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The prevalence of sarcoidosis-related cardiomyopathy is increasing. Sarcoidosis impacts cardiac function through granulomatous infiltration of the heart, resulting in conduction disease, arrhythmia and/or heart failure. Diagnosis of cardiac sarcoidosis can be challenging and requires clinician awareness as well as differentiation from overlapping diagnostic phenotypes such as other forms of myocarditis and arrhythmogenic cardiomyopathy. Clinical manifestations, extracardiac involvement, histopathology, and advanced cardiac imaging can all lend support to a diagnosis of cardiac sarcoidosis. Mainstay therapy for cardiac sarcoidosis is immunosuppression, however no prospective clinical trials exist to guide management. Patients may progress to developing advanced heart failure or ventricular arrhythmia, for which ventricular assist device therapies or heart transplantation may be considered. The existing knowledge gaps in cardiac sarcoidosis call for an interdisciplinary approach to both patient care and future investigation to improve mechanistic understanding and therapeutic strategies.

Background The diagnosis of cardiac sarcoidosis (CS) is challenging. Because of the current limitations of endomyocardial biopsy as a reference standard, physicians rely on advanced cardiac imaging, multidisciplinary evaluation, and diagnostic criteria to diagnose CS. Aims To compare the 3 main available diagnostic criteria in patients clinically judged to have CS. Methods We prospectively included patients clinically judged to have CS by a multidisciplinary sarcoidosis team from November 2016 to October 2017. We included only incident cases (diagnosis of CS within 1 year of inclusion). We applied retrospectively the following diagnostic criteria: the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG), the Heart Rhythm Society (HRS), and the Japanese Circulation Society (JCS) 2016 criteria. Results We identified 69 patients. Diagnostic criteria classified patients as follows: WASOG as highly probable (1.4%), probable (52.2%), possible (0%), some criteria (40.6%), and no criteria (5.8%); HRS as histological diagnosis (1.4%), probable (52.2%), some criteria (40.6%), and no criteria (5.8%); JCS as histological diagnosis (1.4%), clinical diagnosis (58%), some criteria (39.1%), and no criteria (1.4%). Concordance was high between WASOG and HRS (κ = 1) but low between JCS and the others (κ = 0.326). Conclusions A high proportion of patients clinically judged to have CS are unable to be classified according to the 3 main diagnostic criteria. There is low concordance between JCS criteria and the other 2 criteria (WASOG and HRS).

The association between atrial fibrillation (AF) and thromboembolic (TE) complications in left ventricular assist device (LVAD) recipients is controversial, and there is paucity of large-scale data evaluating the impact of AF on early outcomes after device implantation. Using the National Inpatient Sample, we identified hospitalizations where patients underwent LVAD implantation from 2010 to 2015. Multivariate logistic regression was used to evaluate the association of AF on in-hospital outcomes. A total of 18,378 patients (41.7% with AF) underwent LVAD implantation. Patients with AF were older (59.9 vs. 54.0 years, p

Cardiac sarcoidosis (CS) is frequently difficult to treat. Infliximab (IFX) is useful for extracardiac sarcoidosis, but its use in CS has been limited due to concerns about cardiotoxicity and an FDA blackbox warning about use in heart failure. We reviewed 36 consecutive patients treated with infliximab for CS refractory to standard therapies. IFX was initiated for patients with refractory dysrhythmias, moderate to severe cardiomyopathy, and evidence of persistent F-18 fluorodeoxyglucose uptake on positron emission tomography scan, despite standard therapies. We compared the prednisone dose, ejection fraction (EF), and dysrhythmias before and after IFX therapy. The prednisone-equivalent steroid dose decreased from a median of 20 mg at initiation of infliximab to 7.5 at 6 months and 5 mg at 12 months postinitiation of infliximab (p0.001). In the 25 patients with serial EF measurements, no statistically significant difference was detected in EF (41% at baseline, 42% at 6 months). Of the 16 patients with serial dysrhythmia data, there was a trend toward reduction of percent of patients with ventricular tachycardia (VT), from 32% at baseline, to 22% at 6 months and 19% at 12 months (p = 0.07). Adverse events were common, occurring in 6 of 36 patients, with 3 of 36 patients stopping infliximab for a prolonged period. In responder analysis, 24 patients improved in at least 1 of 3 outcome categories. In conclusion, infliximab may be useful for refractory cardiac sarcoidosis.

Increasing awareness of cardiac manifestations of sarcoidosis and the widespread availability of advanced imaging tests have led to a tidal wave of interest in a condition that was once considered rare. In this Focused Review, we explore important clinical questions that may confront specialists faced with possible cardiac involvement. In the absence of an ideal reference standard, three main sets of clinical criteria exist: the Japanese Ministry of Health and Welfare, the Heart Rhythm Society, and the World Association for Sarcoidosis and Other Granulomatous Disorders criteria. Once cardiac sarcoidosis is suspected, clinicians should be familiar with the prevalence of the disease in different clinical scenarios. Before obtaining advanced cardiac imaging, electrocardiogram, ambulatory electrocardiogram, echocardiogram, and B-type natriuretic peptide may be useful. The available therapies for cardiac sarcoidosis include immunosuppression, antiarrhythmic medications, heart failure medications, device therapy, ablation therapy, and heart transplantation. Contemporary data suggest that long-term survival in cardiac sarcoidosis is better than previously believed. There is no randomized controlled trial demonstrating benefits of screening, but screening is recommended based on observational data.

Background Patient limitations guide selection of heart failure therapies, for which indications often specify New York Heart Association Class. Objectives To determine the extent of patient‐reported limitations during daily activities and compare to New York Heart Association class assigned by providers during the same visit, and to left ventricular ejection fraction (LVEF) group. Methods and Results While waiting for their appointment, 948 patients on return visits to an ambulatory HF clinic completed a written questionnaire assessing specific activity limitations, which were compared to physician‐assigned NYHA class during the same visit. Patient‐reported limitation to perform daily activity ranged from 25% for bathing to 61% for yardwork or housework and 71% for jogging or hurrying. Most patients who did not report limitations to perform daily life activities were correctly classified as NYHA I by the physicians (76%), but 12% of the 376 patients classified as NYHA I reported limitations to showering or bathing and 73% reported limitations while doing yardwork or house work. Limitation to walking was reported by 172 patients (50%) classified as class II. Limitations to walking one block were most common in patients with LVEF ≥40% compared to patients with LVEF

Cardiac resynchronization therapy (CRT) has been shown to be beneficial in patients with medically refractory heart failure. Although it has been found to be effective in a wide range of etiologies for nonischemic cardiomyopathy, its role in improving remodeling and survival of patients with cardiac sarcoidosis (CS) remains undefined. We performed a retrospective review of all patients at our institution with CS who underwent implantation of a CRT device from 2007 to 2017. The outcomes of this population were compared with the outcomes of a cohort of patients with nonischemic cardiomyopathy with an etiology other than sarcoidosis. Nineteen patients in our institution with CS underwent CRT implantation during the time period. This group was compared with 311 consecutive patients with other etiologies of nonischemic cardiomyopathy who underwent CRT implantation. CRT improved left ventricular ejection fraction (LVEF) from 28.8% to 35.9% (p

Background Diagnostic endomyocardial biopsy (EMB) in patients with suspected myocarditis helps to direct therapy and guide prognosis. This study aimed to investigate the correlation between the 2007 clinical guideline indications for EMB and the presence of a diagnostic biopsy result and associated outcomes in patients with suspected myocarditis in a national quaternary referral center in a contemporary cohort. Methods All cases of suspected myocarditis referred to the National Cardiac Transplant Centre who underwent EMB between 2009 and 2019 were identified retrospectively through pathology records. Outcomes including subsequent need for inotrope and/or mechanical circulatory support (MCS), heart transplantation and in-hospital mortality were recorded. Results In total, 25 (68% male, mean age of 45 ± 15 years) EMBs were performed for this indication across this time period, 64% (n = 16) of which demonstrated diagnostic results, the majority (75%, n = 12) identifying acute lymphocytic myocarditis, 13% (n = 2) giant cell, one patient (6.3%) eosinophilic and one (6.3%) an immune checkpoint inhibitor myocarditis. The majority of those with histologically confirmed myocarditis had a Class I or IIa guideline indication for EMB (n = 12, 75%). The remaining 4 patients (25%), either met Class IIb criteria (n = 2) or would not have been accounted for in this guideline. The majority of patients requiring inotropes and/or MCS (n = 9/11), and/or heart transplant (n = 3/4), or who later died (n = 4/5) were in the diagnostic biopsy group. Conclusions In this 10-year National referral sample, 75% of patients with histologically confirmed myocarditis had a Class I or IIa indication for EMB, reinforcing the usefulness of traditional guidelines in this contemporary era. However, 25% of patients with a subsequent confirmed histological diagnosis had either none or a less well-established indication for EMB, highlighting the need for clinical suspicion outside of accepted clinical scenarios.

