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To determine if health-related quality of life (HRQoL) improvement after cardiac resynchronization therapy (CRT) correlates with improved left-ventricular ejection fraction (EF).CRT was reported to improve EF and HRQoL in clinical trials of heart failure with reduced EF (HFrEF). It is unknown if improvements in HRQoL reflect EF response to CRT.We included HFrEF patients who underwent CRT and had both pre- and post-CRT HRQoL assessment. EF response was categorized as absent (0% change or decrease), modest (0%-19% increase), or significant (20% increase). We examined the associations between EF response and generic (PROMIS) and HF-specific (KCCQ-12) HRQoL.The group included 115 patients with mean age of 65 years and baseline EF of 31%; 39% were female (n = 45). Nineteen percent (n = 22) had significant, 57% (n = 66) modest, and 23% (n = 27) absent EF responses. AF burden across significant (8.9%), modest (4.8%), and absent EF responders (1.4%) was similar ( P = 0.20). Significant improvements in KCCQ-12 (43.4-57.5, P = 0.003), current health visual analog scale (49.1-55.9, P = 0.042), PROMIS fatigue (58.9-55.1, P = 0.026), and PROMIS satisfaction (42.7-46.4, P = 0.020) resulted following CRT across all groups. There was no association between significant EF improvement and HRQoL by KCCQ-12 (nonresponse, 44.4%; modest response, 33.3%; and significant response, 22.2%) at 1 year ( P = 0.52 across all groups).CRT was associated with a modest to significant EF response in a majority of patients. However, EF response did not significantly correlate with generic or HF-specific HRQoL measures. Further investigations are warranted into determinants of improved HRQoL following CRT.

Background: In Europe, there is greater acceptance of hearts from higher-risk donors for transplantation, whereas in North America, the donor heart discard rate is significantly higher. A Donor Utilization Score (DUS) was used to compare European and North American donor characteristics for recipients included in the International Society for Heart and Lung Transplantation registry from 2000 to 2018. DUS was further evaluated as an independent predictor for 1-year freedom from graft failure, after adjusting for recipient risk. Lastly, we assessed donor-recipient risk matching with the outcome of 1-year graft failure. Methods: DUS was applied to the International Society for Heart and Lung Transplantation cohort using meta-modeling. Posttransplant freedom from graft failure was summarized by Kaplan-Meier survival. Multivariable Cox proportional hazard regression was applied to quantify the effects of DUS and Index for Mortality Prediction After Cardiac Transplantation score on the 1-year risk of graft failure. We present 4 donor/recipient risk groups using the Kaplan-Meier method. Results: European centers accept significantly higher-risk donor hearts compared to North America. DUS 0.45 versus 0.54, P P P P Conclusions: European heart transplantation centers are more likely to accept higher-risk donor hearts than North American centers. Acceptance of borderline-quality donor hearts for lower-risk recipients could improve donor heart utilization without compromising recipient survival.

BACKGROUND: A better understanding is needed of the burdens and benefits of left ventricular assist device (LVAD) implantation on patients’ physical, mental, and social well-being. The purpose of this report was to evaluate the validity of Patient-Reported Outcomes Measurement Information System (PROMIS) measures for LVAD patients and to estimate clinically important score differences likely to have implications for patient treatment or care. METHODS: Adults from 12 sites across all US geographic regions completed PROMIS measures ≥3 months post-LVAD implantation. Other patient-reported outcomes (eg, Kansas City Cardiomyopathy Questionnaire-12 item), clinician ratings, performance tests, and clinical adverse events were used as validity indicators. Criterion and construct validity and clinically important differences were estimated with Pearson correlations, ANOVA methods, and Cohen d effect sizes. RESULTS: Participants’ (n=648) mean age was 58 years, and the majority were men (78%), non-Hispanic White people (68%), with dilated cardiomyopathy (55%), long-term implantation strategy (57%), and New York Heart Association classes I and II (54%). Most correlations between validity indicators and PROMIS measures were medium to large (≥0.3; p CONCLUSIONS: The findings provide convincing evidence for the relevance and validity of PROMIS physical, mental, and social health measures in patients from early-to-late post-LVAD implantation. Findings may inform shared decision-making when patients consider treatment options. Patients with an LVAD, their caregivers, and their clinicians should find it useful to interpret the meaning of their PROMIS scores in relation to the general population, that is, PROMIS may help to monitor a return to normalcy in everyday life. REGISTRATION: URL: https://clinicaltrials.gov ; Unique: identifier: NCT03044535.

