Clinical to Population Prevalence of Hypertrophic Cardiomyopathy Phenotype: Insights From the National Echo Database Australia.

BACKGROUND: There is a paucity of data describing the underlying prevalence of hypertrophic cardiomyopathy (HCM), a primary genetic disorder characterised by progressive left ventricular (LV) hypertrophy and sudden death, from both a clinical and a population perspective. METHODS: We screened the echocardiographic reports of 155,668 men and 147,880 women within the multicentre National Echo Database Australia (NEDA) (2001-2019). End-diastolic wall thickness ≥15 mm anywhere in the left ventricle was identified as a characteristic of an HCM phenotype according to current guideline recommendations. Applying a septal-to-posterior wall thickness ratio >1.3 and LV outflow tract obstruction ≥30 mmHg (when documented), we further identified asymmetric septal hypertrophy and obstructive HCM (oHCM), respectively. The observed pattern of phenotypical HCM within the overall NEDA cohort (>650,000 cases) was then extrapolated to the ∼539,000 (5.7% of adult population) and ∼474,000 (4.8%) Australian men and women, respectively, who were investigated with echocardiography in 2021 on an age-specific basis. RESULTS: Overall, 15,380 cases (mean age 71.1±14.6 years, 10,138 men [65.9%]) with the characteristic HCM phenotype within the NEDA cohort were identified. Of these 15,380 cases, 5,552 (36.1%) had asymmetric septal hypertrophy, and 2,276 of the 10,290 cases with LV outflow tract obstruction profiling data (22.1%) had obstructive HCM. A further 3,389 of 13,715 cases (24.7%) had evidence of LV systolic dysfunction (LV ejection fraction <55%). Within the entire NEDA cohort (including those without LV profiling), HCM was found in 10,138 of 342,161 men (2.96%; 95% confidence interval [CI] 2.91%-3.02%) and 5,242 of 308,539 women (1.70%; 95% CI 1.65%-1.75%). When extrapolated to the Australian population, we estimate that a minimum of 15,971 men and 8,057 women presented with echocardiographic features of phenotypical HCM in 2021. This translates into a minimum caseload/prevalence of ∼17 adult men (∼2.5 in those aged ≤50 years) and eight adult women (∼1 in those aged ≤50 years) per 10,000 population meeting phenotypical HCM criteria. CONCLUSIONS: Using contemporary Australian echocardiographic and population data, we estimate that a minimum of 15,971 (17.5 cases/10,000) men and 8,057 women (8.2 cases/10,000) had echocardiographic evidence of phenotypical HCM in 2021. These disease burden data are particularly relevant as new treatment options are emerging.

Vulnerability to environmental and climatic health provocations among women and men hospitalized with chronic heart disease: insights from the RESILIENCE TRIAL cohort.

AIMS: We aimed to recruit a representative cohort of women and men with multi-morbid chronic heart disease as part of a trial testing an innovative, nurse-co-ordinated, multi-faceted intervention to lower rehospitalization and death by addressing areas of vulnerability to external challenges to their health. METHODS AND RESULTS: The prospective, randomized open, blinded end-point RESILIENCE Trial recruited 203 hospital inpatients (mean age 75.7 ± 10.2 years) of whom 51% were women and 94% had combined coronary artery disease, heart failure, and/or atrial fibrillation. Levels of concurrent multi-morbidity were high (mean Charlson Index of Comorbidity Score 6.5 ± 2.7), and 8.9% had at least mild frailty according to the Rockwood Clinical Frailty Scale. Including the index admission, 19-20% of women and men had a pre-existing pattern of seasonally linked hospitalization (seasonality). Detailed phenotyping revealed that 48% of women and 40% of men had ≥3 physiological factors, and 15% of women and 16% of men had ≥3 behavioural factors likely to increase their vulnerability to external provocations to their health. Overall, 61-62% of women and men had ≥4 combined factors indicative of such vulnerability. Additional factors such as reliance on the public health system (63 vs. 49%), lower education (30 vs. 14%), and living alone (48 vs. 29%) were more prevalent in women. CONCLUSION: We successfully recruited women and men with multi-morbid chronic heart disease and bio-behavioural indicators of vulnerability to external provocations to their health. Once completed, the RESILIENCE TRIAL will provide important insights on the impact of addressing such vulnerability (promoting resilience) on subsequent health outcomes. REGISTRATION: ClinicalTrials.org: NCT04614428.

Pattern and Prognostic Impact of Regional Wall Motion Abnormalities in 255 697 Men and 236 641 Women Investigated with Echocardiography.