BACKGROUND: The pulmonary artery pulsatility index (PAPi) has been studied to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation, but only as a single time point before LVAD implantation. Multiple clinical factors and therapies impact RV function in pre-LVAD patients. Thus, we hypothesized that serial PAPi measurements during cardiac intensive care unit (CICU) optimization before LVAD implantation would provide incremental risk stratification for early RVF after LVAD implantation. METHODS AND RESULTS: Consecutive patients who underwent sequential pulmonary artery catherization with cardiac intensive care optimization before durable LVAD implantation were included. Serial hemodynamics were reviewed retrospectively across the optimization period. The optimal PAPi was defined by the initial PAPi + the PAPi at optimized hemodynamics. RVF was defined as need for a right ventricular assist device or prolonged inotrope use (>14 days postoperatively). Patients with early RVF had significantly lower mean optimal PAPi (3.5 vs 7.5, P < .001) compared with those who did not develop RVF. After adjusting for established risk factors of early RVF after LVAD implantation, the optimal PAPi was independently and incrementally associated with early RVF after LVAD implantation (odds ratio 0.64, 95% confidence interval 0.532−0.765, P < .0001). CONCLUSIONS: Optimal PAPi achieved during medical optimization before LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying dynamic RV reserve.

Introduction The burden of advanced heart failure (HF) is an understudied aspect of Ireland’s chronic HF population. Given an expanding menu of advanced HF therapies, identifying suitable candidates for timely assessment and intervention with progression to heart transplantation or mechanical circulatory support (MCS) if appropriate, is imperative. However, given the intensity of resource and service utilization involved, contemporaneous epidemiological and descriptive data is essential for adequate resource planning and provision. Purpose To identify demographics and outcomes of patients referred to the National Advanced HF and Cardiac Transplant centre, including identifiable markers of advanced HF according to the Heart Failure Association of the European Society of Cardiology (ESC) 2018 position statement. Methods Consecutive patients referred to the national advanced HF clinic over a 9-month period from May 2019 to February 2020 were prospectively included in this registry. Baseline demographics, laboratory, electrocardiogram, echocardiogram parameters were recorded. Markers for advanced HF according to the ESC 2018 ‘I NEED HELP’ criteria (table 1) were documented for each patient. Outcomes including need for admission from outpatient clinic, requirement for inotropes or subsequent MCS and/or heart transplantation and mortality were recorded. Results A total of 32 patients were enrolled (28% female, mean age: 49 ± 12 years, 50% NYHA III or IV) over the 9-month period. The vast majority (81%, n=25) had at least one HF hospitalization in the preceding year, with 25% (n=8) having ≥ 2. Frequency of markers of advanced HF, according to the ‘I NEED HELP’ criteria are outlined in table 1. Notably, 69% of the cohort had ≥ 3 markers of advanced HF. At the time of clinic review, 28% (n=9) required urgent admission for further assessment and management, almost all (89%, 25% of total cohort) of these requiring inotropes. Out of the total cohort, 31% subsequently underwent MCS implantation (median: 33 ± 13 days) or heart transplantation (median 38 ± 22 days) (table 2). At time of clinic visit, 37.5% had a relative contraindication to transplantation with 16% having ≥ 2, the most frequently observed being elevated body mass index (BMI) >30 kg/m2, excess alcohol intake and renal dysfunction with an estimated glomerular filtration rate Conclusion Referrals to the National Advanced HF service in Ireland are presenting at an already markedly advanced stage, with over two-thirds having 3 or more established markers of advanced HF, a quarter requiring direct admission leading to inotropes, and almost a third proceeding to advanced surgical therapies. In addition, more than one third of patients referred had a relative contraindication identified at first consultation, with lifestyle factors accounting for a significant proportion. These findings have implications for development of formal referral pathways and greatly increased resource provision to a hitherto understudied cohort to enable optimal assessment and management for this patient group.

Introduction Diagnostic endomyocardial biopsy (EMB) in patients with myocarditis helps to direct therapy and guide prognosis. The original 2007 joint scientific statement provided guideline indications based on unique clinical scenarios, detailing who should undergo this invasive investigation but have not been studied in a contemporary cohort of suspected myocarditis patients. Purpose To investigate the correlation between the clinical guideline indications for EMB and the presence of a diagnostic biopsy result and associated outcomes in patients with suspected myocarditis in a national quaternary referral center. Methods All cases of suspected myocarditis referred to the National Advanced Heart Failure and Transplant Center between 2009–2019 were identified through pathological records. A thorough retrospective chart review was then performed on all patients. Outcomes including need for inotrope or mechanical circulatory support (MCS), heart transplantation and in-hospital mortality were recorded. Results In total, 25 (68% male, mean age of 45 ± 15 years) EMBs were performed for suspected myocarditis between 2009–2019, 64% (n=16) of which demonstrated diagnostic results. Clinical characteristics of those with histologically confirmed myocarditis are represented in figure 1. Regarding pathologic subtypes, 81% (n=13) identified an acute lymphocytic myocarditis, 13% (n=2) giant cell myocarditis and one patient (6.3%) eosinophillic myocarditis. The majority of those with a histologically confirmed myocarditis had a Class I or IIa guideline indication for EMB (n=12, 75%). All patients requiring inotropes and/or MCS (n=9) and/or heart transplant (n=3) were in this group. The remaining 4 patients (25%), of whom three were diagnosed with acute lymphocytic myocarditis and one an immune checkpoint inhibitor (ICI) myocarditis, either met Class IIb criteria (n=2) or would not have been accounted for in this guideline. Four patients (25%) died during the index admission, one of whom was in the latter group (histologically confirmed myocarditis without a 2007 guideline indication). Conclusions In this National referral sample, 75% of patients with suspected myocarditis had a Class I or IIa indication for EMB, reinforcing the usefulness of these guidelines even in a contemporary era. Further, existing guideline indications appeared to identify a sicker group of patients more frequently requiring inotropes, MCS and/or heart transplant. However, in the contemporary era, 25% of patients had either none or a less well established indication for EMB despite a subsequent confirmed histological diagnosis, including a case of immune checkpoint inhibitor myocarditis, which has emerged since the publication of the 2007 guidelines. This highlights the need for clinical suspicion and correlation outside of accepted clinical scenarios.

Introduction Accurate prevalence data for advanced heart failure (HF), reported to range between 2–10% of the chronic HF population, are lacking. Determining the proportion of patients potentially suitable for referral to a specialist advanced HF center is crucial for accurate service planning and resource provision, particularly in the evolving era of durable mechanical circulatory support. Purpose To identify the population of patients potentially eligible for referral for assessment for advanced surgical therapies to the National Advanced HF and Cardiac Transplant center, using a quick one-page prospective survey. Methods A survey comprising 13 potential markers of advanced HF was developed, modified from the 2018 position statement of the Heart Failure Association of the European Society of Cardiology. This was distributed to 26 HF clinic centers nationally. Each center was asked to complete the survey on consecutive patients over a 3-month period who fulfilled the following three criteria: 1) age 3 months duration. Results In all, 21 of 26 HF clinic centers participated in the survey. Across the period of inclusion, 4950 all-comer HF patients were seen in 21 centers. Of these, 375 fulfilled the inclusion criteria, comprising 279 (74.4%) males with a median age of 57 years. In total, 246 (66%) of the completed surveys had one or more potential markers for advanced HF, representing just under 5% of the total all-comer HF population seen across the same time period. Of these, 67 patients (27%) had at least two, 48 (20%) had three and 40 (16%) had ≥ 4 potential markers. The most frequently noted markers were ≥1 hospitalization or unscheduled clinic review (56%), intolerance to renin-angiotensin-aldosterone system inhibitors due to hypotension or renal dysfunction (29%) and intolerance to beta-blockers due to hypotension (27%). Almost one-quarter of patients reported NYHA Class III or IV symptoms (figure 1). Conclusions In this index prospective National survey, approximately 5% of an all-comer routine HF clinic population and two-thirds of a pre-selected HF with reduced EF

