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Aims Improving renal function (IRF) is paradoxically associated with worse outcomes in acute heart failure (AHF), but outcomes may differ based on response to decongestion. We explored if the relationship of IRF with mortality in hospitalized AHF patients differs based on successful decongestion.Methods and results We evaluated 760 AHF patients from AKINESIS for the relationship between IRF, change in B-type natriuretic peptide (BNP), and 1-year mortality. IRF was defined as a >= 20% increase in estimated glomerular filtration rate (eGFR) relative to admission. Adequate decongestion was defined as a >= 40% decrease in last measured BNP relative to admission. IRF occurred in 22% of patients who had a mean age of 69 years, 58% were men, 72% were white, and median admission eGFR was 49 mL/min/1.73 m(2). IRF patients had more severe heart failure reflected by lower admission eGFR, higher blood urea nitrogen, lower systolic blood pressure, lower sodium, and higher use of inotropes. IRF patients had higher 1-year mortality (25%) than non-IRF patients (15%) (P < 0.01). However, this relationship differed by BNP trajectory (P-interaction = 0.03). When stratified by BNP change, non-IRF patients and IRF patients with decreasing BNP had lower 1-year mortality than either non-IRF and IRF patients without decreasing BNP. However, in multivariate analysis, IRF was not associated with mortality [adjusted hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.7-1.5] while BNP was (adjusted HR 0.5, 95% CI 0.3-0.7). When IRF was evaluated as transiently occurring or persisting at discharge, again only BNP change was significantly associated with mortality.Conclusion Improving renal function is associated with mortality in AHF but not independent of other variables and congestion status. Achieving adequate decongestion, as reflected by lower BNP, in AHF is more strongly associated with mortality than IRF.

Background: Multiple different pathophysiologic processes can contribute to worsening renal function (WRF) in acute heart failure.Methods and Results: We retrospectively analyzed 787 patients with acute heart failure for the relationship between changes in serum creatinine and biomarkers including brain natriuretic peptide, high sensitivity cardiac troponin I, galectin 3, serum neutrophil gelatinase-associated lipocalin, and urine neutrophil gelatinase-associated lipocalin. WRF was defined as an increase of greater than or equal to 0.3 mg/dL or 50% in creatinine within first 5 days of hospitalization. WRF was observed in 25% of patients. Changes in biomarkers and creatinine were poorly correlated (r < 0.21) and no biomarker predicted WRF better than creatinine. In the multivariable Cox analysis, brain natriuretic peptide and high sensitivity cardiac troponin I, but not WRF, were significantly associated with the 1-year composite of death or heart failure hospitali-zation. WRF with an increasing urine neutrophil gelatinase-associated lipocalin predicted an increased risk of heart failure hospitalization.Conclusions: Biomarkers were not able to predict WRF better than creatinine. The 1-year outcomes were associated with biomarkers of cardiac stress and injury but not with WRF, whereas a kidney injury bio-marker may prognosticate WRF for heart failure hospitalization.

Aims Implantable pulmonary artery pressure (PAP) sensors have been shown to reduce heart failure hospitalizations (HFH) in selected patients. The goal of this study was to evaluate the safety and efficacy of a novel wireless PAP monitoring system in patients with heart failure (HF). Methods and results This is a prospective, multi-centre, open-label, single-arm trial evaluating the safety and efficacy of the Cordella (TM) PA Sensor System including the comprehensive Cordella (TM) Heart Failure System (CHFS) in patients with New York Heart Association (NYHA) Class III heart failure with a heart failure hospitalization and/or increase of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) within 12 months of enrolment. The primary efficacy endpoint was the accuracy of PA sensor mean PAP measurements, compared with fluid-filled catheter mean PAP measurements obtained by standard right heart catheterization (RHC) at 90 days post-implant, assessed in all patients with a successful implant. The primary safety endpoint was freedom from adverse events associated with use of the Cordella PA Sensor System through 30 days post-implant, assessed in all patients who entered the cath lab for PA sensor implant. The PA sensor was successfully implanted in 70 patients. Equivalence between the PA sensor and RHC for mean pulmonary artery pressures was excellent with measurements confined within the equivalence bounds of -4.0 to 4.0 mmHg (mean PAP: 0.0 to 2.9 mmHg, P = 0.003). The device safety profile was excellent with 98.6% freedom from Device System Related Complications, defined as invasive treatment, device explant or death. There were no pressure sensor failures. Patients' adherence to daily measurement transmissions of PAP and vital signs was 94%. Conclusions This trial supports the safety and efficacy of the Cordella PA Sensor System and in conjunction with the CHFS enables comprehensive HF management in NYHA class III heart failure patients.

Background Ebsteins anomaly accounts for less than 1% of all congenital cardiac defects. Whilst typically characterised by dysfunction and anatomical defects of the right ventricle and tricuspid valve, it often co-exists with other congenital defects. Less frequently outflow tract obstruction may arise with associated haemodynamic effects and symptoms. In particular there are few reports in the literature of left ventricular outflow tract obstruction. We believe this is because symptomatic outflow tract obstruction as the presenting complaint of this condition is exceptionally rare. Case presentation We report on a 17 year old male who was referred to the general cardiology clinic with symptoms of exertional fatigue and breathlessness. Transthoracic echocardiogram performed as part of the workup led to the diagnosis of Ebstein’s anomaly. In addition to the characteristic features of this congenital abnormality there was significant dilatation of the right atrium with resultant leftward bulging of the intraventricular septum. The anterior mitral valve leaflet was noted to be elongated with accessory chordal apparatus and demonstrated systolic anterior motion. Turbulence was noted in the left ventricular outflow tract leading to a degree of obstruction. Here we discuss the aetiology and mechanisms behind this unusual presentation. Discussion Ebstein’s anomaly arises due to chromosomal rearrangements affecting early morphogenesis of the right ventricle and tricuspid valve. Associations with other congenital defects such as interatrial communications are well documented. Less commonly the structural abnormalities of this condition lead to functional outflow tract obstruction. Whilst cases have previously described right ventricular outflow tract obstruction there are fewer reports of left ventricular outflow tract obstruction in this patient group. The structural defects that result in dilatation of the right atrium and the atrialised portion of the right ventricle can lead to leftward bulging of the interatrial septum. Turbulence can occur in the left ventricular outflow tract with resultant systolic anterior motion of the mitral valve in a mechanism similar to that encountered in hypertrophic cardiomyopathy. This may only become haemodynamically relevant during exertion. Conclusion In the absence of ventricular dysfunction, arrhythmias or syncope we suggest that it is reasonable to adopt an observational strategy to the management of these patients.

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.

