Catheter Ablation for Atrial Fibrillation-Influence of Modifiable Risk Factors and Ablation Modality on Procedural Efficacy and Safety.

BACKGROUND: Modifiable lifestyle risk factors, in particular obesity and related conditions, are important drivers of atrial fibrillation (AF), impacting the severity of symptoms and influence the efficacy and safety of treatment. OBJECTIVE: The study aimed to assess the impact of modifiable lifestyle factors on the effectiveness and safety of AF ablation, and examine the procedural characteristics, efficacy, safety and cost outcomes of cryoballoon vs radiofrequency ablation, in a real-world clinical setting. METHOD: Patients undergoing catheter ablation for AF (June 2017 to December 2020) were included in this retrospective analysis. Efficacy and safety outcomes were obtained from electronic medical records and state-wide databases. The primary outcome was successful isolation of the pulmonary veins and freedom from AF without repeat ablation or ongoing antiarrhythmic therapy at 12 months. RESULTS: The study included 141 patients (mean age 60±11 years, 57% male). The average body mass index (BMI) was 29.2±5.6 kg/m2. Ablation by cryoballoon was undertaken in 59% (radiofrequency 41%). Acutely successful pulmonary vein isolation was achieved in 92%, however, only 52% (n=74) met the primary outcome (successful isolation of the pulmonary veins and freedom from AF without repeat ablation or ongoing antiarrhythmic therapy) at 12 months. Successful management of AF was more likely in patients with lower BMI (p=0.006; particularly with BMI <27 kg/m2; p=0.004) and weight (p=0.003), and in those without obstructive sleep apnoea (p=0.032). The only independent predictor of the primary outcome was BMI (ß=0.25, p=0.004). Over 75% of complications occurred in those with BMI ≥27 kg/m2. CONCLUSIONS: Catheter ablation for AF is more likely to be unsuccessful in patients with uncontrolled risk factors, particularly obesity. Risk factor optimisation may improve procedural success and reduce the risk of procedural complications.

Clinical prediction scores and the utility of time to blood culture positivity in stratifying the risk of infective endocarditis in Staphylococcus aureus bacteraemia.

BACKGROUND: Infective endocarditis (IE) complicates up to a quarter of Staphylococcus aureus bacteraemia (SAB) cases. Risk scores predict IE complicating SAB but have undergone limited external validation, especially in community-acquired infections and those who use IV drugs. Addition of the time to positive culture (TTP) may provide incremental risk prognostication. OBJECTIVES: To externally validate risk scores for predicting IE in SAB and assess the incremental value of TTP. METHODS: The modified Duke score was calculated for adults hospitalized with SAB at a major tertiary institution. All patients underwent echocardiography. Sensitivity and specificity of the risk scores for predicting IE were calculated, and the incremental value of TTP was assessed. RESULTS: One hundred and six cases were analysed and 18 (17%) met definite IE criteria. The optimal TTP to predict IE was 11.5 h (sensitivity 88.9%; specificity 71.6%). The sensitivity of VIRSTA and PREDICT (Predicting risk of endocarditis using a clinical tool) were similar (94.4% for both) and higher than POSITIVE (Prediction Of Staphylococcus aureus Infective endocarditis Time to positivity, IV drug use, Vascular phenomena, pre-Existing heart condition; 77.8%). The receiver-operator characteristic AUCs were VIRSTA 0.83, PREDICT 0.75, POSITIVE 0.89 and TTP 0.85. Adding TTP to VIRSTA (i.e. VIRSTA+) resulted in the highest AUC (0.90), sensitivity (100%) and negative predictive value (100%), albeit with a low specificity (33%). CONCLUSIONS: The VIRSTA and POSITIVE scores were the strongest predictors for IE complicating SAB. The addition of TTP to VIRSTA (VIRSTA+) significantly improved discriminatory value and may be safely used to rationalize echocardiography strategies.

