Inter- and intra-observer variability in the echocardiographic evaluation of wall motion abnormality in patients with ST-elevation myocardial infarction or takotsubo syndrome - A novel approach.

INTRODUCTION AND OBJECTIVES: Using existing transthoracic echocardiographic indices to quantify left ventricular wall motion abnormalities (WMAs) can be difficult due to the variations in the location of the abnormalities within the left ventricle, the quality of examinations, and the inter-/intra-observer variability of available indices. This study aimed to evaluate a new approach for measuring the extent of WMA by calculating the percentage of abnormal wall motion and comparing it to the wall motion score index (WMSI). The study also sought to assess inter- and intra-observer variability. METHODS: The study included 140 echocardiograms from 54 patients presenting with ST-elevation myocardial infarction or Takotsubo syndrome. All patients underwent an echocardiographic examination according to a standard protocol and the images were used to measure the extent of akinesia (proportion akinesia, PrA), akinesia and hypokinesia (proportion akinesia/hypokinesia, PrAH), and WMSI. The inter-observer variability between the two operators was analyzed. The intra-observer analysis was performed by one observer using the same images at least 1 month after the first measurement. The agreement was analyzed using the Pearson correlation coefficient and Bland-Altman plots. RESULTS: Inter- and intra-observer variability for PrA and PrAH were low and comparable to those for WMSI. CONCLUSION: PrA and PrAH are reliable and reproducible echocardiographic methods for the evaluation of left ventricular wall motion.

Isolated diastolic dysfunction is associated with increased mortality in critically ill patients.

PURPOSE: Left ventricular (LV) diastolic dysfunction is important in critically ill patients, but prevalence and impact on mortality is not well studied. We classified intensive care patients with normal left ventricular function according to current diastolic guidelines and explored associations with mortality. MATERIAL AND METHODS: Echocardiography was performed within 24 h of intensive care admission. Patients with reduced LV ejection fraction, regional wall motion abnormality, or a history of cardiac disease were excluded. Patients were classified according to the 2016 EACVI guidelines, Recommendations for the Evaluation of LV Diastolic Function by Echocardiography. RESULTS: Out of 218 patients, 162 (74%) had normal diastolic function, 21 (10%) had diastolic dysfunction, and 35 (17%) had indeterminate diastolic function. Diastolic dysfunction were more common in female patients, older patients and associated with sepsis, respiratory and cardiovascular comorbidity as well as higher SAPS Score. In a risk-adjusted logistic regression model, patients with indeterminate diastolic dysfunction (OR 4.3 [1.6-11.4], p = 0.004) or diastolic dysfunction (OR 5.1 [1.6-16.5], p = 0.006) had an increased risk of death at 90 days compared to patients with normal diastolic function. CONCLUSION: Isolated diastolic dysfunction, assessed by a multi-parameter approach, is common in critically ill patients and is associated with mortality. TRIAL REGISTRATION: Secondary analysis of data from a single-center prospective observational study focused on systolic dysfunction in intensive care unit patients (Clinical Trials ID: NCT03787810.

Pulmonary Hypertension Phenotype Can Be Identified in Heart Failure With Reduced Ejection Fraction Using Echocardiographic Assessment of Pulmonary Artery Pressure With Supportive Use of Pressure Reflection Variables.

