Risk and predictors of sudden death in cardiac sarcoidosis: A systematic review and meta-analysis.

BACKGROUND: To evaluate the risk for ventricular arrhythmia (VA) and sudden cardiac death (SCD) in patients with cardiac sarcoidosis (CS) and determine the prognostic factors. METHODS AND RESULTS: PUBMED, EMBASE and SCOPUS were searched up to 14th April 2020. Studies reporting the incidence of SCD, appropriate ICD therapy in CS patients, or relevant prognostic information in patients having undergone MRI, PET, or programmed electrical stimulation (PES) were included. Nineteen studies consisting of 1247 patients, reported the risk of ICD therapies or SCD over a follow-up period of 1.7-7 years. 22.7% (n = 9; 22.7, 95%CI [16.10-29.36]) of patients in primary and 58.4% (n = 9; 58.42, 95% CI [38.61-78.22]) in secondary prevention cohorts experienced appropriate device therapy or SCD events. 18% (n = 2; 18, 95%CI [14-23]) of patients received ≥5 appropriate therapies. 9 out of 664 patients with confirmed cardiac sarcoidosis but without implanted ICDs died suddenly. 17.9% of patients (n = 4; 17.9, 95%CI [10.80-25.03]) experienced inappropriate device therapy. Positive LGE-MRI and PES were associated with an 8.6-fold (n = 6; RR = 8.60, 95%CI [3.80-19.48]) and 9-fold (n = 5; RR = 9.07, 95%CI [4.65-17.68]) increased risk of VA respectively. Positive LGE-MRI and PET with associated with a 6.8-fold (n = 12; RR = 6.82, 95%CI [4.57-10.18]) and 3.4-fold (n = 7; RR = 3.41, 95%CI [2.03-5.74]) respectively for increased risk of major adverse cardiac events. CONCLUSIONS: The risk of appropriate ICD therapy or sudden cardiac death is high in patients with CS. The presence of LGE-MRI and positive electrophysiology study identify patients at increased risk of ventricular arrhythmias. [CRD42019124220].

Platelet Reactivity Is Independent of Left Atrial Wall Deformation in Patients with Atrial Fibrillation.

It has been documented recently that left atrial (LA) deformation in AF patients (while in AF) is predictive of subsequent stroke risk. Additionally, diminished LA deformation during AF correlates with the presence of LA blood stasis. Given that endothelial function is dependent on laminar blood flow, the present study sought to investigate the effect of diminished LA deformation (during AF) on platelet reactivity and inflammation in AF patients. Patients (n = 17) hospitalised with AF underwent echocardiography (while in AF) for determination of peak positive LA strain (LASp). Whole blood impedance aggregometry was used to measure extent of ADP-induced aggregation and subsequent inhibitory response to the nitric oxide (NO) donor, sodium nitroprusside. Platelet thioredoxin-interacting protein (Txnip) content was determined by immunohistochemistry. LASp tended (p = 0.078) to vary inversely with CHA2DS2VASc scores. However, mediators of inflammation (C-reactive protein, Txnip) did not correlate significantly with LASp nor did extent of ADP-induced platelet aggregation or platelet NO response. These results suggest that the thrombogenic risk associated with LA stasis is independent of secondary effects on platelet aggregability or inflammation.

Standard versus atrial fibrillation-specific management strategy (SAFETY) to reduce recurrent admission and prolong survival: pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Patients are increasingly being admitted with chronic atrial fibrillation, and disease-specific management might reduce recurrent admissions and prolong survival. However, evidence is scant to support the application of this therapeutic approach. We aimed to assess SAFETY--a management strategy that is specific to atrial fibrillation. METHODS: We did a pragmatic, multicentre, randomised controlled trial in patients admitted with chronic, non-valvular atrial fibrillation (but not heart failure). Patients were recruited from three tertiary referral hospitals in Australia. 335 participants were randomly assigned by computer-generated schedule (stratified for rhythm or rate control) to either standard management (n=167) or the SAFETY intervention (n=168). Standard management consisted of routine primary care and hospital outpatient follow-up. The SAFETY intervention comprised a home visit and Holter monitoring 7-14 days after discharge by a cardiac nurse with prolonged follow-up and multidisciplinary support as needed. Clinical reviews were undertaken at 12 and 24 months (minimum follow-up). Coprimary outcomes were death or unplanned readmission (both all-cause), measured as event-free survival and the proportion of actual versus maximum days alive and out of hospital. Analyses were done on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTRN 12610000221055). FINDINGS: During median follow-up of 905 days (IQR 773-1050), 49 people died and 987 unplanned admissions were recorded (totalling 5530 days in hospital). 127 (76%) patients assigned to the SAFETY intervention died or had an unplanned readmission (median event-free survival 183 days [IQR 116-409]) and 137 (82%) people allocated standard management achieved a coprimary outcome (199 days [116-249]; hazard ratio 0·97, 95% CI 0·76-1·23; p=0·851). Patients assigned to the SAFETY intervention had 99·5% maximum event-free days (95% CI 99·3-99·7), equating to a median of 900 (IQR 767-1025) of 937 maximum days alive and out of hospital. By comparison, those allocated to standard management had 99·2% (95% CI 98·8-99·4) maximum event-free days, equating to a median of 860 (IQR 752-1047) of 937 maximum days alive and out of hospital (effect size 0·22, 95% CI 0·21-0·23; p=0·039). INTERPRETATION: A post-discharge management programme specific to atrial fibrillation was associated with proportionately more days alive and out of hospital (but not prolonged event-free survival) relative to standard management. Disease-specific management is a possible strategy to improve poor health outcomes in patients admitted with chronic atrial fibrillation. FUNDING: National Health and Medical Research Council of Australia.