Comparison of high intensity interval training with standard cardiac rehabilitation on vascular function.

OBJECTIVES: To compare the short- and long-term effects of high-intensity interval training (HIIT) with usual care moderate intensity continuous training (MICT) on systemic vascular function and stiffness in patients with coronary artery disease undergoing a cardiac rehabilitation program. DESIGN: Randomized controlled trial. METHODS: Fifty-four patients (age = 63 ± 8 years, 93% male) were randomized to complete 3 sessions/week (2 supervised, 1 home-based) of either (1) 4 × 4-min HIIT or (2) 40-min MICT, for 4 weeks. Patients then continued 3 unsupervised home-based sessions/week of their allocated training for 11 months. Brachial artery flow-mediated dilation, pulse wave velocity, and blood pressure were measured at baseline, 4 weeks, 3 months, 6 months, and 12 months. Data were analyzed using linear mixed modeling and are presented as mean change from baseline (95% CI). RESULTS: HIIT showed a greater improvement in flow-mediated dilation compared to MICT after 4 weeks [1.5% (0.9, 2.1) vs 0.1% (-0.5, 0.8); p = 0.004) but not 12 months [1.2% (-0.2, 2.5) vs 0.4% (-0.8, 1.7); p = 0.153). There were no short- or long-term group differences for changes in pulse wave velocity, peripheral or central blood pressure between HIIT and MICT after 4 weeks, or over 12 months. CONCLUSIONS: A 4-week HIIT program was superior to MICT for improving vascular function, but not arterial stiffness or blood pressure. Over 12 months, changes in vascular function, blood pressure, and arterial stiffness were similar for HIIT and MICT.

Myocarditis and Cardiac Complications Associated With COVID-19 and mRNA Vaccination: A Pragmatic Narrative Review to Guide Clinical Practice.

Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus is likely to remain endemic globally despite widespread vaccination. There is increasing concern for myocardial involvement and ensuing cardiac complications due to COVID-19, however, the available evidence suggests these risks are low. Pandemic publishing has resulted in rapid manuscript availability though pre-print servers. Subsequent article retractions, a lack of standardised definitions, over-reliance on isolated troponin elevation and the heterogeneity of studied patient groups (i.e. severe vs. symptomatic vs all infections) resulted in early concern for high rates of myocarditis in patients with and recovering from COVID-19. The estimated incidence of myocarditis in COVID-19 infection is 11 cases per 100,000 infections compared with an estimated 2.7 cases per 100,000 persons following mRNA vaccination. For substantiated cases, the clinical course of myocarditis related to COVID-19 or mRNA vaccination appears mild and self-limiting, with reports of severe/fulminant myocarditis being rare. There is limited data available on the management of myocarditis in these settings. Clinical guidance for appropriate use of cardiac investigations and monitoring in COVID-19 is needed for effective risk stratification and efficient use of cardiac resources in Australia. An amalgamation of national and international position statements and guidelines is helpful for guiding clinical practice. This paper reviews the current available evidence and guidelines and provides a summary of the risks and potential use of cardiac investigations and monitoring for patients with COVID-19.

Composite Echocardiographic Score to Predict Long-Term Survival Following Myocardial Infarction.