Background Regional wall motion abnormalities (WMAs) after myocardial infarction are associated with adverse remodeling and increased mortality in the short to medium term. Their long-term prognostic impact is less well understood. Methods and Results Via the National Echo Database of Australia (2000-2019), we identified normal wall motion versus WMA for each left ventricular wall among 492 338 individuals aged 61.9±17.9 years. The wall motion score index was also calculated. We then examined actual 1- and 5-year mortality, plus adjusted risk of long-term mortality according to WMA status. Overall, 39 346/255 697 men (15.4%) and 17 834/236 641 women (7.5%) had a WMA. The likelihood of a WMA was associated with increasing age and greater systolic/diastolic dysfunction. A defect in the inferior versus anterior wall was the most and least common WMA in men (8.0% and 2.5%) and women (3.3% and 1.1%), respectively. Any WMA increased 5-year mortality from 17.5% to 29.7% in men and from 14.9% to 30.8% in women. Known myocardial infarction (hazard ratio [HR], 0.86 [95% CI, 0.80-0.93]) or revascularization (HR, 0.87 [95% CI, 0.82-0.92]) was independently associated with a better prognosis, whereas men (1.22-fold increase) and those with greater systolic/diastolic dysfunction had a worse prognosis. Among those with any WMA, apical (HR, 1.08 [95% CI, 1.02-1.13]) or inferior (HR, 1.09 [95% CI, 1.04-1.15]) akinesis, dyskinesis or aneurysm, or a wall motion score index >3.0 conveyed the worst prognosis. Conclusions In a large real-world clinical cohort, twice as many men as women have a WMA, with inferior WMA the most common. Any WMA confers a poor prognosis, especially inferoapical akinesis/dyskinesis/aneurysm.

Incident pulmonary hypertension in 13 488 cases investigated with repeat echocardiography: a clinical cohort study.

Background: We addressed the paucity of data describing the characteristics and natural history of incident pulmonary hypertension. Methods: Adults (n=13 448) undergoing routine echocardiography without initial evidence of pulmonary hypertension (estimated right ventricular systolic pressure, eRVSP <30.0 mmHg) or left heart disease were studied. Incident pulmonary hypertension (eRVSP ≥30.0 mmHg) was detected on repeat echocardiogram a median of 4.1 years apart. Mortality was examined according to increasing eRVSP levels (30.0-39.9, 40.0-49.9 and ≥50.0 mmHg) indicative of mild-to-severe pulmonary hypertension. Results: A total of 6169 men (45.9%, aged 61.4±16.7 years) and 7279 women (60.8±16.9 years) without evidence of pulmonary hypertension were identified (first echocardiogram). Subsequently, 5412 (40.2%) developed evidence of pulmonary hypertension, comprising 4125 (30.7%), 928 (6.9%) and 359 (2.7%) cases with an eRVSP of 30.0-39.9 mmHg, 40.0-49.9 mmHg and ≥50.0 mmHg, respectively (incidence 94.0 and 90.9 cases per 1000 men and women, respectively, per year). Median (interquartile range) eRVSP increased by +0.0 (-2.27 to +2.67) mmHg and +30.68 (+26.03 to +37.31) mmHg among those with eRVSP <30.0 mmHg versus ≥50.0 mmHg. During a median 8.1 years of follow-up, 2776 (20.6%) died from all causes. Compared to those with eRVSP <30.0 mmHg, the adjusted risk of all-cause mortality was 1.30-fold higher in 30.0-39.9 mmHg, 1.82-fold higher in 40.0-49.9 mmHg and 2.11-fold higher in ≥50.0 mmHg groups (all p<0.001). Conclusions: New-onset pulmonary hypertension, as indicated by elevated eRVSP, is a common finding among older patients without left heart disease followed-up with echocardiography. This phenomenon is associated with an increased morality risk even among those with mildly elevated eRVSP.

Elevated blood pressure among adolescents in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: More people from sub-Saharan Africa aged between 20 years and 60 years are affected by end-organ damage due to underlying hypertension than people in high-income countries. However, there is a paucity of data on the pattern of elevated blood pressure among adolescents aged 10-19 years in sub-Saharan Africa. We aimed to provide pooled estimates of high blood pressure prevalence and mean levels in adolescents aged 10-19 years across sub-Saharan Africa. METHODS: In this systematic review and meta-analysis, we searched PubMed, Google Scholar, African Index Medicus, and Embase to identify studies published from Jan 1, 2010, to Dec 31, 2021. To be included, primary studies had to be observational studies of adolescents aged 10-19 years residing in sub-Saharan African countries reporting the pooled prevalence of elevated blood pressure or with enough data to compute these estimates. We excluded studies on non-systemic hypertension, in African people not living in sub-Saharan Africa, with participant selection based on the presence of hypertension, and with adult cohorts in which we could not disaggregate data for adolescents. We independently extracted relevant data from individual studies using a standard data extraction form. We used a random-effects model to estimate the pooled prevalence of elevated blood pressure and mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels overall and on a sex-specific basis. This study is registered with PROSPERO (CRD42022297948). FINDINGS: We identified 2559 studies, and assessed 81 full-text studies for eligibility, of which 36 studies comprising 37 926 participants aged 10-19 years from ten (20%) of 49 sub-Saharan African countries were eligible. A pooled sample of 29 696 adolescents informed meta-analyses of elevated blood pressure and 27 155 adolescents informed meta-analyses of mean blood pressure. Sex data were available from 26 818 adolescents (14 369 [53·6%] were female and 12 449 [46·4%] were male) for the prevalence of elevated blood pressure and 23 777 adolescents (12 864 [54·1%] were female and 10 913 [45·9%] were male) for mean blood pressure. Study quality was high, with no low-quality studies. The reported prevalence of elevated blood pressure ranged from 4 (0·2%) of 1727 to 1755 (25·1%) of 6980 (pooled prevalence 9·9%, 95% CI 7·3-12·5; I?=99·2%, pheterogeneity<0·0001). Mean SBP was 111 mm Hg (95% CI 108-114) and mean DBP was 68 mm Hg (66-70). 13·4% (95% CI 12·9-13·9; pheterogeneity<0·0001) of male participants had elevated blood pressure compared with 11·9% (11·3-12·4; pheterogeneity<0·0001) of female participants (odds ratio 1·04, 95% CI 0·81-1·34; pheterogeneity<0·0001). INTERPRETATION: To our knowledge, this systematic review and meta-analysis is the first systematic synthesis of blood pressure data specifically derived from adolescents in sub-Saharan Africa. Although many low-income countries were not represented in our study, our findings suggest that approximately one in ten adolescents have elevated blood pressure across sub-Saharan Africa. Accordingly, there is an urgent need to improve preventive heart-health programmes in the region. FUNDING: None.

