Predictors of New Onset Atrial Fibrillation Burden in the Critically Ill.

INTRODUCTION: Atrial fibrillation (AF) is common in the intensive care unit (ICU) setting and has been associated with adverse outcomes. In this context, there is increasing research interest in AF burden as a predictor of subsequent adverse events. However, the pathophysiology and drivers of AF burden in the ICU are poorly understood. This study sought to evaluate the predictors of AF burden in critical illness-associated new-onset AF (CI-NOAF). METHODS: Out of 7,030 admissions in a tertiary general ICU between December 2015 and September 2018, 309 patients developed CI-NOAF. AF burden was defined as the percentage of monitored time in AF, as extracted from hourly interpretations of continuous ECG monitoring. Low and high AF burden groups were defined relative to the median AF burden. Clinical, laboratory, and echocardiographic parameters were extracted, and multivariable modelling with binary logistic regression was performed to evaluate for independent associations with AF burden. RESULTS: The median AF burden was 7.0%. Factors associated with increased AF burden were age, dyslipidaemia, chronic kidney disease, increased creatinine, CHA2DS2-VASc score, ICU admission diagnosis category, amiodarone administration, and left atrial area (LAA). Factors associated with lower AF burden were previous alcohol excess, burden of ventilation, the use of inotropes/vasopressors, and beta blockers. On multivariate analysis, increased LAA, chronic kidney disease, and amiodarone use were independently associated with increased AF burden, whereas beta blocker use was associated with lower AF burden. CONCLUSION: Left atrial size and chronic cardiovascular comorbidities appear to be the primary drivers of CI-NOAF burden, whereas factors related to acute illness and critical care intervention paradoxically did not appear to be a substantial driver of arrhythmia burden. Further research is needed regarding drivers of AF and the efficacy of rhythm control intervention in this unique setting.

Exaggerated myocardial torsion may contribute to dynamic left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

Aims: Dynamic left ventricular (LV) outflow tract obstruction (LVOTO) is associated with symptoms and increased risk of developing heart failure in hypertrophic cardiomyopathy (HCM). The association of LVOTO and LV twist mechanics has not been well studied in HCM. The aim of the study was to compare the pattern of LV twist in patients with HCM associated with asymmetrical septal hypertrophy with and without LVOTO. Methods and results: Echocardiography (including speckle tracking) was performed in 212 patients with HCM, divided according to the absence (n = 130) or presence (n = 82) of LVOTO (defined as peak pressure gradient ≥30 mmHg either at rest and/or with Valsalva manoeuvre). Patients with LVOTO were older, had smaller LV dimensions, a higher LV ejection fraction (LVEF), a longer anterior mitral valve leaflet length, and a higher early transmitral pulsed wave to septal tissue Doppler velocity ratio (E/E'). A univariate analysis showed that peak twist was significantly higher in patients with LVOTO compared with patients without LVOTO (19.7 ± 7.3 vs. 15.7 ± 6.0, P = 0.00015). Peak twist was similarly enhanced in patients with LVOTO, manifesting only during Valsalva (19.2 ± 5.6, P = 0.007) and patients with resting LVOTO (19.9 ± 8.0, P = 0.00004) compared with patients without LVOTO (15.7 ± 6.0). A stepwise forward logistic regression analysis showed that LVEF, LV end-systolic dimension indexed to body surface area, anterior mitral valve leaflet length, E/E', and peak twist were all independently associated with LVOTO. Conclusion: This study demonstrates that increased peak LV twist is independently associated with LVOTO in patients with HCM. Peak twist was similarly exaggerated in patients with only latent LVOTO, suggesting that it may play a contributory role to LVOTO in HCM.

Predicting new onset atrial fibrillation post acute myocardial infarction: Echocardiographic assessment of left atrial size.