Background Diabetes mellitus (DM) may occur either pre-heart transplant (HT) or as new onset DM post-HT. We sought to define the contemporary incidence of post-HT DM, evaluate risk factors for post-HT DM, and assess the impact of post-HT DM on major outcomes. Methods The cohort included International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry adult primary HT-alone recipients, transplanted January 1995-June 2017, who survived to 1 year post-HT. DM status was characterized as (1) No DM pre- or post-HT; (2) Pre-HT DM; or (3) Post-HT DM (onset within 5 years of HT). Cox proportional hazards models were constructed to identify risk factors for post-HT DM onset, as well as risk factors for post-HT severe renal dysfunction and death/retransplantation. Results Of 26 263 eligible subjects, 57% had no DM pre- or post-HT, 22% had pre-HT DM; 21% had new onset post-HT DM. Risk factors for the development of post-HT DM included use of tacrolimus or steroids at 1-year post-HT, as well as with higher recipient age, female sex, ischemic cardiomyopathy, higher body mass index (BMI), pre-HT dialysis, and pre-HT steroid use. Post-HT DM within 5 years was associated with increased subsequent severe renal dysfunction (hazard ratio, HR, 1.89; 95% CI 1.77, 2.01) and death/retransplantation (HR 1.38; 95% CI 1.32, 1.45), compared to patients without post-HT DM. Conclusions Post-HT DM is common, occurring in 21% of recipients within 5 years of HT. Post-HT DM is associated with increased risk of severe renal dysfunction and death or retransplantation.

Pain is not uncommon in older adult patients with heart failure (HF) and has been identified as a risk factor for rehospitalization of homebound patients with HF. Little is known about the pain experiences and management of older adults with HF after hospital discharge. We sought to describe pain and other symptoms among homebound older adults with HF using a qualitative and descriptive approach. We conducted semistructured interviews to obtain qualitative data and used the Brief Pain Instrument-Short Form and the Edmonton Symptom Assessment Scale to obtain descriptive data on symptom burden. We interviewed 18 participants within 10 days after hospital discharge. Participants’ mean age was 75.8 ± 9.0 years; 78% were White. The mean pain score at its worst was 5.2 ± 3.1, and for pain interfering with sleep was 4.3 ± 3.41. Most participants managed pain with medications. Using thematic analysis of qualitative data, we identified three distinct categories: (1) the diversity of patients’ pain experiences, (2) the diversity of pain management routines, and (3) patients’ experiences with healthcare providers’ pain assessment and management practices. Our findings show that homebound older adults with HF experience various pain symptoms and receive inconsistent education about how to manage pain from healthcare providers. This study supports the need for better pain assessment and education about the appropriate use of pain medications and nonpharmacologic approaches to pain control for homebound older adults with HF.

Acute renal failure (ARF) and chronic kidney disease (CKD) are associated with short- and long-term morbidity and mortality following heart transplantation (HT). We investigated the incidence and risk factors for developing ARF requiring hemodialysis (HD) and CKD following HT specifically in patients with a left ventricular assist device (LVAD). We examined the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry for heart transplant patients between January 2000 and June 2015. We compared patients bridged with durable continuous-flow LVAD to those without LVAD support. Primary outcomes were ARF requiring HD before discharge following HT and CKD (defined as creatinine >2.5 mg/dl, permanent dialysis, or renal transplant) within 3 years. There were 18,738 patients, with 4,535 (24%) bridged with LVAD support. Left ventricular assist device patients had higher incidence of ARF requiring HD and CKD at 1 year, but no significant difference in CKD at 3 years compared to non-LVAD patients. Among LVAD patients, body mass index (BMI) (odds ratio [OR] = 1.79, p < 0.001), baseline estimated glomerular filtration rate (eGFR) (OR = 0.43, p < 0.001), and ischemic time (OR = 1.28, p = 0.014) were significantly associated with ARF requiring HD. Similarly, BMI (hazard ratio [HR] = 1.49, p < 0.001), baseline eGFR (HR = 0.41, p < 0.001), pre-HT diabetes mellitus (DM) (HR = 1.37, p = 0.011), and post-HT dialysis before discharge (HR = 3.93, p < 0.001) were significantly associated with CKD. Left ventricular assist device patients have a higher incidence of ARF requiring HD and CKD at 1 year after HT compared with non-LVAD patients, but incidence of CKD is similar by 3 years. Baseline renal function, BMI, ischemic time, and DM can help identify LVAD patients at risk of ARF requiring HD or CKD following HT.

