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A right ventricular assist device (RVAD) using a dual-lumen percutaneous cannula inserted through the right internal jugular vein (IJV) might improve weaning in patients with refractory right ventricular (RV) failure. However, the reported experience with this cannula is limited. We reviewed the records of all patients receiving RVAD support with this new dual-lumen cannula at our institution between April 2017 and February 2019. We recorded data on weaning, mortality, and device-specific complications. We compared outcomes among three subgroups based on the indications for RVAD support (postcardiotomy, cardiogenic shock, and primary respiratory failure) and against similar results in the literature. Mean (standard deviation [SD]) age of the 40 patients (29 men) was 53 (15.5) years. Indications for implantation were postcardiotomy support in 18 patients, cardiogenic shock in 12, and respiratory failure in 10. In all, 17 (94%) patients in the postcardiotomy group were weaned from RVAD support, five (42%) in the cardiogenic shock group, and seven (70%) in the respiratory failure group, overall higher than those reported in the literature (49% to 59%) for surgically placed RVADs. Whereas published in-hospital mortality rates range from 42% to 50% for surgically placed RVADs and from 41% to 50% for RVADs with percutaneous cannulas implanted through the right IJV, mortality was 11%, 58%, and 40% in our subgroups, respectively. There were no major device-related complications. This percutaneous dual-lumen cannula appears to be safe and effective for managing refractory RV failure, with improved weaning and mortality profile, and with limited device-specific adverse events.

Background: The 2017 AHA/ACC/HFSA Focused Update of the 2013 ACC/AHA Guidelines for the Management of Heart Failure provided additional support for the clinical use of ACEI, ARBs or ARNIs in conjunction with Evidence-Based Beta Blockers and Aldosterone Antagonists in HFrEF, otherwise known as Guideline-Directed Medical Therapy (GDMT). Although these updates clarified the benefits of GDMT to patient outcomes, low rates of adherence at the provider level for both hospitalized and ambulatory patients continue to be seen. Methods: With the objective of rapidly improving GDMT utilization, as well as improving patient outcomes, the American Heart Association initiated a multidisciplinary collaborative in three metropolitan markets - Chicago, Milwaukee, and St. Louis. Utilizing Get With The Guidelines®-Heart Failure (GWTG-HF), 40 hospitals tracked patients discharged with a primary diagnosis of heart failure and entered data from their inpatient and 30-days post-acute record. An initiative benchmark group was created to track progress and revisions were made to the post-acute care form. Hospitals were provided targeted consultation using hospital-specific data compared to regional and initiative benchmarks. The initiative provided exclusive professional education, including webinars, collaboration meetings, and best-practice recommendations. Results: Between January 1, 2019 and December 31, 2019, 10,532 patients with a primary diagnosis of heart failure, were entered into GWTG-HF from the 40 initiative hospitals, in which 3807 had an EF of Conclusions: The multi-city quality initiative early results show a positive correlation in improving adherence to GDMT in both the hospital and ambulatory setting.

Purpose An increasing number of heart failure patients are being supported by a ventricular assist device (VAD). Historically, assessment of a patient's hemodynamic status and optimization of VAD performance has been conducted using right heart catheterization and/or echocardiography. The HeartWare HVAD flow waveform displays the blood flow rate through the VAD using a flow estimation algorithm. Our hypothesis is the flow waveform can be utilized to calculate blood volume that is processed by the VAD. Methods An image of the HVAD waveform was obtained for five patients (66 ± 13.1 years, 80% male, 60% Caucasian, MAP 81.4 ± 16.9 mmHg, LVEF 22.0 ± 7.1 %, 2560 ± 40 rpms) while hemodynamic measurements were recorded. A program was written that analyzed the waveform image and calculated blood flow through the VAD by applying integration over a cardiac cycle (Figure 1). Stroke volume measured by hemodynamic monitoring was used to determine the percentage of blood flow going through the VAD versus native heart contribution. Results Average stroke volume calculated using measured hemodynamics was 71.0 ± 15.7 mL and VAD cardiac cycle volume was 36.8 ± 7.1 mL giving an average contribution of 52.0% VAD versus 48.0% native heart for the patient cohort. Figure 2 illustrates the results for each patient. Conclusion VAD cardiac cycle volume can aid in quantifying the contribution of the VAD and the workload of the native heart. This algorithm can be utilized as a new metric in optimizing VAD function, improving patient hemodynamics and assessing for myocardial recovery.

Background— Oxidative stress may contribute to heart failure (HF) progression. Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes. Methods and Results— We randomly assigned 253 patients with symptomatic HF, left ventricular ejection fraction ≤40%, and serum uric acid levels ≥9.5 mg/dL to receive allopurinol (target dose, 600 mg daily) or placebo in a double-blind, multicenter trial. The primary composite end point at 24 weeks was based on survival, worsening HF, and patient global assessment. Secondary end points included change in quality of life, submaximal exercise capacity, and left ventricular ejection fraction. Uric acid levels were significantly reduced with allopurinol in comparison with placebo (treatment difference, –4.2 [–4.9, –3.5] mg/dL and –3.5 [–4.2, –2.7] mg/dL at 12 and 24 weeks, respectively, both P P =0.68). At 12 and 24 weeks, there was no significant difference in change in Kansas City Cardiomyopathy Questionnaire scores or 6-minute walk distances between the 2 groups. At 24 weeks, left ventricular ejection fraction did not change in either group or between groups. Rash occurred more frequently with allopurinol (10% versus 2%, P =0.01), but there was no difference in serious adverse event rates between the groups (20% versus 15%, P =0.36). Conclusions— In high-risk HF patients with reduced ejection fraction and elevated uric acid levels, xanthine oxidase inhibition with allopurinol failed to improve clinical status, exercise capacity, quality of life, or left ventricular ejection fraction at 24 weeks. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00987415.