BACKGROUND: Atrial fibrillation (AF) commonly occurs following acute myocardial infarction (AMI). Left atrial (LA) size has been reported to predict new onset AF in this cohort, however, the optimal metric of left atrial size for risk stratification following AMI is unknown. METHODS: Patients presenting to a tertiary hospital with incident AMI (NSTEMI or STEMI) and no history of AF were recruited. All patients underwent guideline-based workup and management for AMI, including transthoracic echocardiographic assessment. Three alternative metrics of left atrial size were determined: LA area, maximal and minimal LA volume indexed to body surface area (LAVImax and LAVImin). The primary endpoint was new onset AF diagnoses. RESULTS: Four hundred thirty three patients were included in the analysis, of which 7.1% had a new diagnosis of AF within a median follow-up of 3.8 years. Univariate predictors of incident AF included age, hypertension, revascularization with CABG, NSTEMI presentation, right atrial area, and all three metrics of LA size. Among three multivariable models created for the prediction of new onset AF utilizing alternate metrics of LA size, LAVImin was the only LA size metric found to be an independent predictor. CONCLUSIONS: LAVImin is an independent predictor of new onset AF post AMI. LAVImin outperforms echocardiographic assessment of diastolic dysfunction and alternative metrics of LA size (including LA area and LAVImax) for risk stratification. Further studies are needed to validate our findings in post AMI patients, and evaluate whether LAVImin holds similar advantages over LAVImax in other cohorts.

Critical illness associated new onset atrial fibrillation: subsequent atrial fibrillation diagnoses and other adverse outcomes.

AIMS: Amongst patients with critical illness associated new onset AF (CI-NOAF), the risk of subsequent atrial fibrillation (AF) diagnoses and other adverse outcomes is unknown, and the role for long-term anticoagulation is unclear. This study sought to determine the factors associated with subsequent AF diagnoses and other adverse outcomes in this cohort. METHODS AND RESULTS: Admissions to a tertiary general intensive care unit (ICU) between December 2015 and September 2018 were screened for AF episodes through hourly analysis of continuous ECG monitoring. Patients with a prior history of AF were excluded. AF burden was defined as the percentage of monitored ICU hours in AF. The primary endpoint was subsequent AF diagnoses, as collated from the statewide electronic medical records. Secondary endpoints included mortality, embolic events, MACE and subsequent anticoagulation. RESULTS: Of 7030 admissions with 509 303 h of monitoring data, 309 patients with CI-NOAF were identified, and 235 survived to discharge. Subsequent AF diagnoses were identified in 75 (31.9%) patients after a median of 413 days. Increased AF burden had the strongest independent association with AF recurrence (OR = 15.03, P = 0.002), followed by increased left atrial area (OR = 1.12, P = 0.01). Only 128 (54.5%) patients had their AF diagnosis acknowledged at ICU discharge, and 50 (21.3%) received anticoagulation at hospital discharge. CONCLUSION: CI-NOAF is often under-recognized, and subsequent AF diagnoses are common post-discharge. AF burden during ICU admission has a strong independent association with subsequent AF diagnoses. Left atrial size is also independently associated with subsequent AF.

Chest pain workup in the presence of atrial fibrillation: impacts on troponin testing, myocardial infarction diagnoses, and long-term prognosis.

AIMS: Patients presenting to the emergency department (ED) with chest pain require evaluation for acute coronary syndrome (ACS). Atrial fibrillation (AF) can lead to troponin (cTn) elevation in the absence of ACS. There is limited evidence informing the impact of AF on the diagnostic performance of cTn testing for the diagnosis of Type 1 myocardial infarction (T1MI), or the association between AF and long-term outcomes in this context. METHODS AND RESULTS: This study used the IMPACT and ADAPT study databases to compile a combined cohort of 3496 adults presenting to ED with chest pain between 2007 and 2014, with early cTn testing during ED workup. The mean age was 56.6 years, and 40.2% were female. Outcomes included adjudicated diagnoses for the index admission and mortality to 1-year after presentation. The specificity of initial cTn testing for T1MI diagnosis was lower for patients in AF compared with those not in AF (79.2% vs. 95.4%, P < 0.001), largely due to a relative increase in Type 2 myocardial infarction diagnoses. Sensitivity for T1MI did not differ between patients with or without AF (88.5% vs. 91.5%, P = 0.485). AF was associated with increased 1-year mortality (10.4% vs. 2.3%, P < 0.001), although this was not significant on multivariable analysis. CONCLUSION: The specificity of serial cTn testing for the diagnosis of T1MI in patients presenting to ED with chest pain is reduced in the presence of AF. Further studies are needed to establish whether optimised cTn thresholds for patients with AF can improve workup and outcomes.