Characteristics of symptoms and symptom change across different heart failure subtypes: a sex-stratified analysis.

AIMS: To examine sex-stratified differences in the association of left ventricular ejection fraction-based heart failure (HF) subtypes and the characteristics and correlates of self-reported changes in HF symptoms. METHODS AND RESULTS: We report a secondary data analysis from 528 hospitalized individuals diagnosed with HF characterised by a reduced, mildly reduced, or preserved ejection fraction [HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), or HF with preserved ejection fraction (HFpEF)] who completed 12-month follow-up within a multicentre disease management trial. There were 302 men (71.1 ± 11.9 years, 58% with HFrEF) and 226 women (77.1 ± 10.6 years, 49% with HFpEF). The characteristics of self-reported symptoms measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and 12-month were analysed. At baseline, shortness of breath and fatigue predominated; with key differences according to HF subtypes in bilateral ankle oedema (both sexes), walking problems (women) and depressive symptoms (men). At 12-month follow-up, most KCCQ scores had not significantly changed. However, 25% of individuals reported worse symptom. In women, those with HFpEF had worse symptoms than those with HFmrEF/HFrEF (P = 0.025). On an adjusted basis, women [odds ratios (OR): 1.78, 95% confidence interval (CI): 1.00-3.16 vs. men], those with coronary artery disease (OR: 2.01, 95% CI: 1.21-3.31) and baseline acute pulmonary oedema (OR: 1.67, 95% CI: 1.02-2.75) were most likely to report worsening symptoms. Among men, worsening symptoms correlated with a history of hypertension (OR: 2.16, 95% CI: 1.07-4.35) and a non-English-speaking background (OR: 2.30, 95% CI: 1.02-5.20). CONCLUSION: We found significant heterogeneity (with potential clinical implications) in the symptomatic characteristics and subsequent symptom trajectory according to the sex and HF subtype of those hospitalized with the syndrome. TRIAL REGISTRATION: ANZCTR12613000921785.

An inevitable or modifiable trajectory towards heart failure in high-risk individuals: insights from the nurse-led intervention for less chronic heart failure (NIL-CHF) study.

AIMS: We extended follow-up of a heart failure (HF) prevention study to determine if initially positive findings of improved cardiac recovery were translated into less de novo HF and/or all-cause mortality (primary endpoint) in the longer term. METHODS AND RESULTS: The Nurse-led Intervention for Less Chronic HF (NIL-CHF) study was a single-centre randomized trial of nurse-led prevention involving cardiac inpatients without HF. At 3 years, 454 survivors (aged 66 ± 11 years, 71% men and 68% coronary artery disease) had the following: (i) a normal echocardiogram (128 cases/28.2%), (ii) structural heart disease (196/43.2%), or (iii) left ventricular diastolic dysfunction/left ventricular systolic dysfunction (LVDD/LVSD: 130/28.6%). Outcomes were examined during median 8.3 (interquartile range 7.8-8.8) years according to these hierarchal groups and change in cardiac status from baseline to 3 years. Overall, 109 (24.0%) participants had a de novo HF admission or died while accumulating 551 cardiovascular-related admissions/3643 days of hospital stay. Progressively worse cardiac status correlated with increased hospitalizations (P < 0.001). The mean rate (95% confidence interval) of cardiovascular admissions/days of hospital stay being 0.09 (0.05-0.12) admissions/0.33 (0.13-0.54) days vs. 0.27 (0.20-0.34) admissions/2.20 (1.36-3.04) days per annum for those with a normal echocardiogram vs. LVDD/LVSD at 3 years. With progressively higher event rates, the adjusted hazard ratio for a de novo HF admission and/or death associated with a structural abnormality (24.5% of cases) and LVDD/LVSD (36.2%) at 3 years was 1.57 (0.82-3.01; P = 0.173) and 2.07 (1.05-4.05; P = 0.035) compared with a normal echocardiogram (10.9%). Mortality also mirrored the direction/extent of cardiac status/trajectory. CONCLUSIONS: These data suggest the positive initial effects of NIL-CHF intervention on cardiac recovery contributed to better long-term outcomes among patients at high risk of HF. However, prevention of HF remains challenging.

Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.

BACKGROUND: Aortic stenosis is the most common cardiac valve disorder requiring clinical management. However, there is little evidence on the societal cost of progressive aortic stenosis. We sought to quantify the societal burden of premature mortality associated with progressively worse aortic stenosis. METHODS: In this observational clinical cohort study, we examined echocardiograms on native aortic valves of 98 565 men and 99 357 women aged 65 years or older across 23 sites in Australia, from Jan 1, 2003, to Dec 31, 2017. Individuals were grouped according to their peak aortic valve velocity in 0·50 m/s increments up to 4·00 m/s or more (severe aortic stenosis), using 1·00-1·99 m/s (no aortic stenosis) as the reference group. Sex-specific premature mortality and years of life lost during a 5-year follow-up were calculated, along with willingness-to-pay to regain quality-adjusted life years (QALYs). FINDINGS: Overall, 20 701 (21·0%) men and 18 576 (18·7%) women had evidence of mild-to-severe aortic stenosis. The actual 5-year mortality in men with normal aortic valves was 32·1% and in women was 26·1%, increasing to 40·9% (mild aortic stenosis) and 52·2% (severe aortic stenosis) in men and to 35·9% (mild aortic stenosis) and 55·3% (severe aortic stenosis) in women. Overall, the estimated societal cost of premature mortality associated with aortic stenosis was AU$629 million in men and $735 million in women. Per 1000 men and women investigated, aortic stenosis was associated with eight more premature deaths in men resulting in 32·5 more QALYs lost (societal cost of $1·40 million) and 12 more premature deaths in women resulting in 57·5 more QALYs lost (societal cost of $2·48 million) when compared with those without aortic stenosis. INTERPRETATION: Any degree of aortic stenosis in older individuals is associated with premature mortality and QALYs. In this context, there is a crucial need for cost-effective strategies to promptly detect and optimally manage this common condition within our ageing populations. FUNDING: Edwards LifeSciences, National Health and Medical Research Council of Australia, and the National Heart, Lung, and Blood Institute.

Incremental Value of Global Longitudinal Strain in the Long-Term Prediction of Heart Failure among Patients with Coronary Artery Disease.

BACKGROUND: Heart failure (HF) remains a common complication for patients with coronary artery disease (CAD), especially after acute myocardial infarction. Although left ventricular ejection fraction (LVEF) is conventionally used to assess cardiac function for risk stratification, it has been shown in other settings to underestimate the risk of HF compared with global longitudinal strain (GLS). Moreover, most evidence pertains to early-onset HF. We sought the clinical and myocardial predictors for late-onset HF in patients with CAD. METHODS: We analyzed echocardiograms (including GLS) in 334 patients with CAD (ages 65 ± 11 years, 77% male) who were enrolled in the Nurse-Led Intervention for Less Chronic Heart Failure trial, a prospective, randomized controlled trial that compared standard care with nurse-led intervention to prevent HF in individuals at risk of incident HF. Long-term (9 years) follow-up was obtained via data linkage. Analysis was performed using a competing-risk model. RESULTS: Baseline LVEF values were normal or mildly impaired (LVEF ≥ 40%) in all subjects. After a median of 9 years of follow-up, 50 (15%) of the 334 patients had new HF admissions, and 68 (20%) died. In a competing-risk model, HF was associated with GLS (hazard ratio = 1.15 [1.05-1.25], P = .001), independent of estimated glomerular filtration rate (hazard ratio = 0.98 [0.97-0.99], P = .045), Charlson comorbidity score (hazard ratio = 1.64 [1.25-2.15], P < .001), or E/e' (hazard ratio = 1.08 [1.02-1.14], P = .01). Global longitudinal strain-but not conventional echocardiographic measures-added incremental value to a clinical model based on age, gender, and Charlson score (area under the curve, 0.78-0.83, P = .01). Global longitudinal strain was still associated with HF development in patients taking baseline angiotensin convertase enzyme inhibitors (hazard ratio = 1.21 [1.11-1.31], P < .01) and baseline beta-blockers (1.17 [1.09, 1.26]; P < .01). Mortality was associated with older men, risk factors (hypertension or diabetes), and comorbidities (AF and chronic kidney disease). CONCLUSIONS: Global longitudinal strain is independently associated with risk of incident HF in patients admitted with CAD and provides incremental prognostic value to standard markers. Identifying an at-risk subgroup using GLS may be the focus of future randomized controlled trails to enable targeted therapeutic intervention.