Background Diabetes mellitus (DM) is an independent predictor of mortality in patients with heart failure (HF). Glycosylated hemoglobin (HbA1c) testing is the standard of care for monitoring glycemic control in DM patients. We sought to investigate the reliability of HbA1c testing in Stage D HF patients who require left ventricular assist device (LVAD) support. Methods We retrospectively reviewed patients who underwent LVAD implantation at an academic medical center between 1/1/2012 and 12/31/2018. We reviewed pre-VAD clinical data to help identify patients who carried a pre-LVAD diagnosis of DM, based on the following American Diabetic Association (ADA) criteria: 1) pre-LVAD glycosylated hemoglobin (HbA1c) ≥6.5% or 2) pre-LVAD HbA1c Results Amongst 108 patients with LVAD implants, 52 (48%) carried a pre-LVAD diagnosis of DM based on the above outlined criteria. Baseline characteristics of DM vs non-DM patients were comparable for age (56 ±11.7 years), gender (male 70%), bridge-to-transplantation LVAD (54%), HeartWare LVAD (77%), and days on LVAD support (325 ±318.9 days), but different for ischemic HF etiology (39% vs 17%, p=0.016), BMI (31.5 ±5.9 vs 27.9 ±6.8 kg/m2, p=0.007), and length of stay following LVAD implant (39 ±29.7 vs 25 ±17.4 days, p=0.005). Thirty-eight out of 52 DM patients had more than 90 days of follow-up while on LVAD support, accounting for a cumulative set of 72 HbA1c/APG readings. Prior to LVAD implant, mean comparisons between HbA1c and eHbA1c were similar (7.2 ±1.4% vs 7.1 ±1.5%, p=0.517). During LVAD support, means of HbA1c and eHbA1c were different (6.4 ±1.6% vs 7.2 ±1.9%, p Conclusion Discrepancies noted between HbA1c and eHbA1c raises concern for the reliability of HbA1c testing for DM management in Stage D HF patients on LVAD support.

Purpose Right ventricular (RV) failure is a frequent complication of left ventricular assist device (LVAD) implantation in patients with end-stage heart failure, impacting 20% of patients. Percutaneous support can be used in this scenario, however prior data supporting this approach showed survival at 30 days or hospital discharge was only 60%. Methods Retrospective review was conducted of all patients who developed severe RV failure requiring percutaneous right ventricular assist device (RVAD) following durable LVAD implant between 01/01/2017 and 07/31/2018. Patient demographics were reviewed in addition to key hemodynamic and laboratory values were collected pre-RVAD implantation and at the time of explant (post-RVAD). Pre-RVAD and post-RVAD data was compared using paired T tests. Survival at 30 days or at date of hospital discharge (whichever was longer) was considered as the primary outcome. Patient hemodynamic measures were evaluated as secondary outcomes. Results Of 41 patients who received LVAD, 10 (24%) developed severe RV failure postoperatively. Baseline characteristics include age 51±14.5 years, with 30% females. Incidence of ischemic cardiomyopathy was 20%. Most patients received LVAD as destination therapy (80%). RVAD support via percutaneous cannulation was maintained for a median duration of 15.5 days (Range - 7 to 23 days). Survival at 30 days or to hospital discharge was 100%. We observed a reduction in central venous pressure from 17.2±4.5 mm(Hg) to 11±3.1 mm(Hg), p=0.004 and an increase in LVAD flow from 4.5±0.8 l/min to 5.1±0.4 l/min, p=0.018. There was a trend towards increase in mixed venous oxygen saturation from 61.5±11.1% to 67.0±7.0%, p=0.224. Conclusion Percutaneous RVAD cannulation for treatment of RV failure after LVAD implantation provides superior early postoperative survival than traditional management techniques. These findings support broader implementation of this technique to further characterize its benefit.