BACKGROUND: Pulmonary hypertension (PH) is frequent in patients with heart failure and reduced ejection fraction (HFrEF) with 2 different phenotypes: isolated postcapillary PH (IpcPH) and, with the worst prognosis, combined pre- and postcapillary PH (CpcPH). The aims of the present echocardiography study were to investigate (1) the ability to identify PH phenotype in patients with HFrEF using the newly adopted definition of PH (mean pulmonary artery pressure >20 mm Hg) and (2) the relationship between PH phenotype and right ventricular (RV) function. METHODS: One hundred twenty-four patients with HFrEF consecutively referred for heart transplant or heart failure workup were included with echocardiography and right heart catheterization within 48 hours. We estimated systolic pulmonary artery pressure (sPAPDoppler) and used a method to detect increased pulmonary vascular resistance (>3 Wood units) based on predefined thresholds of 3 pressure reflection (PRefl) variables (the acceleration time in the RV outflow tract [RVOT], the interval between peak RVOT and peak tricuspid regurgitant velocity, and the RV pressure augmentation following peak RVOT velocity). RESULTS: Using receiver operator characteristic analysis in a derivation group (n = 62), we identified sPAPDoppler ≥35 mm Hg as a cutoff that in a test group (n = 62) increased the likelihood of PH 6.6-fold. The presence of sPAPDoppler >40 mm Hg and 2 or 3 positive PRefl variables increased the probability of CpcPH 6- to 8-fold. A 2-step approach with primarily assessment of sPAPDoppler and the supportive use of PRefl variables in patients with mild/moderate PH (sPAPDoppler 41-59 mm Hg) showed 76% observer agreement and a weighted kappa of 0.63. The steady-state (pulmonary vascular resistance) and pulsatile (compliance, elastance) vascular loading are increased in both IpcPH and CpcPH with a comparable degree of RV dysfunction. CONCLUSIONS: The PH phenotype can be identified in HFrEF using standard echocardiographic assessment of pulmonary artery pressure with supportive use of PRefl variables in patients with mild to moderate PH.

Aortic size predicts aortic dissection in Turner syndrome - A 25-year prospective cohort study.

BACKGROUND: Women with Turner syndrome (TS) have an increased risk of aortic dissection. The current recommended cutoff to prevent aortic dissection in TS is an aortic size index (ASI) of ≥2.5 cm/m2. This study estimated which aortic size had the best predictive value for the risk of aortic dissection, and whether adjusting for body size improved risk prediction. METHODS: A prospective, observational study in Sweden, of women with TS, n = 400, all evaluated with echocardiography of the aorta and data on medical history for up to 25 years. Receiver operating characteristic (ROC) curves, sensitivity and specificity were calculated for the absolute ascending aortic diameter (AAD), ascending ASI and TS specific z-score. RESULTS: There were 12 patients (3%) with aortic dissection. ROC curves demonstrated that absolute AAD and TS specific z-score were superior to ascending ASI in predicting aortic dissection. The best cutoff for absolute AAD was 3.3 cm and 2.12 for the TS specific z-score, respectively, with a sensitivity of 92% for both. The ascending ASI cutoff of 2.5 cm/m2 had a sensitivity of 17% only. Subgroup analyses in women with an aortic diameter ≥ 3.3 cm could not demonstrate any association between karyotype, aortic coarctation, bicuspid aortic valve, BMI, antihypertensive medication, previous growth hormone therapy or ongoing estrogen replacement treatment and aortic dissection. All models failed to predict a dissection in a pregnant woman. CONCLUSIONS: In Turner syndrome, absolute AAD and TS-specific z-score were more reliable predictors for aortic dissection than ASI. Care should be taken before and during pregnancy.

A novel echocardiographic right ventricular dysfunction score can identify hemodynamic severity profiles in left ventricular dysfunction.

PURPOSE: Recognition of congestion and hypoperfusion in patients with chronic left ventricular dysfunction (LVD) has therapeutic and prognostic implications. In the present study we hypothesized that a multiparameter echocardiographic grading of right ventricular dysfunction (RVD) can facilitate the characterization of hemodynamic profiles. METHODS: Consecutive patients (n = 105, age 53 ± 14 years, males 77%, LV ejection fraction 28 ± 11%) referred for heart transplant or heart failure work-up, with catheterization and echocardiography within 48 h, were reviewed retrospectively. Three hemodynamic profiles were defined: compensated LVD (cLVD, normal pulmonary capillary wedge pressure (PCWP < 15 mmHg) and normal mixed venous saturation (SvO2 ≥ 60%)); decompensated LVD (dLVD, with increased PCWP) and LV failure (LVF, increased PCWP and reduced SvO2). We established a 5-point RVD score including pulmonary hypertension, reduced tricuspid annular plane systolic excursion, RV dilatation, ≥ moderate tricuspid regurgitation and increased right atrial pressure. RESULTS: The RVD score [median (IQR 25%;75%)] showed significant in-between the three groups differences with 1 (0;1), 1 (0.5;2) and 3.0 (2;3.5) in patients with cLVD, dLVD and LVF, respectively. The finding of RVD score ≥ 2 or ≥ 4 increased the likelihood of decompensation or LVF 5.2-fold and 6.7-fold, respectively. On the contrary, RVD score < 1 and < 2 reduced the likelihood 11.1-fold and 25-fold, respectively. The RVD score was more helpful than standard echocardiography regarding identification of hemodynamic profiles. CONCLUSIONS: In this proof of concept study an echocardiographic RVD score identified different hemodynamic severity profiles in patients with chronic LVD and reduced ejection fraction. Further studies are needed to validate its general applicability.