BACKGROUND: Whilst the left ventricular ejection fraction (LVEF) remains the primary echocardiographic measure widely utilised for risk stratification following myocardial infarction (MI), it has a number of well recognised limitations. The aim of this study was to compare the prognostic utility of a composite echocardiographic score (EchoScore) composed of prognostically validated measures of left-ventricular (LV) size, geometry and function, to the utility of LVEF alone, for predicting survival following MI. METHODS: Retrospective data on 394 consecutive patients with a first-ever MI were included. Comprehensive echocardiography was performed within 24 hours of admission for all patients. EchoScore consisted of LVEF<50%, left atrial volume index>34 mL/m2, average E/e >14, E/A ratio>2, abnormal LV mass index, and abnormal LV end-systolic volume index. A single point was allocated for each measure to derive a score out of 6. The primary outcome measure was all-cause mortality. RESULTS: At a median follow-up of 24 months there were 33 deaths. On Kaplan-Meier analysis, a high EchoScore (>3) displayed significant association with all-cause mortality (log-rank χ2=74.48 p<0.001), and was a better predictor than LVEF<35% (log-rank χ2=17.01 p<0.001). On Cox proportional-hazards multivariate analysis incorporating significant clinical and echocardiographic predictors, a high EchoScore was the strongest independent predictor of all-cause mortality (HR 6.44 95%CI 2.94-14.01 p<0.001), and the addition of EchoScore resulted in greater increment in model power compared to addition of LVEF (model χ2 56.29 vs 44.71 p<0.001, Harrell's C values 0.83 vs 0.79). CONCLUSIONS: A composite echocardiographic score composed of prognostically validated measures of LV size, geometry, and function is superior to LVEF alone for predicting survival following MI.

Accuracy of dual-energy x-ray absorptiometry for assessing longitudinal change in visceral adipose tissue in patients with coronary artery disease.

BACKGROUND/OBJECTIVE: Visceral adipose tissue (VAT) is a key target of interventions for obesity-related diseases. Dual-energy x-ray absorptiometry (DXA) can estimate VAT, however its accuracy to measure longitudinal change in VAT compared to gold-standard techniques such as magnetic resonance imaging (MRI), has not been studied in adults. This study aimed to determine the accuracy of DXA compared with gold-standard MRI for cross-sectional VAT assessment, and for detecting longitudinal change in VAT. METHODS: Adults with coronary artery disease (64 ± 8 years; BMI 27.8 ± 3.5 kg/m2; 88% male) were assessed for VAT by DXA and MRI at baseline (n = 34) and during implementation of an exercise intervention study at 3- and 12-months (n = 29). To match the 5.2 cm DXA measurement site for Hologic software (InnerCoreTM), VAT cross-sectional area (CSA) was measured by MRI using a single slice at L4/L5 junction, and VAT volume measured by 10 × 5 mm slices over the L4/L5 junction. MRI slices were quantified for VAT using semi-automated specialised software. Relationships between DXA and MRI for cross-sectional VAT and longitudinal change in VAT were determined by linear regression. Accuracy between the methods was assessed by Bland-Altman analysis, with data presented as mean difference (95% confidence interval), lower and upper limits of agreement (LoA). RESULTS: Strong correlations were found between DXA-VAT and MRI-VAT at baseline (r = 0.90; p < 0.001), and longitudinal change in DXA-VAT and MRI-VAT over 3- and 12-months (r = 0.67; p < 0.001). In contrast, Bland-Altman analysis revealed significant overestimation by DXA-VAT volume at baseline by 13% [-104 cm3 (-157, -52 cm3), p < 0.001; LoA (-398, 189 cm3)], and underestimation of change in DXA-VAT volume over 3-months by 33% [-41 cm3 (-77, -4 cm3), p = 0.030; LoA (-228, 147 cm3)] and 12-months by 47% [-65 cm3 (-114, -17 cm3), p = 0.010; LoA (-316, 185 cm3)]. Results were similar for VAT CSA. CONCLUSIONS: Compared with MRI, DXA substantially underestimated longitudinal changes in VAT. Therefore, DXA is not currently a valid alternative to MRI for quantifying VAT changes and may under-represent the effectiveness of interventions for obesity management.

High intensity interval training does not result in short- or long-term dietary compensation in cardiac rehabilitation: Results from the FITR heart study.