BackgroundAtherosclerosis is a chronic inflammatory disease driven by macrophage accumulation in medium and large sized arteries. Macrophage polarization and inflammation are governed by microRNAs (miR) that regulate the expression of inflammatory proteins and cholesterol trafficking. Previous transcriptomic analysis led us to hypothesize that miR-155-5p (miR-155) is regulated by conjugated linoleic acid (CLA), a pro-resolving mediator which induces regression of atherosclerosis in vivo. In parallel, as extracellular vesicles (EVs) and their miR content have potential as biomarkers, we investigated alterations in urinary-derived EVs (uEVs) during the progression of human coronary artery disease (CAD).MethodsmiR-155 expression was quantified in aortae from ApoE−/− mice fed a 1% cholesterol diet supplemented with CLA blend (80:20, cis-9,trans-11:trans-10,cis-12 respectively) which had been previously been shown to induce atherosclerosis regression. In parallel, human polarized THP-1 macrophages were used to investigate the effects of CLA blend on miR-155 expression. A miR-155 mimic was used to investigate its inflammatory effects on macrophages and on ex vivo human carotid endarterectomy (CEA) plaque specimens (n = 5). Surface marker expression and miR content were analyzed in urinary extracellular vesicles (uEVs) obtained from patients diagnosed with unstable (n = 12) and stable (n = 12) CAD.ResultsHere, we report that the 1% cholesterol diet increased miR-155 expression while CLA blend supplementation decreased miR-155 expression in the aorta during atherosclerosis regression in vivo. CLA blend also decreased miR-155 expression in vitro in human THP-1 polarized macrophages. Furthermore, in THP-1 macrophages, miR-155 mimic decreased the anti-inflammatory signaling proteins, BCL-6 and phosphorylated-STAT-3. In addition, miR-155 mimic downregulated BCL-6 in CEA plaque specimens. uEVs from patients with unstable CAD had increased expression of miR-155 in comparison to patients with stable CAD. While the overall concentration of uEVs was decreased in patients with unstable CAD, levels of CD45+ uEVs were increased. Additionally, patients with unstable CAD had increased CD11b+ uEVs and decreased CD16+ uEVs.ConclusionmiR-155 suppresses anti-inflammatory signaling in macrophages, is decreased during regression of atherosclerosis in vivo and is increased in uEVs from patients with unstable CAD suggesting miR-155 has potential as a prognostic indicator and a therapeutic target.

Prompt treatment may mitigate the adverse effects of congestion in the early phase of heart failure (HF) hospitalization, which may lead to improved outcomes. We analyzed 814 acute HF patients for the relationships between time to first intravenous loop diuretics, changes in biomarkers of congestion and multi-organ dysfunction, and 1-year composite endpoint of death or HF hospitalization. B-type natriuretic peptide (BNP), high sensitivity cardiac troponin I (hscTnI), urine and serum neutrophil gelatinase-associated lipocalin (NGAL), and galectin 3 were measured at hospital admission, hospital day 1, 2, 3 and discharge. Time to diuretics was not correlated with the timing of decongestion defined as BNP decrease = 30% compared to admission. Earlier BNP decreases but not time to diuretics were associated with earlier and greater decreases in hscTnI and urine NGAL, and lower incidence of the composite endpoint. After adjustment for confounders, only no BNP decrease at discharge was significantly associated with mortality but not the composite endpoint (p?=?0.006 and p?=?0.062, respectively). In conclusion, earlier time to decongestion but not the time to diuretics was associated with better biomarker trajectories. Residual congestion at discharge rather than the timing of decongestion predicted a worse prognosis.

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 Kidney impairment has been associated with worse outcomes in acute heart failure (AHF), although recent studies challenge this association. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker of kidney tubular injury. Its prognostic role in AHF has not been evaluated in large cohorts. The present study aimed to determine if serumNGAL (sNGAL) or urineNGAL (uNGAL) is superior to creatinine for predicting short-term outcomes in AHF Methods and results The study was conducted in an international, multicentre, prospective cohort consisting of 927 patients with AHF. Admission and peak values of sNGAL, uNGAL and uNGAL/urine creatinine (uCr) ratio were compared to admission and peak serum creatinine (sCr). The composite endpoints were death, initiation of renal replacement therapy, heart failure (HF) readmission and any emergent HF-related outpatient visit within 30 and 60 days, respectively. The mean age of the cohort was 69 years and 62% were male. The median length of stay was 6 days. The composite endpoint occurred in 106 patients and 154 patients within 30 and 60 days, respectively. Serum NGAL was more predictive than uNGAL and the uNGAL/uCr ratio but was not superior to sCr [area under the curve: admission sNGAL 0.61, 95% confidence interval (CI) 0.55- 0.67, and 0.59, 95% CI 0.54- 0.65; peak sNGAL: 0.60, 95% CI 0.54-0.66, and 0.57, 95% CI 0.52- 0.63; admission sCr: 0.60, 95% CI 0.54- 0.64, and 0.59, 95% CI 0.53- 0.64; peak sCr: 0.61, 95% CI 0.55-0.67, and 0.59, 95% CI 0.54- 0.64, at 30 and 60 days, respectively]. NGAL was not predictive of the composite endpoint in multivariate analysis. Conclusions Serum NGAL outperformed uNGAL but neither was superior to admission or peak sCr for predicting adverse events.

Patients with chronic heart failure (CHF) have symptoms and concerns which are inadequately addressed. Patient-reported outcome measures (PROMs) can potentially improve the identification and management of advanced symptoms and palliative concerns. However, these have not been used in CHF.OBJECTIVES: To examine the feasibility and acceptability of using a PROM-the Integrated Palliative care Outcome Scale (IPOS)-together with heart failure nurse education and training to improve the identification and management of symptoms and concerns among patients with CHF.METHODS: A parallel, mixed methods design with an embedded qualitative component was used to examine the feasibility of recruitment, retention, intervention adherence/compliance and follow-up assessment completion (symptom burden, quality of life, psychological well-being). Patient and nurse qualitative semistructured interviews explored intervention and study design feasibility and its acceptability.RESULTS: Conversion to consent was 46.9% (372 screened, 81 approached, 38 recruited). 66% of patient participants completed the IPOS; 6% of IPOS questionnaire items were missing (non-response). Over two-thirds (65.6%) of these missing items related to three patients. No item was consistently missing; appetite was the most frequent missing item (1.4%). 92% of participants who completed the IPOS completed all follow-up assessments (1-2 days, 1-2 weeks and 4-6 weeks post-IPOS completion) with no missing data. The a priori feasibility objectives were met. Patients and nurses reported the intervention and study design feasible and acceptable.CONCLUSIONS: A palliative-specific PROM-based intervention is feasible and acceptable to both patients with CHF and nurses in nurse-led disease management clinics for the purposes of both clinical care and research.

