American Heart Association

Multiple inotrope use at lower doses led to excess 1A candidates in the post-geographic sharing era

Contributor: Steven Stroud

Status 1A heart transplant candidates are critically-ill patients requiring mechanical circulatory support (MCS) or high-dose / multiple inotrope therapy to maintain perfusion. Status 1A candidates are listed as highest priority, and are thus more likely to receive a heart transplant. In 2006, a significant change occurred in the Organ Procurement and Transplantation Network (OPTN) criteria with the intent of increase geographic sharing. Following the update, organs were shared within a 500-mile radius as opposed to offers first being made to all candidates (Status 1A, 1B and 2) within local organ procurement organization.

Parker and colleagues investigated whether this policy change affected clinical practice patterns in care of patients listed for heart transplant. The bottom line: following the policy change transplanted patients were more likely to be on low dose inotropes.

Using the Scientific Registry of Transplant Recipients (SRTR) a comparison was made between heart transplant candidates pre (7/2000-7/11/2006) and post (7/12/2006-7/2015) geographic sharing.Status 1A candidates had the following values analyzed: hemodynamic data, MCS type, inotrope type(s) and doses.Between 2000 and 2006, the number of 1A candidates declined from 656 (22% of total candidates) to 452 (18%). However, from 2006-2015, 965 (26%) candidates were Status 1A. The same trend is seen in 1B candidates as well. Not surprisingly, Status 2 candidates steadily declined from 2000-2015 (1,673, 55% to 1,038, 28%).

Among Status 1A candidates, the inotrope subgroup (candidates without MCS) decreased in the pre-sharing era (256, 11% to 174, 8%), but significantly increased in the post-sharing era (381, 18% in 2015, p<0.001). Specifically, multiple-inotrope therapy increased substantially, with 153 more multiple-inotrope 1A candidates in 2015 compared to 2005 (p<0.001). The mean dose of inotropes within the multiple-inotrope subgroup was lower in the post-sharing era compared to the pre-sharing era (dobutamine dose decreased 49%, dopamine dose decreased 55%, and milrinone dose decreased 29%, p<0.001). Interestingly, the cardiac index slightly increased (2.17 to 2.25 L/min/m2, p=0.044).

The single, high-dose inotrope 1A subgroup had relatively stable dosing of milrinone (p=0.063) and a decrease of dobutamine by 4%, p<0.005. Of note, milrinone was used more frequently in the post-sharing era, with a 10% increase in frequency, p<0.001.

The waitlist survival of 1A candidates also increased in the post-sharing era. In the pre-sharing era, 1A candidates had a 130% higher chance of dying, while in the post-sharing era 1A candidates had a 33% higher chance of dying in comparison to Status 2 candidates. This shift represents a 62% risk reduction in death (comparing the last three years of pre-sharing with 7/12/2006-12/31/2010).

No study is perfect. Not all advanced heart failure patients are included in the SRTR, and although hemodynamic data was provided, there may be other factors not listed contributing to the use of multiple inotropes. Improvements in heart failure medical therapy may also contribute to improved waitlist survival of 1A candidates.

Worth noting, there were 220 more CF-LVAD 1A candidates in 2015 compared to 2005 (p<0.001), which certainly contributed to the growing number of 1A candidates as well.

In a heartbeat… The use of multiple inotropes to shift patients to 1A status contributed to excess 1A transplant candidates in the post-geographic sharing era (7/12/2006-7/2015). Changes in policy that require clear hemodynamic rationale for candidate urgency may help stratify transplant candidates more appropriately.

Study Link: Trends in the Use of Inotropes to List Adult Heart Transplant Candidates at Status 1A

Bonus Points: December 2016 Proposal for six-status allocation system

MRI findings more prognostic than laboratory values in myocarditis

Contributor: Steven Stroud

A cardiac MRI (CMR) is worth a thousand labs. Or, that appears to be the case in myocarditis. Dr. Heidecker et al demonstrated that late gadolinium enhancement (LGE) on CMR is unrelated to cardiac enzymes and inflammatory markers, and more prognostic in myocarditis.

Twenty-four patients were prospectively enrolled (75% male, median age 32, 13% w/ concomitant CAD) at the University of Zurich after being diagnosed with myocarditis. Myocarditis diagnosis was based on clinical features, symptom onset < 10 days, ECG, and elevated high-sensitivity troponin T in the absence of acute obstructive coronary disease.

Visual Abstract: Serum Transthyretin Linked to ATTRwt HF Survival

Contributor: Ike Chinyere

Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in Cardiac Amyloid Disease Associated With Wild-Type Transthyretin

Study Link: Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in Cardiac Amyloid Disease Associated With Wild-Type Transthyretin

The more the merrier? Dose of ACE-I/ARBs and outcomes in HFrEF

Contributor: Steven Stroud

It is reported that more is more for HFrEF patients and angiotensin converting enzyme inhibitor (ACE-I) and angiotensin receptor blocker (ARB) therapy. In a recent meta-analysis of six randomized trials*, higher doses of ACE-I/ARBs were associated with a reduction in all-cause mortality. Of note, when the ARB trial (HEAAL) was taken out of the analysis, higher dose ACE-I alone did not reach statistical significance.

Impaired relaxation and elevated intracellular Ca2+ in contracting myocardium of hypertensive heart disease and HFpEF

Contributor: Steven Stroud

Relaxing can be hard in hypertensive heart disease (HHD). Specifically, for the stiff ventricle destined for HFpEF. Is it a problem with relaxation of myocytes, or is it due to stiffening from fibrosis?

Entry of Ca2+ into the myocyte begins a flood of stored Ca2+, stimulating contraction. The cell can relax only when this Ca2+ is taken away from the contractile apparatus. Along with SERCA and phospholamban, the sarcolemmal Na+/Ca2+ exchanger (NCX) handles this important duty.