Hyponatremia presumably is associated with adverse clinical outcomes in patients with congestive heart failure (CHF), but risk thresholds and economic burden are less studied. The authors analyzed 115,969 patients hospitalized for CHF and grouped them by serum sodium levels (severe hyponatremia, ≤130 mEq/L; hyponatremia, 131-135 mEq/L; normonatremia, 136-145 mEq/L; hypernatremia, >145 mEq/L). Univariable and multivariable analyses on the associated clinical and economic outcomes were performed. The most common abnormality was hyponatremia (15.9%), followed by severe hyponatremia (5.3%) and hypernatremia (3.2%). Hospital mortality was highest for severe hyponatremia (7.6%), followed by hypernatremia (6.7%) and hyponatremia (4.9%) (P

Introduction Heart Failure (HF) readmissions remain a critical issue for health care systems. HF Navigators (HFN) can streamline care transitions. Thus, we used an inpatient HFN to establish early follow up and “hand off” HF pts to an OP Care Coordinator (CC). Methods At our hospital, HF pts can be admitted to multiple IP units. A HF Unit (HFU) primarily admits higher risk pts. A single HFN was recruited to staff the HFU M-F. The HFN linked HF pts to a CC to at discharge. Most HF pts were referred to the OP CC although some pts received only HFN services and no CC due to difficulty identifying HF pts prior to discharge. Over the 14-month period, the HFN established early follow-up and the CC made regular telephone contact post discharge. The incremental contributions of the HFN and CC were evaluated to test the independent impact of each of these roles based on the serial implementation of these roles in distinct hospital units and based on whether or not a particular HF pt was cared for by the HFN and/or the CC. Results Thirty (30) day readmission rates were measured for pts admitted between October 17, 2016 and December 31, 2017. Patients with a primary, discharge diagnosis of HF were analyzed. HFN services were provided on the dedicated HF unit (HFU) as part of a pilot program and were not available on other IP units during this period. Concurrent 30-day all-cause readmission data were stratified and reported based on admitting unit, involvement of the HFN with or without CC. Of the 757 pts (non LVAD or Transplant) who were admitted to units other than the HFU, there were 160 pts readmitted (21.1%). There were 254 high risk (Includes LVAD and transplant pts) HF pts admitted to the HFU, and there were 75 pts readmitted (29.5%) in this cohort. There were 33 (non LVAD or transplant) pts admitted to the HFU with care provided by HFN but who did not receive a referral to CC, and 6 pts were readmitted (18.9%). Finally, of the 169 HF pts were admitted to the HFU and had access to a HFN and CC, with only 9 pts readmitted (5.33%). Conclusions In this analysis, there was a synergistic effect noted to drastically reduce HF readmission rates when an IP HFN and OP CC were involved in the care of hospitalized HF pts. The 5.33% 30 day all cause readmission rates noted is significantly better than rates reported in the literature and reflects the critical role of combining HFN care with care coordination in the OP setting. These data have solidified an interest to expand access to HFN and CC to all IP units and can serve as a model for care delivery to improve readmission rates for this high-risk population.

Background Compare outcomes of ultrafiltration (UF) versus standard intravenous (IV) diuretics by continuous infusion or bolus injection in volume overloaded heart failure (HF) patients. In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated heart Failure (UNLOAD) study, UF produced greater fluid reduction and fewer HF rehospitalizations than IV diuretics in 200 hospitalized HF patients. Outcomes may be due to greater fluid removal, but UF removes more sodium/unit volume than diuretics. Methods and Results Outcomes of 100 patients randomized to UF were compared with those of patients randomized to standard IV diuretic therapy with continuous infusion (32) or bolus injections (68). Choice of diuretic therapy was by the treating physician. Forty-eight hour weight loss (kg): 5.0 ± 3.1 UF, 3.6 ± 3.5 continuous infusion, and 2.9 ± 3.5 bolus diuretics ( P = .001 UF versus bolus diuretic; P > .05 for the other comparisons). Net fluid loss (L): 4.6 ± 2.6 UF, 3.9 ± 2.7 continuous infusion, and 3.1 ± 2.6 bolus diuretics ( P P > .05 for the other comparisons). At 90 days, rehospitalizations plus unscheduled visits for HF/patient (rehospitalization equivalents) were fewer in UF group (0.65 ± 1.36) than in continuous infusion (2.29 ± 3.23; P = .016 versus UF) and bolus diuretics (1.31 ± 1.87; P = .050 versus UF) groups. No serum creatinine differences occurred between groups up to 90 days. Conclusions Despite similar fluid loss with UF and continuous diuretic infusion, fewer HF rehospitalizations equivalents occurred only with UF. Removal of isotonic fluid by UF compared with hypotonic urine by diuretics more effectively reduces total body sodium in congested HF patients.

Background The treatment of acute decompensated heart failure remains problematic and most often requires parenteral therapies. Significant concerns have been expressed regarding risks and benefits of individual therapies, especially nesiritide (NES), but few studies have compared the relative safety of varied intravenous therapies on clinical outcomes. Methods We compared the safety of intravenous diuretics (DIUR), inotropes (INO), and vasodilators (nitroglycerin [NTG]) on mortality rates and worsening renal function in 99 963 inpatients with acutely decompensated heart failure (ADHF). Patients with a diagnosis of ADHF within 48 hours were grouped by intended primary treatment (intravenous agents administered during the first 2 hours of intravenous therapy). Treatments studied were (a) intended monotherapy (DIUR), (b) intended combination therapy (DIUR + NES, NTG, or INO), and (c) sequential therapy (intended DIUR monotherapy followed by a second agent administered >2 hours later). Propensity-matched cohorts and instrumental analysis were used to adjust for differences among patients in treatment groups. Results Intended DIUR monotherapy yielded an unadjusted inpatient mortality rate of 3.2%. After intended DIUR monotherapy, inpatient mortality was not higher for sequential use of NES than for sequential use of NTG (3.4% vs 6.2%, P = .0028). In all regimens, INOs were associated with higher inpatient mortality than were diuretics or vasodilators used alone. The rate of worsening renal function was higher with combination of diuretic-based regimens with NES (risk ratio 1.44, P P = .012) compared with diuretics alone. Conclusions Compared with alternative intravenous regimens, administration of vasodilators, including NES, was not associated with increased inpatient mortality. A large randomized controlled clinical trial is being planned to prospectively address the question of risks and benefits of NES for ADHF.