Incident aortic stenosis in 49 449 men and 42 229 women investigated with routine echocardiography.

OBJECTIVE: We addressed the paucity of data describing the characteristics and consequences of incident aortic stenosis (AS). METHODS: Adults undergoing echocardiography with a native aortic valve (AV) and no AS were studied. Subsequent age-specific and sex-specific incidence of AS were derived from echocardiograms conducted a median of 2.8 years apart. Progressive AV dysfunction and individually linked mortality were examined per AS category. RESULTS: 49 449 men (53.9%, 60.9±15.8 years) and 42 229 women (61.6±16.9 years) with no initial evidence of AS were identified. Subsequently, 6293 (6.9%) developed AS-comprising 5170 (5.6%), 636 (0.7%), 339 (0.4%) and 148 (0.2%) cases of mild, moderate, severe low-gradient and severe high-gradient AS, respectively. Age-adjusted incidence rates of all grades of AS were 17.5 cases per 1000 men/annum and 18.7 cases per 1000 women/annum: rising from ~5 to ~40 cases per 1000/annum in those aged <30 years vs >80 years. Median peak AV velocity increased by +0.57 (+0.36 to +0.80) m/s in mild AS compared with +2.75 (+2.40 to +3.19) m/s in severe high-gradient AS cases between first and last echocardiograms. During subsequent median 7.7 years follow-up, 24 577 of 91 678 cases (26.8%) died. Compared with no AS, the adjusted risk of all-cause mortality was 1.42-fold higher in mild AS, 1.92-fold higher in moderate AS, 1.95-fold higher in severe low-gradient AS and 2.27-fold higher in severe, high-gradient AS cases (all p<0.001). CONCLUSIONS: New onset AS is a common finding among older patients followed up with echocardiography. Any grade of AS is associated with higher mortality, reinforcing the need for proactive vigilance.

Change in ejection fraction and long-term mortality in adults referred for echocardiography.

AIMS: We investigated long-term mortality associated with changes in left ventricular ejection fraction (LVEF) in a large, real-world patient cohort. METHODS AND RESULTS: A total of 117 275 adults (63 ± 16 years, 46% women) had LVEF quantified by the same method ≥6 months apart. This included 17 343 cases (66 ± 15 years, 48% women) being initially investigated for heart failure (HF). During 3.3 [interquartile range (IQR) 1.7-6.0] years from first to last echocardiogram, median change in LVEF was -1 (IQR -8 to +5) units from a baseline of 62% (IQR 54-69%). During subsequent 7.6 (IQR 4.3-10.1) years of follow-up, 11 397 (9.7%) and 34 101 (29.1%) cases died from cardiovascular disease and all causes, respectively. Actual 5-year, all-cause mortality increased from 12% to 29% among those with the smallest to the largest decrease in LVEF (from <5 units to >30 units); the adjusted risk of cardiovascular-related mortality increased two- to eightfold beyond a >10-unit decline in LVEF (vs. minimal change; P < 0.001 for all comparisons). Among those initially investigated for HF (32% with initial LVEF <50%), the adjusted hazard ratio for cardiovascular-related mortality ranged from 0.35 [95% confidence interval (CI) 0.28-0.49] to 4.21 (95% CI 3.30-5.22) for a >30-unit increase to >30-unit decline in LVEF (vs. minimal change; P < 0.001 for both comparisons). A distinctive, bi-directional plateau of improved vs. worsening mortality was evident around a final LVEF of 50% to 55%. CONCLUSIONS: These data, derived from a large, heterogeneous cohort of adults being followed up with echocardiography, suggest that modest LVEF changes (particularly around an LVEF of 50-55%) may be of clinical significance.

International Mind, Activities and Urban Places (iMAP) study: methods of a cohort study on environmental and lifestyle influences on brain and cognitive health.

INTRODUCTION: Numerous studies have found associations between characteristics of urban environments and risk factors for dementia and cognitive decline, such as physical inactivity and obesity. However, the contribution of urban environments to brain and cognitive health has been seldom examined directly. This cohort study investigates the extent to which and how a wide range of characteristics of urban environments influence brain and cognitive health via lifestyle behaviours in mid-aged and older adults in three cities across three continents. METHODS AND ANALYSIS: Participants aged 50-79 years and living in preselected areas stratified by walkability, air pollution and socioeconomic status are being recruited in Melbourne (Australia), Barcelona (Spain) and Hong Kong (China) (n=1800 total; 600 per site). Two assessments taken 24 months apart will capture changes in brain and cognitive health. Cognitive function is gauged with a battery of eight standardised tests. Brain health is assessed using MRI scans in a subset of participants. Information on participants' visited locations is collected via an interactive web-based mapping application and smartphone geolocation data. Environmental characteristics of visited locations, including the built and natural environments and their by-products (e.g., air pollution), are assessed using geographical information systems, online environmental audits and self-reports. Data on travel and lifestyle behaviours (e.g., physical and social activities) and participants' characteristics (e.g., sociodemographics) are collected using objective and/or self-report measures. ETHICS AND DISSEMINATION: The study has been approved by the Human Research Ethics Committee of the Australian Catholic University, the Institutional Review Board of the University of Hong Kong and the Parc de Salut Mar Clinical Research Ethics Committee of the Government of Catalonia. Results will be communicated through standard scientific channels. Methods will be made freely available via a study-dedicated website. TRIAL REGISTRATION NUMBER: ACTRN12619000817145.