Heart failure remains among the most common and morbid health conditions. The Heart Failure Strategically Focused Research Network (HF SFRN) was funded by the American Heart Association to facilitate collaborative, high‐impact research in the field of heart failure across the domains of basic, clinical, and population research. The Network was also charged with developing training opportunities for young investigators. Four centers were funded in 2016: Duke University, University of Colorado, University of Utah, and Massachusetts General Hospital‐University of Massachusetts. This report summarizes the aims of each center and major research accomplishments, as well as training outcomes from the HF SFRN.

Background: Left ventricular assist device (LVAD) unloading and hemodynamic support in patients with advanced chronic heart failure can result in significant improvement in cardiac function allowing LVAD removal; however, the rate of this is generally considered to be low. This prospective multicenter nonrandomized study (RESTAGE-HF [Remission from Stage D Heart Failure]) investigated whether a protocol of optimized LVAD mechanical unloading, combined with standardized specific pharmacological therapy to induce reverse remodeling and regular testing of underlying myocardial function, could produce a higher incidence of LVAD explantation. Methods: Forty patients with chronic advanced heart failure from nonischemic cardiomyopathy receiving the Heartmate II LVAD were enrolled from 6 centers. LVAD speed was optimized with an aggressive pharmacological regimen, and regular echocardiograms were performed at reduced LVAD speed (6000 rpm, no net flow) to test underlying myocardial function. The primary end point was the proportion of patients with sufficient improvement of myocardial function to reach criteria for explantation within 18 months with sustained remission from heart failure (freedom from transplant/ventricular assist device/death) at 12 months. Results: Before LVAD, age was 35.1±10.8 years, 67.5% were men, heart failure mean duration was 20.8±20.6 months, 95% required inotropic and 20% temporary mechanical support, left ventricular ejection fraction was 14.5±5.3%, end-diastolic diameter was 7.33±0.89 cm, end-systolic diameter was 6.74±0.88 cm, pulmonary artery saturations were 46.7±9.2%, and pulmonary capillary wedge pressure was 26.2±7.6 mm Hg. Four enrolled patients did not undergo the protocol because of medical complications unrelated to the study procedures. Overall, 40% of all enrolled (16/40) patients achieved the primary end point, P Conclusions: In this multicenter prospective study, this strategy of LVAD support combined with a standardized pharmacological and cardiac function monitoring protocol resulted in a high rate of LVAD explantation and was feasible and reproducible with explants occurring in all 6 participating sites. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01774656.

Heart failure (HF) is one of the leading causes of rehospitalization in the United States. Due to the complex nature of HF, the provision of Medicare-certified home healthcare services has increased. Medicare-certified home healthcare agencies measure and report patients' outcomes such as functional status, activities of daily living (ADL), and instrumental activities of daily living to the Centers for Medicare and Medicaid Services. These metrics are assessed using the Outcome and Assessment Information Set (OASIS). As a large data set, OASIS has been used to advance care quality in multiple ways including identifying risk factors for negative patient outcomes. However, there is a lack of OASIS analyses to assess the relationship between functional status and the role of other factors, such as pain, in impeding recovery after hospitalization among HF patients. Therefore, the purpose of this study is to identify the relationship between functional status and pain using the OASIS database. Among 489 HF patients admitted to home healthcare, 83% were White, 57% were female, and the median age was 80. Patients who reported daily but not constant activity-interfering pain at discharge demonstrated the least improvement in functional performance as measured by ADLs, whereas patients without activity-interfering pain demonstrated the greatest improvement in ADL performance (p value = 0.0284). Tracking individual patient ADL scores, particularly the frequency of activity-interfering pain, could be a key indicator for clinical focus for patients with HF in the home healthcare setting.