Objectives This study was designed to compare the safety and efficacy of veno-venous ultrafiltration and standard intravenous diuretic therapy for hypervolemic heart failure (HF) patients. Background Early ultrafiltration may be an alternative to intravenous diuretics in patients with decompensated HF and volume overload. Methods Patients hospitalized for HF with ≥2 signs of hypervolemia were randomized to ultrafiltration or intravenous diuretics. Primary end points were weight loss and dyspnea assessment at 48 h after randomization. Secondary end points included net fluid loss at 48 h, functional capacity, HF rehospitalizations, and unscheduled visits in 90 days. Safety end points included changes in renal function, electrolytes, and blood pressure. Results Two hundred patients (63 ± 15 years, 69% men, 71% ejection fraction ≤40%) were randomized to ultrafiltration or intravenous diuretics. At 48 h, weight (5.0 ± 3.1 kg vs. 3.1 ± 3.5 kg; p = 0.001) and net fluid loss (4.6 vs. 3.3 l; p = 0.001) were greater in the ultrafiltration group. Dyspnea scores were similar. At 90 days, the ultrafiltration group had fewer patients rehospitalized for HF (16 of 89 [18%] vs. 28 of 87 [32%]; p = 0.037), HF rehospitalizations (0.22 ± 0.54 vs. 0.46 ± 0.76; p = 0.022), rehospitalization days (1.4 ± 4.2 vs. 3.8 ± 8.5; p = 0.022) per patient, and unscheduled visits (14 of 65 [21%] vs. 29 of 66 [44%]; p = 0.009). No serum creatinine differences occurred between groups. Nine deaths occurred in the ultrafiltration group and 11 in the diuretics group. Conclusions In decompensated HF, ultrafiltration safely produces greater weight and fluid loss than intravenous diuretics, reduces 90-day resource utilization for HF, and is an effective alternative therapy. (The UNLOAD trial; http://clinicaltrials.gov/ct/show/NCT00124137?order=1; NCT00124137).

Objectives The study purpose was to examine “gray zone” B-type natriuretic peptide (BNP) levels (100-500 pg/mL) in terms of associated clinical factors, perceived severity, and outcomes in patients with established congestive heart failure (CHF). Background Although gray zone BNP levels may have diagnostic ambiguity, the implications of these levels in patients with an established diagnosis of CHF have not been examined. Methods REDHOT was a national prospective study in which 464 patients seen in the emergency department with dyspnea had BNP levels drawn. Entrance criteria included a BNP >100 pg/mL; however, physicians were blinded to the actual BNP level. Patients were followed up for 90 days. Results Thirty-three percent had gray zone BNP levels. There was no difference in perceived New York Heart Association class ( P = .32) or admission rates ( P = .76) between the gray zone and non–gray zone groups; 62% of patients with a gray zone BNP were identified as class III or IV CHF. Despite this perceived severity, the 90-day event rate was lower in the gray zone group (19.2% vs 32.9%, respectively, P = .002). Although patients in the gray zone had more symptoms of concomitant pulmonary disease, multivariate analysis could not demonstrate any variable that worsened the prognosis of patients with a gray zone BNP level. Conclusions In patients with established CHF, those with gray zone BNP levels have a better prognosis than those with non–gray zone levels despite being perceived by physicians as having New York Heart Association class III or IV CHF.

Background Previous studies have shown that in patients presenting to the emergency department (ED) with heart failure, there is a disconnect between the perceived severity of congestive heart failure (CHF) by physicians and the severity as determined by B-type natriuretic peptide (BNP) levels. Whether ethnicity plays a role in this discrepancy is unknown. Methods and Results The Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) was a 10-center trial of 464 patients seen in the ED with acute dyspnea and BNP level higher than 100 pg/mL on arrival. Physicians were blinded to BNP levels. Patients were followed for 90 days after discharge. A total of 151 patients identified themselves as white (32.5%) and 294 as black (63.4%). Of these, 90% were hospitalized. African Americans were more likely to be perceived as New York Heart Association class I or II than whites ( P = .01). Blacks who were discharged from the ED had higher median BNP levels than whites who were discharged (1293 vs. 533, P = .004). The median BNP of blacks who were discharged was actually higher than the median BNP of blacks who were admitted (1293 vs. 769, P = .04); the same did not hold true for whites. BNP was predictive of 90-day outcome in both blacks and whites; however, perceived severity of CHF, race, and ED disposition did not contribute to the prediction of events. Conclusion In patients presenting to the ED with heart failure, the disconnect between perceived severity of CHF and severity as determined by BNP levels is most pronounced in African Americans.

