Prevalence of asymptomatic valvular heart disease in the elderly population: a community-based echocardiographic study.

AIMS: With an ageing population, the presence of asymptomatic valvular heart disease (VHD) in the community remains unknown. The aim of this study is to determine the prevalence and associated factors of asymptomatic VHD in individuals ≥60 years old and to evaluate the feasibility of echocardiographic screening for VHD in this population. METHODS AND RESULTS: This was a prospective cohort study conducted between 2007 and 2016 in the UK. Asymptomatic patients with no prior indication for echocardiography were invited to participate and evaluated with a health questionnaire, clinical examination, and transthoracic echocardiography. A total of 10,000 individuals were invited through their general practices. A total of 5429 volunteered to participate, of whom 4237 were eligible for inclusion. VHD was diagnosed in more than a quarter of patients (28.2%). The most common types of VHD were regurgitation of the tricuspid (13.8%), mitral (12.8%), and aortic (8.3%) valves (trivial regurgitation was not included). The rate of prevalence of clinically significant VHD was 2.4% (2.2% moderate and 0.2% severe), with mitral and aortic regurgitation being the most common. The only parameter associated with significant VHD was age (odds ratio 1.07 per 1 year increment, 95% confidence interval 1.05-1.09, P < 0.001). The number needed to scan to diagnose one clinically significant case of VHD is 42 for individuals ≥60 and 15 for those ≥75 years old. CONCLUSION: Asymptomatic VHD is present in a significant proportion of otherwise healthy individuals without known VHD over 60 years old. Age is strongly associated with an increased incidence of significant VHD.

The Association of Obstructive Sleep Apnea in Ischemia with No Obstructive Coronary Artery Disease - A Pilot Study.

Obstructive sleep apnea (OSA) is increasingly recognized to be a risk factor for cardiovascular disease. This pilot study assessed the association of OSA and invasive coronary microvascular function in patients with ischemia with no obstructive coronary artery disease (INOCA). Forty-two patients with angina, were prospectively screened at a single tertiary centre covering the northern metropolitan area of South Australia, from February 2018 to December 2020 (ACTRN12618000149268). Forty patients were invited into to this observational study after coronary angiography demonstrated INOCA and functional coronary vasomotor disorder (n = 40). Twenty one participants subsequently underwent a sleep study for OSA diagnosis while 9 participants had prior formal diagnosis of OSA (ACTRN12618000227291). Of the 30 participants with OSA data, 87% (n = 26) had a diagnosis of OSA. Accordingly, 11 with mild severity, 7 with moderate severity and 8 with severe OSA. No OSA was observed in 4 participants. Participants with OSA were older [61.4±8.7 vs 49.9±9.7, P = 0.002] with similar clinical characteristics for the pattern and severity of angina and other co-morbidities. 73.3% (n = 22) had abnormal functional disorders of the epicardial coronary arteries and/or coronary microcirculation. On multivariate analysis, OSA was the only statistically significant association with functional coronary microvascular disorders [OR 53.95, 1.41 -2065.01, P = 0.032]. This study provided an observation of a significant correlation between INOCA with abnormal coronary vasomotor function and OSA in an Australian cohort. This correlation supports a possible pathophysiological interplay between these two conditions that needs to be further evaluated. The benefit of treatment of OSA in this subset remains unknown.

'Bushfire Season' in Australia: Determinants of Increases in Risk of Acute Coronary Syndromes and Takotsubo Syndrome.

BACKGROUND: Climate change has resulted in an increase in ambient temperatures during the summer months as well as an increase in risk of associated air pollution and of potentially disastrous bushfires throughout much of the world. The increasingly frequent combination of elevated summer temperatures and bushfires may be associated with acute increases in risks of cardiovascular events, but this relationship remains unstudied. We evaluated the individual and cumulative impacts of daily fluctuations in temperature, fine particulate matter of less than 2.5 µm (PM2.5) pollution and presence of bushfires on incidence of acute coronary syndromes and Takotsubo syndrome. METHODS: From November 1, 2019, to February 28, 2020, all admissions with acute coronary syndromes or Takotsubo syndrome to South Australian tertiary public hospitals were evaluated. Univariate and combined associations were sought among each of 1) maximal daily temperature, 2) PM2.5 concentrations, and 3) presence of active bushfires within 200 km of the hospitals concerned. RESULTS: A total of 504 patients with acute coronary syndromes and 35 with Takotsubo syndrome were studied. In isolation, increasing temperature was associated (rs = 0.26, P = .005) with increased incidence of acute coronary syndromes, while there were similar, but nonsignificant correlations for PM2.5 and presence of bushfires. Combinations of all these risk factors were also associated with a doubling of risk of acute coronary syndromes. No significant associations were found for Takotsubo syndrome. CONCLUSION: The combination of high temperatures, presence of bushfires and associated elevation of atmospheric PM2.5 concentrations represents a substantially increased risk for precipitation of acute coronary syndromes; this risk should be factored into health care planning including public education and acute hospital preparedness.

