Medicine (St Vincent's) - Research Publications
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ItemNo Preview AvailablePrognostic and functional importance of both overt and subclinical left ventricular systolic dysfunction in systemic sclerosis.(Elsevier BV, 2024-06)OBJECTIVES: To quantify the frequency and clinical implications of systemic sclerosis (SSc)-associated left ventricular function (LV) impairment. METHODS: Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc with ≥1 echocardiographic LVEF measurement were included. Overt LV dysfunction was indicated by reduced LV ejection fraction (LVEF) and subclinical LV dysfunction was measured using impaired LV global longitudinal strain (LV-GLS>-16 %). Those with secondary causes of LV dysfunction (myocardial ischaemia, valvulopathy and pulmonary arterial hypertension) were excluded. Chi-squared tests, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Generalised estimating equations(GEE) were used to model longitudinal data. Kaplan-Meier and Cox proportional hazard models were used for survival analyses. RESULTS: Of 1141 participants with no co-morbid cardiac disease, 2.4 % ever recorded a LVEF<50 %, while only 0.6 % ever recorded a LVEF≤40 %. LV-GLS data were available for 90 % of participants at one centre (n = 218). Impaired LV-GLS was detected in 21 % despite LVEF≥50 %. Those with a LVEF<50 % were more frequently male (p = 0.01) with dcSSc (p < 0.01), higher inflammatory markers (p < 0.02) and skeletal muscle disease (p < 0.05). In multivariable analyses, recording a LVEF<50 % was associated with increased mortality (HR2.3, 95 %CI1.0-4.8, p = 0.04). Impaired LV-GLS was also associated with poorer survival in univariable analyses (HR3.4, 95 %CI1.0-11.8, p = 0.05). Those with a LVEF<50 % more frequently recorded WHO Class III/IV dyspnoea (OR3.5, 95 %CI1.6-7.7, p < 0.01), with shorter six-minute walk distance (p = 0.01), higher Health Assessment Questionnaire-Disability Index scores (p < 0.01) and lower Short Form-36 Physical Component Summary scores (p = 0.02). Increased dyspnoea (WHO Class III/IV dyspnoea; OR3.6, 95 %CI1.4-9.2, p < 0.01) was also seen in those with impaired LV-GLS. CONCLUSIONS: Both overt and subclinical SSc-associated LV dysfunction are associated with worse survival and impaired physical function. The frequency of abnormal LV-GLS in those with consistently normal LVEF suggests an under-appreciated burden of subtle LV systolic dysfunction in SSc that has a significant impact on patient symptomatology.
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ItemMultidisciplinary team discussion: the emerging gold standard for management of cardiopulmonary complications of connective tissue disease(WILEY, 2023-10)Cardiopulmonary complications of connective tissue diseases (CTDs), particularly pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), are major determinants of morbidity and mortality. Multidisciplinary meetings may improve diagnostic accuracy and optimise treatment. We review the literature regarding multidisciplinary meetings in CTD-ILD and PAH and describe our tertiary centre experience of the role of the multidisciplinary meeting in managing CTD-PAH.
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ItemNo Preview AvailableDisease specific determinants of cardiopulmonary fitness in systemic sclerosis(W B SAUNDERS CO-ELSEVIER INC, 2023-02)OBJECTIVES: We aimed to quantify the burden of exercise intolerance in systemic sclerosis (SSc) and explore the disease features that contribute to impaired exercise capacity (measured as peak oxygen uptake, peak VO2) to provide novel mechanistic insights into the causes of physical disability in SSc. METHODS: Thirty-three SSc patients with no history of cardiac disease and no active myositis underwent cardiac and skeletal muscle MRI, transthoracic echocardiography, pulmonary function tests and cardiopulmonary exercise testing (CPET). CPET results were compared to an age-, sex-, and weight-matched controls with no overt cardiopulmonary disease. Native T1 and T2-mapping sequences were used to quantify diffuse fibroinflammatory myocardial disease and qualitative assessment of skeletal muscle oedema was performed. The associations between parameters of cardiorespiratory function and skeletal muscle abnormalities and peak VO2 were evaluated with linear regression analysis. RESULTS: Exercise capacity was markedly impaired in SSc and significantly reduced when compared to control subjects (percent predicted peak VO2: 70% vs 98%, p < 0⋅01). Diffuse myocardial fibroinflammatory disease (p < 0⋅01) and skeletal muscle oedema (p = 0⋅01) were significantly associated with reduced exercise capacity. There was no association between impaired exercise capacity and left ventricular ejection fraction. CONCLUSION: SSc is associated with marked functional impairment that is not explained by commonly used parameters of cardiac function such as left ventricular ejection fraction. Rather, only more sensitive measures of organ involvement are associated with impaired exercise tolerance. Our results show diffuse interstitial changes of the myocardium and skeletal muscle affect oxygen uptake and are important contributors to functional limitation in SSc.