Background: Worsening renal function (WRF) during acute heart failure (AHF) occurs frequently and has been associated with adverse outcomes, though this association has been questioned. WRF is now evaluated by function and injury. We evaluated whether urine neutrophil gelatinase-associated lipocalin (uNGAL) is superior to creatinine for prediction and prognosis of WRF in patients with AHF. Methods and Results: We performed a multicenter, international, prospective cohort of patients with AHF requiring IV diuretics. The primary outcome was whether uNGAL predicted development of WRF, defined as a sustained increase in creatinine of 0.5 mg/dL or ≥50% above first value or initiation of renal replacement therapy, within the first 5 days. The main secondary outcome was a composite of in-hospital adverse events. We enrolled 927 patients (mean 68.5 years of age, 62% men). The primary outcome occurred in 72 patients (7.8%). The first, peak and the ratio of uNGAL to urine creatinine (area under curves (AUC) ≤ 0.613) did not have diagnostic utility over the first creatinine (AUC 0.662). There were 235 adverse events in 144 patients. uNGAL did not predict (AUCs ≤ 0.647) adverse clinical events better than creatinine (AUC 0.695). Conclusions: uNGAL was not superior to creatinine for predicting WRF or adverse in-hospital outcomes and cannot be recommended for WRF in AHF.

Aims In acute heart failure (AHF), relationships between changes in B-type natriuretic peptide (BNP) and worsening renal function (WRF) and its prognostic implications have not been fully determined. We investigated the relationship between WRF and a decrease in BNP with in-hospital and 1-year mortality in AHF. Methods and results The Acute Kidney Injury NGAL Evaluation of Symptomatic heart faIlure Study (AKINESIS) was a prospective, international, multicentre study of AHF patients. Severe WRF (sWRF) was a sustained increase of >= 44.2 mu mol/L (0.5 mg/dL) or >= 50% in creatinine, non-severe WRF (nsWRF) was a non-sustained increase of >= 26.5 mu mol/L (0.3 mg/dL) or >= 50% in creatinine, and WRF with clinical deterioration was nsWRF with renal replacement therapy, inotrope use, or mechanical ventilation. Decreased BNP was defined as a >= 30% reduction in the last measured BNP compared to admission BNP. Among 814 patients, the incidence of WRF was not different between patients with or without decreased BNP (nsWRF: 33% vs. 31%, P = 0.549; sWRF: 11% vs. 9%, P = 0.551; WRF with clinical deterioration: 8% vs. 10%, P = 0.425). Decreased BNP was associated with better in-hospital and 1-year mortality regardless of WRF, while WRF was associated with worse outcomes only in patients without decreased BNP. In multivariate Cox regression analysis, decreased BNP, sWRF, and WRF with clinical deterioration were significantly associated with 1-year mortality. Conclusions Decreased BNP was associated with better in-hospital and long-term outcomes. WRF was only associated with adverse outcomes in patients without decreased BNP.

Background Anthracycline drugs are effective anticancer agents, but their optimal use is limited in many patients by the associated cardiotoxicity, even at designated safe doses. As conventionally sensitive cardiac troponin-I assays fail to reliably quantify concentrations of cardiac troponin-I below 30 ng/L, we investigated the potential role of high-sensitive cardiac troponin-I in the detection of subclinical cardiomyocyte injury in patients treated with anthracycline agents. Methods Serial high-sensitive cardiac troponin-I concentrations were assessed in 84 patients, receiving anthracycline-containing ( n = 38) and non-anthracycline-containing ( n = 46) regimens. Results were assessed for change from pretreatment levels and evaluated according to unisex and gender-specific 99th percentiles (25 ng/L and M: 34 ng/L, F: 16 ng/L, respectively). Results A significant increase in high-sensitive cardiac troponin-I was observed in the anthracycline cohort following five cycles of treatment, with the greatest change correlating to an absolute δ increase of 30.7 ng/L in the early-dose group (early-dose group: P Conclusions Treatment with anthracycline-based chemotherapeutic regimen demonstrated significant elevations of high-sensitive cardiac troponin-I, indicative of subclinical cardiomyocyte damage. This study demonstrates a role for high-sensitive cardiac troponin-I in evaluating those patients where cardiotoxicity is a concern and a potential future role as a biomarker in optimizing cardioprotective treatments in patients receiving anthracycline therapy.

Background: Worsening renal function (WRF) often occurs during acute heart failure (AHF) and can portend adverse outcomes; therefore, early identification may help mitigate risk. Neutrophil...

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.

Introduction Patients who undergo PPCI in MMUH for STEMI are routinely immediately repatriated to their local hospital, assuming clinical stability. We sought to analyse in hospital mortality rates in the MMUH patients who were not immediately repatriated due to clinical instability and compare this with all STEMI patients from the MMUH catchment area. Methods We performed retrospective analysis on all STEMI cases with PPCI in MMUH from July 2017 until January 2018. Patients were grouped into repatriated and non-repatriated patients. Within the non-repatriated group, patients were further divided into patients who either fell within MMUH catchment area or patients who were clinically too unstable for immediate repatriation. Analysis was performed by direct review of the medical notes for each patient, to ascertain the clinical reasons for not repatriating patients immediately, and to determine survival to discharge. Results There were 209 cases of PPCI for STEMI in MMUH for this six month period. Of these, 36 were from the MMUH catchment (17%). Of the remaining 173 patients eligible for repatriation, 28 (16%) were admitted to the MMUH and not repatriated due to clinical instability. A comparison of clinical characteristics between the MMUH catchment group (36) and the Non-repatriated group (28) respectively (table 1): Arrhythmia 6 v 11 (17% v 39%), Cardiogenic Shock 8 v 16 (22% v 57%), Mechanical Ventilation 4 v 7 (11% v 25%), IABP 2 v 5 (5% v 18%), Mechanical complications 0 v 1 (0% v 3.5%), Vascular access complications 0 v 2 (0% v 7%), Stroke 3 v 3 (8.5% v 11%), OHCA 4 v 3 (11.4% v 10%).In hospital mortality for STEMI patients from MMUH catchment area was 8.3% (3/36). In hospital mortality for non-repatriated patients was significantly higher 21.4% (6/28) (table 2). Overall in hospital mortality for all patients admitted to the MMUH was 14% (9/64). Conclusions At our PPCI centre overall STEMI in hospital mortality rates are increased by a cohort of patients who are more clinically unstable than the majority of STEMI patients. Crude comparison of in-hospital mortality rates can be misleading, particularly with an active repatriation STEMI program.

Background Device Infection is a recognised complication of cardiac implantable electronic device (CIED) insertion. Reported incidence of CIED infection vary widely, and range from 1.0% for pacemakers to up 9.5% for cardiac resynchronisation defibrillators (CRT-d). The risk of infection is 2–4-fold higher for CIED replacement. CIED infection is associated with significant patient morbidity and mortality rate of up to 27% at 2 years. Recently an antibacterial pouch (Tyrx TM, Medtronic) has been developed. This absorbable pouch elutes rifampicin and minocycline from a monofilament polypropylene mesh. Use of the TYRX pouch has been associated with reduced CIED infection. Real-world data on the efficacy of the envelope remains limited. Methods We performed an retrospective review of the CIED infection rate for all devices implanted with a Tyrx TM pouch from September 2015 to October 2017 in our institution. Patient or procedural factors known to increase the risk of infection were documented in each case. Results 63 patients had CIEDs implanted along with a Tyrx TM pouch during the period under review. 14 (22%) were female. The average age at implant was 64 years±13. Five patients had chronic kidney disease (eGFR Conclusion Our study included many patients with factors associated with increased infection rate. Over a mean follow-up period of >1 year, no patients with a CIED implanted along with a TyrxTM antibacterial pouch had CIED pocket infection. Though the numbers under review were small, our results compare very favourably with previously published rates of CIED infection, and lend further support to the use of antibacterial pouches to reduce the risk of device infection.