Predictors of Obstructive Sleep Apnoea (OSA) Population in the Coronary Angiogram Database of South Australia (CADOSA).

Obstructive sleep apnoea (OSA) is increasingly recognized to be a risk factor for cardiovascular disease. This study assessed the prevalence and clinical predictors of OSA in patients undergoing coronary angiography. Consecutive patients undergoing coronary angiography in South Australian public hospitals from 2015 to 2018 were included. Clinical details for consecutive patients undergoing coronary angiography in South Australian public hospitals were captured by the Coronary Angiogram Database of South Australia (CADOSA) registry staff, with OSA identified by patient report. Among the 9,885 patients undergoing coronary angiography for the investigation of chest pain, 11% (n = 1,089) were documented as having OSA. Independent clinical predictors of OSA included male gender (OR 2.22, 1.86-2.65, P < 0.001), diabetes mellitus (OR 1.84, 1.58-2.14, P < 0.001), depression (OR 1.81, 1.55-2.12, P < 0.001), prior heart failure (OR 1.63, 1.22-2.18, P = 0.001), hypertension (OR 1.61, 1.32-1.95, P ≤ 0.001), asthma (OR 1.61, 1.34-1.93, P < 0.001), not a current smoker (OR 1.60, 1.30-1.96, P < 0.001), dyslipidaemia (OR 1.46, 1.22-1.76, P < 0.001), non-acute coronary syndrome presentation (OR 1.45, 1.25-1.69, P < 0.001), chronic lung disease (OR 1.40, 1.12-1.73, P = 0.003), cerebrovascular disease (OR 1.36, 1.07-1.73, P = 0.012), non-obstructive coronary artery disease (NOCAD) (OR 1.30, 1.10-1.55, P = 0.003) and atrial fibrillation/flutter (OR 1.30, 1.06-1.60, P = 0.012). Finally, stable angina (32.1% vs 22.7%) and NOCAD (29.1% vs 26.3%, P = 0.051) were trended more common in patients with OSA versus no OSA. In addition to established risk factors for OSA, this study found NOCAD to be independent predictor of OSA; especially in those presenting with a stable angina presentation. This suggests that coronary vasomotor disorders may be associated with OSA, although further detailed studies are required.

The Utility of Circulating and Imaging Biomarkers Alone and in Combination in Heart Failure.

Clinical trials in the treatment of heart failure have relied on the use of a composite of hard clinical endpoints to evaluate the efficacy of the treatment arm. This has led to prolonged trials requiring large patient cohorts and extensive funding to reach statistical significance. In this paper, we have explored the potential of currently available circulating and imaging biomarkers associated with heart failure as a surrogate for hard clinical end points in clinical trials. This would be expected to result in shorter trials, smaller patient cohorts and limited funding required. We have subsequently theorized on combining circulating and imaging biomarkers as a surrogate for clinical end points such as hospitalization from heart failure and cardiac mortality.

The N-AcetylCysteine and RAMipril in Takotsubo Syndrome Trial (NACRAM): Rationale and design of a randomised controlled trial of sequential N-Acetylcysteine and ramipril for the management of Takotsubo Syndrome.

BACKGROUND: Takotsubo Syndrome(TTS), contrary to historical reports, is now increasingly recognised to be associated with substantial mortality and morbidity, both in the short- and long-term. Although TTS is often precipitated by a catecholamine "pulse", in-hospital hypotension is a common occurrence, increasing the risk of mortality. Furthermore, despite the transient catecholamine stimulus, there is increasing evidence that there are significant long term sequelae, including persistently impaired left ventricular(LV) systolic dysfunction, myocardial oedema with fibrosis, as well as persistent impairment of quality of life. A definitive therapeutic option to limit the extent of initial myocardial injury, and to accelerate recovery in TTS is therefore justified. However to date, there has been a lack of prospective studies in this area. DESIGN AND RATIONALE: NACRAM is a multi-centre, randomised, placebo-controlled trial, sequentially testing early use of intravenous N-acetylcysteine(NAC), followed by/or oral ramipril for 12 weeks. The rationale for utilising these agents is related to their effects on limiting nitrosative stress and expression of the inflammasome activator thioredoxin interacting protein(TXNIP); both processes fundamental to the pathogenesis of TTS. END POINTS: NACRAM is assessing resolution of myocardial oedema on cardiac magnetic resonance imaging(CMR), improvements in LV systolic function as measured by global longitudinal strain(GLS) on echocardiography, quality of life, and inflammatory markers. DISCUSSION: To the best of our knowledge, NACRAM will be the first prospective study to help definitively evaluate a therapeutic option in acute attacks of TTS.

