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Biventricular pacing has been suggested as offering greater hemodynamic benefit than single site pacing in patients with advanced heart failure and left bundle branch block. This was tested using acute multisite pacing. Eighteen such patients were atrialsensed, ventricular multisite paced in random order for 5 minutes. The best achieved measure of cardiac output (CO), pulmonary capillary wedge pressure (PCWP) and left ventricular (LV) + dP/dtmax at RV, LV, and biventricular pacing sites compared. Baseline PCWP, CO, and LV + dP/dtmax were 20 +/- 10 mmHg 4.8 +/- 1.3 L/min and 680 +/- 173 mmHg/s respectively. In all 18 patients CO and in 17 of 18 patients LV + dP/dtmax and PCWP improved with pacing. In the group as a whole, no significant hemodynamic difference between pacing sites was observed in PCWP (pacing site RV 19 +/- 10 mmHg, LV 17 +/- 10, biventricular 18 +/- 11) or CO (RV 5.2 +/- 1.5 L/min, LV 5.1 +/- 1.5, biventricular 5.3 +/- 1.7). Increased stroke volume/PCWP with LV (5.6 +/- 3.7 mLs/mmHg) and biventricular pacing (5.4 +/- 4.0) were not significantly greater compared to RV pacing (4.7 +/- 3.0, ANOVA P = 0.20). Increase in LV + dP/dtmax with pacing at LV (814 +/- 190 mmHg/s) and biventricular (839 +/- 290) sites was not significantly greater than the increase with RV pacing (769 +/- 203 mmHg/s, ANOVA P = 0.30). Pacing in patients with heart failure and conduction delay can produce a hemodynamic benefit. There is individual variation in the pacing site that leads to the greatest improvement. In the group as a whole, biventricular and LV pacing produced only modest improvements compared to RV pacing. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to determine the prognostic significance of estimated creatinine clearance (CrCl) in relation to 6-min walk distance in ambulatory patients with congestive heart failure (HF).Background: Although measurement of renal function is integral to the management of chronic congestive HF, its prognostic implications are not well described and have not been formally evaluated relative to measures of functional capacity.Methods: We analyzed outcomes of the 585 participants of the 6-min walk substudy of the Digitalis Investigation Group (DIG) trial. The CrCl was estimated using the Cockcroft-Gault equation. Predictors of all-cause mortality were identified using semiparametric Cox proportional hazards regression and completely parametric hazard analyses.Results: Most subjects (85%) were New York Heart Association functional class II and III. Mean age was 65 (+/-12) years and mean ejection fraction (EF) 35% (+/-13%). There were 153 (26%) deaths during a median of 2.6 years of follow-up. Mortality by increasing quartiles of estimated CrCl was 37% (18 to 48 ml/min), 29% (47 to 64 ml/min), 18% (64 to 86 ml/min), and 21% (86 to 194 ml/min) with corresponding hazard ratios (HRs) relative to the top quartile of 2.1 (95% confidence interval [CI], 1.4 to 3.3), 1.6 (95% CI, 1.0 to 2.5), and 0.9 (95% CI, 0.5 to 1.5), respectively. In Cox regression analyses, independent predictors of mortality were estimated CrCl (adjusted HR [quartile 1:quartile 4] 1.5; 95% CI, 1.1 to 2.1), 6-min walk distance < or =262 m [adjusted HR, 1.63; 95% CI, 1.12 to 2.27]), EF, recent hospitalization for worsening HF, and need for diuretic treatment. Parametric (hazard) analysis confirmed consistent effects of estimated CrCl on mortality in several subgroups including that of patients with EF >45%.Conclusion: In ambulatory patients with congestive HF, estimated CrCl predicts all-cause mortality independently of established prognostic variables. [ABSTRACT FROM AUTHOR]

Objective: To assess the health related quality of life and psychological wellbeing of patients with dilated cardiomyopathy, and relate these to clinical variables and psychological adjustment.Design: Postal questionnaire survey of 99 adult patients with dilated cardiomyopathy, selected at random from a larger database (60.6% response rate). Assessments included the short form 36 (SF-36) health survey, the hospital anxiety and depression scales, the sleep problems index, and a measure of psychological adjustment to cardiomyopathy.Results: Patients with dilated cardiomyopathy reported significant impairments in physical functioning, role limitations owing to physical and emotional problems, social functioning, mental health, perceptions of general health, sleep, and vitality. Anxiety and depression levels were higher than in population samples. Impairment in several domains of quality of life was associated with low shortening fraction, high left ventricular end diastolic diameter, and the presence of heart failure and mitral regurgitation. Patients with familial cardiomyopathy had less impairment in quality of life than those with non-familial disease. Psychological adjustment scores were associated with several aspects of quality of life and emotional wellbeing. In multivariate analysis, demographic and clinical variables accounted for 0.1-40.7% of the variance in different domains of quality of life, and psychological adjustment scores accounted for an additional 0.5-22.4% of variance.Conclusions: Patients with dilated cardiomyopathy experience pronounced restrictions in quality of life and psychological wellbeing. These limitations are only partly accounted for by symptoms and the severity of underlying disease. Patients may benefit from efforts to improve psychological adjustment to the condition. [ABSTRACT FROM AUTHOR]

