Prognostic Value of Echocardiographic Variables Prior to and Following Initiation of Parenteral Prostacyclin Therapy: An Observational Study.

BACKGROUND: Echocardiographic parameters are used as prognostic markers in patients with pulmonary arterial hypertension (PAH) receiving parenteral (IV or subcutaneous [IV/SC]) prostacyclin therapy. However, data on how posttreatment echocardiographic results associate with outcomes are limited. RESEARCH QUESTION: Are echocardiographic parameters pre- and post-parenteral prostacyclin therapy in patients with PAH associated with long-term outcomes? STUDY DESIGN AND METHODS: In this retrospective cohort study, patients with PAH initiated on IV epoprostenol or IV/SC treprostinil therapy between 2007 and 2016 were included and followed up through May 31, 2020. Survival free from transplant was assessed from the time of IV/SC prostacyclin therapy initiation and from first follow-up echocardiogram following at least 90 days of therapy. RESULTS: Patients with PAH initiated on IV/SC prostacyclin therapy (N = 118) were followed up for a median of 7.3 years. Survival was 86%, 79%, and 69% at 1, 2, and 3 years, respectively. Follow-up echocardiogram in 101 patients (median, 178 days; interquartile range, 140-273 days) showed improvement in five echocardiographic measures: right ventricular function, right ventricular systolic pressure, right ventricular diastolic diameter, left ventricular diastolic diameter, and tricuspid regurgitation (TR) severity. TR severity and pericardial effusion were associated with survival from IV/SC therapy initiation, whereas right ventricular diastolic diameter, right atrial (RA) size, TR severity, and inferior vena cava characteristics were associated with survival from first follow-up. In a multivariable analysis incorporating other prognostic measures at first follow-up, walk distance, functional class, N-terminal pro-B-type natriuretic peptide, and RA size resulted in the best fit model for survival. INTERPRETATION: Echocardiographic variables improved following IV/SC therapy, and multiple echocardiographic measures associated significantly with survival, particularly when reassessed after at least 90 days of therapy. RA size in particular may be useful in prognostication in follow-up of patients with PAH on IV/SC therapy.

Markers of Immune Function in Heart Transplantation: Implications for Immunosuppression and Screening for Rejection.

PURPOSE OF REVIEW: Recent developments in high-throughput DNA and RNA sequencing technologies have facilitated the development of noninvasive assays to monitor heart transplant rejection. In this review, we summarize existing assays employed for the surveillance of allograft rejection, as well as promising future directions for such tests in the molecular biology field. RECENT FINDINGS: The AlloMap genome expression profiling assay remains the only noninvasive test for rejection surveillance and is incorporated into the International Society of Heart and Lung Transplantation guidelines. Other efforts have focused on messenger RNA (mRNA), microRNA (miRNA), and donor-derived cell-free DNA (dd-cfDNA) as potential viable biomarkers. Mitochondrial pathways in allograft necroptosis and inflammation signaling may represent a novel direction for future research endeavors. Although endomyocardial biopsy remains the gold standard, several converging areas of molecular biology could soon yield successful alternative methods of heart transplant rejection monitoring, with the distinct advantage of avoiding procedural complications.

Invasive Hemodynamic Red Flags to Left Ventricular Assist Device Implantation.

Reliable identification of patients at high risk for right ventricular failure is very important. We identify 4 parameters as hemodynamic red flags to left ventricular assist device implantation.

Noninvasive Assessment of Cardiac Output: Accuracy and Precision of the Closed-Circuit Acetylene Rebreathing Technique for Cardiac Output Measurement.

Background Accurate assessment of cardiac output is critical to the diagnosis and management of various cardiac disease states; however, clinical standards of direct Fick and thermodilution are invasive. Noninvasive alternatives, such as closed-circuit acetylene (C2H2) rebreathing, warrant validation. Methods and Results We analyzed 10 clinical studies and all available cardiopulmonary stress tests performed in our laboratory that included a rebreathing method and direct Fick or thermodilution. Studies included healthy individuals and patients with clinical disease. Simultaneous cardiac output measurements were obtained under normovolemic, hypovolemic, and hypervolemic conditions, along with submaximal and maximal exercise. A total of 3198 measurements in 519 patients were analyzed (mean age, 59 years; 48% women). The C2H2 method was more precise than thermodilution in healthy individuals with half the typical error (TE; 0.34 L/min [r=0.92] and coefficient of variation, 7.2%) versus thermodilution (TE=0.67 [r=0.70] and coefficient of variation, 13.2%). In healthy individuals during supine rest and upright exercise, C2H2 correlated well with thermodilution (supine: r=0.84, TE=1.02; exercise: r=0.82, TE=2.36). In patients with clinical disease during supine rest, C2H2 correlated with thermodilution (r=0.85, TE=1.43). C2H2 was similar to thermodilution and nitrous oxide (N2O) rebreathing technique compared with Fick in healthy adults (C2H2 rest: r=0.85, TE=0.84; C2H2 exercise: r=0.87, TE=2.39; thermodilution rest: r=0.72, TE=1.11; thermodilution exercise: r=0.73, TE=2.87; N2O rest: r=0.82, TE=0.94; N2O exercise: r=0.84, TE=2.18). The accuracy of the C2H2 and N2O methods was excellent (r=0.99, TE=0.58). Conclusions The C2H2 rebreathing method is more precise than, and as accurate as, the thermodilution method in a variety of patients, with accuracy similar to an N2O rebreathing method approved by the US Food and Drug Administration.

Diuretic Strategies in Acute Decompensated Heart Failure.

PURPOSE OF REVIEW: The burden of heart failure in the United States is growing rapidly to epic proportions with serious clinical implications for patients and economic strain for healthcare systems. One of the most common reasons for hospitalization in acute decompensated heart failure (ADHF) is excess volume accumulation which leads to untoward symptoms including dyspnea,orthopnea, and edema. RECENT FINDINGS: Over the past several decades, there has been great interest in exploring various decongestive strategies in order to achieve symptomatic improvement and favorable clinical outcomes. These include different modalities of loop diuretic administration, the adjunctive use of non-loop diuretics, and other diuretic sparing strategies. Herein, we provide an appraisal of these decongestive strategies and discuss novel concepts predicting clinical outcomes based on diuretic response and decongestive adequacy while discussing commonly encountered problems such as worsening renal function in ADHF.