The aim of this study was to investigate short- and long-term compensatory effects on dietary intake following high intensity interval training (HIIT) compared with usual care moderate intensity continuous training (MICT) during and following a cardiac rehabilitation program. This study investigates secondary outcomes of a clinical trial. Ninety-three participants with coronary artery disease enrolled in a 4-week cardiac rehabilitation program, were randomised to 1) 4x4-minute HIIT; or 2) 40-min of MICT (usual care). Patients were instructed to complete 3 weekly sessions (2 supervised, 1 home-based) for 4-weeks, and 3 weekly home-based sessions thereafter for another 48-weeks. Dietary intake was measured by telephone-based 24-h recall over 2 day at baseline, 4-weeks, 3-months, 6-months, and 12-months. Three-Factor Eating Questionnaire was used to measure dietary behaviour and Leeds Food Preference Questionnaire used to measure food preferences. Appetite was assessed by a visual analogue scale and appetite-regulating hormones. There was no change over the study period or differences between groups for daily energy intake at 4-weeks or 12-months. There were also no group differences for any other measures of dietary intake, fasting hunger or appetite-related hormones, dietary behaviour, or food preferences. These findings suggest that compared to moderate intensity exercise, HIIT does not result in compensatory increases of energy intake or indicators of poor diet quality. This finding appears to be the same for patients with normal weight and obesity. HIIT can therefore be included in cardiac rehabilitation programs as an adjunct or alterative to MICT, without concern for any undesirable dietary compensation.

Infective Endocarditis: A Contemporary Study of Microbiology, Echocardiography and Associated Clinical Outcomes at a Major Tertiary Referral Centre.

BACKGROUND: The epidemiology of infective endocarditis (IE) continues to evolve, with antimicrobial resistance and clinical outcomes largely dependent on the environment of acquisition. This study aimed to provide a contemporary review of the microbiology and antimicrobial management of IE and report echocardiographic findings and predictors of adverse outcomes in community-acquired and health care-associated IE. METHODS: Consecutive presentations of IE to a major Australian tertiary referral centre between January 2011 and April 2016 were examined. Culprit organisms and resistance patterns were recorded, as was transthoracic and transoesophageal echocardiography. Real-world antimicrobial prescription and use of an outpatient parenteral antimicrobial therapy (OPAT) service were also assessed, and clinical outcomes analysed. RESULTS: Of 204 consecutive cases, 30% were associated with health care, a group with a higher burden of comorbidities and more prone to complications. Health care-associated cases had lower rates of surgical intervention but higher mortality. A history of intravenous drug use (IVDU) conferred risk for recurrent IE whereas multivalvular involvement predicted heart failure hospitalisation. Staphylococcus aureus was isolated in 45%. Whilst methicillin resistance remains low, the prevalence of S. aureus IE is increasing. Single antimicrobial agents were commonly used (83%) and therapy via OPAT was safe and significantly reduced length of hospital stay. Not undergoing transoesophageal echocardiography (TOE) or definitive surgical management conferred poorer prognosis. CONCLUSIONS: The epidemiology of IE is evolving and there is need for updated epidemiological data and associated clinical outcomes. Environment of acquisition remains important in the face of increasing health care provision and the changing predominance of culprit microorganisms.

Implementation of a pharmacist-led penicillin allergy de-labelling service in a public hospital.

BACKGROUND: Inaccurate allergy labelling results in inappropriate antimicrobial management of the patient, which may affect clinical outcome, increase the risk of adverse events and increase costs. Inappropriate use of alternative antibiotics has implications for antimicrobial stewardship programmes and microbial resistance. METHODS: All adult inpatients labelled as penicillin allergic were identified and screened for eligibility by the study pharmacist. An accurate allergy and medication history was taken. Patients were 'de-labelled', underwent oral challenge or were referred to an immunology clinic, if study criteria were met. All patients included in the study were followed-up 1 year after intervention. RESULTS: Two hundred and fifty eligible patients with a label of 'penicillin allergy' were identified. The prevalence of reported penicillin allergy at Middlemore Hospital was 11%. We found that 80% of study patients could be 'de-labelled'. Of those, 80% were 'de-labelled' after an interview with the pharmacist alone, 16% had an uneventful oral challenge and 4% were deemed to be inappropriately labelled after referral to an immunology clinic. Appropriately labelled patients accounted for 20% of the study population. Changes to inpatient antibiotic therapy were recommended in 61% of 'de-labelled' patients, of which no patients had adverse events after commencing on penicillin antibiotics. At the 1 year follow-up, 98% of patients who were 'de-labelled' had no adverse events to repeated administration of penicillin antibiotics. CONCLUSIONS: This study showed that a pharmacist-led allergy management service is a safe option to promote antimicrobial stewardship and appropriate allergy labelling.