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ItemMyocardial fibrosis and arrhythmic burden in systemic sclerosis(OXFORD UNIV PRESS, 2022-11-02)OBJECTIVES: Cardiac complications of SSc are a leading cause of SSc-associated death. Cardiac imaging for identifying substrate abnormality may be useful in predicting risk of cardiac arrhythmias or future cardiac failure. The aim of this study was to quantify the burden of asymptomatic fibro-inflammatory myocardial disease using cardiac magnetic resonance imaging (CMR) and assess the relationship between asymptomatic myocardial fibrosis and cardiac arrhythmias in SSc. METHODS: Thirty-two patients with SSc with no documented history of pulmonary vascular or heart disease underwent CMR with gadolinium and 24-h ambulatory ECG. Focal myocardial fibrosis was assessed using post-gadolinium imaging and diffuse fibro-inflammatory myocardial disease quantified using T1- and T2-mapping. CMR results were compared with an age- and sex-matched control group. RESULTS: Post-gadolinium focal fibrosis was prevalent in SSc but not controls (30% vs 0%, p < 0.01).. T1-mapping values (as a marker of diffuse fibrosis) were greater in SSc than controls [saturated recovery single-shot acquisition (SASHA): 1584 ms vs 1515 ms, P < 0.001; shortened Modified look locker sequence (ShMOLLI): 1218 ms vs 1138 ms, p < 0.001]. More than one-fifth (22.6%) of the participants had ventricular arrhythmias on ambulatory ECG, but no associations between focal or diffuse myocardial fibrosis and arrhythmias were evident. CONCLUSION: In SSc patients without evidence of overt cardiac disease, a high burden of myocardial fibrosis and arrhythmias was identified. However, there was no clear association between focal or diffuse myocardial fibrosis and arrhythmias, suggesting CMR may have limited use as a screening tool to identify SSc patients at risk of future significant arrhythmias.
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ItemRisk factors for asymptomatic echocardiographic abnormalities that predict symptomatic heart failure(WILEY PERIODICALS, INC, 2022-02)AIMS: Risk factors for asymptomatic echocardiographic abnormalities that predict symptomatic heart failure (HF) may provide insight into early mechanisms of HF pathogenesis. We examined risk factors associated with asymptomatic echocardiographic structural, systolic, and diastolic abnormalities, separately and in combination, and interactions between risk factors, in the prospective community-based SCReening Evaluation of the Evolution of New HF (SCREEN-HF) Study cohort of 3190 participants at increased risk of cardiovascular disease. METHODS AND RESULTS: Inclusion criteria were age ≥ 60 years with one or more of hypertension, diabetes, ischaemic heart disease, valvular heart disease, abnormal heart rhythm, cerebrovascular disease, or renal impairment. Exclusion criteria were known HF, ejection fraction < 50%, or >mild valve abnormality. Structural, systolic, and diastolic echocardiographic abnormalities were defined according to the Atherosclerosis Risk in Communities study criteria, and risk factors for asymptomatic structural, systolic, and diastolic abnormalities were identified using logistic regression analysis. In multivariable analysis, increased body mass index (BMI), non-steroidal anti-inflammatory drug therapy, and alcohol intake were risk factors for isolated structural abnormality, whereas male gender, increased heart rate, atrial fibrillation (AF), angiotensin-converting enzyme inhibitor therapy, and obstructive sleep apnoea were associated with a lower risk. Moreover, male gender, smoking, increased systolic blood pressure, and physical inactivity were risk factors for isolated systolic abnormality, whereas increased pulse pressure and antihypertensive therapy were associated with a lower risk. Furthermore, increased age, blood pressure, amino-terminal pro-B-type natriuretic peptide level, and warfarin therapy (associated with AF) were risk factors for isolated diastolic abnormality, whereas increased heart rate and triglyceride level (associated with BMI) were associated with a lower risk. The association of increased heart rate with lower risk of structural and diastolic abnormalities was independent of β-blocker therapy. Interactions between risk factors differed for structural, systolic, and diastolic abnormalities. CONCLUSIONS: The different risk factors for asymptomatic structural, systolic, and diastolic abnormalities that predict symptomatic HF, and the interactions between risk factors, illustrate how these structural, systolic, and diastolic abnormalities represent unique trajectories that lead to symptomatic HF. Improved understanding of these trajectories may assist in the design of HF prevention strategies.