AIMS The utility of combined assessment of both frailty and cognitive impairment in hospitalized heart failure (HF) patients for incremental post-discharge risk stratification, using handgrip strength and Mini-Cog as feasible representative parameters, was investigated. METHODS AND RESULTS A prospective, single-centre cohort study of older adults (age ≥65) hospitalized for HF being discharged to home was performed. Pre-discharge, grip strength was assessed using a dynamometer (Jamar hydrolic hand dynamometer, Lafayette Instruments, Lafayette, IN, USA) and was defined as weak if the maximal value was below the gender-derived and body mass index-derived cut-offs according to Fried criteria. Cognition was assessed using the Mini-Cog. The presence of impairment was defined as a score of

Cardiogenic shock from biventricular failure that requires acute mechanical circulatory support carries high 30 day mortality. Acute mechanical circulatory support can serve as bridge to orthotopic heart transplant (OHT) in selected patients. We report a patient with biventricular failure secondary to rapidly progressive cardiac sarcoidosis refractory to medical management who was bridged to OHT with Impella 5.0 and Impella RP—temporary left and right ventricular assist devices, respectively. This is the first successful bridge to transplantation using these devices in biventricular heart failure and cardiogenic shock. We discuss considerations for using this strategy over veno‐arterial extracorporeal membrane oxygenation or surgically implanted assist devices in patients with cardiogenic shock and biventricular failure as a bridge to OHT.

Background: Secondary palliative care (SPC) provides several benefits for patients with cardiovascular disease, but historically, it has been underutilized in this population. Prior research suggests a low rate of SPC consultation by surgical teams in general, but little is known about how surgical teams utilize SPC in the setting of severe cardiovascular disease. Aim: To determine if surgical team assignment affects the probability of SPC for inpatients dying of cardiovascular disease. Design: Retrospective, cohort study. Methods: We identified all inpatients at a large cardiac hospital who had anticipated death under the care of a cardiology, cardiac surgery, or vascular surgery team in 2016. Our primary outcome was referral to SPC, including palliative medicine consultation or inpatient hospice care. Informed by univariate analysis, we created a multivariable logistic regression model, the significance of which was assessed with the Wald test. Results: Two hundred thirty-seven patients were included in our analysis: 93 (39%) received SPC and 144 (61%) were “missed opportunities.” Secondary palliative care was less frequent in patients assigned to a surgical, versus medical, team (11% vs 47%, P < .001). On multivariate analysis, surgical versus medical team assignment was the strongest risk-adjusted predictor of SPC (odds ratio [OR]: 0.10, P < .001). Other predictors of SPC included do not resuscitate status on admission (OR: 14, P < .001), length of stay (OR = 1.05/day, P < .001), and having Medicare (OR = 3.9, P = .002). Conclusions: Primary inpatient care by a surgical team had a strong inverse relationship with SPC. This suggests a possible cultural barrier within surgical disciplines to SPC.

Purpose Antifungal prophylaxis in heart transplantation is not universally prescribed in our institution. We reviewed the incidence of invasive fungal diseases (IFD) in heart transplants, risk factors, and diagnostic yield of culture and nonculture-based testing for IFD. Methods A 5-year retrospective audit of heart transplant recipients in a national transplant centre from 2015 to 2019 was conducted. Proven and probable IFD were identified based on host factors, clinical features and mycological evidence outlined by the updated EORTC/MSGERC definitions. Results The incidence of proven or probable IFD was 14% (11/77) with 207 median days (IQR 54.5-306) post-transplant to diagnosis. 4 (36%) cases occurred 0.05). Of the 7 with rejection, median time from transplant to 1st rejection was 17 days (IQR11-51), and 1st rejection to IFD was 125 days (IQR 44-191). 45% (5/11) with IFD had required post-operative renal replacement therapy. 45% had neutrophils Conclusion Antifungal surgical prophylaxis could have prevented 1 IFD. A cohort of high-risk heart transplant recipients may benefit from antifungal prophylaxis.

Background It is increasingly recognized that pump thrombosis most likely represents the end stage of a complex interaction between the patient-pump interface. We hypothesized that early patient/pump mismatch, as manifested by suboptimal left ventricular (LV) unloading early after left ventricular assist device (LVAD) implantation, may be a harbinger of increased risk for later LVAD thrombosis. Methods In 64 patients (59 ± 11 years old, 78% men, 44% destination therapy) discharged alive without thrombosis or other device malfunction after first HeartMate II LVAD implantation (between January 2011 and June 2014), LV dimensions in end diastole (LVIDd) and end systole (LVIDs) were compared between pre-implant and optimal set speed pre-discharge echocardiography. LV dimension decrement indices (pre-implant dimension − optimal set speed dimension ÷ pre-implant dimension × 100) for LVIDd [LVIDdDI] and LVIDs [LVIDsDI] were calculated. Results The incidence of pump thrombosis was 0.06 per patient year ( n = 18, median time 8 [interquartile range 2, 17] months). Baseline characteristics including pre-operative LVIDd and LVIDs were similar between LVAD thrombosis and no thrombosis groups. After ventricular assist device implantation, set speed and other ramp parameters did not differ between groups. However, LVIDdDI (19 ± 13% vs 25 ± 11%, p = 0.04) and LVIDsDI (16 ± 16% vs 27 ± 13%, p = 0.008) were significantly lower in patients with later pump thrombosis. A cutoff value of ≤15% using receiver operating characteristic curve analysis was 83% sensitive for LVIDdDI and LVIDsDI for predicting pump thrombosis. Patients with LVIDdDI of >15% vs ≤15% were significantly more likely to be free of pump thrombosis over a median follow-up period of 15 (interquartile range 9, 26) months (log-rank test, p = 0.045). Conclusions LV dimension decrement index at optimized speed setting on pre-discharge echocardiography is associated with LVAD thrombosis.

Introduction Mitral regurgitation (MR) resulting from a markedly dilated left ventricle (LV) is common in advanced heart failure patients undergoing LV assist device (LVAD) implant. Significant MR post-LVAD therapy can contribute to worsening pulmonary venous hypertension, right ventricular (RV) failure, morbidity and mortality. Our aim was to examine the impact of MR severity on survival outcomes in patients on LVAD support. Methods A single-center retrospective chart review was conducted for any patient with LVAD implant for demographic, clinical, and echocardiographic variables. Post-LVAD MR severity was used to categorize patients into minimal or significant MR groups. Significant (severe) MR was defined by the presence of EROA ≥0.4cm2, regurgitant volume ≥60ml, regurgitant fraction ≥50%, jet >40% of LA, or grade ≥2+. Results 270 patients (mean age 57 ± 12 years) were analyzed. The majority were male (84%), and had non-ischemic cardiomyopathy (60%), bridge-to-transplant LVAD therapy (52%), significant pre-implant MR (75%), and minimal post-LVAD MR (87%). Median survival time after LVAD implant was 5.96 vs 4.74 years among patients with minimal vs significant MR, respectively (p=0.50). No significant difference was seen between groups even after adjusting for age, gender and device indication (hazard ratio 1.49 [95% CI 0.91, 2.24], p=0.119). Median survival time post-LVAD was 4.90 vs 5.41 years among patients with vs without grade ≥1 MR improvement post-LVAD, respectively (p=0.30). Overall, 28 patients (45%) and 75 patients (36%) died in the respective significant and minimal MR cohorts post-LVAD. Conclusions In our cohort, a minority of patients had persistence of significant MR on LVAD support. Survival outcomes on LVAD support or as bridge to heart transplant did not differ based on MR severity post-LVAD implant. Future studies are warranted on the implications of post-LVAD MR severity on hospital readmission burden.