Introduction: Accurate assessment of the risk of adverse outcomes can assist in the management of patients with heart failure (HF). Hypothesis: Health-related quality of life (HRQoL) can improve prediction of HF outcomes beyond that of the more traditional clinical disease characteristics. Methods: We included consecutive patients with HF with reduced ejection fraction (HFrEF) who were seen in the HF clinic and completed patient reported outcome assessment (PROs) as part of routine care. Elastic net and gradient boosting regression analysis were used to build predictive models for HF hospitalization, heart transplant, left ventricular assist device implantation or death (composite outcome), including a range of clinical variables and PRO results as covariates. Results: There were 1,165 patients with HFrEF (mean age 60.5±16.2, 65% male) with median follow-up time of 490 days. Addition of PROs to more traditional risk factors improved model performance, as analyzed by C-statistics. The gradient boosting regression was chosen as the final model based on superior prediction performance - c-statistic 0.733 and favorable stratification of patient risk - Figure 1A . The Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ) and PROMIS dimensions of Satisfaction with social roles and activities and Physical function were covariates with high variable importance measure in the model. The predictive value of PROs was also confirmed by determining freedom from the composite endpoint in the 20th, 50th and 80th percentiles of PRO strata, while assigning the remaining clinical variables a median value ( Figure 1B ). In this analysis, PROs discriminated outcomes independent of other clinical characteristics. Conclusions: HRQoL appears to significantly modify outcome in HFrEF. Routine assessment of PROs could help to more accurately assess risk of adverse outcomes and personalize informed treatment decisions.

Background: Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD. Methods: The study enrolled consecutive LVAD patients across 4 study sites. A blinded echocardiographer evaluated the degree of structural (LV internal dimension at end-diastole [LVIDd]) and functional (LV ejection fraction [LVEF]) change after LVAD. Patients experiencing an improvement in LVEF ≥40% and LVIDd ≤6.0 cm were termed responders, absolute change in LVEF of ≥5% and LVEF Results: Among 358 LVAD patients, 34 (10%) were responders, 112 (31%) partial responders, and the remaining 212 (59%) were nonresponders. The use of guideline-directed medical therapy for heart failure was higher in partial responders and responders. Structural changes (LVIDd) followed a different pattern with significant improvements even in patients who had minimal LVEF improvement. With mechanical unloading, the median reduction in LVIDd was −0.6 cm (interquartile range [IQR], −1.1 to −0.1 cm; nonresponders), −1.1 cm (IQR, −1.8 to −0.4 cm; partial responders), and −1.9 cm (IQR, −2.9 to −1.1 cm; responders). Similarly, the median change in LVEF was −2% (IQR, −6% to 1%), 9% (IQR, 6%–14%), and 27% (IQR, 23%–33%), respectively. Conclusions: Reverse cardiac remodeling associated with durable LVAD support is not an all-or-none phenomenon and manifests in a continuous spectrum. Defining 3 stages across this continuum can inform clinical management, facilitate the field of myocardial plasticity, and improve the design of future investigations.

Introduction: The volume of solid organ transplantation in the US has increased in recent years. Few data are available characterizing thoracic transplantation patterns and outcomes by citizenship status. Methods: Citizenship at the time of transplantation was characterized among thoracic organ transplantation recipients in the US between 2013 and 2018 using United Network for Organ Sharing data. The non-US citizen group included non-US citizen/US residents, non-US citizen/non-US residents who travelled to the US for transplantation, and non-US citizen/non-US residents who travelled to the US for reasons other than transplantation. Cox regression models were constructed to examine the association between citizenship status and death or graft failure, accounting for age, sex, race, and payment method. Results: Among 31,174 thoracic organ transplantations, number of non-US citizen thoracic organ recipients increased from 90 in 2013 to 221 in 2018 (a 146% increase). Proportion of non-US citizen recipients (of all recipients) similarly increased from 2.0% in 2013 to 3.7% in 2018 (Figure 1a). Non-US citizens were, on average, younger than US citizens (46±19 vs 51±19 years, p Conclusions: Between 2013 and 2018, there was a modest increase in non-US citizen recipients of thoracic organ transplantation. Non-US citizens have similar risk-adjusted patient and graft survival when undergoing thoracic organ transplantation compared with US citizens.