Non-invasive Risk Stratification for Coronary Artery Disease: Is It Time for Subclassifications?

PURPOSE OF REVIEW: Coronary artery disease (CAD) is the leading contributor to cardiovascular disease; it is the most prevalent non-communicable disease globally and has high morbidity, mortality and health care cost. Risk stratification is defined as prevention or containment of disease prior to it occurring or progressing, and non-invasive surrogates include history, examination, biomarkers and non-invasive imaging. This review aims to highlight advancement in current diagnostic strategies and explores gaps for CAD secondary to atherosclerosis and non-obstructive vascular diseases. RECENT FINDINGS: Cardiac risk scores have largely proven inadequate in risk stratifying heterogeneous patient populations. Greater emphasis should also be provided to posttest risk stratification. Non-invasive imaging with MRI is the most accurate but least cost efficacious presently due to availability and expertise. Echocardiography and nuclear imaging have good accuracy, but radiation limits the latter. Novel echocardiographic technologies may increase its appeal. Cardiac CT angiography is increasingly promising. Non-invasive and minimally invasive imaging has significantly influenced the cost-efficacy trajectory of coronary artery disease diagnosis and management. Recent studies suggest that future guidelines will incorporate more subclassifications from the findings of these novel technologies and for more diverse patient demographics.

Early Use of N-acetylcysteine With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction]).

BACKGROUND: Contemporary ST-segment-elevation myocardial infarction management involves primary percutaneous coronary intervention, with ongoing studies focusing on infarct size reduction using ancillary therapies. N-acetylcysteine (NAC) is an antioxidant with reactive oxygen species scavenging properties that also potentiates the effects of nitroglycerin and thus represents a potentially beneficial ancillary therapy in primary percutaneous coronary intervention. The NACIAM trial (N-acetylcysteine in Acute Myocardial Infarction) examined the effects of NAC on infarct size in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention. METHODS: This randomized, double-blind, placebo-controlled, multicenter study evaluated the effects of intravenous high-dose NAC (29 g over 2 days) with background low-dose nitroglycerin (7.2 mg over 2 days) on early cardiac magnetic resonance imaging-assessed infarct size. Secondary end points included cardiac magnetic resonance-determined myocardial salvage and creatine kinase kinetics. RESULTS: Of 112 randomized patients with ST-segment-elevation myocardial infarction, 75 (37 in NAC group, 38 in placebo group) underwent early cardiac magnetic resonance imaging. Median duration of ischemia pretreatment was 2.4 hours. With background nitroglycerin infusion administered to all patients, those randomized to NAC exhibited an absolute 5.5% reduction in cardiac magnetic resonance-assessed infarct size relative to placebo (median, 11.0%; [interquartile range 4.1, 16.3] versus 16.5%; [interquartile range 10.7, 24.2]; P=0.02). Myocardial salvage was approximately doubled in the NAC group (60%; interquartile range, 37-79) compared with placebo (27%; interquartile range, 14-42; P<0.01) and median creatine kinase areas under the curve were 22 000 and 38 000 IU·h in the NAC and placebo groups, respectively (P=0.08). CONCLUSIONS: High-dose intravenous NAC administered with low-dose intravenous nitroglycerin is associated with reduced infarct size in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention. A larger study is required to assess the impact of this therapy on clinical cardiac outcomes. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. URL: http://www.anzctr.org.au/. Unique identifier: 12610000280000.

Brain natriuretic peptide: a biomarker for all cardiac disease?