Differential patterns of disease and injury in Mozambique: New perspectives from a pragmatic, multicenter, surveillance study of 7809 emergency presentations.

BACKGROUND: There is a paucity of primary data to understand the overall pattern of disease and injuries as well as related health-service utilization in resource-poor countries in Africa. OBJECTIVE: To generate reliable and robust data describing the pattern of emergency presentations attributable to communicable disease (CD), non-communicable disease (NCD) and injuries in three different regions of Mozambique. METHODS: We undertook a pragmatic, prospective, multicentre surveillance study of individuals (all ages) presenting to the emergency departments of three hospitals in Southern (Maputo), Central (Beira) and Northern (Nampula) Mozambique. During 24-hour surveillance in the seasonally distinct months of April and October 2016/2017, we recorded data on 7,809 participants randomly selected from 39,124 emergency presentations to the three participating hospitals. Applying a pragmatic surveillance protocol, data were prospectively collected on the demography, clinical history, medical profile and treatment of study participants. FINDINGS: A total of 4,021 males and 3,788 (48.5%) females comprising 630 infants (8.1%), 2,070 children (26.5%), 1,009 adolescents (12.9%) and, 4,100 adults (52.5%) were studied. CD was the most common presentation (3,914 cases/50.1%) followed by NCD (1,963/25.1%) and injuries (1,932/24.7%). On an adjusted basis, CD was more prevalent in younger individuals (17.9±17.7 versus 26.6±19.2 years;p<0.001), females (51.7% versus 48.7%-OR 1.137, 95%CI 1.036-1.247;p = 0.007), the capital city of Maputo (59.6%) versus the more remote cities of Beira (42.8%-OR 0.532, 95%CI 0.476-0.594) and Nampula (45.8%-OR 0.538, 95%CI 0.480-0.603) and, during April (51.1% versus 49.3% for October-OR 1.142, 95%CI 1.041-1.253;p = 0.005). Conversely, NCD was progressively more prevalent in older individuals, females and in the regional city of Beira, whilst injuries were more prevalent in males (particularly adolescent/young men) and the northern city of Nampula. On a 24-hour basis, presentation patterns were unique to each hospital. INTERPRETATION: Applying highly pragmatic surveillance methods suited to the low-resource setting of Mozambique, these unique data provide critical insights into the differential pattern of CD, NCD and injury. Consequently, they highlight specific health priorities across different regions and seasons in Southern Africa.

Prevalence and profile of "seasonal frequent flyers" with chronic heart disease: Analysis of 1598 patients and 4588 patient-years follow-up.

BACKGROUND: Peaks and troughs in cardiovascular events correlated with seasonal change is well established from an epidemiological perspective but not a clinical one. METHODS: Retrospective analysis of the recruitment, baseline characteristics and outcomes during minimum 12-month exposure to all four seasons in 1598 disease-management trial patients hospitalised with chronic heart disease. Seasonality was prospectively defined as ≥4 hospitalisations (all-cause) AND >45% of related bed-days occurring in any one season during median 988 (IQR 653, 1394) days follow-up. RESULTS: Patients (39% female) were aged 70 ±â€¯12 years and had a combination of coronary artery disease (58%), heart failure (54%), atrial fibrillation (50%) and multimorbidity. Overall, 29.9% of patients displayed a pattern of seasonality. Independent correlates of seasonality were female gender (adjusted OR 1.27, 95% CI 1.01-1.61; p = 0.042), mild cognitive impairment (adjusted OR 1.51, 95% CI 1.16-1.97; p = 0.002), greater multimorbidity (OR 1.20, 95% CI 1.15-1.26 per Charlson Comorbidity Index Score; p < 0.001), higher systolic (OR 1.01, 95%CI 1.00-1.01 per 1 mmHg; p = 0.002) and lower diastolic (OR 0.99, 95% CI 0.98-1.00 per 1 mmHg; p = 0.002) blood pressure. These patients were more than two-fold more likely to die (adjusted HR 2.16, 95% CI 1.60-2.90; p < 0.001) with the highest and lowest number of deaths occurring during spring (31.7%) and summer (19.9%), respectively. CONCLUSIONS: Despite high quality care and regardless of their diagnosis, we identified a significant proportion of "seasonal frequent flyers" with concurrent poor survival in this real-world cohort of patients with chronic heart disease.

Left Ventricular Dysfunction and Exercise Capacity Trajectory: Implications for Subclinical Heart Failure Staging Criteria.