Background: Patients with heart failure (HF) often have multiple chronic conditions that may impact health-related quality of life (HRQOL) despite HF therapy. We sought to determine the association between noncardiac comorbidities and HRQOL in ambulatory patients with advanced HF. Methods: Baseline data from 373 subjects in REVIVAL (Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life) were analyzed using multivariable general linear models to evaluate the relationship between comorbidities and HRQOL (EuroQol Visual Analogue Scale, EQ-5D-3L Index Score, and Kansas City Cardiomyopathy Questionnaire). The primary independent variables were a comorbidity index (sum of 14 noncardiac conditions), a residual comorbidity index (without depression), and depression alone. The median (25th to 75th percentile) number of comorbidities was 3 (2–4). Results: Increasing comorbidity burden was associated with a reduction in generic (EQ-5D Index, P =0.005) and HF-specific (Kansas City Cardiomyopathy Questionnaire, P =0.001) HRQOL. The residual comorbidity index was not associated with HRQOL when depression included in the model independently, while depression was associated with HRQOL across all measures. Participants with depression (versus without) scored on average 13 points (95% CI, 8–17) lower on the EuroQol Visual Analogue Scale, 0.15 points (95% CI, 0.12–0.18) lower on the EQ-5D Index, and 24.9 points (95% CI, 21.2–28.5) lower on the Kansas City Cardiomyopathy Questionnaire overall summary score. Conclusions: While noncardiac comorbidities were prevalent in ambulatory advanced HF patients, only depression was associated with decreased generic and HF-specific HRQOL. Other than depression, the presence of noncardiac comorbidities should not impact expected gains in HRQOL following ventricular assist device implantation, provided the conditions are not a contraindication to implant. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01369407.

Background: Patient-reported outcome (PRO) assessments are commonly used in clinical heart failure (HF) trials and have been shown to be valid, reliable, sensitive measures of patients’ symptoms, function and quality of life, as well as prognostic of clinical events. To be used in routine care, they also need to be interpretable to providers and patients. Patients’ perspectives on PRO collection and results communication have not been studied. Methods: We conducted a mixed methods study of 24 ambulatory adult HF patients (50% men) who completed PROs as part of care at a HF clinic. Study procedures included (1) qualitative telephone interviews and (2) quantitative surveys following interviews. We employed thematic analysis to analyze and code transcripts using an iterative coding process and descriptive statistics to analyze the survey. Qualitative findings were purposefully linked to quantitative results. Findings: Three themes in qualitative analyses were linked to the quantitative survey: 1. Utility of data: Most participants noted that PRO questionnaires were a useful tool to better understand their health if their providers discussed the results with them, and to provide additional information to help improve their treatment. Ninety-two % (22/24) of participants strongly agreed or agreed (SA/A) and 8% (2/24) were neutral that completing the questionnaires changed their care and improved their health. Ninety-six % (23/24) of participants SA/A and 4% (1/24) were neutral that completing the questionnaires would make evaluation of their well-being more accurate. 2. Length and frequency of data collection: Most participants felt that questionnaire length (13-29 questions completed in 3-8 minutes on average) and frequency of implementation (at every visit) were satisfactory. Sixty-three % (15/24) and 37% (9/24) of participants felt that maximum number of questions should be 5-15 and >15, respectively. Eighty-three % (20/24) and 17% (4/24) of participants felt that maximum time required for completion should be 5 or 10 and >10 minutes, respectively. 3. Communication with providers: Most participants noted that their providers discussed results of PRO questionnaires with them only once or not at all and participants who had this discussion with their providers felt that providers understood their responses. Sixty-two % (15/24), 21% (5/24) and 17% (4/24) of participants SA/A, were neutral and disagreed or strongly disagreed that their providers effectively discussed results of their PROs with them. Conclusions: Qualitative results provided depth and interpretability of quantitative survey results. These results indicate successful implementation and utility of PRO questionnaires in the HF clinic, while highlighting a need for more frequent discussion of PRO results between providers and patients. Further use of PROs may lead to improved cardiovascular health and prognosis in HF.