This study compares the clinical features, management, and outcome in men and women from a consecutive, unselected series of patients with acute myocardial infarction (AMI) who were admitted to a university cardiac center over a 3-year period. It is a retrospective observational study of 1,059 admissions with AMI identified through the Hospital In-Patient Enquiry (HIPE) registry, validated according to Minnesota Manual criteria, and followed for a period of up to 5 years (median 36 months). Women comprised 40% of all admissions, had a higher hospital mortality (24% vs. 16%, p<0.001), and were less likely to receive thrombolysis (23% vs. 33%, p<0.01), admission to coronary care (65% vs. 77%, p<0.001), or subsequent invasive or noninvasive investigations (55% vs. 63%, p<0.01). However, women with AMI were older than men with AMI (71 vs. 65 years, p<0.001). After adjusting for age, differences that remained significant were prevalence of hypertension (odds ratio [OR] 2.12, 95% confidence intervals [CI] 1.56 to 2.88) and cigarette smoking (OR 0.47, 95% CI 0.35 to 0.65), management in coronary care (OR 0.66, 95% CI 0.49 to 0.88), and hospital mortality (OR 1.48, 95% CI 1.07 to 2.04). Excess mortality occurred predominantly in women <65 years old (18% vs. 8%, OR [multivariate] 2.35, 95% CI 1.19 to 4.56), among whom multivariate analysis demonstrated a significantly lower thrombolysis rate (OR 0.48, 95% CI 0.27 to 0.86). In this group, lack of thrombolysis independently predicted hospital mortality (OR 5.37, 95% CI 1.45 to 19.82). Female gender was not an independent predictor of mortality following AMI (OR 1.42, 95% CI 0.90 to 2.26). Thus, among unselected patients, female gender is associated with, but not an independent predictor of, reduced survival after AMI. Gender differences in mortality are greatest in younger patients, who are less likely to receive thrombolysis and in whom lack of thrombolysis is independently associated with mortality after AMI. [ABSTRACT FROM AUTHOR]