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ItemSubaortic Stenosis: What Lies Beneath.(Elsevier BV, 2018-08)• DSS is generally an acquired and progressive condition. • Subaortic stenosis often takes the form of a discrete crescentic fibromuscular ridge in the LVOT. • DSS should be considered when an elevated aortic Doppler gradient is seen in the presence of normal aortic leaflet mobility. • Surgery is considered when the peak instantaneous gradient is >50 to 60 mm Hg. • DSS has a high rate of recurrence following surgical intervention.
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ItemKidney age-chronological age difference (KCD) score provides an age-adapted measure of kidney function(BMC, 2021-04-26)BACKGROUND: Given the age-related decline in glomerular filtration rate (GFR) in healthy individuals, we examined the association of all-cause death or cardiovascular event with the Kidney age - Chronological age Difference (KCD) score, whereby an individual's kidney age is estimated from their estimated GFR (eGFR) and the age-dependent eGFR decline reported for healthy living potential kidney donors. METHODS: We examined the association between death or cardiovascular event and KCD score, age-dependent stepped eGFR criteria (eGFRstep), and eGFR < 60 ml/min/1.73 m2 (eGFR60) in a community-based high cardiovascular risk cohort of 3837 individuals aged ≥60 (median 70, interquartile range 65, 75) years, followed for a median of 5.6 years. RESULTS: In proportional hazards analysis, KCD score ≥ 20 years (KCD20) was associated with increased risk of death or cardiovascular event in unadjusted analysis and after adjustment for age, sex and cardiovascular risk factors. Addition of KCD20, eGFRstep or eGFR60 to a cardiovascular risk factor model did not improve area under the curve for identification of individuals who experienced death or cardiovascular event in receiver operating characteristic curve analysis. However, addition of KCD20 or eGFR60, but not eGFRstep, to a cardiovascular risk factor model improved net reclassification and integrated discrimination. KCD20 identified individuals who experienced death or cardiovascular event with greater sensitivity than eGFRstep for all participants, and with greater sensitivity than eGFR60 for participants aged 60-69 years, with similar sensitivities for men and women. CONCLUSIONS: In this high cardiovascular risk cohort aged ≥60 years, the KCD score provided an age-adapted measure of kidney function that may assist patient education, and KCD20 provided an age-adapted criterion of eGFR-related increased risk of death or cardiovascular event. Further studies that include the full age spectrum are required to examine the optimal KCD score cut point that identifies increased risk of death or cardiovascular event, and kidney events, associated with impaired kidney function, and whether the optimal KCD score cut point is similar for men and women. TRIAL REGISTRATION: ClinicalTrials.gov NCT00400257 , NCT00604006 , and NCT01581827 .
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ItemPrediction of incident heart failure by serum amino-terminal pro-B-type natriuretic peptide level in a community-based cohort(WILEY, 2019-04)AIMS: We investigated which serum amino-terminal pro-B-type-natriuretic peptide (NT-proBNP) levels inform heart failure (HF) risk in a community-based population at increased cardiovascular disease (CVD) risk. METHODS AND RESULTS: Inclusion criteria were age ≥ 60 years with one or more of self-reported hypertension, diabetes, heart disease, abnormal heart rhythm, cerebrovascular disease, or renal impairment. Exclusion criteria were known HF, ejection fraction (EF) < 50%, or more than mild valve abnormality. NT-proBNP levels were measured in 3842 participants on enrolment. HF was diagnosed in 162 participants at a median of 4.5 (interquartile range 2.7-5.4) years after enrolment, 73 with HF with preserved EF (HFpEF), 53 with HF with reduced EF (HFrEF), and 36 with valvular HF (VHF). Areas under the receiver operating characteristic curve (AUC) for 5-year prediction of total HF were similar for NT-proBNP alone (0.79, 95% confidence interval 0.74-0.83) and a 7-parameter multivariable model (0.82, 0.77-0.86, P = 0.035). NT-proBNP cut-points of 11, 16, and 25 pmol/L for individuals aged 60-69, 70-79, and ≥ 80 years, respectively, achieved sensitivities > 76% and specificities of 47-69% for 5-year prediction of total HF in men and women in all three age groups. Sensitivities were ≥ 75% in most subgroups according to body mass index, estimated glomerular filtration rate, and the presence or absence of atrial fibrillation, pacemaker, or CVD, and for the prediction of HFpEF, HFrEF and VHF. CONCLUSION: Age-specific serum NT-proBNP levels inform prognosis, and hence therapeutic decisions, regarding HF risk in individuals at increased CVD risk.