Heart failure (HF) is a major medical problem in the United States, imposing significant economic burden on the health care system. Despite therapeutic advances, HF-associated morbidity and mortality continue to increase. Compliance with therapeutic guidelines for the management of chronic HF is far from ideal, increasing the likelihood that patients will experience multiple episodes of acute decompensated heart failure (ADHF) during the course of HF disease. Prevention, streamlined inpatient care, effective vasoactive therapy, and initiation of proven long-term therapies, including angiotensin-converting enzyme (ACE) inhibitors and beta-blockers, are all targets for improvement. Because of the chronic nature of heart failure, a successful disease management program for ADHF must also include effective outpatient care.

The Follow-Up Serial Infusions of Nesiritide pilot study was designed to assess the safety and tolerability of outpatient serial infusions of nesiritide in 210 patients with decompensated heart failure who were randomly assigned to usual care only or usual care plus weekly infusions of nesiritide at dosages of 0.005 or 0.01 microg/kg/min for 12 weeks. The mean age +/- SD of the entire population was 67 +/- 13 years; 70% were men, and 80% were white. Mean baseline serum creatinine levels were 1.8 +/- 0.7 mg/dl, and mean left ventricular ejection fraction was 0.28 +/- 0.15%. Diabetes mellitus was present in 106 patients (50%), and atrial arrhythmias were present in 100 patients (48%). A totalof 1,645 nesiritide infusions was administered; 11 (1%) were discontinued due to an adverse event. All treatment groups had a similar frequency of adverse events and experienced improvements in quality of life. Administration of nesiritide resulted in acute decreases in aldosterone and endothelin-1 concentrations. Although there were no statistically significant differences among groups by outcome, prospectively defined higher risk subgroups demonstrated significant decreases in cardiovascular events. These results demonstrate the safety and feasibility of administering nesiritide in an outpatient setting. Additional studies are needed to determine the effect of outpatient serial infusions of nesiritide on rates of morbidity and mortality in advanced heart failure.

Objectives The purpose of this study was to examine the relationships among B-type natriuretic peptide (BNP) levels within the diagnostic range, perceived congestive heart failure (CHF) severity, clinical decision making, and outcomes of the CHF patients presenting to emergency department (ED). Background Since BNP correlates with the presence of CHF, disease severity, and prognosis, we hypothesized that BNP levels in the diagnostic range offer value independent of physician decision making with regard to critical outcomes in emergency medicine. Methods The Rapid Emergency Department Heart failure Outpatient Trial (REDHOT) study was a 10-center trial in which patients seen in the ED with shortness of breath were consented to have BNP levels drawn on arrival. Entrance criteria included a BNP level >100 pg/ml. Physicians were blinded to the actual BNP level and subsequent BNP measurements. Patients were followed up for 90 days after discharge. Results Of the 464 patients, 90% were hospitalized. Two-thirds of patients were perceived to be New York Heart Association (NYHA) functional class III or IV. The BNP levels did not differ significantly between patients who were discharged home from the ED and those admitted (976 vs. 766, p = 0.6). Using logistic regression analysis, an ED doctor's intention to admit or discharge a patient had no influence on 90-day outcomes, while the BNP level was a strong predictor of 90-day outcome. Of admitted patients, 11% had BNP levels 200 pg/ml was 9% and 29%, respectively (p = 0.006). Conclusions In patients presenting to the ED with heart failure, there is a disconnect between the perceived severity of CHF by ED physicians and severity as determined by BNP levels. The BNP levels can predict future outcomes and thus may aid physicians in making triage decisions about whether to admit or discharge patients. Emerging clinical data will help further refine biomarker-guided outpatient therapeutic and monitoring strategies involving BNP.

Mechanical circulatory support device (MCSDs) have evolved during the past 2 decades to become accepted bridging therapy for patients with irreversible hemodynamic deterioration while awaiting cardiac transplantation. More recently, based on the results of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) study, MCSD therapy has become available as permanent or destination therapy for a restricted population of patients with advanced heart failure (AHF) not thought to be appropriate transplant candidates. The potential proliferation of new devices and the possible expansion of the target populations bring new responsibilities. Unlike pharmaceutical trials that have included thousands of patients, trials with MCSDs will continue to be performed on a relatively small scale because equipoise for randomization can be undermined by the unmasked nature of mechanical support, the logistics of study finances, and the continuous device improvements—all of which constrain trial size and duration. Currently, insufficient evidence beyond REMATCH criteria exists for refining potential long-term MCSD therapy candidate cohorts, and application of this challenging therapy is complicated further by the degree of institutional commitment, surgical expertise, multidisciplinary skills, available devices, and overall experience required for the successful application of mechanical circulatory support. The REMATCH trial was a landmark study that demonstrated the benefit of MCSDs in patients with AHF not eligible for transplantation. Patients supported with MCSDs had significantly better survival at 1 year than did patients with advanced end-stage heart failure who were treated medically (many with long-term parenteral inotropes). Although a survival benefit was clear, it was only over a 2-year time period, and morbidity was substantial, particularly with respect to infections, neurologic events, and pump malfunctions. These observations force us to consider carefully patient selection and the infrastructure of centers with strategies developed to provide this type of care. In the United States, the Food and Drug Administration (FDA) approval of the HeartMate From Columbia University, New York, New York; Cleveland Clinic Foundation, Cleveland, Ohio; Harvard University, Boston, Massachusetts; Stanford University, Stanford, California; University of Alabama at Birmingham, Birmingham, Alabama; University of California at Los Angeles, Los Angeles, California; University of Minneapolis, Minneapolis, Minnesota; Midwest Heart Specialists, Downers Grove, Illinois; Tufts–Northeast Medical Center, Boston, Massachusetts; University of Pittsburgh, Pittsburgh, Pennsylvania. Submitted February 7, 2002. Reprint requests: Mario C. Deng, MD, The Heart Failure Center and Division of Circulatory Physiology, Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital, Milstein Hospital Building, Room 5-407, 177 Fort Washington Avenue, New York, New York 10032. Telephone: 212-305-0200. Fax: 212-305-7439. E-mail: md785@columbia. edu J Heart Lung Transplant 2003;22:365–369 Copyright © 2003 by the International Society for Heart and Lung Transplantation. 1053-2498/03/$–see front matter doi:10.1016/S1053-2498(03)00073-1