Aims: Many European healthcare providers struggle to adopt multidisciplinary, integrated care pathways for people with heart failure (HF) as recommended by the European Society of Cardiology. PRO-HF (Program to Optimize Heart Failure Patient Pathways) was developed to help clinicians identify strengths, gaps, and shortcomings in their HF pathways and support tailored interventions to optimize pathways and enhance patient care. We report initial findings from baseline assessments of HF pathway characteristics and challenges from 10 hospitals in six European countries (France, Ireland, Portugal, Spain, The Netherlands, and United Kingdom)., Methods and Results: Baseline assessments were holistic appraisals of full HF services to calibrate current status and development needs and assist management teams in prioritizing improvement projects. Assessments were performed using a comprehensive checklist of measures covering the HF patient journey from diagnosis to ongoing follow-up. These included a digital survey sent to full HF care teams and one-to-one interviews. The digital survey focused on four key areas (HF outpatient clinic; remote patient management; efficient device implantation and inpatient pathways; and network maximization) and 16 dimensions of excellence. Priority areas and themes for action identified in baseline assessments were (i) provision of HF specialist care; (ii) data capture and analysis; (iii) institutional care protocols; (iv) hospital-wide strategies; and (v) multidisciplinary teams (MDTs). Suboptimal specialist care of emergency inpatients was an issue at all hospitals and prioritized at 8/10. Availability and accessibility of data on patients, activities, and outcomes was an issue at all hospitals and prioritized by 4/10. A lack of clear protocols, templates, and tools for some HF activities created variability in patient care (e.g., HF specialist consultations, diagnostic testing, follow-up appointments, medications, and device eligibility) and inefficient use of clinician time. This made it difficult to initiate new technologies (e.g., remote patient monitoring) due to the risk of overburdening staff. MDTs were frequently understaffed. Multiple interventions were identified to address gaps and shortcomings that could be tailored to specific needs of individual hospitals (e.g., inpatient pathway optimization, creation/optimization of HF outpatient clinics, development of an HF performance dashboard, enhancement of protocol adherence, streamlining cardiac resynchronisation therapy pathways, and MDT coordination)., Conclusions: PRO-HF provides a valuable opportunity to identify gaps and significant shortcomings in HF pathways in European hospitals. Preliminary findings from hospitals that have initiated suggested changes to address these challenges are encouraging, though longer-term follow-up from more hospitals is needed to confirm the impact of PRO-HF on HF pathway optimization and patient care., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: In the SIRONA 2 trial, the safety and efficacy of pulmonary artery (PA) pressure (PAP)-guided heart failure (HF) management using a novel PAP sensor were assessed at 30 and 90 days, respectively, and both endpoints were met. The current study examines the prespecified secondary endpoints of safety and accuracy of the PA sensor along with HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance through 12 months., Methods and Results: SIRONA 2 is a prospective, multi-centre, open-label, single-arm trial evaluating the Cordella™ PA Sensor System in 70 patients with New York Heart Association (NYHA) functional class III HF with a prior HF hospitalization and/or increase of N-terminal pro-brain natriuretic peptide within 12 months of enrolment. Sensor accuracy was assessed and compared with measurements obtained by standard right heart catheterization (RHC). Safety was defined as freedom from prespecified adverse events associated with use of the Cordella PA Sensor System and was assessed in all patients who entered the cath lab for PA sensor implant. HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance were also assessed. At 12 months, there was good agreement between the Cordella PA Sensor System and RHC, with the average difference for mean PAP being 2.9 ± 7.3 mmHg. The device safety profile was excellent with 98.4% freedom from device/system-related complications. There were no pressure sensor failures. HF hospitalizations and mortality were low with a rate of 0.33 event per patient year. Symptoms as assessed by NYHA (P < 0.0001) and functional capacity as measured by 6 min walk test (P = 0.02) were significantly improved. Patients' adherence to daily transmissions of PAP and vital signs measurements was 95%., Conclusions: Long-term follow-up of the SIRONA 2 trial supports the safety and accuracy of the Cordella PA Sensor System in enabling comprehensive HF management in NYHA class III HF patients., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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™ PA Sensor System including the comprehensive Cordella™ 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., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Atherosclerosis 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)., Methods: miR-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., Results: Here, 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., Conclusion: miR-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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Fitzsimons, Oggero, Bruen, McCarthy, Strowitzki, Mahon, Ryan, Brennan, Barry, Perretti and Belton.)

Background: Recruitment challenges contribute to the paucity of palliative care research with advanced chronic heart failure patients., Aim: To describe the challenges and outline strategies of recruiting advanced chronic heart failure patients., Design: A feasibility study using a pre-post uncontrolled design., Setting: Advanced chronic heart failure patients were recruited at two nurse-led chronic heart failure disease management clinics in Ireland Results: Of 372 patients screened, 81 were approached, 38 were recruited (46.9% conversion to consent) and 25 completed the intervention. To identify the desired population, a modified version of the European Society of Cardiology definition was used together with modified New York Heart Association inclusion criteria to address inter-study site New York Heart Association classification subjectivity. These modifications substantially increased median monthly numbers of eligible patients approached (from 8 to 20) and median monthly numbers recruited (from 4 to 9). Analysis using a mortality risk calculator demonstrated that recruited patients had a median 1-year mortality risk of 22.7 and confirmed that the modified eligibility criteria successfully identified the population of interest. A statistically significant difference in New York Heart Association classification was found in recruited patients between study sites, but no statistically significant difference was found in selected clinical parameters between these patients., Conclusion: Clinically relevant modifications to the European Society of Cardiology definition and strategies to address New York Heart Association subjectivity may help to improve advanced chronic heart failure patient recruitment in clinical settings, thereby helping to address the paucity of palliative care research this population.

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.

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., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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.