Estimating the cost of achieving basic water, sanitation, hygiene, and waste management services in public health-care facilities in the 46 UN designated least-developed countries: a modelling study.

BACKGROUND: An alarming number of public health-care facilities in low-income and middle-income countries lack basic water, sanitation, hygiene (WASH), and waste management services. This study estimates the costs of achieving full coverage of basic WASH and waste services in existing public health facilities in the 46 UN designated least-developed countries (LDCs). METHODS: In this modelling study, in-need facilities were quantified by combining published counts of public facilities with estimated basic WASH and waste service coverage. Country-specific per-facility capital and recurrent costs to deliver basic services were collected via survey of country WASH experts and officials between Sept 24 and Dec 24, 2020. Baseline cost estimates were modelled and discounted by 5% per year. Key assumptions were adjusted to produce lower and upper estimates, including adjusting the discount rate to 8% and 3% per year, respectively. FINDINGS: An estimated US$6·5 billion to $9·6 billion from 2021 to 2030 is needed to achieve full coverage of basic WASH and waste services in public health facilities in LDCs. Capital costs are $2·9 billion to $4·8 billion and recurrent costs are $3·6 billion to $4·8 billion over this time period. A mean of $0·24-0·40 per capita in capital investment is needed each year, and annual operations and maintenance costs are expected to increase from $0·10 in 2021 to $0·39-0·60 in 2030. Waste management accounts for the greatest share of costs, requiring $3·7 billion (46·6% of the total) in the baseline estimates, followed by $1·8 billion (23·1%) for sanitation, $1·5 billion (19·5%) for water, and $845 million (10·7%) for hygiene. Needs are greatest for non-hospital facilities ($7·4 billion [94%] of $7·9 billion) and for facilities in rural areas ($5·3 billion [68%]). INTERPRETATION: Investment will need to increase to reach full coverage of basic WASH and waste services in public health facilities. Financial needs are modest compared with current overall health and WASH spending, and better service coverage will yield substantial health benefits. To sustain services and prevent degradation and early replacement, countries will need to routinely budget for operations and maintenance of WASH and waste management assets. FUNDING: WHO (including underlying grants from the governments of Japan, the Netherlands, and the UK), World Bank (including an underlying grant from the Global Water Security and Sanitation Partnership), and UNICEF. TRANSLATIONS: For the Arabic, French and Portuguese translations of the abstract see Supplementary Materials section.

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVES: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.

Erratum: Reliable phase-contrast flow volume magnetic resonance measurements are feasible without adjustment of the velocity encoding parameter.

[This corrects the article DOI: 10.1117/1.JMI.7.6.063502.].

Regional left ventricular systolic dysfunction associated with critical illness: incidence and effect on outcome.

