001). In a regression model of traditional risk factors for AF including age, gender, hypertension, coronary artery disease, diabetes, and renal insufficiency, black race remained an independent risk factor for AF (OR 1.45 [1.23 - 1.70], p &lt; 0.001). Finally, time to event analysis showed no difference in freedom from AF and no difference in freedom from AF or death (Figure). Conclusions: In a large cohort of HF patients, incident AF was similar in blacks and whites. Although prior studies have indicated a low prevalence and incidence of AF in blacks compared with whites, the development of AF appears to be a common finding in both races after a diagnosis of CHF.