Patient-centred care (PCC) is recommended in policy documents for chronic heart failure (CHF) service provision, yet it lacks an agreed definition. A systematic review was conducted to identify PCC interventions in CHF and to describe the PCC domains and outcomes. Medline, Embase, CINAHL, PsycINFO, ASSIA, the Cochrane database, clinicaltrials.gov, key journals and citations were searched for original studies on patients with CHF staged II-IV using the New York Heart Association (NYHA) classification. Included interventions actively supported patients to play informed, active roles in decision-making about their goals of care. Search terms included 'patient-centred care', 'quality of life' and 'shared decision making'. Of 13,944 screened citations, 15 articles regarding 10 studies were included involving 2540 CHF patients. Three studies were randomised controlled trials, and seven were non-randomised studies. PCC interventions focused on collaborative goal setting between patients and healthcare professionals regarding immediate clinical choices and future care. Core domains included healthcare professional-patient collaboration, identification of patient preferences, patient-identified goals and patient motivation. While the strength of evidence is poor, PCC has been shown to reduce symptom burden, improve health-related quality of life, reduce readmission rates and enhance patient engagement for patients with CHF. There is a small but growing body of evidence, which demonstrates the benefits of a PCC approach to care for CHF patients. Research is needed to identify the key components of effective PCC interventions before being able to deliver on policy recommendations.

Background: The detection of elevations in cardiorenal biomarkers, such as troponins, B-type natriuretic peptides (BNPs), and neutrophil gelatinase-associated lipocalins, are associated with poor outcomes in patients hospitalized with acute heart failure. Less is known about the association of these markers with adverse events in chronic right ventricular dysfunction due to pulmonary hypertension, or whether their measurement may improve risk assessment in the outpatient setting., Methods and Results: We performed a cohort study of 108 patients attending the National Pulmonary Hypertension Unit in Dublin, Ireland, from 2007 to 2009. Cox proportional hazards analysis and receiver operating characteristic curves were used to determine predictors of mortality and hospitalization. Death or hospitalization occurred in 50 patients (46.3%) during the median study period of 4.1 years. Independent predictors of mortality were: 1) decreasing 6-minute walk test (6MWT; hazard ratio [HR] 12.8; P < .001); 2) BNP (HR 6.68; P < .001); and 3) highly sensitive troponin (hsTnT; HR 5.48; P < .001). Adjusted hazard analyses remained significant when hsTnT was added to a model with BNP and 6MWT (HR 9.26, 95% CI 3.61-23.79), as did the predictive ability of the model for death and rehospitalization (area under the receiver operating characteristic curve 0.81, 95% CI 0.73-0.90)., Conclusions: Detection of troponin using a highly sensitive assay identifies a pulmonary hypertension subgroup with a poorer prognosis. hsTnT may also be used in a risk prediction model to identify patients at higher risk who may require escalation of targeted pulmonary vasodilator therapies and closer clinical surveillance., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To ascertain whether a name can influence a person's health, by assessing whether people with the surname "Brady" have an increased prevalence of bradycardia., Design: Retrospective, population based cohort study., Setting: One university teaching hospital in Dublin, Ireland., Participants: People with the surname "Brady" in Dublin, determined through use of an online telephone directory., Main Outcome Measure: Prevalence of participants who had pacemakers inserted for bradycardia between 1 January 2007 and 28 February 2013., Results: 579 (0.36%) of 161,967 people who were listed on the Dublin telephone listings had the surname "Brady." The proportion of pacemaker recipients was significantly higher among Bradys (n=8, 1.38%) than among non-Bradys (n=991, 0.61%; P=0.03). The unadjusted odds ratio (95% confidence interval) for pacemaker implantation among individuals with the surname Brady compared with individuals with other surnames was 2.27 (1.13 to 4.57)., Conclusions: Patients named Brady are at increased risk of needing pacemaker implantation compared with the general population. This finding shows a potential role for nominative determinism in health.

Background: Hypertrophic cardiomyopathy (HCM) is a genetic condition, and relatives of affected persons may be at risk. Cardiac troponin biomarkers have previously been shown to be elevated in HCM. This study examines the new highly-sensitive cardiac troponin I (hsTnI) assay in a HCM screening population., Methods: Nested case-control study of consecutive HCM sufferers and their relatives recruited from May 2010 to September 2011. After informed consent, participants provided venous blood samples and clinical and echocardiographic features were recorded. Associations between the natural log (ln) of the contemporary troponin I (cTnI) and hsTnI assays and markers of cardiac hypertrophy were examined. Multiple regression models were fitted to examine the predictive ability of hsTnI for borderline or definite HCM., Results: Of 107 patients, 24 had borderline and 19 had definite changes of HCM. Both TnI assays showed significant, positive correlations with measures of cardiac muscle mass. After age and sex adjustment, the area under the receiver operator characteristic (AUROC) curve for the outcome of HCM was 0.78, 95% CI [0.65, 0.90], for ln(hsTnI), and 0.66, 95% CI [0.51, 0.82], for ln(cTnI) (p=0.11). Including the hsTnI assay in a multiple-adjusted "screening" model for HCM resulted in a non-significant improvement in both the AUROC and integrated discrimination index., Conclusions: Both cTnI and hsTnI show a graded, positive association with measures of cardiac muscle mass in persons at risk of HCM. Further studies will be required to evaluate the utility of these assays in ECG- and symptom-based identification of HCM in at-risk families.

