Single-center utilization of donor-derived cell-free DNA testing in the management of heart transplant patients.

BACKGROUND: Gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) are useful in acute rejection (AR) surveillance in orthotopic heart transplant (OHT) patients. We report a single-center experience of combined GEP and dd-cfDNA testing for AR surveillance. METHODS: GEP and dd-cfDNA are tested together starting at 2 months post-OHT. After 6 months, combined testing was obtained before scheduled endomyocardial biopsy (EMB), and EMB was canceled with a negative dd-cfDNA. This approach was compared to using a GEP-only approach, where EMB was canceled with a negative GEP. We evaluated for frequency of EMB cancellation with dd-cfDNA usage. RESULTS: A total of 153 OHT patients over a 13-month period underwent 495 combined GEP/dd-cfDNA tests. 82.2% of dd-cfDNA tests were below threshold. Above threshold results identified high-risk patients who developed AR. 378 combined tests ≥6 months post-OHT resulted in cancellation of 83.9% EMBs as opposed to 71.2% with GEP surveillance alone. There were 2 acute cellular and 2 antibody-mediated rejection episodes, and no significant AR ≥6 months. CONCLUSION: Routine dd-cfDNA testing alongside GEP testing yielded a significant reduction in EMB volume by re-classifying GEP (+) patients into a lower risk group, without reduction in AR detection. The addition of dd-cfDNA identified patients at higher risk for AR.

Implementation of Best Practice Alert in an Electronic Medical Record to Limit Lower-Value Inpatient Echocardiograms.

There are increasing efforts nationally and at our institution to reduce lower-value care, including some use of imaging studies such as transthoracic echocardiography (TTE). In an effort to avoid repeating unnecessary studies on inpatients who recently underwent TTE, we implemented a best practice alert (BPA) in our electronic health record to notify ordering clinicians that a TTE had been performed in the past 6 months. The BPA requires the ordering clinician to acknowledge the alert and provide a reason for proceeding with the order and provides a link to ASE AUC criteria. Data on initial use were reviewed after approximately 6 months (February 16, 2017 to September 12, 2017.) This included review of the number of TTE orders removed, number reordered within the same day, subspecialty of ordering clinician, type of ordering clinician (MD vs NP, and so on), and length of stay in patients with orders that were confirmed versus removed. Independent t tests, Chi-square, and Fisher's exact tests were used for analysis. Over 209 days, the BPA triggered 3,226 times with 20% of these TTEs cancelled by the ordering clinician and remaining cancelled after 24 hours. There were no statistically significant differences in the proportion of removed TTE orders between subspecialties or types of clinician (p = 0.144.) There was no statistically significant difference in the length of stay in patients with orders kept (9.2 days) compared with orders cancelled (10.5 days). An electronic health record alert triggered by an order for an inpatient TTE within 6 months of a previous study effectively reduced study volume by 20%.

Surrogate markers of rejection.

PURPOSE OF REVIEW: There is continued interest in defining viable noninvasive alternatives to endomyocardial biopsy (EMB) for monitoring recipients of orthotopic heart transplantation for episodes of rejection. This review summarizes the evidence of clinical utility for both available and emerging surrogate markers of rejection. RECENT FINDINGS: A variety of imaging modalities and peripheral biomarkers has been evaluated for this purpose and to date have had inadequate accuracy to replace EMB. Gene expression profile analysis is the most promising complementary technology to emerge, but there is insufficient clinical trial evidence at this time to allow gene expression profile as a substitution for EMB in all but a select group of patients. SUMMARY: The gold standard at this time for routine surveillance of orthotopic heart transplantation rejection remains EMB. However, on the basis of recent clinical trial results, gene expression profile analysis appears to be a useful adjunctive tool in monitoring for rejection and may permit a significant reduction in the frequency of EMB in low-risk patients.

Comparison of functional status, electrocardiographic, and echocardiographic parameters to mortality in endomyocardial-biopsy proven cardiac amyloidosis.

