Antonio L. Perez

Increased mortality with elevated plasma endothelin-1 in acute heart failure: an ASCEND-HF biomarker substudy

Endothelin‐1 (ET‐1) is an endogenous vasoconstrictor implicated in pulmonary and systemic hypertension, as well as ventricular dysfunction, through effects on vascular smooth muscle, the kidneys, and cardiomyocytes. We aimed to determine the association between serial ET‐1 levels and acute heart failure patient outcomes.

Circulating Kidney Injury Molecule-1 Levels in Acute Heart Failure Insights From the ASCEND-HF Trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure)

OBJECTIVES This study sought to determine the relationship of KIM-1 levels with adverse clinical outcomes in acute decompensated heart failure (ADHF). BACKGROUND Kidney injury molecule (KIM)-1 is a biomarker expressed by the nephron in acute tubular injury, and is a sensitive and specific marker for early acute kidney injury. Although commonly measured in urine, KIM-1 levels are also detectable in plasma, but its clinical and prognostic utility in ADHF is unknown. METHODS Baseline, 48- to 72-h, and 30-day KIM-1 plasma levels were measured in 874 subjects in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial. Multivariable logistic and Cox models were used to assess the relationship between KIM-1 levels and outcomes during and after ADHF. RESULTS The median circulating KIM-1 level at baseline was 375.4 pg/ml (interquartile range [IQR]: 237.0 to 633.1 pg/ml), at 48 to 72 h was 373.7 pg/ml (IQR: 220.3 to 640.5 pg/ml), and at 30 days was 382.6 pg/ml (IQR: 236.5 to 638.0 pg/ml). There were no associations between KIM-1 levels and any 30-day outcomes. In univariable analysis, both baseline and follow-up KIM-1 were associated with greater 180-day mortality risk. However, after adjusting for blood urea nitrogen or creatinine in addition to established risk predictors from ASCEND-HF, higher KIM-1 at all time points during hospitalization was not associated with in-hospital or post-discharge outcomes (all p > 0.05), but KIM-1 levels measured at 30 days were associated independently with 180-day mortality (hazard ratio: 1.49; p = 0.04). CONCLUSIONS In our study cohort, circulating KIM-1 at baseline and during hospitalization was not associated with adverse clinical outcomes in ADHF after adjusting for standard indices of kidney function.

Patients Not Meeting PARADIGM-HF Enrollment Criteria Are Eligible for Sacubitril/Valsartan on the Basis of FDA Approval: The Need to Close the Gap

The approval of sacubitril/valsartan by the U.S. Food and Drug Administration (FDA) in July 2015 marked a significant advance in pharmacotherapy available for patients with heart failure (HF) with reduced ejection fraction (HFrEF) in the United States [(1)][1]. The approval of this therapy was

TWO-THIRDS OF HEART FAILURE PATIENTS WHO MEET THE FDA-APPROVED INDICATION FOR SACUBITRIL/VALSARTAN DO NOT MEET PARADIGM-HF ENROLLMENT CRITERIA AFTER RECENT HOSPITALIZATION

The angiotensin-neprilysin inhibitor sacubitril/valsartan was approved by FDA for NYHA FC II-IV chronic heart failure (HF) patients with reduced ejection fraction (HFrEF) based on the PARADIGM-HF trial, which excluded patients with low GFR, low baseline BP, and ACE inhibitor (ACE-I) and beta blocker

Burden and consequences of retained cardiovascular implantable electronic device lead fragments after heart transplantation

We performed a retrospective review of 402 consecutive patients who underwent heart transplantation at our institution between January 2009 and March 2017. A retained cardiovascular implantable electronic device (CIED) fragment was identified after transplantation in 49 of the 301 patients (16.2%) with CIED at baseline. Patients with retained fragments had leads with longer dwell times (median 2596 [1982, 3389] vs 1384 [610, 2202] days, P < .001), higher prevalence of previously abandoned leads (14.3% vs 2.8%, P = .003), and dual‐coil defibrillator leads (98% vs 81%, P = .001) compared with patients without retained fragments. Five patients (10%) with retained CIED fragments underwent magnetic resonance imaging without adverse events. There was no difference in overall mortality between patients with and without CIED fragments (12% vs 11%, P = .81) Patients with retained fragments located in the superior vena cava had significantly higher fluoroscopic times (3.3 vs 2.9 minutes, P = .024) during subsequent endomyocardial biopsies. In a competing risk analysis, presence of a retained CIED fragment was associated with upper extremity deep venous thrombosis (sub hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.17‐4.10, P = .014) but not bloodstream infection after adjusting for potential confounders. In summary, retained CIED fragments are common after heart transplantation, and are associated with longer radiation exposure during biopsy procedures and upper extremity deep venous thrombosis.