OBJECTIVES: This study aimed to determine the association of stage B heart failure (SBHF) and its constituent left ventricular (LV) abnormalities with trajectory of exercise capacity over time, and assess whether this association is modified by reversion of these LV abnormalities to normal. BACKGROUND: The LV abnormalities of SBHF may coincide with a reduction in exercise capacity that precedes the overt exercise intolerance of clinical heart failure (HF). Determining the predictive capacity of established and novel SBHF criteria for exercise capacity decline may improve HF risk stratification. METHODS: LV structure/function (echocardiography) and exercise capacity (6-min walk distance [6MWD]) were assessed at baseline and 3-year follow-up in 268 patients from the NIL-CHF (Nurse-led Intervention for Less Chronic Heart Failure) study (all stage A [SAHF] or SBHF). Changes (Δ) in 6MWD were compared between SAHF and SBHF and across each of 4 constituent components of SBHF: LV hypertrophy, regional wall motion abnormality(ies) (RWMA), left ventricular systolic dysfunction (LVSD) (ejection fraction <45%) and elevated early diastolic filling/annular velocity ratio (E/e' ≥15). RESULTS: Δ6MWD was similar in those with SAHF (n = 141) and SBHF (n = 127; -5 m [95% confidence interval (CI): -21 to +11 m]; covariate-adjusted). However, within the setting of SBHF there was substantive heterogeneity; that is, reductions in 6MWD were observed with persistent elevated E/e' (-34 m [95% CI: -62 to -6 m]) and persistent LVSD (-41 m [95% CI: -74 to -8 m]), but not with LV hypertrophy (+17 m [95% CI: -15 to +49 m) or RWMA (+5 m [-27 to +36 m]), nor in patients whose elevated E/e' or LVSD reverted to normal by 3 years (p > 0.10). CONCLUSIONS: Elevated E/e' is associated with a similar degree of exercise capacity decline to LVSD, supporting that both LV functional criteria be considered in distinguishing SBHF from SAHF. That reversion of either manifestation of LV dysfunction was associated with preserved exercise capacity advocates targeting of these factors by HF preventive interventions.

Malignant and Benign Phenotypes of Multimorbidity in Heart Failure: Implications for Clinical Practice.

BACKGROUND: The impact of different patterns of multimorbidity in heart failure (HF) on health outcomes is unknown. OBJECTIVES: The aim of this study was to test the hypothesis that, independent of the extent of comorbidity, there are distinctive phenotypes of multimorbidity that convey an increased risk for premature mortality in patients hospitalized with HF. METHODS: We analyzed the clinical profile and health outcomes of 787 patients hospitalized with HF participating in a multidisciplinary HF management program with a minimum 12-month follow-up. A Classification and Regression Tree model was applied to explore the distinctive combinations of 10 most prevalent concurrent conditions (other than coronary artery disease and hypertension) associated with 12-month all-cause mortality. RESULTS: Mean (SD) age was 74 (12) years (59% men), and 65% had left ventricular systolic dysfunction. Most patients (88%) had 3 or more comorbid conditions, with a mean of 4.3 concurrent conditions in addition to HF. A total of 248 patients (32%) died (median, 663 [IQR, 492-910] days), including 142 deaths (18%) within 12 months. Patients with concurrent dysrhythmia, anemia, and respiratory disease experienced significantly higher 12-month all-cause mortality than those without these conditions (36.1% vs 3.6%, respectively; hazard ratio, 6.1 [95% confidence interval, 2.0-19.1]). Overall, this "malignant" phenotype of multimorbidity was associated with not only a markedly increased risk of all-cause mortality but also more unplanned readmissions, longer inpatient stays, and highest costs in the short (30-day) and longer terms when compared with more "benign" phenotypes of multimorbidity. CONCLUSIONS: We found a differential pattern of health outcomes according to pattern of comorbidity present in older patients hospitalized with HF and exposed to postdischarge, multidisciplinary management.

Multimorbidity and the Risk of All-Cause 30-Day Readmission in the Setting of Multidisciplinary Management of Chronic Heart Failure: A Retrospective Analysis of 830 Hospitalized Patients in Australia.