Background: Implantable cardiac sensors have shown promise in reducing rehospitalization for heart failure (HF), but the efficacy of noninvasive approaches has not been determined. The objective of this study was to determine the accuracy of noninvasive remote monitoring in predicting HF rehospitalization. Methods: The LINK-HF study (Multisensor Non-invasive Remote Monitoring for Prediction of Heart Failure Exacerbation) examined the performance of a personalized analytical platform using continuous data streams to predict rehospitalization after HF admission. Study subjects were monitored for up to 3 months using a disposable multisensor patch placed on the chest that recorded physiological data. Data were uploaded continuously via smartphone to a cloud analytics platform. Machine learning was used to design a prognostic algorithm to detect HF exacerbation. Clinical events were formally adjudicated. Results: One hundred subjects aged 68.4±10.2 years (98% male) were enrolled. After discharge, the analytical platform derived a personalized baseline model of expected physiological values. Differences between baseline model estimated vital signs and actual monitored values were used to trigger a clinical alert. There were 35 unplanned nontrauma hospitalization events, including 24 worsening HF events. The platform was able to detect precursors of hospitalization for HF exacerbation with 76% to 88% sensitivity and 85% specificity. Median time between initial alert and readmission was 6.5 (4.2–13.7) days. Conclusions: Multivariate physiological telemetry from a wearable sensor can provide accurate early detection of impending rehospitalization with a predictive accuracy comparable to implanted devices. The clinical efficacy and generalizability of this low-cost noninvasive approach to rehospitalization mitigation should be further tested. Registration: URL: https://www.clinicaltrials.gov . Unique Identifier: NCT03037710.

Heart transplantation has become a standard therapy option for advanced heart failure. The translation of heart transplantation from innovative experiments to long-term clinical success has married prescient insights with discipline and organization in the domains of surgical techniques, organ preservation, immunosuppression, organ donation and transplantation logistics, infection control, and long-term graft surveillance. This review explores the key milestones of the past 50 years of heart transplantation and discusses current challenges and promising innovations on the clinical horizon.

Background: Gastrointestinal bleeding (GIB) is a leading cause of morbidity during continuous-flow left ventricular assist device (CF-LVAD) support. GIB risk assessment could have important implications for candidate selection, informed consent, and postimplant therapeutic strategies. The aim of the study is to derive and validate a predictive model of GIB in CF-LVAD patients. Methods and Results: CF-LVAD recipients at the Utah Transplantation Affiliated Hospitals program between 2004 and 2017 were included. GIB associated with a decrease in hemoglobin ≥2 g/dL was the primary end point. A weighted score comprising preimplant variables independently associated with GIB was derived and internally validated. A total of 351 patients (median age, 59 years; 82% male) were included. After a median of 196 days, GIB occurred in 120 (34%) patients. Independent predictors of GIB included age >54 years, history of previous bleeding, coronary artery disease, chronic kidney disease, severe right ventricular dysfunction, mean pulmonary artery pressure 107 mg/dL. A weighted score termed Utah bleeding risk score, effectively stratified patients based on their probability of GIB: low (0–1 points) 4.8%, intermediate (2–4) 39.8%, and high risk (5–9) 83.8%. Discrimination was good in the development sample (c-index: 0.83) and after internal bootstrap validation (c-index: 0.74). Conclusions: The novel Utah bleeding risk score is a simple tool that can provide personalized GIB risk estimates in CF-LVAD patients. This scoring system may assist clinicians and investigators in designing tailored risk-based strategies aimed at reducing the burden posed by GIB in the individual CF-LVAD patient and healthcare systems.

Background: Cardiac allograft vasculopathy (CAV) remains an important source of mortality after heart transplant. The aim of our study was to identify structural and microvasculature changes in severe CAV. Methods and Results: The study group included heart transplant recipients with severe CAV who underwent retransplantation (severe CAV, n=20). Control groups included time from transplant matched cardiac transplant recipients without CAV (transplant control, n=20), severe ischemic cardiomyopathy patients requiring left ventricular assist device implantation (ischemic control, n=18), and normal hearts donated for research (donor control, n=10). We collected baseline demographic information, echocardiography data, and performed histopathologic examination of myocardial microvasculature. Echocardiographic features of severe CAV included lack of eccentric remodeling and presence of significant diastolic dysfunction. In contrast, diastolic function was preserved in transplant control subjects. Histopathologic examination showed increased interstitial fibrosis among severe CAV, transplant controls, and ischemic control patients. Compared with transplant controls, severe CAV subjects had reduced capillary density and increased capillary wall thickness ( P Conclusions: Our results suggest that the marked diastolic dysfunction and resultant symptoms in patients with severe CAV may be secondary to the loss of microvasculature and remodeling of remaining microvessels rather than a consequence of interstitial fibrosis. The clinical significance and potential therapeutic implications of these unique microvasculature characteristics warrant further investigation.