Secondary and infiltrative cardiomyopathies are the least common forms of cardiomyopathy and often are the most difficult to treat. In all cases, efforts should be made to establish a specific diagnosis because the removal or avoidance of the causative agent (eg, alcohol, cocaine, persistent tachycardia) holds the best promise for reversal of ventricular dysfunction. Patients who present with a dilated cardiomyopathy (DCM) should be treated with standard heart failure therapy. However, the "standard" is changing and clinicians need to take heed of results of recent trials establishing the role of beta-blockers, aldosterone, and angiotensin receptor antagonists in addition to the regimen of digoxin, diuretics and angiotensin-converting enzyme (ACE) inhibitors. In contrast, patients who present with a more infiltrative clinical picture often manifest more diastolic dysfunction and need strict volume control to maintain euvolemia. For patients with biopsy-proven myocarditis, immunosuppressive therapy generally should be considered in an effort to maintain and potentially improve ventricular function. Patients with sarcoid heart disease have shown the greatest response to high-dose corticosteroids. Patients with hemochromatosis related cardiomyopathy should be treated with iron chelation therapy and phlebotomy. The role of cardiac transplantation is limited, as most of the secondary and infiltrative causes of cardiomyopathy are associated with an adverse posttransplant outcome. Other surgical options, such as left ventricular assist devices, may offer hope to patients who would otherwise be ineligible for cardiac transplantation. On the horizon, biventricular pacing and treatments targeted at cytokines and hormonal receptors hold the promise of improving symptoms and prolonging survival by counteracting the deleterious effects of these secondary mediators.

Background: B-type natriuretic peptide (BNP) is an established biomarker for diagnosis of acute heart failure (HF). However, criteria for interpreting BNP changes over time prior to clinical decompensation have not been well established. Methods: BNP concentrations were followed in 192 patients with HF who had at least 5 BNP measurements over 6 month to 2 year period. Decompensation was defined as a hospitalization for HF. For patients (N = 30) who had a recent (within 2 weeks) BNP measured prior to decompensation, BNP concentrations were examined to determine if there was a significant rise prior to decompensation. Results: For patients who had a BNP concentration measured within 2 weeks of decompensation, there was a significant increase in BNP concentration prior to decompensation. When patients with a baseline BNP 200 pg/ mL) decompensated, their concentrations changed by 62% ( p

Hyponatremia presumably is associated with adverse clinical outcomes in patients with congestive heart failure (CHF), but risk thresholds and economic burden are less studied. The authors analyzed 115,969 patients hospitalized for CHF and grouped them by serum sodium levels (severe hyponatremia, ≤130 mEq/L; hyponatremia, 131-135 mEq/L; normonatremia, 136-145 mEq/L; hypernatremia,145 mEq/L). Univariable and multivariable analyses on the associated clinical and economic outcomes were performed. The most common abnormality was hyponatremia (15.9%), followed by severe hyponatremia (5.3%) and hypernatremia (3.2%). Hospital mortality was highest for severe hyponatremia (7.6%), followed by hypernatremia (6.7%) and hyponatremia (4.9%) (P.0001). Compared with normonatremia, risk-adjusted mortality was highest for severe hyponatremia (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.59-1.99), followed by hypernatremia (OR, 1.55; 95% CI, 1.34-1.80) and hyponatremia (OR, 1.29; 95% CI, 1.19-1.40; all P.0001). Risk-adjusted hospital prolongation was greater for each level of sodium abnormality than for normonatremia, ranging from 0.42 (CI, 0.26-0.60) days for hypernatremia to 1.28 (CI, 1.11-1.47) days for severe hyponatremia. Risk-adjusted attributable hospital cost increase was highest for severe hyponatremia ($1132; CI, $856-$1425; all (P.0001). Sodium abnormalities were common in patients hospitalized for CHF. Adverse outcomes resulted not only from severe hyponatremia, but also from mild hyponatremia and hypernatremia.