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.

Background: 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., Aims: The objective of this study was to quantify recent trends in troponin usage and costs in a cross-section of hospitals., Methods: 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., Results: 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 was 115,612 (interquartile range 80,452, 140,918). An analysis of results of assays performed in one centre found that the majority (91 %) of troponin assays performed were in the normal range., Conclusions: 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.

Aims: To determine if newer criteria for diagnosing and staging acute kidney injury (AKI) during heart failure (HF) admission are more predictive of clinical outcomes at 30 days and 1 year than the traditional worsening renal function (WRF) definition., Methods: We analyzed prospectively collected clinical data on 637 HF admissions with 30-day and 1-year follow-up. The incidence, stages, and outcomes of AKI were determined using the following four definitions: KDIGO, RIFLE, AKIN, and WRF (serum creatinine rise ≥0.3 mg/dl). Receiver operating curves were used to compare the predictive ability of each AKI definition for the occurrence of adverse outcomes (death, rehospitalization, dialysis)., Results: AKI by any definition occurred in 38.3% (244/637) of cases and was associated with an increased incidence of 30-day (32.3 vs. 6.9%, χ(2) = 70.1; p < 0.001) and 1-year adverse outcomes (67.5 vs. 31.0%, χ(2) = 81.4; p < 0.001). Most importantly, there was a stepwise increase in primary outcome with increasing stages of AKI severity using RIFLE, KDIGO, or AKIN (p < 0.001). In direct comparison, there were only small differences in predictive abilities between RIFLE and KDIGO and WRF concerning clinical outcomes at 30 days (AUC 0.76 and 0.74 vs. 0.72, χ(2) = 5.6; p = 0.02) as well as for KDIGO and WRF at 1 year (AUC 0.67 vs. 0.65, χ(2) = 4.8; p = 0.03)., Conclusion: During admission for HF, the benefits of using newer AKI classification systems (RIFLE, AKIN, KDIGO) lie with the ability to identify those patients with more severe degrees of AKI who will go on to experience adverse events at 30 days and 1 year. The differences in terms of predictive abilities were only marginal.

Background: Family-based cardiac screening programmes for persons at risk for genetic cardiac diseases are now recommended. However, the psychological wellbeing and health related quality of life (QoL) of such screened patients is poorly understood, especially in younger patients. We sought to examine wellbeing and QoL in a representative group of adults aged 16 and over in a dedicated family cardiac screening clinic., Methods: Prospective survey of consecutive consenting patients attending a cardiac screening clinic, over a 12 month period. Data were collected using two health measurement tools: the Short Form 12 (version 2) and the Hospital Anxiety and Depression Scale (HADS), along with baseline demographic and screening visit-related data. The HADS and SF-12v.2 outcomes were compared by age group. Associations with a higher HADS score were examined using logistic regression, with multi-level modelling used to account for the family-based structure of the data., Results: There was a study response rate of 86.6%, with n=334 patients providing valid HADS data (valid response rate 79.5%), and data on n=316 retained for analysis. One-fifth of patients were aged under 25 (n=61). Younger patients were less likely than older to describe significant depression on their HADS scale (p<0.0001), although there were overall no difference between the prevalence of a significant HADS score between the younger and older age groups (18.0% vs 20.0%, p=0.73). Significant positive associates of a higher HADS score were having lower educational attainment, being single or separated, and being closely related to the family proband. Between-family variance in anxiety and depression scores was greater than within-family variance., Conclusions: High levels of anxiety were seen amongst patients attending a family-based cardiac screening clinic.Younger patients also had high rates of clinically significant anxiety. Higher levels of anxiety and depression tends to run in families, and this has implications for family screening and intervention programmes.

Aim: To describe the natural history, management and outcomes of peripartum cardiomyopathy (PPCM) in an unselected Northern European population., Methods: 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., Results: 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., Conclusions: 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.

Aims: The aim of this 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 QTc 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: A total of 180 patients on stable MMT attending for daily methadone doses, over a 6-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 [standard deviation (SD)] methadone dose 80.4 ± 27.5 mg. 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 = 0.13) or methadone dose (P = 0.33). 8.8% of patients had evidence of prolonged QTc interval (8.3% male QTc ≥ 450 ms and 0.5% female QTc ≥ 470 ms), with 11.1% (n = 20) having QTc intervals > 450 ms., Conclusions: Drug-induced corrected QT 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 relationship. The presence of cocaine metabolites in urine does not appear to be associated with increased corrected QT 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., (© 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.)