Introduction Brugada syndrome (BrS) is a hereditary sodium channelopathy that can result in ventricular arrhythmia (VA) and death. Characteristic coved ST elevation in the early precordial leads is transient, most often precipitated by fever or sleep. Sodium channel blockers such as Ajmaline can unmask these changes. However, a widespread variation in infusion protocols is evident in BrS studies. The two most prevalent protocols originate from the BrS Consensus reports. A total dose of 1 mg/kg was originally infused at a rate of 10 mg/min, however the same dose can be given over 5 min using a newer protocol. Patients greater than 50 kg will therefore receive a faster rate. This is the largest study to date that has included both protocols to assess risk of VA. Methods A review of consecutive ajmaline tests done in the Mater Hospital was undertaken over a ten-year period from March 2008. The initial protocol of 1 mg/kg infused at 10 mg/min was changed to 1 mg/kg over 5 min in December 2014. In August 2016, due to a perceived increased risk in VA, the original protocol was reinstated. High precordial lead position was used in the second and third intercostal spaces. Results A total of 209 consecutive ajmaline tests were performed over the ten-year period. 166 were infused at the 10 mg/min rate and 43 at the 5 min rate. 3 patients developed VA, all of which received the 5 min protocol (p=0.0086) (Fisher’s exact test). Two of these cases required electrical cardioversion and none had evidence of ischaemic heart disease. The weight (Kg)/dose (mg) for the three VA patients were 98, 90 and 71. Conclusion In this study there was a significant increase in the rate of VA in patients who received the 5 min infusion. The test is terminated when diagnostic criteria is met, however a greater dose has already been given with the 5 min rate, which may explain the progression to VA. These findings are in keeping with the two largest studies that utilised either of these protocols and included VA rates. The first demonstrated that 9/503 (1.8%) positive tests in a group receiving the 5 min rate had VA, while the other study found that 0/89 positive tests in a group getting the 10 mg/minute rate had VA. Of note neither of these studies examined differences in the rate of infusion as a potentially confounding variable. This study is the first to demonstrate that these infusion protocols should not be considered as interchangeable in terms of safety profile. Figure 1 Discrepancies in the rate of ajmaline administration between 2 infusion protocols in one patient who had VA (weight 98 kg). Figure 2 ECG tracing of V1H showing normal sinus rhythm transitioning into type one Brugada pattern and ultimately ventricular fibrillation in a patient receiving the 5 min infusion rate.

Purpose Post transplant malignancy is a common long term complication due to immunosuppression. The aim of this study was to assess the incidence, type of malignancies and evaluate risks associated with development of malignancy in heart transplant recipients at our institution Methods Patients transplanted from March 1998 to March 2018 were included in the study. Data was collected from patient's medical records retrospectively. Skin cancers were not included and patients with pre-transplant malignancy were excluded from the study. Results Of 229 patients, 11% (n=25) patients developed malignancy, 96% (n=24) were male and 4%(n=1) were females. The median time from transplant to diagnosis of malignancy was 9.32 years (0.9-18.1yrs) and the mean age at diagnosis was 66.8± 7.25 years. Most common malignant neoplasm was Lung Cancer (39%, n=9) followed by Colorectal (17%, n=4) and Prostate cancer (9%, n=3). Kaplan Meir survival rate for patients without malignancy post transplant was 18.2 years and with malignancy was 12.1 years. Patient's transplanted after 55 years or above were at higher risk of developing malignancy with p value reaching statistical significance(p=0.006) Conclusion Post transplant malignancy is a common long term complication affecting patient's survival post transplantation. Lung cancer is the most common sold organ malignancy. Patients transplanted after 55 years of age or above are relatively at higher risk for developing malignancy. Early intervention by aggressive screening is required to diagnose malignancy.

We assessed adherence to European Society of Cardiology heart rate guidelines (i.e. heart rates less than 70 bpm) in patients with chronic stable heart failure. We also investigated the percent of patients on target doses of rate controlling drugs.Multicenter study involving 549 patients from 12 heart failure centers in the Republic of Ireland. Patients in sinus rhythm with stabilized heart failure treatment and without recent cardiac events were included. Resting heart rates, demographics, co-morbidities and heart failure therapies were recorded.Heart rates ≥ 70 bpm were noted in 176 (32.1%) patients with 117 (21.3%) having rates75 bpm. Non-achievement of target heart rates were unrelated to age, gender or most cardiovascular risk factors. However, 42% of patients with diabetes (p0.01), 56% of those with COPD (p0.0001) and 46% of those with NYHA Class 3 (p0.05) did not achieve target heart rates. Fifty eight (11%) subjects were not on beta-blockers and of these forty subjects (69%) (p0001) did not achieve target heart rates. Of those on beta-blockers only 25% were at target dose. However, beta-blocker dosage was unrelated to achieving target heart rates. Ivabradine was used in 11% of patients with 10% at target dosage.This study highlights that a third of "stabilized" chronic heart failure patients have not reached recommended target heart rates. Respiratory problems, diabetes and marked dyspnea were associated with poorer rate control. Guideline unawareness, inadequate beta-blocker titration and under use of ivabradine may prevent patients gaining the proven benefits of heart rate control.

Background: Palliative care needs of patients with chronic heart failure are poorly recognised. Policy makers advise a patient-centred approach to holistically assess patients’ needs and care goals. Patient-reported outcome measures are proposed to facilitate patient-centred care. Aim: To explore whether and how a palliative care–specific patient-reported outcome intervention involving the Integrated Palliative care Outcome Scale influences patients’ experience of patient-centred care in nurse-led chronic heart failure disease management clinics. Design: A feasibility study using a parallel mixed-methods embedded design was undertaken. The qualitative component which examined patients and nurses experience of the intervention is reported here. Semi-structured interviews were conducted and analysed using framework analysis. Setting/participants: Eligible patients attended nurse-led chronic heart failure disease management clinics in two tertiary referral centres in Ireland with New York Heart Association functional class II–IV. Nurses who led these clinics were eligible for inclusion. Results: In all, 18 patients and all 4 nurses involved in the nurse-led clinics were interviewed. Three key themes were identified: identification of unmet needs, holistic assessment and patient empowerment. The intervention impacted on processes of care by enabling a shared understanding of patients’ symptoms and concerns, facilitating patient–nurse communication by focusing on these unmet needs and empowering patients to become more involved in clinical discussions. Conclusion: This Integrated Palliative care Outcome Scale–based intervention empowered patients to become more engaged in the clinical consultation and to highlight their unmet needs. This study adds to the evidence for the mechanism of action of patient-reported outcome measures to improve patient-centred care and will help inform outcome selection for future patient-reported outcome measure research.