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.

Phenotypic variability within the desminopathies: A case series of three patients.

The DES gene encodes desmin, a key intermediate filament of skeletal, cardiac and smooth muscle. Pathogenic DES variants produce a range of skeletal and cardiac muscle disorders collectively known as the desminopathies. We report three desminopathy cases which highlight the phenotypic heterogeneity of this disorder and discuss various factors that may contribute to the clinical differences seen between patients with different desmin variants and also between family members with the same variant.

Estimation of prevalence of transthyretin (ATTR) cardiac amyloidosis in an Australian subpopulation using bone scans with echocardiography and clinical correlation.

BACKGROUND: Bone scans differentiate transthyretin (ATTR) cardiac amyloidosis from light chain amyloidosis and other causes of increased left ventricular (LV) wall thickness. We examined the prevalence and implications of cardiac uptake in the general population. METHODS: Patients were included based on having undertaken a bone scan for non-cardiac indications using Technetium 99m hydroxymethylene diphosphonate (HMDP) or Technetium 99m methylene diphosphonate (MDP). Blinded image review was undertaken. Positive was defined as cardiac uptake ≥ rib AND heart/whole body ratio (H/WB) > 0.0388. Echocardiography and clinical records were reviewed. RESULTS: 6918 patients were included. 15/3472 HMDP scans were positive (14 males, 1 female): none in individuals aged < 65; 1.44% in males and 0.17% in females ≥ 65; 6.15% in males and 1.69% in females ≥ 85. Only 1/3446 MDP scans were positive. All HMDP positive patients had increased septal wall thickness on echocardiography. H/WB correlated positively with LV mass, and negatively with LV ejection fraction. No individual had an explanation other than ATTR for their positive scan. CONCLUSION: In this Australian subpopulation, the prevalence of positive bone scans consistent with cardiac ATTR is 0% in individuals aged < 65. Prevalence increased with age, reaching 6.15% in men ≥ 85. The amount of HMDP uptake correlated with echocardiographic features of more advanced cardiac involvement. MDP does not appear useful in ATTR.

Determinants of Diastolic Dysfunction Following Myocardial Infarction: Evidence for Causation Beyond Infarct Size.

BACKGROUND: The determinants of severe diastolic dysfunction (DD) following myocardial infarction (MI) are not well defined. This study sought to define the determinants of severe DD (restrictive mitral inflow pattern on Doppler echocardiography [RFP]) in patients with a first-ever MI, with particular emphasis on the impact of infarct size. METHODS: Retrospective single-centre study including consecutive patients admitted to a tertiary referral centre with a first-ever non-ST-elevation-MI (NSTEMI) or ST-elevation-MI (STEMI) (n=477). Peak troponin-I (Peak-TnI) was used as the principal measure of infarct size, whilst left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were regarded as surrogate measures. Echocardiography was performed within 24 hours of admission for all patients. RFP was defined as E/A ratio >2.0 or E/A ratio >1.5 and E-wave deceleration time <140 ms. RESULTS: A total of 69 patients (14.5%) had RFP. Peak-TnI levels were higher in the RFP group (32.6±32.7 versus 16.9±25.2 µg/L, p<0.001). In sequential multivariable models incorporating significant clinical, angiographic and left ventricular (LV) size-related variables, Peak-TnI (OR 1.98, p=0.001), WMSI (OR 2.34, p=0.048) and LVEF (OR 0.97, p=0.044) were independent predictors of RFP. Presence of diabetes was also an independent predictor in all the models constructed. When patients were stratified according to an LVEF of 50%, 39% of RFP patients had a preserved LVEF (RFP/preserved EF group), and these patients had lower Peak-TnI levels compared to the RFP/reduced EF group (14.4±18.7 vs 44.5±35.5 µg/L). CONCLUSIONS: Whilst infarct size is a major determinant of severe diastolic dysfunction after MI, a significant subset of patients develop severe diastolic dysfunction despite a small infarct size and preserved LVEF, highlighting that other factors such as pre-existing diastolic dysfunction due to risk factors such as diabetes have an important role in causation.

Hypertrophic Cardiomyopathy: Challenging the Status Quo?