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 = 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 = 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.

Criteria of organ-specific autoimmunity are fulfilled in a subset of patients with myocarditis/dilated cardiomyopathy (DCM). In particular, circulating heart-reactive autoantibodies are found in such patients and symptom-free relatives. These autoantibodies are directed against multiple antigens, some of which are expressed in the heart (organ-specific), others in heart and some skeletal muscle fibres (partially heart-specific) or in heart and skeletal muscle (muscle-specific). Distinct autoantibodies have different frequency in disease and normal controls. Different techniques detect one or more antibodies, thus they cannot be used interchangeably for screening. It is unknown whether the same patients produce more antibodies or different patient groups develop autoimmunity to distinct antigens. IgG antibodies, shown to be cardiac- and disease-specific for myocarditis/DCM, can be used as autoimmune markers for relatives at risk as well as for identifying patients in whom immunosuppression may be beneficial. Some autoantibodies may also have a functional role, but further work is needed.

Background: Idiopathic dilated cardiomyopathy is often familial, and apparently healthy relatives may have latent, early, or undiagnosed established disease., Objective: To determine the prevalence and natural history of asymptomatic cardiac abnormalities among sampled relatives of unselected patients referred for management of dilated cardio-myopathy., Design: Prospective cohort study., Patients: 767 asymptomatic relatives of 189 consecutive unselected patients with dilated cardiomyopathy., Measurements: Clinical evaluation, including history, physical examination, electrocardiography, and echocardiography, was performed. Participants were classified in accordance with published echocardiographic criteria. Sampled relatives who did not have evidence of dilated cardiomyopathy at the initial evaluation were followed for a median of 57 months (range, 1 to 133 months)., Results: Of the 767 patients evaluated, 592 (77.2%) were assessed as healthy, 35 (4.6% [95% CI, 3.7% to 7.6%]) had dilated cardiomyopathy, 119 (15.5% [CI, 12.5% to 18.8%]) had left ventricular enlargement without systolic dysfunction, and 21 (2.7% [CI, 1.9% to 4.9%]) had depressed fractional shortening without ventricular dilatation. At follow-up, progression to dilated cardiomyopathy occurred in 13 (10%) relatives with left ventricular enlargement or depressed fractional shortening versus 3 (1.3%) healthy relatives. In a multivariate model, only left ventricular enlargement or depressed fractional shortening independently predicted progression to dilated cardiomyopathy (hazard ratio, 10.0 [CI, 2.8 to 35.5]; P < 0.001)., Limitations: Because relatives had to be willing to participate and be available geographically, selection bias may have occurred., Conclusion: Treatable asymptomatic dilated cardiomyopathy was identified in 4.6% of asymptomatic relatives. In addition, left ventricular enlargement and depressed fractional shortening were common in asymptomatic relatives of patients with dilated cardiomyopathy and were associated with a statistically significant medium-term risk for disease progression. Evaluation of relatives of patients with cardiomyopathy is recommended.

Background: The growing epidemic of congestive heart failure in the setting of limited donor-organ availability has mandated continued development and increased utilization of medical and surgical alternatives to cardiac transplantation. We sought to assess current disposition and outcomes of patients recently referred for transplant evaluation to a single high-throughput tertiary referral center., Methods and Results: We performed a retrospective observational review of consecutive patients with advanced heart failure who were assessed initially in an outpatient setting by a heart failure cardiologist, with a view to transplant or nontransplant surgical alternatives between 1995 and 2000. Of 1174 consecutive referrals (mean age 55.1 [+/-12.7], 74% male), 588 (50%) were recommended for medical treatment (mean age 55.3 [+/-12.4], 72% male) and 200 (17%) for nontransplant surgery, principally coronary artery bypass grafting, mitral valve repair, infarct exclusion, partial left ventriculectomy, or combinations thereof (mean age 57.8 [+/-10.6], 76% male). A minority, 418 (36%), were initially listed for cardiac transplantation (mean age 53.5 [+/-13.9], 80% male). Of these, 74 (18% of listed) died waiting (34 on left ventricular assist device support), 45 were delisted (27 for improved clinical status), and 217 (18% of referred group) have been transplanted. The 3-year survival (Kaplan-Meier) was equivalent (82%) in the transplanted and nontransplant surgery groups (excluding partial left ventriculectomy patients)., Conclusion: In current clinical practice less than one fifth of transplant referrals are ultimately transplanted, reflecting both a limited donor supply and the application of alternative, nontransplant strategies. Medium-term survival in patients suitable for alternative surgical strategies equals that of cardiac transplantation.

