Restoring microvascular circulation with diagnostic ultrasound and contrast agent: Rationale and Design of the REDUCE trial.

OBJECTIVES: This study aims to evaluate the efficacy and cost-effectiveness of sonothrombolysis delivered pre and post primary percutaneous coronary intervention (pPCI) on infarct size assessed by cardiac MRI, in patients presenting with STEMI, when compared against sham procedure. BACKGROUND: More than a half of patients with successful pPCI have significant microvascular obstruction and residual infarction. Sonothrombolysis is a therapeutic use of ultrasound with contrast enhancement that may improve microcirculation and infarct size. The benefits and real time physiological effects of sonothrombolysis in a multicentre setting are unclear. METHODS: The REDUCE (Restoring microvascular circulation with diagnostic ultrasound and contrast agent) trial is a prospective, multicentre, patient and outcome blinded, sham-controlled trial. Patients presenting with STEMI will be randomized to one of two treatment arms, to receive either sonothrombolysis treatment or sham echocardiography before and after pPCI. This tailored design is based on preliminary pilot data from our centre, showing that sonothrombolysis can be safely delivered, without prolonging door to balloon time. Our primary endpoint will be infarct size assessed on day 4±2 on Cardiac Magnetic Resonance (CMR). Patients will be followed up for six months post pPCI to assess secondary endpoints. Sample size calculations indicate we will need 150 patients recruited in total. CONCLUSIONS: This multicentre trial will test whether sonothrombolysis delivered pre and post primary PCI can improve patient outcomes and is cost-effective, when compared with sham ultrasound delivered with primary PCI. The results from this trial may provide evidence for the utilization of sonothrombolysis as an adjunct therapy to pPCI to improve cardiovascular outcomes in STEMI. ANZ Clinical Trial Registration number: ACTRN 12620000807954.

Index of Microcirculatory Resistance to predict microvascular obstruction in STEMI: A systematic review and meta-analysis.

BACKGROUND: Microvascular obstruction (MVO) is an independent predictor of adverse cardiac events after ST-elevation myocardial infarction (STEMI). The Index of Microcirculatory Resistance (IMR) may be a useful marker of MVO, which could simplify the care pathway without the need for Cardiac Magnetic Resonance (CMR). We assessed whether the IMR can predict MVO in STEMI patients. METHODS AND RESULTS: We conducted a systematic review and meta-analysis, including articles where invasive IMR was performed post primary percutaneous coronary intervention (PCI) in addition to MVO assessment with cardiac MRI. We searched PubMed, Scopus, Embase, and Cochrane databases from inception until January 2023. Baseline characteristics, coronary physiology and cardiac MRI data were extracted by two independent reviewers. The random-effects model was used to pool the data. Among 15 articles identified, nine articles (n = 728, mean age 61, 81% male) contained IMR data stratified by MVO. Patients with MVO had a mean IMR of 41.2 [95% CI 32.4-50.4], compared to 25.3 [18.3-32.2] for those without. The difference in IMR between those with and without MVO was 15.1 [9.7-20.6]. Meta-regression analyses demonstrated a linear relationship between IMR and TIMI grade (ß = 0.69 [0.13-1.26]), as well as infarct size (ß = 1.18 [0.24-2.11]) or ejection fraction at 6 months (ß = -0.18 [-0.35 to -0.01]). CONCLUSION: In STEMI, patients with MVO had 15-unit higher IMR than those without. IMR also predicts key prognostic endpoints such as infarct size, MVO, and long-term systolic function.