New Diastology Guidelines: Evolution, Validation and Impact on Clinical Practice.

The 2016 American Society of Echocardiography/European Association of Echocardiography (ASE/EACVI) guidelines on the assessment of diastolic function sought to simplify the assessment of diastolic function by recommending a streamlined, stepped approach with a focus on four key variables. Haemodynamic validation using simultaneous cardiac catheterisation and echocardiographic assessment of diastolic function have shown robust prediction of left ventricular filling pressure (LVFP) using the streamlined 2016 algorithms, with favourable comparisons to the 2009 guidelines. Similarly, prognostic validation data demonstrates that the 2016 algorithms are easier to implement in clinical practice, have superior inter-observer reliability across a broad range of observer experience, and are better at predicting clinical outcomes. Furthermore, published data show improved classification of clinical heart failure patients. However, increased specificity of the updated 2016 guidelines results in a lower prevalence of diastolic dysfunction compared to the 2009 recommendations. Further refinement of guidelines for the identification and diagnosis of diastolic dysfunction is possible through incorporation of new diastolic parameters.

Coronary artery fistula following surgical myectomy for hypertrophic obstructive cardiomyopathy: a case report.

Background: Coronary artery fistula is a rare, but recognized complication of surgical myectomy. Although most communicate with the right heart, a large fistula into the left ventricular cavity may result in a shunt haemodynamically analogous to aortic regurgitation. Understanding the variable presentation of iatrogenic coronary fistulae and the optimal evaluation strategy is critical to obtaining a timely diagnosis and instituting treatment. Case summary: We report the case of a 57-year-old renal transplant recipient admitted for evaluation of presyncope, one-year post-surgical myectomy for hypertrophic obstructive cardiomyopathy. An iatrogenic coronary artery fistula was suspected by transthoracic echocardiography, and later confirmed with both non-invasive and invasive coronary angiography. Discussion: We highlight various cardiac imaging modalities that confirmed the diagnosis of coronary artery fistula and helped to determine the clinical significance. We report the tailored approach often required to determine the anatomic and haemodynamic characteristics of coronary fistulae and outline potential management strategies.

Recommendations for objective cardiovascular assessment to inform clinical exercise prescription: An Exercise Physiologist and Physiotherapist expert consensus.

OBJECTIVES: Exercise is beneficial in managing cardiovascular health. Objective assessments of cardiovascular function assist in identifying the presence or absence of exertional symptoms, and functional and physiological thresholds necessary to inform safe and effective exercise programmes. This study aimed to generate expert consensus on assessments of cardiovascular function to support clinical decision-making for professionals providing clinical exercise services. DESIGN: Three-round e-Delphi. METHODS: Expert Exercise Physiologists and Physiotherapists were recruited to participate in an e-Delphi. Experts were asked to list all objective cardiovascular assessments deemed necessary to inform safe and effective exercise prescription. In subsequent e-Delphi rounds, experts rated the importance of each item, provided a rationale to support their assertions, and reconsidered others' ratings and rationale to shift or reaffirm their position. These results were then translated into a clinical guidance document by the authors in consultation with a Cardiologist and an experienced Exercise Physiologist with expertise in cardiovascular assessment. RESULTS: Thirty-one experts participated in the e-Delphi and fourteen participants completed all three rounds. Forty objective assessments were initially suggested. Six items reached consensus by the end of Round 2 (resting and exercise heart rate, resting, exercise, and recovery blood pressure, and peak exercise-induced rating of perceived exertion). One additional item reached consensus in Round 3 (exercise oxygen saturation). CONCLUSIONS: In the absence of research evidence, the collective experience and insights of an expert panel can inform an evidence gap. Further research is required to determine the feasibility of implementing these seven assessments in practice where CV assessment is indicated.