A 25-year-old male was discovered to have an asymptomatic pericardial effusion during routine pre-employment medical evaluation. During pericardiocentesis 1200 ml of milky-white fluid was obtained; subsequent biochemical evaluation confirmed the chylous nature of this fluid. Following thorough evaluation a diagnosis of isolated chylopericardium was made. Following several recurrences he underwent thoracotomy with ligation of the thoracic duct and creation of a pericardial window. There are relatively few published reports of true isolated chylopericardium and the aetiology and pathogenesis remain unknown. A primary abnormality of the thoracic lymphatic valve system is postulated. The most effective treatment is surgical with ligation of the thoracic duct above the diaphragm and creation of a pericardial window

Objective: To determine the effect of multisite pacing on left ventricular function., Design: Prospective observational study., Patients: 18 patients with heart failure with a dilated poorly functioning left ventricle (LV) and left bundle branch block., Interventions: 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., Main Outcome Measures: 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., Results: 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 efficiency < or = 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, p < 0.05). 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%)., Conclusions: 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.

Background and Aim: 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., Methods: 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 dimension >112% predicted, normal fractional shortening), 24 dilated cardiomyopathy patients and 14 controls., Results: 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)., Conclusion: the short-term scaling component ( proportional, variant(1)) is reduced in asymptomatic relatives of dilated cardiomyopathy patients who have LVE.

Background: Hypertrophic cardiomyopathy (HCM) is an inherited disease of the sarcomere characterised clinically by myocardial hypertrophy and its consequences. Phenotypic expression is heterogeneous even within families with the same aetiological mutation and may be influenced by additional genetic factors., Objective: To determine the influence of genetic polymorphisms of the renin-angiotensin-aldosterone system (RAAS) on ECG and two dimensional echocardiographic left ventricular hypertrophy (LVH) in genetically identical patients with HCM., Patients and Methods: Polymorphisms of five RAAS components were determined in 26 gene carriers from a single family with HCM caused by a previously identified myosin binding protein C mutation. Genotypes associated with a higher activation status of the RAAS were labelled "pro-LVH genotypes"., Results: There was a non-biased distribution of pro-LVH genotypes in the gene carriers. Those without pro-LVH genotypes did not manifest cardiac hypertrophy whereas gene carriers with pro-LVH genotypes did (mean (SD) left ventricular muscle mass 190 (48) v 320 (113), p = 0.002; interventricular septal thickness 11.5 (2.0) v 16.4 (6.7), p = 0.01; pathological ECG 0% (0 of 10) v 63% (10 of 16), respectively). Multivariate analysis controlling for age, sex, and hypertension confirmed an independent association between the presence of pro-LVH polymorphisms and left ventricular mass. When each polymorphism was assessed individually, carriers of each pro-LVH genotype had a significantly greater left ventricular mass than those with no pro-LVH mutation; these associations, with the exception of cardiac chymase A AA polymorphism (p = 0.06), remained significant in multivariate analysis., Conclusion: Genetic polymorphisms of the RAAS influence penetrance and degree of LVH in 26 gene carriers from one family with HCM caused by a myosin binding protein C mutation.

Antagonism of adverse neuro-endocrine responses is the current paradigm by which chronic congestive cardiac failure is treated. Several recent large-scale randomized, controlled trials have confirmed the benefits of beta-adrenergic blocking agents in this regard. In light of the present heart failure 'epidemic', appropriate organization of services is mandatory to ensure that as many patients as possible can benefit from this life-saving therapy.

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/mm(2) in patients with DCM, 4/mm(2) in relatives with LVE and 0 in control subjects (p = 0.04). Using a threshold of >7 cells/mm(2), 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 < 0.001)., 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 investigate whether viral infection acts as a trigger factor for the development of dilated cardiomyopathy in genetically predisposed individuals with a family history of disease., Setting: Patients attending the cardiomyopathy unit in a cardiac tertiary referral centre., Design: Nested polymerase chain reaction (nPCR) was used to determine whether enteroviral, adenoviral, or cytomegaloviral nucleic acids were detectable in the myocardium of 19 asymptomatic relatives of patients with dilated cardiomyopathy; all these relatives had echocardiographic abnormalities thought to represent early disease. Explanted hearts from patients with end stage dilated cardiomyopathy were also studied and were compared with 25 controls (ischaemic heart disease (21), valvar heart disease (2), hypertrophic cardiomyopathy (1), restrictive cardiomyopathy (1)). Myocardial tissue from two fatal cases of culture positive coxsackie myocarditis was used as a positive control., Results: No viral nucleic acid was detected in any group other than in those with myocarditis. Spiking of random wells with purified recombinant viral nucleic acids confirmed the sensitivity and reproducibility of the assays., Conclusions: Myocardial viral infection is not detectable in relatives of patients with dilated cardiomyopathy who are suspected of having early disease. There is no evidence that viruses act as a trigger factor for initiating the dilated cardiomyopathy in these patients.