A 78-year-old man with atrial flutter/fibrillation unresponsive to 3 cardioversions, 1 flutter, and 2 left atrial ablations, myocardial infarction in 2000 treated with a stent to the left anterior descending coronary, hypertension, bilateral carpal tunnel surgery (15 years before), and lumbar spinal stenosis presented with anemia in March 2015. He also complained of dysphagia and was referred for an esophagogastroduodenoscopy. Esophageal biopsies revealed esophagitis. The submucosal vessels in both the duodenal and gastric biopsies showed the presence of a slight thickening by acellular eosinophilic material that raised the possibility of amyloid on routine hematoxylin and eosin–stained slides (Figure [A] and [B]). This finding prompted investigation with Congo red stain, which demonstrated gastric and duodenal amyloid deposition within the submucosal blood vessels. Figure. Patient with wild-type cardiac amyloidosis. A , Duodenal submucosa with abnormal vessels that appear thickened by waxy, eosinophilic amorphous material suggestive of amyloid. B , Gastric biopsy with abnormal vessels within the muscularis mucosae wherein the vessels appear thickened by waxy, eosinophilic amorphous material suggestive of amyloid. C , Transthoracic echocardiogram in the parasternal view demonstrates septal thickness of 1.1 cm and posterior wall thickness of 0.9 cm. D , Cardiac magnetic resonance with septal thickness of 1.4 cm. E , 12-lead ECG shows atrial fibrillation, mild criteria for left ventricular hypertrophy, and nonspecific …

See Article by Parker et al The national heart allograft allocation algorithm established by the Organ Procurement and Transplantation Network has undergone several major changes over the years. The main goals of these policy modifications have been to respond to the evolving treatment options for advanced heart failure patients, minimize the risk of death on the waiting list, and maximize the benefit of transplant.1 An aspirational goal has also been to achieve as much uniformity as possible in the practical application of the allocation algorithm. Every modification of the allocation policy in the past has been met with a good dose of anxiety in anticipation of what the implemented change will mean. Will the benefits to transplant candidates predicted by the statistical modeling of waiting list events be realized? Will the change affect the required level of staffing or the established process logistics of organizations participating in donation, procurement, and transplantation? Will the change alter transplant volumes at one’s transplant center? Yet, the more contentious aspect has typically been the issue of uniform application of the policy from one transplant program to another and from patient to patient—a subject matter that can be best characterized as fairness. In this issue of Circulation: Heart Failure , Parker et al2 present their evaluation of one aspect of the fairness of the current heart allocation in the United States. They hypothesized that changes have taken place over time in the listing practices under the current Organ Procurement and Transplantation Network allocation …

In this review, we first discuss the evolution and current controversies in antibody detection methodology for transplant candidates. Then, we summarize how immunologists and transplant clinicians integrate new evidence with their understanding of how recipient alloantibodies influence patient management and posttransplant outcomes.New advances in solid-phase assays have allowed a more accurate and discriminate appraisal of preformed antibodies. As a result, sensitized patients who are awaiting suitable heart donors can now be better risk-stratified and screened by virtual crossmatch. Yet, the progress in the field also brings to light some new contentious issues in need of further exploration and consideration. Some of these issues are explored in this review: are the new solid-phase assays too sensitive? What are the reasons for and the clinical implications of inconsistencies in results between the different techniques? Which antibodies from a growing list are clinically pertinent? What is the role of the virtual crossmatch? And how do antibodies impact posttransplant outcomes?Serologic detection of preformed or de-novo donor anti-human leukocyte antigen (HLA) antibodies has been closely linked to allograft rejection and poor outcomes. Although welcome, new histocompatibility testing methods also pose new challenges in clinical decision-making. Increased interaction between the clinicians and the histocompatibility laboratory is paramount to better understand the significance of antibodies, to maximize safe donor organ use, and to improve the overall posttransplant outcomes.