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.

Aims Sudden arrhythmic death syndrome (SADS) occurs when a person suffers a sudden, unexpected death, with no cause found at postmortem examination. We aimed to describe the cardiac screening outcomes in a population of relatives of SADS victims Methods and results Prospective and retrospective cohort study of consecutive families attending the Family Heart Screening clinic at the Mater Misericordiae Hospital in Dublin, Ireland, from January 2007 to September 2011. Family members of SADS victims underwent a standard screening protocol. Adjunct clinical and postmortem information was sought on the proband. Families who had an existing diagnosis, or where the proband had epilepsy, were excluded. Of 115 families identified, 73 were found to fit inclusion criteria and were retained for analysis, with data available on 262 relatives. Over half of the screened family members were female, and the mean age was 38.6 years (standard deviation 15.6). In 22 of 73 families (30%), and 36 of 262 family members (13.7%), a potentially inheritable cause of SADS was detected. Of the population screened, 32 patients (12.2%) were treated with medication, and 5 (1.9%) have received implantable cardiac defibrillators. Of the five families with long QT syndrome (LQTS) who had a pathogenic gene mutation identified, three carried two such mutations. Conclusion In keeping with international estimates, 30% of families of SADS victims were found to have a potentially inherited cardiac disease. The most common positive finding was LQTS. Advances in postmortem standards and genetic studies may assist in achieving more diagnoses in these families.

We read with interest the case presented by Alexander and colleagues1 describing episodes of chest tightness in a healthy endurance athlete, with subsequent findings of coronary vasospasm, with polymorphic ventricular tachycardia in the setting of spasm events, and an aborted …

The role of troponin quantification in evaluation of patients with suspected acute coronary syndrome is established, but with cost implications. Emerging high-sensitivity troponin and novel multi-marker assays herald further resource implications.The objective of this study was to quantify recent trends in troponin usage and costs in a cross-section of hospitals.A cross-sectional survey seeking data on troponin usage and costs from six tertiary referral, public access teaching hospitals for consecutive years between 2003 and 2009 was carried out.A median annual increase in the volume of troponin assays requested was identified in all six hospitals, with an average median annual increase of 6.9 % across hospitals (interquartile range 3.4, 10.1 %). This annual increase was not accompanied by a corresponding increase in volume of patients presenting to the Emergency Department (ED) with chest pain. The majority (44-67 %) of troponin requests originated in the ED of hospitals. The median annual spend on troponins per hospital waseuro115,612 (interquartile rangeeuro80,452,euro140,918). An analysis of results of assays performed in one centre found that the majority (91 %) of troponin assays performed were in the normal range.An annual increase in troponin requests without a corresponding increase in patient activity raises the possibility of increasingly indiscriminate troponin testing. The cumulative direct and indirect costs of inappropriate testing are significant. Corrective strategies are necessary to improve patient selection and testing protocols, particularly in the advent of the high-sensitivity troponin assays and novel multi-marker strategies.

To describe the natural history, management and outcomes of peripartum cardiomyopathy (PPCM) in an unselected Northern European population.A retrospective single-center observational study was performed at a tertiary referral heart failure and transplantation unit. Outcomes measured were baseline demographics, clinical presentation, course, and treatment. Echocardiographic findings were compared at baseline, 2 months, and 6 months.Twelve cases of PPCM were identified between 2002 and 2008. Mean age was 34.7 years. Nine patients were multiparous and nine had preeclampsia. Ten patients presented in the first week postpartum. Two patients required inotropic support. Mean ejection fraction (EF) at presentation was 27% (SD = 8%) which improved to 47% (SD = 13%) at 6 months. At this time, 10 patients were asymptomatic and 6 had recovered normal cardiac function. Left ventricular (LV) function improved but did not reach normal limits in five cases. One case with persistent severe LV dysfunction required cardiac transplantation. One patient suffered an arrhythmic death several years after the 6 months follow-up period.PPCM is a rare condition. With appropriate therapy, a good clinical outcome is common but not universal. Continued deterioration requiring ventricular support and cardiac transplantation can occur. In our cohort, older maternal age, multiparity, and preeclampsia appeared to be risk factors.

Background: Patients receive education before implantable cardioverter defibrillator (ICD) implantation. Patients’ understanding of ICD therapy requires investigation. Methods: A retrospective cohort study was carried out at two implant centers where patients are educated during a consenting process pre-ICD implantation. Questionnaires examining understanding of ICD therapy were completed during telephone interviews of patients with ICDs. Results: Of 75 patients interviewed, 62 (83%) were male. The median age at time of ICD implantation was 64 years (standard deviation [SD] = 9.4; range: 29–82 years). The median interval from implantation to interview was 3 years (SD = 1.9; range: 0.1–9.0 years). Despite 83% (62 of 75) claiming to understand the reason for ICD implantation, no patient suggested arrhythmia termination when describing the indication. Of shock recipients, 60% (12 of 20) felt poorly prepared for shock therapy. Of patients who experienced a device-related complication, 83% (10 of 12) reported feeling inadequately forewarned of complications. Excluding patients with cardiac resynchronization therapy defibrillators (n = 6), 65% (45 of 69), 52% (36 of 69), 50% (35 of 69), and 61% (42 of 69) believe their ICD reduces risk of heart attack and improves breathing, exercise capacity, and heart function, respectively. Ninety-three percent (70 of 75) are satisfied with their decision to accept ICD therapy. Only 12% (9 of 75) believe they will want to inactivate therapies in setting of terminal illness. Conclusions: Despite preimplantation education, patient comprehension of the risks and benefits of ICD therapy is poor. Patients’ expectations of ICD therapy may be inappropriate. Education strategies before and after implantation require improvement. (PACE 2012; 35:1097–1102)