AIMS: Left ventricular (LV) dysfunction can be triggered by non-cardiac disease, such as sepsis, hypoxia, major haemorrhage, or severe stress (Takotsubo syndrome), but its clinical importance is not established. In this study, we evaluate the incidence and impact on mortality of LV dysfunction associated with critical illness. METHODS AND RESULTS: In this single-centre, observational study, consecutive patients underwent an echocardiographic examination within 24 h of intensive care unit (ICU) admission. LV systolic dysfunction was defined as an ejection fraction (EF) < 50% and/or regional wall motion abnormalities (RWMA). A cardiologist assessed patients with LV dysfunction for the presence of an acute or chronic cardiac disease, and coronary angiography was performed in high-risk patients. Of the 411 patients included, 100 patients (24%) had LV dysfunction and in 52 (13%) of these patients, LV dysfunction was not attributed to a cardiac disease. Patients with LV dysfunction and non-cardiac disease had higher mortality risk score (Simplified Acute Physiologic Score 3 score), heart rate, noradrenaline doses, and lactate levels as well as decreased EF, stroke volume, and cardiac output compared with patients with normal LV function. Diagnoses most commonly associated with LV dysfunction and non-cardiac disease were sepsis, respiratory insufficiency, major haemorrhage, and neurological disorders. RWMA (n = 40) with or without low EF was more common than global hypokinesia (n = 12) and was reversible in the majority of cases. Twelve patients had a circumferential pattern of RWMA in concordance with Takotsubo syndrome. Crude 30 day mortality was higher in patients with LV dysfunction and non-cardiac disease compared with patients with normal LV function (33% vs. 18%, P = 0.023), but not after risk adjustment (primary outcome) {odds ratio [OR] 1.56 [confidence interval (CI) 0.75-3.39], P = 0.225}. At 90 days, crude mortality was 44% and 22% (P = 0.002), respectively, in these groups. This difference was also significant after risk adjustment [OR 2.40 (CI 1.18-4.88), P = 0.016]. CONCLUSIONS: Left ventricular systolic dysfunction is commonly triggered by critical illness, is frequently seen as regional hypokinesia, and is linked to an increased risk of death. The prognostic importance of LV dysfunction in critical illness might be underestimated.

The usefulness of left ventricular volume and aortic diastolic flow reversal for grading chronic aortic regurgitation severity - Using cardiovascular magnetic resonance as reference.

Echocardiographic evaluation of chronic aortic regurgitation (AR) severity can lead to diagnostic ambiguity due to few feasible parameters or incongruent findings. The aim of the present study was to improve the diagnostic usefulness of left ventricular (LV) enlargement and aortic end-diastolic flow velocity (EDFV) using cardiovascular magnetic resonance (CMR) as reference. Patients (n = 120) were recruited either prospectively (n = 45) or retrospectively (n = 75). Severe AR (CMR regurgitant fraction > 33%) was present in 51% and 93% of the patients had LV ejection fraction ≥ 50%. EDFV and LV end-diastolic volume index (EDVI) were assessed by echocardiography using the traditional (excluding trabeculae) and recommended approach (including trabeculae). The patients were randomised to a derivation (n = 60) or a test group (n = 60). EDVI (traditional/recommended) to rule in (>99/118 ml/m2) and rule out severe AR (≤75/87 ml/m2) were identified using ROC analyses in the derivation group. The corresponding thresholds for EDFV were >17 cm/s and ≤10 cm/s. In the test group, the positive/negative likelihood ratios to rule in/rule out severe AR using EDVI were 10.0/0.14 (traditional), 6.2/0.11 (recommended), and using EDFV were 10.2/0.08. To rule in and rule out severe AR using derived cut-off values instead of >2 SD reduced the false positives by 92%, whereas using EDFV ≤10 cm/s instead of ≤20 cm/s reduced the false negatives by 94%. In conclusion, EDVI and EDFV as quantitative parameters are useful to rule in or rule out severe chronic AR. Importantly, other causes of LV enlargement have to be considered.

Importance of through-plane heart motion correction for the assessment of aortic regurgitation severity using phase contrast magnetic resonance imaging.