Medicaid Insurance and Psychosocial Status in Patients Evaluated for Heart Transplantation

Health insurance coverage, particularly Medicaid, has been a focal point in the national debate. Medicaid was designed to provide health care for vulnerable patients with limited financial resources; now, ironically, the program itself has become vulnerable [(1)][1] due to increasing health care

THE HOSPITAL READMISSION MODEL POORLY PREDICTS 30-DAY REHOSPITALIZATION IN HEART FAILURE

Background: Accurately predicting risk for 30-day readmission after hospital discharge remains challenging in heart failure (HF) patients. The HOSPITAL readmission model, which predicts readmission risk based upon clinical variables, has been derived and validated in general and subspecialty medical

Echocardiography in Mechanical Circulatory Support

Echocardiography is the front line modality in the evaluation of advanced heart failure patients requiring mechanical circulatory support. The use of continuous-flow left ventricular assist devices (LVADs) continues to expand across numerous centers in the country, as both a bridge to transplantation and as destination therapy. Patients being evaluated for LVAD therapy require thorough pre-operative cardiac evaluation by echocardiography of biventricular function, the aortic, tricuspid and mitral valves, the ascending aorta, the atria and atrial septum. After LVAD implantation, echocardiography can effectively evaluate flow velocities into the apical inflow cannula and from the ascending aorta outflow cannula, left ventricular decompression, frequency of aortic valve opening, right ventricular function and degree of aortic, mitral and tricuspid regurgitation. Patients with suspected LVAD malfunction should undergo urgent echocardiography to help identify possible causes, including hypovolemia, valvular dysfunction, tamponade, thrombosis and cannula malposition. Echocardiography also plays a key role in the evaluation and management of patients with percutaneous catheter devices that provide temporary mechanical support in cardiogenic shock and during high risk cardiovascular procedures. It is important to become competent in the echocardiographic assessment of patients who are being evaluated for and receiving mechanical circulatory support, as they can develop critical complications that can be managed successfully if promptly diagnosed.

Endothelin‐1 is independently associated with 180‐day mortality after adjusting for body mass index

Monneret et al.1 raise the possibility that overweight and obesity may be confounding the independent association between baseline endothelin-1 (ET-1) and 180-day mortality in patients with acute decompensated heart failure which we previously reported in a cohort from the ASCEND-HF trial.2 In an effort to assess this possibility, we included body mass index (BMI) as a covariate in an additional multivariable analysis (which also included age, systolic blood pressure, and blood urea nitrogen). Baseline ET-1 was found to be independently associated with 180-day mortality [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.3–2.0, P < 0.0001] after adjustment for BMI. This independent association persisted when NT-proBNP was added as a covariate in the analysis (HR 1.4, 95% CI 1.1–1.7, P = 0.004). Monneret et al.1 also raise for discussion the relationship between ET-1, obstructive sleep apnoea (OSA), and mortality. A recent large study involving 1117 hospitalized patients with acute decompensated heart failure who underwent sleep testing showed that OSA was independently associated with 3-year post-discharge mortality.3 However, the association between ET-1 and OSA is not as clearly defined. In one recent echo-based study, ET-1 was found to be significantly correlated with both patient BMI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . and pulmonary artery pressure, irrespective of history of OSA.4 History of sleep study-proven OSA was not documented in ASCEND-HF subjects; therefore, we cannot use data from the ASCEND-HF trial to assess further the relationship between ET-1, OSA, and mortality—a question that merits investigation using other cohorts. The authors also highlight a well-described phenomenon regarding changes in ET-1 levels depending on patient positioning. In one study that measured salivary endothelin in healthy and congestive heart failure patients, endothelin increased 1.5to 1.8-fold after supine subjects took a seated position for 20–40 min, irrespective of their heart failure history. Endothelin returned back to baseline when subjects returned to the supine position.5 While our study did not control for patient position at the time of blood sampling, all of our baseline and 24–48 h samples were obtained on hospitalized patients with acute decompensated heart failure. Increasing ET-1 levels associated with a seated or standing position introduce variability in the range of ET-1 concentrations within a population. This variability would be expected to decrease the measured association between ET-1 and mortality in our study, unless an association between seated or standing position at the time of blood sampling and increased risk of mortality exists. Accounting for physiological variability in a biomarker’s level is an important consideration before it can be used for clinical care; lipids are measured fasting because short-term dietary intake affects triglyceride levels and, therefore, LDL calculation. However, these considerations are unlikely to undermine the independent association between ET-1 and mortality we have previously described.2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest: none declared.

THE SYSTEMIC INFLAMMATION-BASED GLASGOW PROGNOSTIC SCORE AND CARDIOVASCULAR RISK IN STABLE PATIENTS UNDERGOING ELECTIVE CARDIAC EVALUATION

The Glasgow Prognostic Score (GPS) is a simple inflammation based prognostic score combining C-reactive protein (CRP) and albumin and is a strong, well validated prognostic tool in patients with cancer. Although systemic inflammation is a well understood cardiovascular risk factor, the prognostic