Introduction Hereditary transthyretin amyloidosis (hATTR) is a progressive multisystem disorder with a wide clinical spectrum. In the Irish population, the T60A variant is the most common genotype. We aimed to describe the spectrum of patients with T60A hATTR attending an Irish national amyloid clinic. Methods The medical, laboratory and radiological records of all patients attending our cardiac amyloidosis referral clinic with a confirmed diagnosis of T60A variant hATTR were reviewed. Results The T60A mutation accounted for 94% of our hATTR population (15 patients; 60% male; median age at diagnosis of 65 years [IQR = 63,67], median follow up 10 months [IQR 4,60]). The majority (80%) were symptomatic at presentation with the remainder referred for family screening. Ten patients (66%) had a family history suggestive of amyloidosis; six of these had a first degree relative with a T60A mutation. Neurological manifestations predated cardiac manifestations and were present in 93% of patients at the time of diagnosis (peripheral neuropathy in 80% and autonomic neuropathy in 95%). Five patients (33%) had undergone a bilateral carpal tunnel release procedure at a median of 11 years (IQR 9, 13) pre-diagnosis. Symptoms of heart failure were present in 53% during follow up (New York Heart Association class II 40%; class III 13%; the remainder remained asymptomatic) while 33% had a heart failure hospitalisation over the past year. All patients had cardiac involvement at presentation by Technitium-99m, 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy (Perugini Grade 2 in 40%; Grade 3 in 60%). Only those with symptoms had ventricular hypertrophy on echocardiography (median left ventricular wall thickness 2cm (IQR 1.5, 2.5); median right ventricular (RV) wall thickness 0.8cm [IQR 0.68, 0.92]). Due to abnormalities on haematological testing, 9 patients (60%) required tissue confirmation of ATTR (RV endomyocardial biopsy in 5; rectal, bladder or fat pad in 3; bone marrow aspirate in 1). All patients were heterozygous for the T60A variant. All patients received disease modifying treatment at some point during follow-up (diflunisal 80%; doxycycline 7%; patisiran 33% and tafamidis 7%). All patients with Perugini grade 2 on initial Tc-DPD imaging progressed to grade 3 on repeat imaging at a median interval of 18 months (IQR 6.75, 36). Conclusions T60A variant hATTR presents with a mixed phenotype of polyneuropathy and heart failure. Neurological manifestations are more prevalent at an earlier stage while cardiac involvement by TC-DPD is already at an advanced stage at the time of diagnosis irrespective of symptoms and progressed over short term follow-up in our cohort.

Purpose To determine overall survival outcomes and outcomes according to gender and era of transplantation, for cardiac transplant recipients in the Republic of Ireland and compare these against international published registry data. Methods A retrospective registry was created of all heart transplants performed in the National Heart and Lung Transplant Centre, Dublin between 1985 and 2019. Kaplan Meier analysis and log rank comparison testing were performed for overall mortality as well as subgroup analyses. This data was then compared to international figures published annually by the ISHLT. Results Overall survival: Median survival was 13.27 years in comparison to 10.9 years internationally over a similar time period. Gender differences: 22.4% of transplants were in females. Median survival in males was 13.9 years and 12.07 years in females (p=0.028). Internationally, median survival was 10.7 years for males and 11.7 years for females. Decade transplanted: Median survival increased from 10.25 years for transplants performed in the 1980s to 15.03 years for those performed 2000-2009 (p=0.034) with survival curves suggesting improved survival for those transplanted after 2010. This compares favourably to ISHLT data: 10.5 years (1992-2001) and 12.4 years (2002-2008). One year survival: This increased from 69.5% for transplants performed in the 1980s, 78% for 1990-1999; 81% for 2000-2009 and 89% for 2010-2019. Conditional on survival to 1 year: Overall median survival was 16.07 years. This has increased from 12.9 years for transplants performed in the 1980s to 18.27 years for those performed 2000-2009 (p=0.069). Conclusion Survival rates post cardiac transplantation in the Republic of Ireland have increased significantly from the beginning of the program in 1985 and compare favourably to international registry data. Based on data since 2000, 1 year survival is now 89%; median survival is at least 15 years and conditional on surviving to 1 year, median survival is at least 18.27 years.

Purpose Identify the prevalence and associates of ISHLT grade ≥2R acute cellular rejection (≥2CR) and its impact on survival post heart transplantation in a well-phenotyped, modern era Irish cohort all of whom receive induction therapy. Methods Retrospective analysis of 88 patients who underwent heart transplantation between 2014 and 2019 (mean age 49.8 ± 13.02 years; female 29.5%). Data was collected on recipient and donor anthropometrics, HLA profile, panel reactive antibodies (PRAs) ischaemia time, cytomegalovirus (CMV) serostatus and endomyocardial biopsy results over a median follow up of 2.04 years (IQR 3.18). Kaplan Meier survival, univariate and multivariate cox regression analysis were performed. Results Standard immunosuppression was with basiliximab induction, a calcineurin inhibitor, steroid and antimetabolite. All-cause mortality at 1 year was 14%. In those patients surviving to first biopsy (n=82), 55% experienced at least 1 episode of ≥2CR at a median time of 53.5 days (IQR 149) and cumulative survival was reduced in this group (p=0.04). More than 1 episode of ≥2CR was not associated with an incremental mortality risk. Intermediate-high risk CMV serostatus was independently associated with increased mortality on multivariate analysis (HR 3.16; 95%CI 1.04-9.65; p=0.04) but not with an increased risk of ≥2CR. There was no association between ischaemic time, PRAs, other recipient/donor matching characteristics, number of HLA mismatches or mismatches confined to any of the 6 HLA subclasses on survival or development of ≥2CR. Conclusion In a modern era Irish cohort where induction therapy is standard, patients who experienced ≥1 episode of ≥2CR post transplant had reduced survival. Intermediate-high risk CMV serostatus was the only independent associate of increased mortality but not for ≥2CR. Further work in an extended cohort will focus on understanding the mechanisms underpinning rejection in this contemporary population and its consequences.

Background Higher body mass index ( BMI ) is associated with lower circulating levels of N‐terminal‐pro‐b‐type natriuretic peptide ( NT ‐pro BNP ). The Interaction between BMI and NT ‐pro BNP with respect to clinical outcomes is not well characterized in patients with acute heart failure. Methods and Results A total of 686 patients from the biomarker substudy of the ASCEND ‐ HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated HF ) clinical trial with documented NT ‐pro BNP levels at baseline were included in the present analysis. Patients were classified by the World Health Organization obesity classification (nonobese: BMI 2 , Class I obesity: BMI 30–34.9 kg/m 2 , Class II obesity BMI 35–39.9 kg/m 2 , and Class III obesity BMI ≥40 kg/m 2 ). We assessed baseline characteristics and 30‐ and 180‐day outcomes by BMI class and explored the interaction between BMI and NT ‐pro BNP for these outcomes. Study participants had a median age of 67 years (55, 78) and 71% were female. NT ‐pro BNP levels were inversely correlated with BMI ( P NT ‐pro BNP levels were associated with higher 180‐day mortality (adjusted hazard ratio for each doubling of NT ‐pro BNP, 1.40; 95% confidence interval, 1.16, 1.71; P NT ‐pro BNP on 180‐day death was not modified by BMI class (interaction P =0.24). Conclusions The prognostic value of NT ‐pro BNP was not modified by BMI in this acute heart failure population. NT ‐pro BNP remains a useful prognostic indicator of long‐term mortality in acute heart failure even in the obese patient. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT00475852.

Continuous-flow left ventricular assist devices (LVAD) have become an increasingly utilized treatment strategy for patients with end-stage heart failure. Despite the improved outcomes evident with current generation pumps, proper patient selection remains crucial to minimize the risk of potential adverse events. The evolving use of these devices as destination therapy (DT) has led to growing numbers of patients with higher risk comorbid conditions being evaluated as potential LVAD candidates. Understanding which patient and disease-specific characteristics increase postoperative morbidity and mortality is paramount as this technology continues to expand and the experience with select populations remains limited. Presented here is a case of a patient with systemic lupus erythematosus receiving a HeartWare LVAD as DT complicated by recurrent, diffuse spontaneous bleeding. The case presented here highlights a potential unique bleeding complication in a high-risk patient cohort and underscores the need to enhance our understanding of factors influencing outcomes in high-risk populations after LVAD therapy.

