Citations

Purpose of review Despite human leukocyte antigen (HLA) matching and monitoring for donor-specific HLA antibodies, antibody-mediated rejection and chronic rejection in the form of allograft vasculopathy and chronic graft dysfunction continue to occur. There has been increasing interest in non-HLA antibodies as mediators of these changes. Recent findings In this review, we discuss the recent literature describing the importance of non-HLA antibodies in organ transplantation and summarize the literature evaluating such antibodies in heart transplantation. Summary Monitoring of non-HLA antibodies requires additional measurement standardization and correlation of specific antibodies with outcomes. However, there is promise that identification with newer immunoproteomic techniques and therapy toward such antibodies may improve long-term graft outcomes and decrease acute rejection and allograft vasculopathy.

Abstract Aims Left atrial (LA) function is impaired in heart failure with preserved ejection fraction (HFpEF) and predicts disease severity and risk of adverse outcome. We sought to evaluate whether LA strain could enhance diagnosis of HFpEF. Methods and results Consecutive patients with unexplained exertional dyspnoea and image quality suitable for measuring LA strain underwent invasive cardiopulmonary exercise testing to ascertain the presence of HFpEF or non-cardiac causes of dyspnoea (NCD). LA reservoir strain was measured in all patients, while LA conduit and booster strain were measured in patients with sinus rhythm. LA strain was measurable in 363 of 378 examinations (96.5%; HFpEF: 238, NCD: 125). LA reservoir strain (29 ± 16% vs. 40 ± 13%, P < 0.0001) and conduit strain (18 ± 10% vs. 22 ± 10%, P = 0.0001) were significantly impaired in HFpEF compared to NCD. Of all echocardiographic indices, LA reservoir strain best discriminated HFpEF from NCD [area under the curve (AUC) 0.719, P < 0.0001], outperforming E/e' (AUC difference +0.117, P < 0.0001), LA enlargement (+0.090, P = 0.001), tricuspid regurgitation velocity > 2.8 m/s (+0.082, P = 0.0085), left ventricular hypertrophy (+0.0159, P < 0.0001) and left ventricular global longitudinal strain (+0.0198, P < 0.0001). Indexing LA reservoir strain to estimated LA pressure (E/e') as a surrogate for LA compliance further improved diagnostic performance (AUC 0.772, P < 0.0001; +0.053 compared to LA reservoir strain alone, P = 0.003). Conclusion Left atrial reservoir strain may provide enhanced diagnostic accuracy beyond conventional echocardiographic measures to discriminate HFpEF from NCD. Further study is required to verify the diagnostic utility of LA strain.

Background Optimal management of patients with severe mitral stenosis ( MS ) and low transmitral gradient is incompletely understood. Methods and Results We examined 101 consecutive patients with severe rheumatic MS (mitral valve area ≤1.5 cm 2 ) who underwent balloon valvuloplasty. Low gradient was defined as mean transmitral gradient <10 mm Hg and low flow as stroke volume index ≤35 mL/m 2 by echocardiography. Symptoms and mortality data were collected. Systolic, diastolic, and arterial function were characterized by measuring left ventricular (LV) end‐systolic elastance, LV stiffness constant (β), diastolic capacitance (predicted LV end‐diastolic volume at a common LV filling pressure of 30 mm Hg), and effective arterial elastance. Low gradient (<10 mm Hg) was present in 55 patients, including low flow/low gradient in 11 and normal flow/low gradient in 44 patients, and high gradient was present in 46 patients. Participants with low‐flow/low‐gradient (LG) MS were older with higher rates of atrial fibrillation (64%) and subvalvular thickening, higher afterload, and decreased LV compliance with lower ejection fraction (57±10% versus 65±4% versus 63±6%, P =0.002) but similar end‐systolic elastance compared with patients with normal‐flow/ LG and high‐gradient MS . The normal‐flow/ LG group had larger mitral valve area and lower left atrial pressure by catheterization, as well as favorable long‐term outcomes compared with the low‐flow/ LG and high‐gradient MS group. A total of 40% of patients with LG MS had no symptomatic benefit from valvuloplasty compared with 18% of patients with high‐gradient MS ( P =0.02). Conclusions Presence of low gradient in patients with severe MS was associated with lesser symptomatic benefit from valvuloplasty. In the subset with low stroke volume index, this may be related to independent ventricular‐vascular uncoupling, decreased LV compliance, and high prevalence of atrial fibrillation in addition to intrinsic MS .

Rationale: Pulmonary vascular resistance fails to decrease appropriately during exercise in patients with heart failure with preserved ejection fraction (HFpEF). Interventions that enhance pulmonary vasodilation might be beneficial in this cohort but could also worsen left atrial hypertension, exacerbating lung congestion. Intravenous β-agonists reduce pulmonary vascular resistance but are not suitable for chronic use. Objective: We hypothesized that the inhaled β-adrenergic agonist albuterol would improve pulmonary vasodilation during exercise in patients with HFpEF, without increasing left heart filling pressures. Methods and Results: We performed a randomized, double-blind, placebo-controlled trial testing the effects of inhaled albuterol on resting and exercise hemodynamics in subjects with HFpEF using high-fidelity micromanometer catheters and expired gas analysis. The primary end point was pulmonary vascular resistance during exercise. Subjects with HFpEF (n=30) underwent resting and exercise hemodynamic assessment and were then randomized 1:1 to inhaled, nebulized albuterol or placebo. Rest and exercise hemodynamic testing was then repeated. Albuterol improved the primary end point of exercise pulmonary vascular resistance as compared with placebo (−0.6±0.5 versus +0.1±0.7 WU; P =0.003). Albuterol enhanced cardiac output reserve and right ventricular pulmonary artery coupling, reduced right atrial and pulmonary artery pressures, improved pulmonary artery compliance, and enhanced left ventricular transmural distending pressure (all P <0.01), with no increase in pulmonary capillary hydrostatic pressures. Conclusions: Albuterol improves pulmonary vascular reserve in patients with HFpEF without worsening left heart congestion. Further study is warranted to evaluate the chronic efficacy of β-agonists in HFpEF and other forms of pulmonary hypertension. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02885636.