Cardiac amyloidosis (CA) is generally associated with a poor prognosis and significantly increased mortality. We sought to identify predictors of longer-term survival in patients with endomyocardial biopsy (EMB)-documented CA. Forty-five consecutive patients with EMB-documented CA were studied from January 1998 to December 2003. Age, gender, New York Heart Association class, medications, presence of light-chain amyloid, and electrocardiographic voltage were recorded. Baseline left ventricular (LV) ejection fraction, deceleration time, diastolic function, LV mass, ventricular septal thickness, and myocardial performance index ([isovolumic contraction time + isovolumic relaxation time]/ejection time) were recorded. Mean age was 66 +/- 10 years with 34 men (76%). New York Heart Association class >II was noted in 26 patients (58%) and low voltage on electrocardiogram (S wave [lead V(1)] + R wave [lead V(5)] < or =15) in 12 (27%). Mean LV ejection fraction, ventricular septal thickness, and LV mass were 46 +/- 13%, 1.7 +/- 0.42 cm, and 303 +/- 114 g, respectively. Deceleration time < or =150 ms was found in 19 (42%) and myocardial performance index >0.6 in 15 (33%). At a median follow-up of 1.7 years, there were 25 deaths (56%). On univariate Kaplan-Meier analysis, New York Heart Association class >II, deceleration time <150 ms, and beta-blocker use were associated with increased mortality (log-rank statistic p values <0.001, <0.05, and 0.01, respectively). On Cox proportional hazard survival analysis, only New York Heart Association class was significantly associated with increased mortality (hazard ratio 3.92, 1.92 to 7.95, p = 0.0002). In conclusion, in patients with EMB-documented CA, longer-term survival is more strongly associated with New York Heart Association functional class compared with electrocardiographic and echocardiographic variables.

Abnormally thickened papillary muscle resulting in dynamic left ventricular outflow tract obstruction: an unusual presentation of hypertrophic cardiomyopathy.

We report the case of a symptomatic 18-year-old patient, gene-positive for hypertrophic cardiomyopathy (HCM), who presented with symptomatic dynamic left ventricular outflow tract (LVOT) obstruction caused by an abnormally thickened papillary muscle in the absence of septal hypertrophy. This was confirmed using multimodality imaging, including echocardiography and magnetic resonance imaging. He successfully underwent surgery for papillary muscle realignment without septal myectomy.

Delayed hyper-enhancement magnetic resonance imaging provides incremental diagnostic and prognostic utility in suspected cardiac amyloidosis.

OBJECTIVES: We sought to assess the diagnostic accuracy and incremental prognostic value of delayed hyper-enhancement cardiac magnetic resonance (DHE-CMR) compared with electrocardiographic and transthoracic echocardiographic (TTE) parameters in such patients. BACKGROUND: Utility of DHE-CMR in the diagnosis of patients with suspected cardiac amyloidosis (CA) has recently been demonstrated, but its incremental prognostic utility is unclear. METHODS: Forty-seven consecutive patients (mean age 63 years, 70% men, 55% New York Heart Association functional class >II) with suspected CA who underwent electrocardiography (ECG), TTE, DHE-CMR, and biopsy (38 endomyocardial, 9 extracardiac) were studied. Low voltage on ECG was defined as S-wave in lead V(1) + R-wave in lead V(5) or V(6) <15 mm. TTE parameters, including deceleration time, E/E' ratio, and diastolic grade were recorded. CMR was considered positive with diffuse DHE of the subendocardium extending to adjacent myocardium. All-cause mortality was ascertained. RESULTS: In the study population, 59% had low voltage on ECG, 30% had abnormal deceleration time < OR = 150 ms, 38% had E/E' ratio >15, and 47% had advanced (pseudonormal or restrictive) diastology.The diagnostic accuracy of DHE-CMR in patients undergoing endomyocardial biopsy was as follows: sensitivity 88%, specificity 90%, positive predictive value 88%, and negative predictive value 90%. On multivariable logistic regression testing of the diagnostic ability of various noninvasive imaging parameters, only DHE-CMR was significant (Wald chi-square statistic 9.6, p < 0.01). At 1-year post-biopsy, there were 9 (19%) deaths. On Cox proportional hazards analysis, only positive DHE-CMR was a predictor of 1-year mortality (Wald chi-square statistic 4.91, p = 0.03). CONCLUSIONS: A characteristic DHE-CMR pattern is more accurate for diagnosis and is a stronger predictor of 1-year mortality in patients with suspected CA as compared with other noninvasive parameters.

Pulmonary artery intimal sarcoma: a brief case series.

Primary pulmonary artery intimal sarcomas are often diagnosed only at the time of surgery or autopsy as a result of few specific findings both clinically and on imaging studies. We report two cases of this rare and lethal malignancy, both of which were initially thought to be manifestations of thromboembolic disease. In the case of one man, the diagnosis was delayed several months, at which point attempted surgical resection was not feasible. In the second case the echocardiographic and computed tomographic results generated further evaluation. This led to a more prompt diagnosis and treatment extending the patient's survival. In addition, we describe the echocardiographic findings that lent support to the need for surgical intervention and histologic diagnosis.