PURPOSE OF REVIEW: To evaluate new development in the utility of brain natriuretic peptide and N-Terminal brain natriuretic peptide (BNP/NT-Pro-BNP) in the management of various cardiovascular diseases. The determination of plasma BNP levels has an established role in the discrimination of pulmonary oedema from other causes of acute dyspnoea, and there is increasing evidence of the utility of BNP/NT-Pro-BNP assay both as a prognostic tool in chronic heart failure and as a means of guiding therapy in heart failure patients aged below 70 years. RECENT FINDINGS: Findings have substantially extended the clinical utility of BNP/NT-Pro-BNP assay. In heart failure with preserved left ventricular ejection fraction, BNP elevation may also facilitate diagnosis, although its precise utility is uncertain.In the acute catecholamine-induced myocardial inflammatory condition of Tako-Tsubo cardiomyopathy (TTC), BNP/NT-Pro-BNP elevations are marked and persist for at least 3 months, despite the absence of pulmonary oedema. In TTC, BNP/NT-Pro-BNP therefore serves as an ancillary diagnostic measure as well as a marker of recovery. Among other conditions in which BNP assay may provide prognostic information are atrial fibrillation (in which the extent of elevation predicts thromboembolic risk) and pulmonary hypertension. SUMMARY: BNP/NT-Pro-BNP assay has widespread utility as an adjunct to cardiovascular disease diagnosis and management.

Slowly resolving global myocardial inflammation/oedema in Tako-Tsubo cardiomyopathy: evidence from T2-weighted cardiac MRI.

OBJECTIVE: Tako-Tsubo cardiomyopathy (TTC) is associated with regional left ventricular dysfunction, independent of the presence of fixed coronary artery disease. Previous studies have used T2-weighted cardiac MRI to demonstrate the presence of periapical oedema. The authors sought to determine the distribution, resolution and correlates of oedema in TTC. PATIENTS: 32 patients with TTC were evaluated at a median of 2 days after presentation, along with 10 age-matched female controls. Extent of oedema was quantified both regionally and globally; scanning was repeated in patients with TTC after 3 months. Correlations were sought between oedema and the extent of hypokinesis, catecholamine release, release of N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and markers of systemic inflammatory activation (high-sensitivity C-reactive protein and platelet response to nitric oxide). RESULTS: In the acute phase of TTC, T2-weighted signal intensity was greater at the apex than at the base (p<0.0001) but was nevertheless significantly elevated at the base (p<0.0001), relative to control values. Over 3 months, T2-weighted signal decreased substantially, but remained abnormally elevated (p<0.02). The regional extent of oedema correlated inversely with radial myocardial strain (except at the apex). There were also direct correlations between global T2-weighted signal and (1) plasma normetanephrine (r=0.39, p=0.04) and (2) peak NT-proBNP (r=0.39, p=0.03), but not with systemic inflammatory markers. CONCLUSIONS: TTC is associated with slowly resolving global myocardial oedema, the acute extent of which correlates with regional contractile disturbance and acute release of both catecholamines and NT-proBNP.

N-terminal pro-brain natriuretic protein levels in takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TTC) is characterized by reversible left ventricular (LV) systolic dysfunction independent of fixed coronary disease or coronary spastic pathogenesis. A number of investigators have documented marked elevation of natriuretic peptide levels at presentation in such patients. We sought to determine the pattern, extent, and determinants of the release of N-terminal pro-B type natriuretic peptide/B type natriuretic peptide (NT-proBNP/BNP) in patients with TTC. We evaluated NT-proBNP/BNP release acutely and during the first 3 months in 56 patients with TTC (96% women, mean age 69 ± 11 years). The peak plasma NT-proBNP levels were compared to the pulmonary capillary wedge pressure and measures of regional and global LV systolic dysfunction (systolic wall stress, wall motion score index, and LV ejection fraction) as potential determinants of NT-proBNP/BNP release. In patients with TTC, the plasma concentrations of NT-proBNP (median 4,382 pg/ml, interquartile range 2,440 to 9,019) and BNP (median 617 pg/ml, interquartile range 426 to 1,026) were substantially elevated and increased significantly during the first 24 hours after the onset of symptoms (p = 0.001), with slow and incomplete resolution during the 3 months thereafter. The peak NT-proBNP levels exhibited no significant correlation with either pulmonary capillary wedge pressure or systolic wall stress. However, the peak NT-proBNP level correlated significantly with the simultaneous plasma normetanephrine concentrations (r = 0.53, p = 0.001) and the extent of impairment of LV systolic function, as measured by the wall motion score index (r = 0.37, p = 0.008) and LV ejection fraction (r = -0.39, p = 0.008). In conclusion, TTC is associated with marked and persistent elevation of NT-proBNP/BNP levels, which correlated with both the extent of catecholamine increase and the severity of LV systolic dysfunction.