Spontaneous coronary artery dissection, fibromuscular dysplasia, and biventricular stress cardiomyopathy: a case report.

Background: Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome and is associated with fibromuscular dysplasia (FMD). The diagnosis of stress cardiomyopathy in patients with SCAD and FMD is uncommon, though an important consideration given the shared risk profile. Complications of severe left ventricular (LV) dysfunction associated with stress cardiomyopathy, such as LV thrombus, complicate the management of SCAD where anticoagulation is controversial in the context of SCAD-associated intramural haematoma. Case summary: A 65-year-old female presented with non-ST elevation myocardial infarction with a recent diagnosis of hypertension but no other traditional cardiovascular risk factors. There was, however, a family history of early cardiac death from myocardial infarction affecting her mother. Echocardiography demonstrated severe biventricular dysfunction with circumferential akinesis of the mid to apical segments. Coronary angiography demonstrated type 2A SCAD involving the first diagonal artery. Cardiac magnetic resonance imaging (MRI) confirmed a diagnosis of stress cardiomyopathy with biventricular involvement, complicated by LV apical thrombus and a focal region of myocardial infarction. Vascular imaging confirmed the presence of FMD. Guideline-directed heart failure therapy in addition to clopidogrel and rivaroxaban was prescribed. Follow-up contrast echocardiography at six-weeks confirmed resolution of LV dysfunction and resolution of the LV thrombus with no adverse events. Discussion: The dual diagnosis of SCAD and stress cardiomyopathy is uncommon. Cardiac MRI was useful for confirming the diagnosis of stress cardiomyopathy and the presence of LV thrombus, where anticoagulation may complicate the management of intramural haematoma in patients with concomitant SCAD and FMD.

Acute elevation of triglycerides increases left ventricular contractility and alters ventricular-vascular interaction.

Acute elevation of circulating lipids, such as the postprandial state, contributes to increased cardiovascular risk. However, the effect of acutely elevated triglycerides on arterial and left ventricular function is not completely understood. We aimed to assess whether an acute increase in triglycerides affects ventricular-vascular interaction. Fifteen healthy men (age, 49 ± 8 yr) underwent blinded, randomized infusion of saline and intravenous fat emulsion to acutely raise plasma triglycerides. All subjects underwent both randomization trials, in random order on two separate days. Ventricular-vascular interaction measures were recorded by tonometry (central blood pressure) and echocardiography (left ventricular volumes, strain, and strain rate) at baseline and after 1 h infusion. Net ventricular-vascular interaction was defined by the effective arterial elastance (E(A))-to-left ventricular end-systolic elastance (E(LV)) ratio (E(A)/E(LV)). When compared with saline, the infusion of intravenous fat emulsion increased triglycerides and free fatty acids (ΔP < 0.001 for both) and improved left ventricular contractility (ΔE(LV), end-systolic volume and strain rate; P < 0.05 for all). However, arterial function was unchanged (ΔE(A), brachial and central blood pressure; P > 0.05 for all). Overall, E(A)/E(LV) was decreased by an infusion of intravenous fat emulsion (P = 0.004) but not saline (P > 0.05, P = 0.001 for Δ between trials). We conclude that intravenous fat emulsion and acute elevation of blood lipids (including triglycerides and free fatty acids) alter ventricular-vascular interaction by increasing left ventricular contractility without affecting arterial load. These findings may have implications for cardiovascular responses to parenteral nutrition.

Adherence to High-Intensity Interval Training in Cardiac Rehabilitation: A REVIEW AND RECOMMENDATIONS.