Left ventricular (LV) assist devices (LVADs) are increasingly used in everyday clinical practice either as a bridge for end-stage heart failure (HF) patients to heart transplantation or as a permanent (destination) therapy.1,2 Yet, there is still significant uncertainty about the consequences of this intervention both at the level of the detailed myocardial biology (ie, biological outcomes) and at the functional cardiovascular response of the patient at the organ level (ie, clinical outcomes). The LVAD patient population presents a series of significant advantages as far as research is concerned. First, LVAD therapy offers the ability to acquire paired human myocardial tissue at LVAD implantation and again on LVAD removal. The ability to obtain human tissue and the possibility for its serial examination before and after any therapeutic investigational therapy combined with LVADs provide an important opportunity for in-depth study of the changes in the structure and function of the diseased human heart caused by the specific investigational therapy. Second, this population represents a relatively safe investigational platform because the hemodynamic support provided by VADs makes these patients significantly less vulnerable to any arrhythmic3 or hemodynamic adverse events potentially associated with new aggressive investigational therapies. Third, the volumes of potential study subjects for these investigations (ie, patients who receive LVADs) are rapidly increasing; because of a lack of donor organs and incremental progress in device design and durability, the number of advanced HF patients with LVADs has been continuously increasing.1,2 These 3 research advantages create an ideal setting for various new HF therapies to test their potential efficacy in LVAD patients. Fourth, this population offers an opportunity to investigate the effects of the LVAD-induced removal of excess mechanical load, which drives the vicious cycle of myocardial remodeling and eventually leads to the clinical HF syndrome. …

Introduction: Pulmonary Arterial Hypertension (PAH) is a rapidly progressive disease with high mortality. We reviewed randomized controlled trials (RCTs) to evaluate the effect of pulmonary vasodilators on mortality in PAH. Hypothesis: Our objective was to determine the effect of PAH medicines on survival, and the impact of trial design on outcomes. Methods: We conducted a meta-analysis using MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus (inceptions-May 2014) of all RCTs treating PAH with pulmonary vasodilators. Data on all-cause mortality and hemodynamics were abstracted. Summary relative risks (RR) and 95% confidence intervals (CI) for outcomes were calculated using a random effects model comparing various pulmonary vasodilators with control. Results: The analysis included 31 RCTs (6,271 patients, 77% female, range of mean age 30-57 years). Median follow up was 12 weeks (18 trials had ≤ 12 weeks follow up, and only 5 followed patients ≥ 6 months). When analyzed together (n = 14), FDA-approved pulmonary vasodilators demonstrated a mortality benefit with RR = 0.77 (95% CI = 0.60 - 099, I 2 = 0%). When analyzed by vasodilator type, prostacyclins were the only class of agents with significant mortality benefit, RR = 0.61 (95% CI 0.38-0.98, I 2 = 1%). Oral pulmonary vasodilators demonstrated no significant benefit on PAH mortality, RR = 0.85 (95% CI 0.65-1.12, I 2 = 0.0%), but we could not exclude a clinically meaningful benefit or harm. Many studies reported ≤1 death in at least one treatment arm. When we limited the analysis to only studies with at least 2 deaths in both treatment arms (n=9), the mortality benefit for pulmonary vasodilators was no longer significant (RR 0.86, CI 0.66-1.12, I 2 =0%), but the point estimate was below 1 and we could not exclude a reduction or increase in risk. For studies with the shorter follow up of ≤ 12 weeks, the RR of mortality for active treatment arm was 0.54 (95% CI 0.35-0.83), compared to trials with > 12 weeks of follow up where the RR of mortality was not significant at 0.91 (95% CI 0.67-1.22). Conclusion: There is an observed mortality benefit for prostacyclins in PAH. For the oral pulmonary vasodilators, there is no observed mortality benefit based on either design of trials, length of follow up or efficacy of the agents studied.

Body piercing has become an increasingly common practice in the United States and elsewhere. Although perceived as a relatively safe practice, it poses the risk of numerous infectious complications. Oral body piercing in particular has significant potential risk given the known relationship of oral flora to bacteremia. We describe a patient who developed infective endocarditis shortly after undergoing oral piercing.

A 67-year-old woman with a history of hypertension, diabetes mellitus, and hyperlipidemia presented with mild exertional dyspnea of several-month’s duration. An ECG (Figure 1) done 1 month earlier had shown Q-waves and 1-mm ST-elevation in leads II, III, and aVF, a new finding compared with an ECG done 2 years earlier. A pharmacological stress test showed inferior infarct …