BACKGROUND: Multimorbidity has an adverse effect on health outcomes in hospitalized individuals with chronic heart failure (CHF), but the modulating effect of multidisciplinary management is unknown. OBJECTIVE: The aim of this study was to test the hypothesis that increasing morbidity would independently predict an increasing risk of 30-day readmission despite multidisciplinary management of CHF. METHODS: We studied patients hospitalized for any reason with heart failure receiving nurse-led, postdischarge multidisciplinary management. We profiled a matrix of expected comorbidities involving the most common coexisting conditions associated with CHF and examined the relationship between multimorbidity and 30-day all-cause readmission. RESULTS: A total of 830 patients (mean age 73 ± 13 years and 65% men) were assessed. Multimorbidity was common, with an average of 6.6 ± 2.4 comorbid conditions with sex-based differences in prevalence of 4 of 10 conditions. Within 30 days of initial hospitalization, 216 of 830 (26%) patients were readmitted for any reason. Greater multimorbidity was associated with increasing readmission (4%-44% for those with 0-1 to 8-9 morbid conditions; adjusted odds ratio, 1.25; 95% confidence interval, 1.13-1.38) for each additional condition. Three distinct classes of patient emerged: class 1-diabetes, metabolic, and mood disorders; class 2-renal impairment; and class 3-low with relatively fewer comorbid conditions. Classes 1 and 2 had higher 30-day readmission than class 3 did (adjusted P < .01 for both comparisons). CONCLUSIONS: These data affirm that multimorbidity is common in adult CHF inpatients and in potentially distinct patterns linked to outcome. Overall, greater multimorbidity is associated with a higher risk of 30-day all-cause readmission despite high-quality multidisciplinary management. More innovative approaches to target-specific clusters of multimorbidity are required to improve health outcomes in affected individuals.

Mild cognitive impairment is associated with subclinical diastolic dysfunction in patients with chronic heart disease.

Background: To examine mild cognitive impairment and its associations with subclinical cardiac dysfunction in patients with chronic heart disease yet to develop the clinical syndrome of chronic heart failure (CHF). Methods and results: Patients from the Nurse-led Intervention for Less Chronic Heart Failure Study (n = 373 with chronic heart disease other than CHF; 64 ± 11 years, 69% men) were screened for mild cognitive impairment [Montreal cognitive assessment (MoCA) score <26] and underwent echocardiographic/clinical profiling. We investigated associations of mild cognitive impairment and MoCA cognitive domain subscores with global cardiac status ('normal' vs. 'diastolic dysfunction' vs. 'other cardiac abnormality') and individual echocardiographic parameters. Patients with mild cognitive impairment (n = 161; 43%) demonstrated a higher age-adjusted prevalence of diastolic dysfunction (37% vs. 24%; P < 0.05). Multivariate logistic regression (adjusted for age, sex, and other relevant clinical factors) indicated that the odds of mild cognitive impairment were two-times higher with diastolic dysfunction (P = 0.030) and 1.7-times higher with 'other cardiac abnormalities' (P = 0.082) vs. normal cardiac status. In turn, mild cognitive impairment was predicted by left-ventricular (LV) filling pressure (based on the ratio of early diastolic filling and annular velocities; adjusted odds ratio 1.07 per unit increase, P = 0.022), but not LV structural parameters. Specific deficits in the cognitive domains of executive functioning and visuo-constructional abilities were also independently predicted by diastolic dysfunction (P < 0.05). Conclusion: Mild cognitive impairment is prevalent in patients with subclinical chronic heart disease at high-risk of CHF. Independent associations with LV diastolic dysfunction suggest a link between cardiac and cognitive functioning beyond shared risk factors.

Economic evaluation of a nurse-led home and clinic-based secondary prevention programme to prevent progressive cardiac dysfunction in high-risk individuals: The Nurse-led Intervention for Less Chronic Heart Failure (NIL-CHF) randomized controlled study.

OBJECTIVE: The objective of this study was to assess the cost-effectiveness of a long-term, nurse-led, multidisciplinary programme of home/clinic visits in preventing progressive cardiac dysfunction in patients at risk of developing de novo chronic heart failure (CHF). METHODS: A trial-based analysis was conducted alongside a pragmatic, single-centre, open-label, randomized controlled trial of 611 patients (mean age: 66 years) with subclinical cardiovascular diseases (without CHF) discharged to home from an Australian tertiary referral hospital. A nurse-led home and clinic-based programme (NIL-CHF intervention, n = 301) was compared with standard care ( n=310) in terms of life-years, quality-adjusted life-years (QALYs) and healthcare costs. The uncertainty around the incremental cost and QALYs was quantified by bootstrap simulations and displayed on a cost-effectiveness plane. RESULTS: During a median follow-up of 4.2 years, there were no significant between-group differences in life-years (-0.056, p=0.488) and QALYs (-0.072, p=0.399), which were lower in the NIL-CHF group. The NIL-CHF group had slightly lower all-cause hospitalization costs (AUD$2943 per person; p=0.219), cardiovascular-related hospitalization costs (AUD$1142; p=0.592) and a more pronounced reduction in emergency/unplanned hospitalization costs (AUD$4194 per person; p=0.024). When the cost of intervention was added to all-cause, cardiovascular and emergency-related readmissions, the reductions in the NIL-CHF group were AUD$2742 ( p=0.313), AUD$941 ( p=0.719) and AUD$3993 ( p=0.046), respectively. At a willingness-to-pay threshold of AUD$50,000/QALY, the probability of the NIL-CHF intervention being better-valued was 19%. CONCLUSIONS: Compared with standard care, the NIL-CHF intervention was not a cost-effective strategy as life-years and QALYs were slightly lower in the NIL-CHF group. However, it was associated with modest reductions in emergency/unplanned readmission costs.