PURPOSE: High-intensity interval training (HIIT) is gaining popularity as a training approach for patients attending cardiac rehabilitation (CR). While the literature has focused on the efficacy of HIIT for improving cardiorespiratory fitness (CRF), particularly when compared with moderate intensity exercise, less emphasis has been placed on adherence to HIIT. The aim of this review was to summarize the current literature regarding adherence to HIIT in CR patients with coronary artery disease. REVIEW METHODS: A review identified 36 studies investigating HIIT in CR patients with coronary artery disease. Methods and data were extracted for exercise or training adherence (to attendance, intensity, and duration), feasibility of protocols, and CRF. The review summarizes reporting of adherence; adherence to HIIT and comparator/s; the influence of adherence on changes in CRF; and feasibility of HIIT. SUMMARY: Adherence to the attendance of HIIT sessions was high and comparable with moderate-intensity exercise. However, adherence to the intensity and duration of HIIT was variable and underreported, which has implications for determining the treatment effect of the exercise interventions being compared. Furthermore, additional research is needed to investigate the utility of home-based HIIT and long-term adherence to HIIT following supervised programs. This review provides recommendations for researchers in the measurement and reporting of adherence to HIIT and other exercise interventions to facilitate a sufficient and consistent approach for future studies. This article also highlights strategies for clinicians to improve adherence, feasibility, and enjoyment of HIIT for their patients.

Strain engraftment competition and functional augmentation in a multi-donor fecal microbiota transplantation trial for obesity.

BACKGROUND: Donor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the degree, variation, and stability of strain engraftment have not yet been assessed in the context of multiple donors. METHODS: We conducted a double-blinded randomized control trial of FMT in 87 adolescents with obesity. Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6, 12, and 26 weeks post-treatment were analyzed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients' gut microbiomes. RESULTS: Multi-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterized by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardize FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains. CONCLUSION: Our study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harbored diverse microbial species and genes and were characterized by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity. TRIAL REGISTRATION: The Gut Bugs trial was registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12615001351505 ). TRIAL PROTOCOL: The trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.

Hemodynamic Validation of the E/e' Ratio as a Measure of Left Ventricular Filling Pressure in Patients With Non-ST Elevation Myocardial Infarction.

The E/e' ratio has an established role in the assessment of left ventricular filling pressure (LVFP) in stable patients, but its accuracy in acute myocardial ischemia is less well established. The aim of this study was to validate the relation between the E/e' ratio and invasively measured LVFP in patients with non-ST elevation myocardial infarction (NSTEMI). A total of 120 unselected patients with NSTEMI underwent cardiac catheterization with measurement of left ventricular end-diastolic pressure (LVEDP; elevated ≥15 mm Hg) and Doppler echocardiography with either simultaneous (n = 30) or same-day (n = 90) measurement of E/e'. Patients were aged 64.1 ± 11.8 years, 72% were male and mean left ventricular ejection fraction was 48.0 ± 20.9%. Septal, lateral, and average E/e' ratios all showed a significant correlation with LVEDP (Pearson's r: 0.42, 0.43, 0.48, respectively [all p <0.001]). Receiver operating characteristics curves showed an area under the curve of 0.72, 0.72, and 0.75 (all p <0.001) for septal, lateral, and average E/e', respectively. The sensitivity, specificity, positive (PPV), and negative (NPV) predictive values for the guideline-recommended threshold of average E/e' >14 for elevated LVEDP was 27%, 93%, 79%, and 44%, respectively. Utilizing lower E/e' boundaries of 6, 7, and 8 for lateral, average, and medial E/e', respectively, improved the NPV to ≥80% for each parameter. In conclusion, the E/e' ratio is a robust measure of LVFP during acute NSTEMI using upper and lower thresholds to achieve a high PPV and NPV, respectively, with the use of adjunctive guideline-recommend measures required in patients with nonconclusive E/e'.