Purpose PAPi (pulmonary artery pulsatility index) is a predictor of early right ventricular failure (RVF) post left ventricular assist device (LVAD) implantation and has been studied using hemodynamics from single, isolated time points. Since multiple clinical factors and therapies are known to impact RV function in pre-LVAD patients, we hypothesized that serial PAPi measurements would provide incremental risk stratification for early post-LVAD RVF. Methods A total of 394 consecutive patients undergoing primary durable LVAD implantation at our center from 2004 to 2017 were retrospectively enrolled. Serial invasive hemodynamics obtained during inpatient swan guided therapy (77%) or consecutive outpatient right heart catheterizations were recorded. The lowest, highest (“Best”), change (“Delta”) and most proximal PAPi to LVAD implant were calculated. RVF was defined as need for RVAD or prolonged inotrope use > 14 days post-operatively. Multivariate logistic regression determining independent associates of early RVF was performed. Results RVF occurred in 82 of the 394 patients (21%). Those who developed early RVF had significantly lower mean Delta PAPi (2.0 vs 5.3, p Conclusion The best PAPi achieved during medical optimization prior to LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying RV reserve.

Purpose Right ventricular dysfunction (RVD) and mitral regurgitation (MR) are associated with poor outcomes after left ventricular assist device (LVAD) implantation, and residual MR post-implantation may be associated with poor RV outcomes. We sought to assess predictors of change in MR in patients implanted with continuous flow (CF) LVADs. Methods 286 patients implanted with CF-LVADs between Jan 2011 - Dec 2015 were analyzed. Demographic, laboratory, clinical and hemodynamic data were obtained from electronic records. Echocardiograms within 3-months prior to and within 3-months after surgery were reviewed. A total of 35 potential predictors of change in MR severity pre and post LVAD underwent initial univariable analysis. Variables with p Results Mean age was 57 (± 12) years, 84% were male, bean LVEF was 17 (± 6.4) %, and indexed left ventricular end diastolic volume (LVEDVi) was 130 (± 61) ml/m2. For changes in MR post-op, age, LVEDVi, indexed left atrial volume, degree of pre-op MR, diabetes mellitus, CKD, INTERMACS level, cardiac output, cardiac index, RV stroke work index, sphericity index, average mitral annular diameter, tenting area and coaptation length were identified. On multivariable analysis, LVEDVi and degree of pre-op MR were significant predictors (p = 0.010 and Conclusion For changes in degree of MR, higher pre-operative LVEDVi was associated with worse MR post-surgery, and more severe pre-op MR was associated with improvement in degree of MR post-operatively. These findings suggest pre-implant echocardiographtic assessment of LV size and MR severity can identify patients at increased risk of post-LVAD significant MR. Further analysis is needed to verify the findings of this exploratory study and to determine the effect on clinical outcomes.

QRS Fragmentation and QTc in Hypertrophic CardiomyopathyBackground QRS fragmentation (fQRS) and prolonged QTc interval on surface ECG are prognostic in various cardiomyopathies other than hypertrophic cardiomyopathy (HCM). The association between fQRS and prolonged QTc duration with occurrence of ventricular tachyarrhythmias or sudden cardiac death (VTA/SCD) in patients with HCM was explored. Methods and Results One hundred and ninety-five clinical HCM patients were studied. QTc duration was derived applying Bazett's formula; fQRS was defined as presence of various RSR’ patterns, R or S notching and/or >1 additional R wave in any non-aVR lead in patients without pacing or (in)complete bundle branch block. The endpoints comprised SCD, ECG documented sustained VTA (tachycardia or fibrillation) or appropriate implantable cardioverter defibrillator (ICD) therapies (antitachycardia pacing [ATP] or shock) for VTA in ICD recipients (n = 58 [30%]). QT prolonging drugs recipients were excluded. After a median follow-up of 5.7 years (IQR 2.7–9.1), 26 (13%) patients experienced VTA or SCD. Patients with fQRS in ≥3 territories (inferior, lateral, septal, and/or anterior) (p = 0.004) or QTc ≥460 ms (p = 0.009) had worse cumulative survival free of VTA/SCD than patients with fQRS in

Background— Better survival for overweight and obese patients after ST-segment–elevation myocardial infarction (STEMI) has been demonstrated. The association between body mass index (BMI), outcome, and left ventricular (LV) structure and function after STEMI, including LV longitudinal strain (global longitudinal strain), was evaluated. Methods and Results— First patients with STEMI undergoing primary percutaneous coronary intervention (n=1604; mean age, 61±12 years; 75% men) had BMI measured on admission, and 2-dimensional transthoracic echocardiography performed within 48 hours. Patients were categorized based on standard criteria (normal/underweight, BMI2 [n=486]; overweight, 25≤BMI2 [n=820]; obese, BMI≥30 kg/m 2 [n=298]). LV global longitudinal strain was measured using speckle-tracking analysis. Primary outcome measure was all-cause mortality. Compared with normal/underweight patients, obese patients were younger and more likely to have diabetes mellitus, hypertension, and hyperlipidemia and have higher discharge blood pressures. Despite no significant differences in infarct size, obese patients had significantly more impaired LV global longitudinal strain (−13.7±3.8 versus −15.0±4.2% and −15.0±4.1%; P P =0.04) after STEMI during a median follow-up of 5.2 (3.6, 6.9) years on Kaplan–Meier analysis, a significant nonlinear association between BMI and all-cause mortality across the range of BMI was seen, persisting after adjustment for age and sex. Conclusions— Obese patients demonstrate greater adverse LV remodeling and more impaired LV deformation after STEMI compared with those with normal BMI, amid similar infarct characteristics. Normal weight patients continue to demonstrate the worst survival, suggesting that the potential nonadverse effect of higher BMI in this population is independent of LV function.

Aims To explore the association of changes in weight and fluid during treatment for acute heart failure (AHF) with clinical endpoints. Methods and Results Weight and net fluid changes recorded at 72–96 hours in 708 AHF patients enrolled in Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure, Cardiorenal Rescue Study in Acute Decompensated Heart Failure, and Renal Optimization Strategies Evaluation in Acute Heart Failure studies were compared with freedom from congestion at 72–96 hours and a composite endpoint of death, rehospitalization, and unplanned hospital visit at 60 days. Weight loss was concordant with net fluid loss in 55%, discordant and less than expected for fluid loss in 34%, and paradoxically discordant or more than expected for fluid loss in 11% of patients. Weight loss, but not fluid loss, was associated with freedom from congestion (odds ratio per 1-kg weight loss = 1.11 [1.03–1.19]) and a nominal reduction in the composite endpoint (hazard ratio per 1-kg weight loss = 0.98 [0.95–1.00]). Outcomes were similar in patients with concordant and discordant weight-fluid loss. Conclusion During treatment for AHF, early changes in weight may be more useful for identifying response to therapy and for predicting outcomes than net fluid output. Nearly one-half of patients receiving decongestive therapies demonstrate discordant changes in weight and fluid; however, discordance was not associated with outcomes.

Myocardial strain analysis by speckle-tracking echocardiography, which can detect subtle abnormalities in left atrial (LA) function, may offer unique insights into LA pathophysiology in patients with cryptogenic stroke (CS). The aim of this study was to investigate whether LA reservoir strain by speckle-tracking echocardiography, as a measure of LA compliance, is impaired in patients with CS and no history of atrial fibrillation.A retrospective case-control study of 742 patients (mean age, 59 ± 13 years; 54% men; 371 with CS and 371 control subjects) was conducted. LA reservoir strain was quantified using speckle-tracking echocardiography.LA strain was significantly lower among patients with CS than control subjects (30 ± 7.3% vs 34 ± 6.7%, P .001). Current smoking (odds ratio [OR], 2.6; 95% CI, 1.7-4.0; P .001), systolic blood pressure (OR, 1.17 per 10 mm Hg increase; 95% CI, 1.06-1.29; P = .001), antihypertensive treatment (OR, 0.45; 95% CI, 0.30-0.66; P .001), larger indexed left ventricular end-systolic volume (OR, 1.04; 95% CI, 1.01-1.07; P = .02), higher E/E' ratio (OR, 1.06; 95% CI, 1.01-1.11; P = .01), mitral regurgitation (OR, 1.8; 95% CI, 1.2-2.7; P = .003), and lower LA reservoir strain (OR, 1.07 per 1% reduction; 95% CI, 1.05-1.10; P .001) were independently associated with CS. Importantly, LA reservoir strain conferred incremental discriminatory value in the identification of patients with CS (likelihood ratio P .001).Subtle LA dysfunction, as assessed by LA reservoir strain with speckle-tracking echocardiography, is associated with CS independent of other cardiovascular risk factors. These findings suggest a potential role for LA strain to risk-stratify patients in the prevention of stroke.