Navigating the fine line between benefit and risk in chronic atrial fibrillation: rationale and design of the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY).

BACKGROUND: Health outcomes associated with atrial fibrillation (AF) continue to be poor and standard management often does not provide clinical stability. The Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY) compares the efficacy of a post-discharge, nurse-led, multi-disciplinary programme to optimise AF management with usual care. METHODS: SAFETY is a prospective, multi-centre, randomised controlled trial with blinded-endpoint adjudication. A target of 320 hospitalised patients with a chronic form of AF will be randomised (stratified by "rate" versus "rhythm" control) to usual post-discharge care or the SAFETY Intervention (SI). The SI involves home-based assessment, extensive clinical profiling and the application of optimal gold-standard pharmacology which is individually tailored according to a "traffic light" framework based on clinical stability, risk profile and therapeutic management. The primary endpoint is event-free survival from all-cause death or unplanned readmission during 18-36 months follow-up. Secondary endpoints include rate of recurrent hospital stay, treatment success (i.e. maintenance of rhythm or rate control and/or application of anti-thrombotic therapy without a bleeding event) and cost-efficacy. RESULTS: With study recruitment to be completed in early 2012, the results of this study will be available in early 2014. CONCLUSIONS: If positive, SAFETY will represent a potentially cost-effective and readily applicable strategy to improve health outcomes in high risk individuals discharged from hospital with chronic AF.

Epidemiology and diagnosis of heart failure with preserved left ventricular ejection fraction: rationale and design of the study.

AIMS: Despite major advances in our understanding of 'systolic' heart failure, at present the epidemiology, pathophysiology, and therapy of heart failure with preserved left ventricular ejection fraction (HFpEF) is poorly understood, in large part because of the lack of robust and widely accepted diagnostic criteria. Although there is a good evidence base for the treatment of systolic heart failure, similar data are lacking for the treatment of HFpEF. Methods In our study, we will screen a consecutive series of 5000 subjects aged ≥60 from the community. Following symptom questionnaire and echocardiography, metabolic exercise testing will be used to confirm whether or not patients thought clinically to have HFpEF are in fact exercise limited and that this limitation is cardiac in origin. Blood samples for plasma brain natriuretic peptide (BNP) will be taken at rest and following exercise in symptomatic patients and matching controls. CONCLUSIONS: At the end of our study we will establish community prevalence and population characteristics of HFpEF, and also evaluate the diagnostic accuracy of current echocardiography parameters and BNP for the diagnosis of the condition.

Heart failure with preserved ejection fraction is characterized by dynamic impairment of active relaxation and contraction of the left ventricle on exercise and associated with myocardial energy deficiency.

OBJECTIVES: We sought to evaluate the role of exercise-related changes in left ventricular (LV) relaxation and of LV contractile function and vasculoventricular coupling (VVC) in the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and to assess myocardial energetic status in these patients. BACKGROUND: To date, no studies have investigated exercise-related changes in LV relaxation and VVC as well as in vivo myocardial energetic status in patients with HFpEF. METHODS: We studied 37 patients with HFpEF and 20 control subjects. The VVC and time to peak LV filling (nTTPF, a measure of LV active relaxation) were assessed while patients were at rest and during exercise by the use of radionuclide ventriculography. Cardiac energetic status (creatine phosphate/adenosine triphosphate ratio) was assessed by the use of (31)P magnetic resonance spectroscopy at 3-T. RESULTS: When patients were at rest, nTTPF and VVC were similar in patients with HFpEF and control subjects. The cardiac creatine phosphate/adenosine triphosphate ratio was reduced in patients with HFpEF versus control subjects (1.57 +/- 0.52 vs. 2.14 +/- 0.63; p = 0.003), indicating reduced energy reserves. Peak maximal oxygen uptake and the increase in heart rate during maximal exercise were lower in patients with HFpEF versus control subjects (19 +/- 4 ml/kg/min vs. 36 +/- 8 ml/kg/min, p < 0.001, and 52 +/- 16 beats/min vs. 81 +/- 14 beats/min, p < 0.001). The relative changes in stroke volume and cardiac output during submaximal exercise were lower in patients with HFpEF versus control subjects (ratio exercise/rest: 0.99 +/- 0.34 vs. 1.25 +/- 0.47, p = 0.04, and 1.36 +/- 0.45 vs. 2.13 +/- 0.72, p < 0.001). The nTTPF decreased during exercise in control subjects but increased in patients with HFpEF (-0.03 +/- 12 s vs. +0.07 +/- 0.11 s; p = 0.005). The VVC decreased on exercise in control subjects but was unchanged in patients with HFpEF (-0.01 +/- 0.15 vs. -0.25 +/- 0.19; p < 0.001). CONCLUSIONS: Patients with HFpEF have reduced cardiac energetic reserve that may underlie marked dynamic slowing of LV active relaxation and abnormal VVC during exercise.