Background: Many patients with heart failure remain symptomatic and have a poor prognosis despite existing treatments. Decreases in myocardial contractility and shortening of ventricular systole are characteristic of systolic heart failure and might be improved by a new therapeutic class, cardiac myosin activators. We report the first study of the cardiac myosin activator, omecamtiv mecarbil, in patients with systolic heart failure. Methods: We undertook a double-blind, placebo-controlled, crossover, dose-ranging, phase 2 trial investigating the effects of omecamtiv mecarbil ( formerly CK-1827452 ), given intravenously for 2, 24, or 72 h to patients with stable heart failure and left ventricular systolic dysfunction receiving guideline-indicated treatment. Clinical assessment ( including vital signs, echocardiograms, and electrocardiographs ) and testing of plasma drug concentrations took place during and after completion of each infusion. The primary aim was to assess safety and tolerability of omecamtiv mecarbil. This study is registered at ClinicalTrials.gov, NCT00624442. Findings: 45 patients received 151 infusions of active drug or placebo. Placebo-corrected, concentration-dependent increases in left ventricular ejection time ( up to an 80 ms increase from baseline ) and stroke volume ( up to 9·7 mL ) were recorded, associated with a small reduction in heart rate ( up to 2·7 beats per min; p < 0·0001 for all three measures ). Higher plasma concentrations were also associated with reductions in end-systolic ( decrease of 15 mL at > 500 ng/mL, p=0·0026 ) and end-diastolic volumes ( 16 mL, p=0·0096 ) that might have been more pronounced with increased duration of infusion. Cardiac ischaemia emerged at high plasma concentrations ( two patients, plasma concentrations roughly 1750 ng/mL and 1350 ng/mL ). For patients tolerant of all study drug infusions, no consistent pattern of adverse events with either dose or duration emerged. Interpretation: Omecamtiv mecarbil improved cardiac function in patients with heart failure caused by left ventricular dysfunction and could be the first in class of a new therapeutic agent. Funding: Cytokinetics Inc.

Background: Quality metrics for heart failure (HF) are increasingly utilized as an indicator of quality care. Mean length of stay (LOS) is a commonly utilized metric that is made available to the public but variability in LOS is not reported. Efforts to cohort HF pts in the hospital improve quality of care but the effect on LOS is less well defined. Methods: As part of an ongoing performance improvement project at ChristianaCare, LOS was evaluated using standard descriptive statistics. A LOS distribution was also generated monthly to visualize LOS variability. Comparisons were made for HF pts cohorted on a dedicated HF unit (HFU) vs. all other units (Other) and by inclusion/exclusion of HF pts with prolonged LOS > 10 days to reduce the effects of outliers. Results: 71 % of all HF patients were discharged in < 5 days, 82 % in < 10 days. Mean LOS (March 07–March 08) for HF was 6.63 days overall (6.1 HFU vs. 7.2 other; p = 0.05). After exclusion of long LOS HF pts, mean LOS fell to 4.4 days (4.3 HFU vs. 4.5 Other; p = 0.06). Median LOS for all HF patients was 5.0 days regardless of location. The standard deviation of LOS was significantly lower for HFU patients (4.5 vs. 11.5 days, p < 0.02) The LOS graph (Graph 1) highlights the wide variability in LOS and how mean statistics may be misleading. Conclusions: Mean LOS can be misleading as a metric for quality of HF care provided as outliers significantly impact this value. Other statistics and graphical displays can more accurately reflect quality of care. In addition, cohorting of HF patients significantly reduces overall variability in LOS and suggests a more consistent approach to acute HF care.

Early diagnosis and treatment of acute decompensated heart failure (ADHF) results in improved clinical outcomes, reduced resource utilization, improved quality of life, and lower treatment costs. Currently, heart failure results in nearly 1 million hospitalizations annually in the United States, and 50% of hospitalized patients are readmitted within 6 months of initial discharge. The costs associated with resource utilization are substantial. Despite the personal and societal burden of this condition, until recently, very little progress had been made in optimizing treatment of ADHF. Nesiritide, a human recombinant B-type natriuretic peptide, is a safe, effective vasodilator that can be easily used early in the emergency department to improve outcomes in ADHF.

IL-15 (p 0,005). To study whether the hyporesponsiveness is the result of regulation by Foxp3 /GITR T-cells or IL-10 producing cells we examined the mRNA expression levels of FoxP3, GITR and IL-10 after allogeneic stimulation. No difference was found in Foxp3 and GITR mRNA levels between responders and non-responders. In contrast, IL-10 mRNA expression was significantly higher in the population in which cytotoxic responsiveness against donor-antigens was not detectable (p 0,009). In conclusion, cardiac allograft recipients can develop donorspecific cytotoxic hyporesponsiveness, which is associated with high mRNA levels of IL-10. This observation suggests that in these patients the anti-donor response is suppressed by IL-10 producing regulators. Therefore, this group of cardiac allograft patients holds candidates for immunosuppression tapering protocols.