Aims: The aim of the study was to investigate the frequency of corrected QT interval (QTc) prolongation in a methadone maintenance therapy (MMT) population, and to examine potential associations between this QTс interval and methadone dose as well as concurrent use of opiates, cocaine, and benzodiazepines. Design: Cross-sectional study of patients attending a specialist drug treatment clinic from July 2008 to January 2009. Setting: Single centre inner city specialist drug treatment clinic Ireland. Participants: 180 patients on stable MMT attending for daily methadone doses, over a six month period, where a total of 376 patients were attending during the study period. Measurements: All patients agreeing to participate in the study underwent 12-lead electrocardiograms and QTc analysis, as well as analysis of urine toxicology screen results for opiates, benzodiazepines, and cocaine. ECGs were carried out prior to methadone dose being received, regardless of time of day (trough ECG). Findings: The average age was 32.6 ± 7.1 years, with mean (SD) methadone dose 80.4 ± 27.5mg. The mean (SD) QTc was 420.9 ± 21.1 ms, range 368-495 ms. Patients who had a positive toxicology screen for opiates were receiving significantly lower doses of methadone (77.8 ± 23.5 mg versus 85.0 ± 21.4 mg, p = 0.04). No significant association was noted between QTc-interval prolongation and presence of cocaine metabolites in the urine (p = 0.14) or methadone dose (p = 0.33). 8.8% of patients had evidence of prolonged QTc interval (8.3% male QTc ≥ 450ms and 0.5% female QTc ≥ 470 ms), with 11.1% (n = 20) having QTc intervals > 450ms. Conclusions: Drug-induced QTc interval prolongation is evident (ranging from 8.8-11.1%, depending on definition applied) in patients receiving relatively low daily doses of methadone therapy, with no evidence of a dose-response relationships. The presence of cocaine metabolites in urine does not appear to be associated with increased QTc-interval. Increased awareness of cardiac safety guidelines, including relevant clinical and family history, baseline, and trough dose ECG monitoring, should be incorporated into methadone maintenance therapy protocols.

In 2009, the International Society for Heart and Lung Transplantation (ISHLT) recognized the importance of infectionrelated morbidity and mortality in patients using ventricular assist devices (VADs) and the growing need for a consensusbased expert opinion to provide standard definitions of infections in these patients. The aim of these standard definitions is to improve clinical-investigator communication, allowing meaningful comparison in practice and outcomes between different centers and different VAD devices. In 2010, a core group of experts, including infectious diseases specialists, cardiologists, pathologists, radiologists, and cardiothoracic surgeons, formed an ISHLT Infectious Diseases Working Group to develop agreed criteria for definitions of infections in VAD patients. These definitions have been created by adapting and expanding on existing standardized definitions, which are based on the pathophysiology of equivalent infectious processes in prosthetic devices, such as cardiac prosthetic valve infections, intravascular catheter-related infections, and prosthetic joint infections. These definitions have been divided into 3 sections: VAD-specific infections, VAD-related infections, and non-VAD infections. Owing to the constant shortage of donor organs, new allocation systems, and improved medical therapies for congestive cardiac failure, the overwhelming trend in cardiac transplantation has been toward listing principally the most critically ill patients, that is, those requiring inpatient inotropic therapy for mechanical circulatory support (MCS). The ventricular assist device (VAD) has an expanding role in the management of these patients, both as a bridge to transplantation and as a destination therapy (ie, alternative to transplantation). According to United Network of Organ Sharing (UNOS) registry data, 9,000 transplant candidates have undergone MCS since 1999, comprising 33% of all listed patients and 75% of all listed inpatients. 1

Aims To test the hypothesis that the QS interval of ventricular ectopic beats (VEBs) (ventricular ectopic QS interval, VEQSI) would provide a marker for the presence of structural heart disease and a predictor of mortality. Methods and results We interviewed and examined 2332 patients undergoing Holter ECG monitoring for clinical indications. In persons with VEBs, the morphologies were counted and the QS interval was measured for each of these morphologies. The duration of the broadest VEB, measured from the QRS onset in the derivation showing the earliest onset to its end in the derivation showing the latest termination, was taken as that patient’s VEQSI. Survival was ascertained from public health records. Of 15 electrocardiographic variables pre-selected as potential prognostic indicators, VEQSI demonstrated the strongest association with the presence of structural heart disease (P ¼ 0.013). Thirty-four persons died in 16+ 4 months follow-up. Univariate predictors of mortality are age, history of myocardial infarction, maximum heart rate, QS interval, the number of VEB morphologies, and the VEQSI. On multivariate analysis, only age (P , 0.001) and the number of VEB morphologies (P ¼ 0.02) predicted mortality. Conclusion VEQSI predicts the presence of structural heart disease. The number of VEB morphologies in a Holter recording predicts all-cause mortality.

Background— In autoimmune disorders, circulating autoantibodies identify healthy relatives at risk years before clinical presentation. Healthy relatives of patients with dilated cardiomyopathy (DCM) who have echocardiographic changes, including left ventricular enlargement or depressed fractional shortening at baseline, have increased medium-term risk for DCM development. Approximately one third of relatives have serum anti-heart autoantibodies (AHAs) at baseline; we intended to assess their potential role in predicting DCM development. Methods and Results— Baseline evaluation, including electrocardiography, echocardiography, and AHA, was performed in 592 asymptomatic relatives of 169 consecutive DCM patients (291 males and 301 females; mean age 36±16 years). Relatives were classified in accordance with published echocardiographic criteria; those who did not have DCM were followed up (median of 58 months). DCM among relatives was diagnosed by echocardiography at follow-up. Of the 592 individuals evaluated, 77% were assessed as normal, 4.4% as having DCM, and 19% as possibly affected on the basis of depressed fractional shortening without ventricular dilatation in 17 and left ventricular enlargement without systolic dysfunction in 94. Five-year follow-up of 311 relatives revealed that 26 had progressed (13 to DCM, 11 to left ventricular enlargement, and 2 to depressed fractional shortening). Relatives who developed DCM were more frequently AHA-positive than those who did not (69% versus 37%, P =0.02). Five-year probability of progression to DCM, among normal or possibly affected relatives, was higher in AHA-positive cases ( P =0.03). By Cox regression, positive AHAs at baseline were independent predictors of progression (RR 2.26, CI 1 to 5.1, P =0.03). Conclusions— Among healthy relatives of DCM patients, AHAs are independent predictors of disease development within 5 years.

Objectives: High sensitivity cardiac troponin T and I (hs-cTnT and hs-cTnI) assays show analytical, diagnostic and prognostic improvement over contemporary sensitive cTn assays. However, given the importance of troponin in the diagnosis of myocardial infarction, implementing this test requires rigorous analytical and clinical verification across the total testing pathway. This was the aim of this study. Design and methods: Analytical verification included assessment of critical outlier frequency, for hs-cTnI and cTnI assays. Concordance for paired cTnI and hs-cTnI measurements (n=1096) was verified using 99th percentiles for both genders (cTnI: 30 ng/L, hs-cTnI: 25 ng/L) and for men and women separately (hs-cTnI: M: 34;F: 16 ng/L). Discordant data was correlated with clinical and laboratory information. Diagnosis of Acute Coronary Syndrome (ACS) or Non-ACS was adjudicated by two cardiologists independently. Results: The hs-cTnI assay showed a lower (10-fold) critical outlier rate (0.091%) and more detectable results above the limit of detection (LOD) (23.4%) and 99th percentile (2.4%), compared to cTnI. Analytical concordance between the two assays was high (94.5%) but decreased (91.7%) when gender-specific hs-cTnI cut-offs were used. The hs-cTnI assay gave fewer false negatives (up to 1.0%) but disproportionately more false positives (up to 6.7%) overall, which improved (3.9%) for serial measurements. Conclusions: Laboratories should analytically and clinically verify hs-cTn assays before use, with attention to performance and the clinical and diagnostic algorithms that support appropriate testing and result interpretation. Work in the pre- and post-analytical phases is necessary to augment the analytical improvement in the new era of troponin testing. Keywords: Troponin, High sensitivity, Acute Coronary Syndrome