PURPOSE: To elucidate the influence of through-plane heart motion on the assessment of aortic regurgitation (AR) severity using phase contrast magnetic resonance imaging (PC-MRI). APPROACH: A patient cohort with chronic AR (n = 34) was examined with PC-MRI. The regurgitant volume (RVol) and fraction (RFrac) were extracted from the PC-MRI data before and after through-plane heart motion correction and was then used for assessment of AR severity. RESULTS: The flow volume errors were strongly correlated to aortic diameter (R = 0.80, p < 0.001) with median (IQR 25%;75%): 16 (14; 17) ml for diameter>40mm, compared with 9 (7; 10) ml for normal aortic size (p < 0.001). RVol and RFrac were underestimated (uncorrected:64 ± 37 ml and 39 ± 17%; corrected:76 ± 37 ml and 44 ± 15%; p < 0.001) and ~ 20% of the patients received lower severity grade without correction. CONCLUSION: Through-plane heart motion introduces relevant flow volume errors, especially in patients with aortic dilatation that may result in underestimation of the severity grade in patients with chronic AR.

Importance of complex blood flow in the assessment of aortic regurgitation severity using phase contrast magnetic resonance imaging.

This study aimed to investigate if and how complex flow influences the assessment of aortic regurgitation (AR) using phase contrast MRI in patients with chronic AR. Patients with moderate (n = 15) and severe (n = 28) chronic AR were categorized into non-complex flow (NCF) or complex flow (CF) based on the presence of systolic backward flow volume. Phase contrast MRI was performed repeatedly at the level of the sinotubular junction (Ao1) and 1 cm distal to the sinotubular junction (Ao2). All AR patients were assessed to have non-severe AR or severe AR (cut-off values: regurgitation volume (RVol) ≥ 60 ml and regurgitation fraction (RF) ≥ 50%) in both measurement positions. The repeatability was significantly lower, i.e. variation was larger, for patients with CF than for NCF (≥ 12 ± 12% versus ≥ 6 ± 4%, P ≤ 0.03). For patients with CF, the repeatability was significantly lower at Ao2 compared to Ao1 (≥ 21 ± 20% versus ≥ 12 ± 12%, P ≤ 0.02), as well as the assessment of regurgitation (RVol: 42 ± 34 ml versus 54 ± 42 ml, P < 0.001; RF: 30 ± 18% versus 34 ± 16%, P = 0.01). This was not the case for patients with NCF. The frequency of patients that changed in AR grade from severe to non-severe when the position of the measurement changed from Ao1 to Ao2 was higher for patients with CF compared to NCF (RVol: 5/26 (19%) versus 1/17 (6%), P = 0.2; RF: 4/26 (15%) versus 0/17 (0%), P = 0.09). Our study shows that complex flow influences the quantification of chronic AR, which can lead to underestimation of AR severity when using PC-MRI.

Grading right ventricular dysfunction in left ventricular disease using echocardiography: a proof of concept using a novel multiparameter strategy.

AIMS: Grading right ventricular dysfunction (RVD) in patients with left ventricular (LV) disease has earned little attention. In the present study, we established an echocardiographic RVD score and investigated how increments of the score correspond to RVD at right heart catheterization. METHODS AND RESULTS: We included 95 patients with LV disease consecutively referred for heart transplant or heart failure work-up with catheterization and echocardiography within 48 h. The RVD score (5 points) included well-known characteristics of the development from compensated to decompensated right ventricular (RV) function: pulmonary hypertension, reduced RV strain, RV area dilatation, moderate/severe tricuspid regurgitation, and increased right atrial pressure (RAP) by echocardiography. Comparing three groups with increments of RVD score [1 (mild), 2-3 (moderate), and 4-5 (severe)] showed more advanced RVD with increasing RV end-diastolic pressure (P < 0.001) and signs of uncoupling to load (reduced ratio between RV and pulmonary artery elastance, P < 0.001) and more spherical RV shape (RV area/length, P < 0.001). Receiver operating characteristic curve analysis for detection of severe RV (RAP ≥ 10 mmHg) showed for the RVD score an area under the curve of 0.88 compared with 0.69, 0.68, and 0.64 for RV strain, tricuspid annular plane systolic excursion, and fractional area change, respectively. A patient with RVD score ≥ 4 had a 6.7-fold increase in likelihood of severe RVD, and no patient with RVD score ≤ 1 had severe RVD. CONCLUSIONS: In this proof of concept study, a novel RVD score outperformed the widely used longitudinal parameters regarding grading of RVD severity, with a potential role for refined diagnosis, follow-up, and prognosis assessment in heart failure patients.