Hypertrophic cardiomyopathy (HCM) is the most common cardiovascular genetic disorder. While our mechanistic understanding has been informed by elegant gene discovery studies that led to the term "disease of the sarcomere", more recent investigations have challenged the single-gene hypothesis. Multimodality imaging has allowed better phenotyping to facilitate early diagnosis, identify treatable phenocopies, and guide management. While HCM remains an important cause of sudden death, recent studies have reported a substantial cumulative burden of heart failure and atrial fibrillation in middle-aged and older individuals. Nonetheless, improvements in risk stratification have allowed early intervention to transition HCM from being a common cause of sudden death in the young to a treatable chronic disease.

Accuracy of Cardiac Nurse Acquired and Measured Three-Dimensional Echocardiographic Left Ventricular Ejection Fraction: Comparison to Echosonographer.

BACKGROUND: Three-dimensional echocardiography (3D-Echo) performed by novice health care staff to measure left ventricular ejection fraction (LVEF) could allow cost-effective screening and monitoring for left ventricular systolic dysfunction (LVSD) prior to the development of heart failure. The aim of this study was to determine feasibility and accuracy of cardiac nurses (after completing focussed training) independently acquiring 3D-Echo images, and measuring LVEF using semi-automated software when compared to an echosonographer. METHODS: One echosonographer and three cardiac nurses acquired 3D-Echo images on 73 patients (62 ± 16 years, 62% male) with good image quality, and subsequently measured LVEF using a semi-automated algorithm. RESULTS: Overall feasibility was 89% with the three nurses successfully acquiring 3D-Echo images suitable for LVEF assessment in 65 of the 73 patients. High accuracy (r = 0.82; p < 0.0001) with minimal bias (+0.1, -10.6 to +10.8 limits of agreement; p = 0.91) was observed comparing the nurses to the echosonographer for measuring LVEF. Individual nurses demonstrated high feasibility (86%-92%), accuracy (r = 0.83-0.87; all p < 0.0001) and intra-observer reproducibility (r = 0.96-0.97; all p < 0.0001), with good inter-observer consistency in accuracy compared to the echosonographer (one-way analysis of variance p = 0.559). CONCLUSIONS: We have demonstrated that, following a focussed training protocol, it was feasible for cardiac nurses to acquire 3D-Echo images of sufficient image quality to allow measurement of LVEF using a semi-automated algorithm, with comparable accuracy and intra-observer variability to an expert echosonographer. This could potentially allow the broader application of echocardiography to screen for LVSD in high-risk cohorts.

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'.

Echocardiographic predictors of all-cause mortality in patients with left ventricular ejection fraction >35%: Value of guideline based assessment of diastolic dysfunction.

BACKGROUND: Recent data suggests that the majority of cardiac deaths in patients with heart failure occur in patients with a left ventricular ejection fraction (LVEF) >35%. This study sought to determine the value of guideline based assessment of diastolic dysfunction in predicting all-cause mortality in patients with a first-ever myocardial infarction (MI) with an LVEF >35%. METHODS: A retrospective single centre study involving 383 patients with a first-ever MI (STEMI or NSTEMI) with LVEF >35% was performed. Clinical, angiographic and echocardiographic data were obtained from prospectively maintained institutional databases. Outcomes data were obtained from national death registry. Echocardiography was performed early post-admission for all patients. Significant diastolic dysfunction (DD) was defined was grade 2/3 diastolic dysfunction according to current American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. RESULTS: At a median follow up of 2 years, there were 32 deaths. On Cox proportional hazards multivariate analysis incorporating significant clinical variables (age, chronic kidney disease and extent of coronary artery disease), significant DD (HR 2.57, 95%CI 1.16-5.68, p = 0.020) and left ventricular end-diastolic volume index (HR 1.03, 1.04-1.07, p = 0.021) were the only independent echocardiographic predictors of all-cause mortality. Intermodel comparisons using model χ2 and Harrel's-C confirmed incremental value of DD. In the subgroup with LVEF 36-55% (n = 176), significant DD was the only independent echocardiographic predictor (HR 3.56, 95%CI 2.46-9.09, p = 0.006). CONCLUSIONS: The presence of significant DD identifies patients with LVEF >35% following MI who are at a higher risk of all-cause mortality, and who may benefit from further risk stratification and treatment.