INTRODUCTION A 2015 Institute Of Medicine statement "Transforming Health Care Scheduling and Access: Getting to Now", has increased concerns regarding patient wait times. Although waiting times have been widely studied, little attention has been paid to the role of patient arrival times as a component of this phenomenon. To this end, we investigated patterns of patient arrival at scheduled ambulatory heart failure (HF) clinic appointments and studied its predictors. We hypothesized that patients are more likely to arrive later than scheduled, with progressively later arrivals later in the day. METHODS AND RESULTS Using a business intelligence database we identified 6,194 unique patients that visited the Cleveland Clinic Main Campus HF clinic between January, 2015 and January, 2017. This clinic served both as a tertiary referral center and a community HF clinic. Transplant and left ventricular assist device (LVAD) visits were excluded. Punctuality was defined as the difference between 'actual' and 'scheduled' check-in times, whereby negative values (i.e., early punctuality) were patients who checked-in early. Contrary to our hypothesis, we found that patients checked-in late only a minority of the time (38% of visits). Additionally, examining punctuality by appointment hour slot we found that patients scheduled after 8AM had progressively earlier check-in times as the day progressed (P < .001 for trend). In both a Random Forest-Regression framework and linear regression models the most important risk-adjusted predictors of early punctuality were: later in the day appointment hour slot, patient having previously been to the hospital, age in the early 70s, and white race. CONCLUSIONS Patients attending a mixed population ambulatory HF clinic check-in earlier than scheduled times, with progressive discrepant intervals throughout the day. This finding may have significant implications for provider utilization and resource planning in order to maximize clinic efficiency. The impact of elective early arrival on patient's perceived wait times requires further study.

Aims Limited data exist on the risk of developing cardiac sarcoidosis (CS) and/or adverse events in sarcoidosis patients. Using LV global longitudinal strain (GLS), an emerging sensitive parameter of LV function, we evaluated the prevalence of subclinical cardiac dysfunction in sarcoidosis and investigated whether LVGLS predicts adverse outcomes in this population. Methods and results A total of 130 patients with proven sarcoidosis undergoing echocardiography at our referral centre were identified. Following exclusion of those with evidence of CS (n = 14) or other pre-existing structural heart disease (n = 16), 100 patients (55 ± 13 years, 48% male, 90% pulmonary involvement) and 100 age- and gender-matched controls were included. LVGLS was measured by speckle-tracking analysis. The primary endpoint was a composite of all-cause mortality, heart failure hospitalization, device implantation, new arrhythmias, or future development of CS on advanced cardiac imaging modalities. LVGLS was significantly impaired in sarcoidosis patients compared with controls (–17.3 ± 2.5 vs. –20.0 ± 1.6%, P

The morbidity and mortality associated with heart failure (HF) represents a significant public health challenge. Stage D HF identifies a distinct subgroup of advanced HF patients characterized by adverse clinical and hemodynamic factors which warrant evaluation for specialized advanced management strategies and/or consideration of palliative care in tandem with the same recommendations for goal-directed optimal medical therapy as earlier stages of HF. In fact, one of the inherent markers of progression to stage D disease is the need to withdraw previously tolerated neurohormonal agents in the setting of systemic circulatory limitations or renal dysfunction. Furthermore, the requirement for aggressive diuresis in the setting of borderline blood pressures and renal insufficiency is often complicated by worsening renal impairment. Assessment of the appropriate need for inotropic support, given the significant complications associated with their use, is also a frequently encountered challenge complicating the medical management of Stage D HF. This review outlines some of the most relevant challenges of pharmacological therapy in stage D HF and describes current and future strategies that may be employed to overcome some of these obstacles.

Speckle-tracking-derived global longitudinal strain (GLS) is a more sensitive method of detecting left ventricular (LV) functional recovery after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis. However, it remains unknown whether LV function improves in patients with low-flow, low-gradient severe aortic stenosis (LFLGSAS) after TAVI. The aim of the present was to evaluate LV functional recovery and remodeling after TAVI in patients with LFLGSAS.Sixty-eight patients (57% men; mean age, 79.1 ± 7.1 years) with LFLGSAS treated with TAVI were evaluated. LV function and remodeling were investigated before TAVI and at 6 and 12 months after TAVI. All echocardiographic data were prospectively collected, and GLS was retrospectively analyzed.Among patients with LFLGSAS, 35 (52%) had low LV ejection fraction (LVEF) (50%), and 33 (48%) had preserved LVEF (≥50%). The low-LVEF group had significantly more impaired GLS than the group with preserved LVEF (-8.3 ± 2.6% vs -13.3 ± 3.5%, P.001). LV systolic function improved after TAVI in both groups. Although in the group of patients with low LVEF, all functional parameters improved, in the group of patients with preserved LVEF, only strain-derived parameters significantly improved. There were significant decreases in absolute LV wall thickness and relative wall thickness and a trend toward decreased LV mass index in both LVEF groups. LV volumes decreased significantly in those with low LVEF but not in those with preserved LVEF. Baseline GLS but not LVEF group was independently associated to GLS improvement at 12 months after TAVI.Patients with LFLGSAS with low and preserved LVEF had a significant improvement in LV function after TAVI, as assessed by GLS. Absolute and relative LV wall thickness decreased in both groups of patients, but only those with low LVEF had reductions in LV volumes.

The identification of patients at risk for developing left ventricular (LV) remodeling after acute myocardial infarction (AMI) has crucial prognostic implications. The aims of this study were (1) to investigate the relationship between peak subepicardial and subendocardial twist and infarct transmurality, as assessed using contrast-enhanced magnetic resonance imaging, and (2) to evaluate the association between peak subepicardial and subendocardial twist and LV remodeling 6 months after AMI.A total of 213 patients with ST-segment elevation AMIs who underwent three-dimensional echocardiography for LV volumes and functional assessment and two-dimensional speckle-tracking analysis for the evaluation of LV twist (subendocardial vs subepicardial) were retrospectively included. A subgroup of 40 patients underwent magnetic resonance imaging within 2 months for infarct size quantification.Peak subepicardial twist was strongly related to infarct size (number of segments with transmural scar: r(2) = 0.526, P.001; total scar score: r(2) = 0.515, P.001) compared with peak subendocardial twist (number of segments with transmural scar: r(2) = 0.379, P.001; total scar score: r(2) = 0.331, P.001). In the overall population, 44 patients (21%) developed significant LV remodeling at 6-month follow-up (LV end-systolic volume increase ≥ 15%). These patients showed significantly more impaired peak subepicardial and subendocardial twist at baseline compared with patients without LV remodeling (4.5 ± 1.3° vs 9.4 ± 3.5°, P.001; 7.0 ± 3.2° vs 12.9 ± 5.8°, P.001, respectively). Importantly, peak subepicardial twist (odds ratio, 0.241; 95% confidence interval, 0.134-0.431; P.001) and peak troponin T (odds ratio, 1.152; 95% confidence interval, 1.006-1.320; P = .041) were independently associated with the development of LV remodeling.Peak subepicardial twist strongly reflects infarct transmurality as assessed with magnetic resonance imaging and is independently associated with LV remodeling after AMI.