the relationship between left atrial volume index (LAVI) to PkVO2. Methods: In 82 patients with advanced systolic dysfunction (EF 19 8%), we measured LAVI by the biplane area-length method from apical 4 and 2-chamber views (indexed for body surface area). PkVO2 was measured by metabolic cart during maximal exercise and further adjusted to lean body mass (PkVO2lean). We have previously demonstrated that PkVO2lean cutoff of 19 ml/kg/min is better predictor of event free survival than unadjusted PkVO2. Results: In patients whose PkVO2lean was 19 ml/kg/min, the mean LAVI was 44.8 ml/m whereas LAVI was 54.7 ml/m2 in patients with PkVO2lean 19 ml/kg/min (p 0.04). An LAVI 65 ml/m 2 predicts PkVO2lean 19 ml/kg/min with a positive predictive value of 77% and a negative predictive value of 68%. Conclusions: Left atrial volume, a simple echocardiographic parameter, provides discriminatory prediction for functional circulatory impairment further in patients with severe systolic dysfunction. Thus, this investigation suggests that the finding of an increased left atrial volume index 65ml/m reflects worse diastolic dysfunction and should prompt assessment of metabolic reserve by cardiopulmonary stress testing.

sion (PH) is an essential component of pre-operative evaluation for cardiac transplantation in advanced heart failure. Sildenafil, a specific phosphodiesterase-5 inhibitor, has been shown to decrease pulmonary vascular resistance (PVR) and might serve as an important agent in evaluating heart failure related secondary PH. Methods: We evaluated 12 consecutive patients (50 14 years, 7 men, 6 non-ischemic cardiomyopathy, left ventricular ejection fraction 25 15%) with chronic heart failure and severe PH. Patients received oral doses of sildenafil 25 mg 50 mg (up to 3 doses 8 hours apart). All patients had a pulmonary artery catheter for invasive hemodynamic measurements and serial alterations in pulmonary artery pressures (PAP) were assessed. Result: PH was not responsive to use of baseline medications which included milrinone (n 7), dobutamine (n 7), nitroprusside (n 1) and nesiritide (n 3). Within 2 hours of the first oral dose of sildenafil, significant hemodynamic improvements were noted.

transplantation increases the risk of postoperative complications. The purpose of our current study was to test this hypothesis by evaluating 50 patients who were transplanted at our facility over the past six years. Seventeen (34%) of these patients had received amiodarone prior to transplantation while the remaining thirtythree (64%)had not. Endpoints of the study included: length of hospital stay, survival to hospital discharge, 30 day mortality, 6 month mortality, 1 year mortality, number of days ventilated, ARDS, hepatic failure, number of days paced, need for permanent pacemaker, refractory hypotension, and bleeding complications. There were no significant differences between the two groups in age, sex, etiology of heart failure, LVEF, preoperative platelet or INR values. Patients in the amiodarone group, however, were more likely to be on an assist device or IABP prior to transplantation compared to the non-amiodarone group (47% vs 12%, p50.005). There were no significant differences between the amiodarone and non-amiodarone groups in length of stay (21 vs 17 days, p50.72), 6 month mortality (29% vs 15%, p50.19), 1 year mortality (27% vs 18%, p50.5), days ventilated (8 vs 6, p50.7), ARDS (6% vs 0, p50.16), hepatic failure (18% vs 9%, p50.4), days paced (2 vs 2, p50.67), need for permanent pacemaker (0 vs 3%, p50.47), or refractory hypotension (18% vs 9%, p50.4). Amiodarone patients were less likely to survive to hospital disharge (71% vs 94%, p50.02) and a trend was seen for 30 day mortality (18% vs 3%, p50.07). They were also more likely to experience a bleeding complication (41% vs 9%, p50.007), even when patients on mechanical assist devices were excluded (33% vs 7%, p50.04). In conclusion, amiodarone patients were not at increased risk of ARDS, bradycardia, hepatic failure, or refractory hypotension. Amiodarone patients did experience more bleeding complications in the postoperative period. This finding has important clinical implications for many cardiac transplantation patients and warrants further investigation.

Objectives We sought to determine if ultrafiltration before intravenous (IV) diuretics in patients with decompensated heart failure and diuretic resistance results in euvolemia and early discharge without hypotension or worsening renal function. Background Heart failure patients with renal insufficiency and diuretic resistance have increased hospital mortality and length of stay. Peripheral veno-venous ultrafiltration may re-establish euvolemia and diuretic responsiveness. Methods Ultrafiltration was initiated within 4.7 ± 3.5 h of hospitalization and before IV diuretics in 20 heart failure patients with volume overload and diuretic resistance (age 74.5 ± 8.2 years; 75% ischemic disease; ejection fraction 31 ± 15%) and continued until euvolemia. Re-evaluation was each hospital day, at 30 days, and at 90 days. Results A total of 8,654 ± 4,205 ml were removed with ultrafiltration. Twelve patients (60%) were discharged in ≤3 days. One patient was readmitted in 30 days. Weight (p = 0.006), Minnesota Living with Heart Failure scores (p = 0.003), and Global Assessment (p = 0.00003) improved after ultrafiltration and at 30 and 90 days. Median B-type natriuretic peptide levels decreased after ultrafiltration (from 1,230 pg/ml to 788 pg/ml) and at 30 days (815 pg/ml) (p = 0.035). Blood pressure, renal function, and medications were unchanged. Conclusions In heart failure patients with volume overload and diuretic resistance, ultrafiltration before IV diuretics effectively and safely decreases length of stay and readmissions. Clinical benefits persist at three months.