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ItemRisk factor management in a contemporary Australian population at increased cardiovascular disease risk(WILEY, 2018-06)BACKGROUND: Effective management of cardiovascular and chronic kidney disease risk factors offers longer, healthier lives and savings in healthcare. AIM: To examine risk factor management in participants of the SCReening Evaluation of the Evolution of New Heart Failure study, a self-selected population at increased cardiovascular disease risk recruited from members of a health insurance fund in Melbourne and Shepparton, Australia. METHODS: Inclusion criteria were age ≥ 60 years with one or more self-reported ischaemic or other heart diseases, irregular or rapid heart rhythm, cerebrovascular disease, renal impairment or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known heart failure or cardiac abnormality on echocardiography or other imaging. Medical history, clinical examination, full blood examination and biochemistry (without lipids and glycated haemoglobin (HbA1c)) were performed for 3847 participants on enrolment, and blood pressure, lipids and HbA1c were measured 1-2 years after enrolment for 3203 participants. RESULTS: Despite 99% of 3294 participants with hypertension receiving antihypertensive medication, half had blood pressures >140/90 mmHg. Approximately 77% of participants were overweight or obese, with one third being obese. Additionally, 74% of participants at high cardiovascular disease risk had low-density lipoprotein cholesterol levels ≥2 mmol/L, one third of diabetic participants had HbA1c >7%, 22% had an estimated glomerular filtration rate < 60 mL/min/1.73m2 , and substantial proportions had under-utilisation of antiplatelet therapy and anticoagulation for atrial fibrillation and were physically inactive. CONCLUSIONS: This population demonstrated substantial potential to reduce cardiovascular and renal morbidity and mortality and healthcare costs through more effective management of modifiable risk factors.
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ItemDiastolic dysfunction and mortality in 436 360 men and women: the National Echo Database Australia (NEDA)(OXFORD UNIV PRESS, 2021-05)AIMS: To examine the characteristics/prognostic impact of diastolic dysfunction (DD) according to 2016 American Society of Echocardiography (ASE) and European Society of Cardiovascular Imaging (ESCVI) guidelines, and individual parameters of DD. METHODS AND RESULTS: Data were derived from a large multicentre mortality-linked echocardiographic registry comprising 436 360 adults with ≥1 diastolic function measurement linked to 100 597 deaths during 2.2 million person-years follow-up. ASE/European Association of Cardiovascular Imaging (EACVI) algorithms could be applied in 392 009 (89.8%) cases; comprising 11.4% of cases with 'reduced' left ventricular ejection fraction (LVEF < 50%) and 88.6% with 'preserved' LVEF (≥50%). Diastolic function was indeterminate in 21.5% and 62.2% of 'preserved' and 'reduced' LVEF cases, respectively. Among preserved LVEF cases, the risk of adjusted 5-year cardiovascular-related mortality was elevated in both DD [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.22-1.42; P < 0.001] and indeterminate status cases (OR 1.11, 95% CI 1.04-1.18; P < 0.001) vs. no DD. Among impaired LVEF cases, the equivalent risk of cardiovascular-related mortality was 1.51 (95% CI 1.15-1.98, P < 0.001) for increased filling pressure vs. 1.25 (95% CI 0.96-1.64, P = 0.06) for indeterminate status. Mitral E velocity, septal e' velocity, E:e' ratio, and LAVi all correlated with mortality. On adjusted basis, pivot-points of increased risk for cardiovascular-related mortality occurred at 90 cm/s for E wave velocity, 9 cm/s for septal e' velocity, an E:e' ratio of 9, and an LAVi of 32 mL/m2. CONCLUSION: ASE/EACVI-classified DD is correlated with increased mortality. However, many cases remain 'indeterminate'. Importantly, when analysed individually, mitral E velocity, septal e' velocity, E:e' ratio, and LAVi revealed clear pivot-points of increased risk of cardiovascular-related mortality.