Background Coronary heart disease is one of the leading risk factors for the development of heart failure (HF). Despite major improvements in the management of acute coronary syndromes (ACS), HF remains the most common cause of readmission after ACS, followed by myocardial re-infarction. We sought to evaluate the risks and predictors for HF admission after ACS. Methods Using the national readmission database (NRD), we examined discharge data from 2010 until 2015 and identified all patients age 18 years and older with ACS recorded as the primary discharge diagnosis; we then excluded all patients with a prior diagnosis of HF. Chi-square test and Wilcoxon rank-sum test were used to compare proportions and continuous variables, respectively. We used logistic regression modeling to estimate the unadjusted odds of readmission for the covariates of interest. Results We identified 1,322,335 patients discharged after an ACS (36.2% STEMI). Of these, 56,345 (4.2%) were readmitted within 90-days with a new primary diagnosis of HF. The most common individual risk factors associated with HF admission were the presence of atrial fibrillation (OR 1.71), diabetes (OR 1.62) and lung disease (OR 1.49). The most common predictors for HF admission were STEMI (OR 1.28), development of acute kidney injury (AKI) (OR 1.49), length of stay > 5 days (OR 1.77) and discharge against medical advice (OR 1.88). Revascularization during index admission for ACS was a strong predictor against HF admission (OR of 0.61 and 0.49 for PCI and CABG respectively). Self-pay or private insurance were also associated with lower rates of HF admissions (OR 0.68 and 0.57, respectively). Conclusions Readmission for new-onset HF occurs in close to 5% of patients after ACS. The presence of atrial fibrillation, diabetes, development of AKI or prolonged hospitalization identifies a higher risk cohort at the time of discharge.

Introduction Current guidelines recommend against listing for heart transplantation (HTx) if there is evidence of fixed pulmonary hypertension (fPH) given that these patients tend to have poor post-HTx outcomes. The purpose of this study is to investigate the feasibility of left ventricular assist device (LVAD) implantation as a bridge to candidacy (BTC) in patients with fPH through a systematic review and meta-analysis of published literature. Methods We systematically searched Medline, Embase & the Cochrane library through December 31, 2018 for studies reporting patients with fPH treated with LVADs as a BTC for HTx. The primary outcome analyzed percentage of patients within each cohort achieving reversibility of pulmonary hemodynamics and the secondary endpoint was the time necessary to improve hemodynamics. Studies meeting inclusion criteria were assessed with the Newcastle-Ottawa tool. We performed a random-effects meta-analysis using pooled proportions and heterogeneity was examined using I2 statistics. All statistical analyses were carried out using Stata/IC 14.2. Results A total of 8 studies (6 retrospective cohorts and 2 prospective cohorts) including 207 patients (89% male, mean age 49.46 years) formed part of our analysis. Continuous flow LVADs were used in 176 patients (79%). Our meta-analysis showed 97% reversal of fPH (95% CI, 88-100%) (Figure 1). The mean response time was of 5.33 months (95% CI: 3.67-7.00). Out of the initial 207 patients, 80% (95% CI:61-98%) were effectively bridged to receive a HTx. Conclusions Our findings show that in patients unable to be listed for HTx due to fPH, a BTC strategy with LVAD implantation is associated with improvement in pulmonary hemodynamics with a mean response time of approximately 5 months. Further studies evaluating long-term outcomes in these patients are warranted.

Purpose Atrial fibrillation (AF) is a known risk factor for thromboembolic complications. However, there is paucity of large-scale data on its influence on outcomes in patients undergoing left ventricular assist device (LVAD) implantation. Methods Using the National Inpatient Sample, we identified patients who underwent LVAD implantation from 2010-2014. Multivariate logistic regression was used to evaluate the impact of AF on in-hospital outcomes. Results A total of 15,483 patients (40.68% with AF) underwent LVAD implantation. Patients with AF were older (59.7 vs 54.2 years), more commonly male (80 vs 73.8%), and had a greater burden of comorbidities (Elixhauser 7.1 vs 6.2). Compared to patients without AF, patients with AF had lower in-hospital mortality (9.6 vs 15.3%; OR 0.49; p Conclusion AF is common in LVAD recipients but is not associated with increased mortality, thromboembolic or bleeding complications during the index admission for LVAD placement. Patients with known AF are typically chronically anticoagulated, possibly related to less early thromboembolic events. Further studies analyzing the differences between these two groups in more detail, including anticoagulation strategies in AF patients and possible confounding clinical and/or echocardiographic variables, are warranted to understand the potential decreased risk of patients with AF found in this cohort.

Background Mitoxantrone is an effective disease-modifying therapy in multiple sclerosis (MS), but its use is limited by cardiotoxicity. We evaluated global myocardial function, including myocardial performance index (MPI), on echocardiography in MS patients after remote mitoxantrone treatment. Methods and Results Consecutive patients (n = 50) treated with standard-protocol mitoxantrone from 2002 to 2010 in our center were identified. After exclusion of those who had died (n = 4; all noncardiac) or had developed interim cardiovascular disease or risk factors (n = 3), 33 (mean age 49 ± 11 years, 45% male, median follow-up 77 months, mean cumulative dose 72 mg/m 2 ) of the remaining patients (77%) underwent 2-dimensional echocardiography. A comparison group of 17 age- and sex-matched control subjects were included. No significant differences occurred in standard echocardiographic parameters between groups. However, mean MPI (defined as isovolumic contraction time plus isovolumic relaxation time (IVRT) divided by ejection time) was significantly higher in patients (0.51 ± 0.12 vs 0.39 ± 0.06; P = .02) owing to a significantly prolonged IVRT (81 ± 25 vs 60 ± 9 ms; P = .04). Overall MPI was >0.5 in 18 patients compared with none of the control subjects (54.5% vs 0%; P Conclusions A subclinical form of global myocardial dysfunction reflecting primarily diastolic dysfunction may be present in MS patients after remote standard-dose mitoxantrone treatment.

Background Quantitative three-dimensional (3D) dobutamine stress echocardiography (DSE) for myocardial ischemia detection may be an adjuvant to left ventricular (LV) wall-motion analysis. The aim of the current study was to assess the association between global 3D LV excursion during DSE and the presence of significant coronary artery disease (CAD) on coronary angiography. Methods Three-dimensional DSE was performed in 40 patients (67±12 years, 68% male) who underwent subsequent coronary angiography (median 1.6 months later). Using 3D echocardiography, global LV excursion was measured (in a total of 680 segments) at rest and peak dose and the change between stages was calculated (peak-rest=∆global LV excursion). Significant CAD was defined as >70% stenosis on coronary angiography. Results In total, 25 patients (63%) demonstrated significant CAD on coronary angiography. At rest, global LV excursion was similar in patients with and without significant CAD (5.1±0.2 vs 5.0±0.2 mm, P=.74). However, patients with significant CAD demonstrated a worsening in global LV excursion from rest to peak stress (from 5.1±0.2 to 4.1±0.2 mm, P

The Heart Failure Clinical Research Network (HFN) was established in 2008 on behalf of the NIH National Heart, Lung and Blood Institute, with the primary goal of improving outcomes in heart failure (HF) by designing and conducting high-quality concurrent clinical trials testing interventions across the spectrum of HF. Completed HFN trials have answered several important and relevant clinical questions concerning the safety and efficacy of different decongestive and adjunctive vasodilator therapies in hospitalized acute HF, phosphodiesterase-5 inhibition and nitrate therapies in HF with preserved ejection fraction, and the role of xanthine oxidase inhibition in hyperuricemic HF. These successes, independent of the "positive" or "negative" result of each individual trial, have helped to shape the current clinical care of HF patients and serve as a platform to inform future research directions and trial designs.

Right ventricular (RV) function has not been systematically assessed in sarcoidosis. The aim of this study was to assess the prevalence and associates of RV dysfunction in sarcoidosis using global longitudinal peak systolic strain (GLS). Furthermore, whether RV dysfunction was associated with clinical outcomes was investigated.A total of 88 patients with sarcoidosis (mean age, 54 ± 13 years; 51% men) without known sarcoid-related or other structural heart disease or alternative etiologies of pulmonary hypertension were retrospectively included. RV GLS was measured using two-dimensional speckle-tracking echocardiography, and patients were stratified (using a previously defined cutoff value) as having preserved (RV GLS -19%) or impaired (RV GLS ≥ -19%) RV function. An age- and gender-matched control group (n = 50) was included. The main outcome was all-cause mortality or clinical heart failure (hospitalization or New York Heart Association functional class ≥ III and/or deterioration by one or more classes).RV GLS was significantly reduced (-20.1 ± 4.6 vs -24.6 ± 1.8%, P = .001) in patients compared with control subjects. Patients with impaired RV function (n = 41) were older and had worse pulmonary function, worse left ventricular diastolic function, and lower tricuspid annular plane systolic excursion compared with patients with preserved RV function (n = 47). Lower tricuspid annular plane systolic excursion and diabetes were independent correlates of RV GLS. Over a median follow-up period of 37 months, 19 clinical end points occurred. Patients with impaired RV function were more likely to experience the clinical end point (log-rank P = .003).RV contractile dysfunction, identified using RV GLS, is common in patients with sarcoidosis without manifest cardiac involvement or pulmonary hypertension and is associated with adverse outcome. RV GLS may therefore be useful to detect sarcoidosis-related RV dysfunction at an earlier and potentially modifiable stage.