The use of implantable cardiac defibrillators (ICDs) for the prevention of sudden cardiac death (SCD) in patients with ischemic and non-ischemic cardiomyopathies is well described. However, little is known about the role these devices might play in the prevention of SCD in orthotopic heart transplant (OHT) recipients. Nevertheless, in some transplant centers, 1.5% to 2% of recipients receive ICD implants for the prevention of SCD. Sudden death after transplant is common, with estimates suggesting SCD is the mode of death in up to 35% of recipients. In a population of patients with heart failure, almost all arrhythmic deaths are a result of ventricular tachyarrhythmia, whereas in the transplant population the most commonly described terminal arrhythmias are asystole and electromechanical dissociation (EMD). As outcomes continue to improve after OHT, the natural history of arrhythmia occurrence in these patients is changing. Therefore, we describe our experience of ICD implants in a heart transplant population. Our report summarizes all adult OHT recipients who had ICDs implanted for the prevention of SCD. ICD implantation was deemed appropriate if the patient was considered at high risk for SCD by at least 2 experienced clinicians. Highrisk features included angiographic severity of cardiac allograft vasculopathy (CAV), ejection fraction, previously documented ventricular arrhythmias, and prior unexplained syncope. Outcome data on death and retransplantation were also collected. Between 1983 and 2012, 296 transplants were performed, and of these patients, 10 (3.4%) had an ICD inserted after transplantation. All patients had devices for primary prevention of SCD. Table 1 summarizes the baseline characteristics of the patients, and electrocardiogram findings are presented in Table 2. All patients who underwent ICD insertion had survived 410 years after transplant. The mean age at OHT was 39 14.2 years. Mean time from OHT to ICD was 16 6 years. The indications for ICD insertion were severe CAV in 8 patients and sustained ventricular tachycardia in 2 patients. Before device insertion, 2 patients had experienced unexplained syncope. Table 3 summarizes the individual indications for ICD and subsequent events. The mean follow-up after device implantation was 29 12 months. One patient had successful anti-tachycardia pacing (ATP) for ventricular tachycardia 13 months after ICD implantation. One patient died of SCD. Postmortem device interrogation showed ventricular fibrillation, appropriately shocked by the device with the restoration of sinus rhythm; however, subsequent EMD resulted in death. This patient (patient 5) had been listed for retransplantation on the basis of severe symptomatic diastolic dysfunction and CAV. Also, this patient had defibrillation threshold testing at the time of ICD implantation with no adverse clinical sequelae. At routine follow-up, 1 patient had a 6-beat run of ventricular tachycardia monitored. To date, there have been no complications or infections associated with ICD insertion, and there have been no inappropriate device therapies delivered. Heart transplantation has become the most effective treatment for end-stage heart disease. Improvements in surgical technique, immunosuppression, and patient monitoring have yielded 1-year survival rates of almost 90% and 10-year survival of 450%. The mortality in the later years after transplant is about 4% per year, and this is significantly higher than the age-matched general population. SCD after transplant is a major contributor to this higher mortality. In a retrospective analysis of modes of death in 194 HT recipients, Vaseghi et al identified 41 sudden deaths; terminal rhythms were available in 26 of these. Asystole was the most common rhythm (34%), followed by pulseless electrical activity (20%) and ventricular fibrillation (10%). This study may suggest that denervation of the donor heart can alter susceptibility to ventricular tachyarrhythmias and reduce the potential mortality benefit of ICDs in this unique cohort of patients. CAV has emerged as the primary cause of late graft failure and death. Heart transplant recipients with significant ventricular dysfunction and CAV have the highest risk of SCD. CAV may lead to ischemia, infarction, and left ventricular dysfunction, acting as a substrate for ventricular arrhythmias. Higher grades of CAV have also been associated with longer Q–Tc intervals, which have independently been shown to be a predictor of sudden cardiac death. Cogert et al reported sudden death of 2 OHT patients with severe CAV within 4 months of ICD placement. In 2 further descriptions of sudden deaths in OHT patients with severe CAV and functioning ICDs by Marzoa-Rivas et al, EMD Table 1 Baseline Characteristics of OHT Patients Receiving ICD

The first Irish heart transplant was performed on the 10th of September 1985. Over the next 20 years, 229 transplants were performed in 228 recipients. To evaluate the success of the first generation of cardiac transplantation in Ireland. Analysis of clinical outcomes and survival statistics for patients undergoing heart transplantation in Ireland and comparison with international standards. There has been a steady improvement in transplant outcome over this time and survival figures for recipients between 2000 and 2004 show a hospital, 1-year and 5-year survival rate of 85.7%, 84.1% and 76.8% respectively Thirty-eight of the 99 heart transplants performed between 1985 and 1994 are still alive more than 10 years later and the longest survivor is now 19 years post transplantation. The results compare favourably with international figures. Heart transplantation offers excellent longterm survival and quality of life but remains challenged by a shortage of suitable donor organs.

Specialist palliative care (SPC) services are increasingly integrated with chronic heart failure (CHF) services. Left ventricular assist devices (LVADs) represent an advance in the management of advanced CHF, but may pose ethical challenges for SPC services providing care to this population. The patient received an LVAD as 'bridge-to-heart-transplant,' but subsequently experienced multiple cerebral haemorrhages, resulting in neurological deficits, and severe functional impairment. The risk of further cerebral events precluded ongoing anticoagulation, and she was transferred to an SPC inpatient unit for symptom control and end-of-life care. Following discussion within the multi-disciplinary team and with the patient's family, LVAD support was withdrawn, and the patient died peacefully. This piece reviews the ethical considerations that informed decision-making, in particular, autonomy, informed consent and futility. In addition, the question of the nature of LVADs is debated and how the perceptions of the patient, and others, of the device may influence decision-making around withdrawal of treatment.

We describe a patient who developed multi-organ failure with reactive hemophagocytic syndrome secondary to disseminated histoplasmosis 8 months after orthotopic heart transplantation. The patient responded fully to a prolonged course of therapy with amphotericin B and remains free of recurrence. Disseminated histoplasmosis and reactive hemophagocytic syndrome have rarely been described in the setting of cardiac transplantation and never before in combination.