Reliable phase-contrast flow volume magnetic resonance measurements are feasible without adjustment of the velocity encoding parameter.

Purpose: To show that adjustment of velocity encoding (VENC) for phase-contrast (PC) flow volume measurements is not necessary in modern MR scanners with effective background velocity offset corrections. Approach: The independence on VENC was demonstrated theoretically, but also experimentally on dedicated phantoms and on patients with chronic aortic regurgitation ( n = 17 ) and one healthy volunteer. All PC measurements were performed using a modern MR scanner, where the pre-emphasis circuit but also a subsequent post-processing filter were used for effective correction of background velocity offset errors. Results: The VENC level strongly affected the velocity noise level in the PC images and, hence, the estimated peak flow velocity. However, neither the regurgitant blood flow volume nor the mean flow velocity displayed any clinically relevant dependency on the VENC level. Also, the background velocity offset was shown to be close to zero ( < 0.6 cm / s ) for a VENC range of 150 to 500 cm / s , adding no significant errors to the PC flow volume measurement. Conclusions: Our study shows that reliable PC flow volume measurements are feasible without adjustment of the VENC parameter. Without the need for VENC adjustments, the scan time can be reduced for the benefit of the patient.

Projected health-care resource needs for an effective response to COVID-19 in 73 low-income and middle-income countries: a modelling study.

BACKGROUND: Since WHO declared the COVID-19 pandemic a Public Health Emergency of International Concern, more than 20 million cases have been reported, as of Aug 24, 2020. This study aimed to identify what the additional health-care costs of a strategic preparedness and response plan (SPRP) would be if current transmission levels are maintained in a status quo scenario, or under scenarios where transmission is increased or decreased by 50%. METHODS: The number of COVID-19 cases was projected for 73 low-income and middle-income countries for each of the three scenarios for both 4-week and 12-week timeframes, starting from June 26, 2020. An input-based approach was used to estimate the additional health-care costs associated with human resources, commodities, and capital inputs that would be accrued in implementing the SPRP. FINDINGS: The total cost estimate for the COVID-19 response in the status quo scenario was US$52·45 billion over 4 weeks, at $8·60 per capita. For the decreased or increased transmission scenarios, the totals were $33·08 billion and $61·92 billion, respectively. Costs would triple under the status quo and increased transmission scenarios at 12 weeks. The costs of the decreased transmission scenario over 12 weeks was equivalent to the cost of the status quo scenario at 4 weeks. By percentage of the overall cost, case management (54%), maintaining essential services (21%), rapid response and case investigation (14%), and infection prevention and control (9%) were the main cost drivers. INTERPRETATION: The sizeable costs of a COVID-19 response in the health sector will escalate, particularly if transmission increases. Instituting early and comprehensive measures to limit the further spread of the virus will conserve resources and sustain the response. FUNDING: WHO, and UK Foreign Commonwealth and Development Office.

Financing Global Common Goods for Health: When the World is a Country.

"Global functions" of health cooperation refer to those activities that go beyond the boundaries of individual nations to address transnational issues. This paper begins by presenting a taxonomy of global functions and laying out the key value propositions of investing in such functions. Next, it examines the current funding flows to global functions and the estimated price tag, which is large. Given that existing financing mechanisms have not closed the gap, it then proposes a suite of options for directing additional funding to global functions and discusses the governance of this additional funding. These options are organized into resource mobilization mechanisms, pooling approaches, and strategic purchasing of global functions. Given its legitimacy, convening power, and role in setting global norms and standards, the World Health Organization (WHO) is uniquely placed among global health organizations to provide the overarching governance of global functions. Therefore, the paper includes an assessment of WHO's financial situation. Finally, the paper concludes with reflections on the future of aid for health and its role in supporting global functions. The concluding section also summarizes a set of key priorities in financing global functions for health.