Frailty is defined as a biological syndrome reflecting impaired physiologic reserve and heightened vulnerability to stressors. The evolving profile of heart failure (HF), increased survival of aging patients with complex comorbidities in parallel with the growing population undergoing mechanical circulatory support as lifetime therapy, means that advanced HF specialists are becoming aware of the burden of frailty and its downstream consequences on postintervention outcomes in these patients. The limited data available to date suggest that frailty is highly prevalent in patients with advanced HF and appears to provide prognostic information not captured by traditional risk assessment.

Objectives This study evaluated the prevalence, profile, and prognosis of severe obesity in a large contemporary acute heart failure (AHF) population. Background Better prognosis has been reported for obese heart failure (HF) patients than nonobese HF patients, but in other cardiovascular populations, this effect has not been demonstrated for severely obese patients. Methods A cohort of 795 participants with body mass index (BMI) measured at time of admission and complete follow-up were identified from enrollment in 3 contemporary AHF trials (DOSE [Diuretic Strategies Optimization Evaluation], CARRESS-HF [Cardiorenal Rescue Study in Acute Decompensated Heart Failure], and ROSE [Renal Optimization Strategies Evaluation in Acute Heart Failure]). Patients were divided into 4 BMI categories according to standard World Health Organization criteria, as follows: normal weight: 18.5 to 25 kg/m 2 [n = 128]; overweight: 25 to 29.9 kg/m 2 [n = 209]; mild-to-moderate obese: 30 to 39.9 kg/m 2 [n = 301]; and severely obese: ≥40 kg/m 2 [n = 157]). The relationship between BMI and 60-day composite outcome (death, rehospitalization, or unscheduled provider visit) was investigated. Results Patients with severe obesity (19.7%) were younger, more often female, hypertensive, diabetic, and more likely to have higher blood pressures and left ventricular ejection fraction, and lower N-terminal pro-B-type natriuretic peptide and troponin I levels than other BMI category patients. Following admission for AHF, patients with normal weight showed the highest risk of 60-day composite outcome, followed by patients who were severely obese. Overweight and mild-moderately obese patients showed lowest risk. Conclusions Nearly one-fifth of AHF patients enrolled in contemporary randomized clinical trials are severely obese. A U-shaped curve for short-term prognosis according to BMI is seen in AHF. These findings may help to better inform both HF clinical care and future clinical trial planning.

Aims Dobutamine stress echocardiography (DSE) is frequently performed to assess left ventricular (LV) contractile reserve in patients following myocardial infarction (STEMI). Given that resting LV sublayer twist assessment has been proposed as a marker of infarct transmurality, this study aimed to investigate whether response of LV subepicardial twist on DSE represents a novel quantitative marker of contractile reserve. Methods and results First STEMI patients treated with primary percutaneous coronary intervention with a resting wall motion abnormality in greater than or equal to two segment(s) at 3 months who underwent full protocol DSE were included. Two-dimensional speckle-tracking was used to calculate LV subepi- and subendocardial twist—defined as the net difference (in degrees) of apical and basal rotation for each sublayer—at rest and peak-dose stages. Primary end point was a ≥5% absolute LV ejection fraction (LVEF) improvement between 3 and 6 months. In total, 61 patients (mean age 61 ± 12, 87% male) were included, of whom 48% ( n = 29) demonstrated follow-up LVEF improvement. Mean change in both LV subepicardial (ΔLVsubepi) twist (2.4 ± 3.0 vs. 0.00 ± 2.0°, P = 0.001) and LV subendocardial (ΔLVsubendo) twist (2.7 ± 4.5 vs. 0.25 ± 4.5°, P = 0.04) from rest to peak was significantly higher in LVEF improvers. ΔLVsubepi (odds ratio, OR 1.5, 95% confidence interval, CI 1.1–2.0, P = 0.007), but not ΔLVsubendo (OR 1.1, 95% CI 0.99–1.3, P = 0.07), twist was independently associated with follow-up LVEF improvement following adjustment for baseline LVEF and β-blockade. Conclusion In post-STEMI patients with resting regional dysfunction, the response of LV subepicardial twist on DSE is associated with follow-up LV function improvement, suggesting recruitment in subepicardial function following STEMI reflects greater extent of contractile reserve.

Background— The value of left atrial (LA) diameter, volume, and strain to risk stratify hypertrophic cardiomyopathy patients for new-onset atrial fibrillation (AF) was explored. Methods and Results— A total of 242 hypertrophic cardiomyopathy patients without AF history were evaluated by (speckle-tracking) echocardiography. During mean follow-up of 4.8±3.7 years, 41 patients (17%) developed new-onset AF. Multivariable analysis showed LA volume (≥37 mL/m 2 ; hazard ratio, 2.68; 95% confidence interval, 1.30–5.54; P =0.008) and LA strain (≤23.4%; hazard ratio, 3.22; 95% confidence interval, 1.50–6.88; P =0.003), but not LA diameter (≥45 mm; hazard ratio, 1.67; 95% confidence interval, 0.84–3.32; P =0.145), as independent AF correlates. Importantly, 59% (n=24) of AF events occurred despite a baseline LA diameter 2 and LA strain >23.4% versus ≤23.4% had superior 5-year AF-free survival of 93% versus 80% ( P =0.003) and 98% versus 74% ( P =0.002), respectively. Importantly, LA volume 2 and strain >23.4% yielded high negative predictive value (93% and 98%, respectively) for new-onset AF. Likelihood ratio test indicated incremental value of LA volume assessment ( P =0.011) on top of LA diameter to predict new-onset AF in hypertrophic cardiomyopathy patients with LA diameter P =0.126). Conclusions— LA diameter, volume, and strain all relate to new-onset AF in hypertrophic cardiomyopathy patients. In patients with normal LA size, however, both LA volume and strain further refine risk stratification for new-onset AF.

Residual ischemia detection after ST-segment elevation myocardial infarction (STEMI) during dobutamine stress echocardiography (DSE) using visual analysis is challenging. The aim of the present study was to investigate the feasibility and accuracy of two-dimensional speckle-tracking strain DSE to detect significant coronary artery disease (CAD) after STEMI.First STEMI patients (n = 105; mean age, 60 ± 11 years; 86% men) treated with primary percutaneous coronary intervention undergoing full-protocol DSE at 3 months and repeat coronary angiography within 1 year were retrospectively included. Using two-dimensional speckle-tracking echocardiography, segmental and global left ventricular peak longitudinal systolic strain (PLSS) at rest and peak stress and change (Δ) in PLSS were measured. Significant CAD was defined as detection of70% diameter stenosis at coronary angiography.In total, 1,653 (93%) and 1,645 (92%) segments were analyzable at rest and peak stress, respectively. At follow-up, 38 patients (36%) showed significant angiographic CAD. These patients demonstrated greater worsening in global PLSS from rest to peak (-16.8 ± 0.5% to -12.6 ± 0.5%) compared with patients without significant CAD (-16.6 ± 0.4% to -14.3 ± 0.3%; group-stage interaction P.001). The optimal cutoff of ΔPLSS for the detection of significant CAD on receiver operating characteristic curve analysis was ≥1.9% (area under the curve, 0.70; sensitivity, 87%; specificity, 46%; accuracy, 60%). Using a sentinel segment approach (apex, midposterior, and midinferior for the left anterior descending, left circumflex, and right coronary artery territories, respectively), larger segmental ΔPLSS was also independently associated with significant CAD (odds ratio, 1.1; 95% CI, 1.1-1.2).Two-dimensional speckle-tracking echocardiographic strain analysis is feasible on DSE after STEMI and represents a promising new technique to detect significant angiographic CAD at follow-up.