To determine the effect of multisite pacing on left ventricular function.Prospective observational study.18 patients with heart failure with a dilated poorly functioning left ventricle (LV) and left bundle branch block.Pacing for 5 minutes in random order at the right ventricle (RV) apex, RV outflow tract, mid posterolateral LV, RV apex and LV simultaneously, and RV outflow tract and LV simultaneously. The best achieved measurements with RV, LV, and biventricular pacing were compared.LV dimension, filling characteristics, and long axis indices were measured on echocardiography simultaneously with LV pressure. Cycle efficiency (%)--that is, the ratio of the area of the acquired pressure dimension loop to that of the ideal loop for that segment--quantified coordination.The pacing site that gave the best achieved cycle efficiency differed between patients (biventricular in five, LV in two, RV in seven, and no site in four). In patients with baseline incoordination (cycle efficiencyor = 72%, n = 12) cycle efficiency improved significantly with RV pacing (cycle efficiency 76%, p = 0.01) but not with LV (65%) or biventricular (67%) pacing. LV based pacing induced premature short axis contraction in a subset of patients (n = 4), which was associated with a prolonged time from the Q wave on the ECG to the onset of inward movement of the long axis (from apex to mitral ring): biventricular 145 ms, LV 105 ms, RV 85 ms (biventricular v RV, p0.05). Excluding patients with baseline incoordination in whom premature activation occurred, pacing at all sites led to a similar increase in cycle efficiency (RV 78%, LV 72%, biventricular 73%).Ventricular coordination can be improved with pacing in patients with baseline incoordination. Short and long axis fibres may be asynchronised in a subset of patients with LV or biventricular pacing, which may worsen coordination. The clinical significance of these findings remains to be defined.

asymptomatic relatives of patients with familial dilated cardiomyopathy who have left ventricular enlargement [LVE] are at risk for progression to dilated cardiomyopathy. A novel index of the fractal correlation properties of heart rate variability (HRV), the short-term scaling component (proportional, variant(1)) in detrended fluctuation analysis, is a promising prognostic tool in left ventricular dysfunction. The aim of this study was to compare values of proportional, variant(1) and conventional HRV indices in LVE relatives with dilated cardiomyopathy patients and normal controls.time-domain and spectral HRV measures, and the short-term scaling component ( proportional, variant(1)) were assessed from 24-h Holter recordings from 22 LVE relatives (left ventricular end-diastolic dimension112% predicted, normal fractional shortening), 24 dilated cardiomyopathy patients and 14 controls.the time domain index SDNN was lower in dilated cardiomyopathy patients [101.8(+/-44.0)] than in LVE relatives [161.7(+/-53.9)] or controls [152.9(+/-51.4)], P=0.01. Similarly, triangular index and spectral measures were reduced in dilated cardiomyopathy patients but not in LVE relatives or controls. In contrast, the short term scaling component ( proportional, variant(1)) in detrended fluctuation analysis was reduced in both dilated cardiomyopathy patients [1.06(+/-0.33)] and in LVE relatives [1.15 (+/-0.20)], compared with controls [1.32(+/-0.16)], P=0.01. Among DCM patients the short-term scaling component ( proportional, variant(1)) was significantly associated with echocardiographic deterioration during follow-up (3.7+/-2.1 year) (P=0.004).the short-term scaling component ( proportional, variant(1)) is reduced in asymptomatic relatives of dilated cardiomyopathy patients who have LVE.

Objectives This study investigated whether apparently healthy relatives of patients with idiopathic dilated cardiomyopathy (DCM) who have left ventricular enlargement (LVE) have biopsy evidence of underlying myocardial disease. Background Left ventricular enlargement with normal systolic function is common among asymptomatic relatives of patients with DCM. Although there is circumstantial evidence to suggest that LVE may be a marker of early DCM, its pathophysiologic significance remains uncertain. Methods Over six years, 767 asymptomatic relatives of 183 consecutive patients with DCM were evaluated: 37 (5%) had DCM and 104 (14%) had LVE (left ventricular end-diastolic dimension >112% predicted) with normal systolic function. Right ventricular biopsy was performed in 32 relatives with LVE, 14 patients with symptomatic DCM and 6 control subjects with normal ventricular function undergoing elective coronary artery bypass graft surgery. Histologic and immunohistochemical analyses, including quantitative double immunofluorescence, were performed for leukocyte markers (CD3 and CD68), intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen class II antigens (DR and DQ). Results Histologic findings consistent with DCM were present in 50% of the patients with DCM, 25% of the relatives with LVE and 0% of the control subjects. The median CD3 count was 2.4/mm2in patients with DCM, 4/mm2in relatives with LVE and 0 in control subjects (p = 0.04). Using a threshold of >7 cells/mm2, 21% of patients with DCM and 25% of relatives with LVE were CD3-positive (p = 0.01). Quantitative analysis demonstrated DR expression on 55.8 ± 22.8%, 63.5 ± 18.8% and 30.9 ± 15.7% of the endothelial surface in patients with DCM, relatives and control subjects, respectively (p = 0.003). Corresponding values for ICAM expression were 35.6 ± 15.1%, 36.7 ± 14.5% and 17.3 ± 7.9% (p = 0.013). When combining inflammatory and histologic changes, 28 (86%) of LVE, 14 (100%) of DCM and no control biopsies were abnormal (p Conclusions Most asymptomatic relatives of patients with DCM with LVE have histopathologic and immunopathologic findings similar to those of patients with established disease. Clinical identification and follow-up of such individuals are warranted to prevent presentation with advanced DCM and to enable assessment of interventions aimed at attenuating disease progression.

Objective. To evaluate the prevalence, clinical features, and pattern of inheritance of familial dilated cardiomyopathy (DCM) in heart transplant patients. Patients and method. Patients with idiopathic DCM who had undergone heart transplantation were invited to participate. Patients with alcohol abuse were not excluded. A clinical evaluation, 12-lead ECG, echocardiogram, blood tests, and DNA extraction were performed in patients and relatives. Familial DCM was defined as the presence of at least one relative with idiopathic DCM. Possible familial DCM was considered when at least one relative had left ventricular enlargement (LVE) (> 112% predicted LVEDD). Results. One hundred and ninety-nine relatives of 43 families were studied. DCM was familial in 11 probands (25.6%) and possibly familial in 11 (25.6%). Fifteen relatives had DCM (7.5%), 26 (13.1%) LVE, and 5 (2.5%) hypertrophic cardiomyopathy. The pattern of inheritance was autosomal dominant in most families. Five probands (3 with familial DCM) had antecedents of consanguinity and possible recessive inheritance. Six probands (14%, 1 with familial DCM) had relatives with conduction system defects. Creatine kinase was moderately increased in 9 relatives (4.5%), 3 of them with LVE. Fifteen patients had at least moderate alcohol intake. Three of them had familial DCM (relatives without alcohol abuse) and 6 had possible familial DCM. Conclusions. The prevalence of familial DCM is high in patients who undergo heart transplant. Left ventricular enlargement, conduction system abnormalities, and elevated creatine kinase may be early markers of familial disease. Hypertrophic cardiomyopathy is present in some relatives of patients with idiopathic DCM. Familial DCM is present in patients with a previous diagnosis of alcoholic DCM.