Background: A previous study suggested that severe left-ventricular hypertrophy (maximum wall thickness > or = 30 mm) in patients with hypertrophic cardiomyopathy is associated with a risk of sudden cardiac death sufficient to warrant consideration for implantation of a cardioverter defibrillator (ICD). However, the prognostic significance of left-ventricular hypertrophy in relation to other clinical risk factors is poorly characterised., Methods: We studied 630 patients consecutively referred to one hospital in London, UK (mean age 37 years [SD 16]; 382 male; mean follow-up 59 months). Patients underwent two-dimensional and doppler echocardiography, upright exercise testing, and Holter monitoring., Findings: 39 patients died suddenly or had an appropriate ICD discharge; nine died from progressive heart failure; 11 from other cardiovascular causes and 23 from non-cardiac causes. There was a trend towards higher probability of sudden death or ICD discharge with increasing wall thickness (p=0.029, relative risk per 5 mm increment 1.31 [95% CI 1.03-1.66]). Of the 39 patients who died suddenly or had an ICD discharge, ten had a wall thickness of 30 mm or more. Patients with wall thickness of 30 mm or more had higher probability of sudden death or ICD discharge than patients with wall thickness less than 30 mm (p=0.049, 2.07 [1.00-4.25]. When considered together, the number of additional risk factors (one to three) was a better predictor of risk of sudden death or ICD discharge than wall thickness (p=0.0001, relative risk per additional factor 2.00 [1.43-2.79] vs p=0.058, 1.26 per 5 mm increment [0.99-1.60]). There was no relation between the pattern of hypertrophy and survival., Interpretation: The risk of sudden death associated with a wall thickness of 30 mm or more in patients without other risk factors is insufficient to justify aggressive prophylactic therapy. Most sudden deaths occurred in patients with wall thickness less than 30 mm, so the presence of mild hypertrophy cannot be used to reassure patients that they are at low risk.

Objectives: We sought to identify patients with hypertrophic cardiomyopathy (HCM) at high risk of sudden death (SD)., Background: Relatively low mortality rates in HCM make conventional analysis of multiple clinical risk markers for SD problematic. This study used a referral center registry to investigate a smaller number of generally accepted noninvasive risk markers., Methods: We studied 368 patients (14 to 65 years old, 239 males) with HCM. There were five variables: nonsustained ventricular tachycardia (NSVT), syncope, exercise blood pressure response (BPR), family history of sudden death (FHSD) and left ventricular wall thickness (LVWT)., Results: During follow-up (3.6+/-2.5 years [range 2 days to 9.6 years]), 36 patients (9.8%) died, 22 of them suddenly. Two patients received heart transplants. The six-year SD-free survival rate was 91% (95% confidence interval [CI] 87% to 95%). In the Cox model, there was a significant pairwise interaction between FHSD and syncope (p = 0.01), and these were subsequently considered together. The multivariate SD risk ratios (with 95% CIs) were 1.8 for BPR (0.7 to 4.4) (p = 0.22); 5.3 for FHSD and syncope (1.9 to 14.9) (p = 0.002); 1.9 for NSVT (0.7 to 5.0) (p = 0.18) and 2.9 for LVWT (1.1 to 7.1) (p = 0.03). Patients with no risk factors (n = 203) had an estimated six-year SD-free survival rate of 95% (95% CI 91% to 99%). The corresponding six-year estimates (with 95% CIs) for one (n = 122), two (n = 36) and three (n = 7) risk factors were 93% (87% to 99%), 82% (67% to 96%) and 36% (0% to 75%), respectively. Patients with two or more risk factors had a lower six-year SD survival rate (95% CI) compared with patients with one or no risk factors (72% [56% to 88%] vs. 94% [91% to 98%]) (p = 0.0001)., Conclusions: This study demonstrates that patients with multiple risk factors have a substantially increased risk of SD sufficient to warrant consideration for prophylactic therapy.