Prophylaxis to Prevent Cardiotoxicity in Patients Receiving Anthracycline for Breast Cancer: A Combined Bayesian and Frequentist Network Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: The benefits in survivorship gained with anthracycline (ANT)-based chemotherapies for breast cancer are unfortunately mitigated for some patients by irreversible cardiotoxicity. Randomised controlled trials (RCTs) have explored multiple cardioprotection options, however, it remains unclear which drug is most effective in preserving left ventricular ejection fraction (LVEF). This study aimed to perform a systematic review and network meta-analysis, using Bayesian and frequentist approaches, of RCTs evaluating cardioprotective agents. METHODS: Two authors searched four databases (CENTRAL, Cochrane Reviews, MEDLINE, SCOPUS), to find RCTs evaluating cardioprotective agents. Trial populations were limited to patients with breast cancer without prior ANT exposure. The primary outcome was mean LVEF change pre and post ANT dosing. Our primary analysis utilised a Bayesian approach, while our sensitivity analysis used frequentist methodology (Prospero registration number CRD42020199580). RESULTS: From 4,007 search results, we identified 12 RCTs, with their various trial arms considered separately-nine beta-blocker (BB), two angiotensin-converting enzyme inhibitor /angiotensin receptor blockers [(AA)+BB=AABB], one AA, one spironolactone, one statin-evaluating 1,126 patients (age 50.5 years). Bayesian network meta-analysis showed no difference in LVEF preservation between AA (1.3%, 95% credible interval [-0.20, 2.9]), BB (0.77, [-0.21, 1.8]), AABB (0.84 [-1.1, 2.8]), spironolactone (0.72, [-2.3, 3.7]) or statin (0.60, [-2.4, 3.6]) when compared against placebo. However, the frequentist analysis showed benefits from using AA (mean difference, 1.32% [0.32, 2.33]) and BB (mean difference, 0.76% [0.12, 1.4]). CONCLUSIONS: There is insufficient evidence to support prophylactic cardioprotection to prevent EF reduction. However, frequentist analysis suggested that AA or BBs provide cardioprotection. Thus, for those already on other anti-hypertensives, switching to AA or BBs could be considered.

Integrating Cardio-Oncology Across the Research Pipeline, Policy, and Practice in Australia-An Australian Cardiovascular Alliance Perspective.

Over 18 million people worldwide were diagnosed with cancer in 2020, including over 150,000 people in Australia. Although improved early detection and treatment have increased the survival rates, cardiotoxic treatment and inadequate management of cardiovascular risk factors have resulted in cardiovascular disease (CVD) being one of the leading causes of non-cancer-related death and disability among cancer survivors. International guidelines outline the standards of care for CVD risk surveillance and management. However, Australian cardio-oncology policies and clinical guidelines are limited. There is increasing growth of cardio-oncology research in Australia and support from leading Australian professional bodies and advocacy and research networks, including the Cardiac Society of Australia and New Zealand, the Clinical Oncology Society of Australia, the National Heart Foundation of Australia, and the Australian Cardiovascular Alliance (ACvA). Thus, opportunities to drive multidisciplinary cardio-oncology initiatives are growing, including grant funding, position statements, and novel research to inform new policies. The ACvA has a unique flagship structure that spans the translational research pipeline from drug discovery to implementation science. This article aims to highlight how multidisciplinary cardio-oncology innovations could intersect with the seven ACvA flagships, and to showcase Australian achievements in cardio-oncology thus far. We summarise eight key priority areas for future cardio-oncology research that emerged. These strategies will strengthen cardio-oncology research and care in Australia, and drive new guidelines, policies, and government initiatives to ensure equity in health outcomes for all cardio-oncology patients.

Health Economic Analysis of CMR: A Systematic Review.

INTRODUCTION: Uptake of cardiac magnetic resonance (CMR) in Australia has been limited by issues of cost and access. There is a need to inform future application of CMR by evaluating pertinent health economic literature. We sought to perform a systematic review on the health economic data as it pertains to CMR. METHODS: Eight databases (biomedical/health economic) were searched for relevant articles highlighting economic evaluations of CMR. Following screening, studies that reported health economic outcomes (e.g., dollars saved, quality adjusted life years [QALY] and cost effectiveness ratios) were included. Data on cost effectiveness, clinical/disease characteristics, type of modelling were extracted and summarised. RESULTS: Thirty-eight (38) articles informed the systematic review. Health economic models used to determine cost effectiveness included both trial-based studies (n=14) and Markov modelling (n=24). Comparative strategies ranged from nuclear imaging, stress echocardiography and invasive angiography. The disease states examined included coronary artery disease (23/38), acute coronary syndrome (3/38), heart failure (5/38) and miscellaneous (7/38). The majority of studies (n=29/38) demonstrated CMR as a strategy which is either economically dominant, cost-effective or cost-saving. CONCLUSION: This systematic review demonstrates that CMR is cost-effective depending on diagnostic strategy, population and disease state. The lack of standardised protocols for application of CMR, economic models used and outcomes reported limits the ability to meta-analyse the available health economic data.

Cardiac Autonomic Impacts of Bushfire Smoke-A Prospective Panel Study.

BACKGROUND: Air pollution is associated with cardiovascular disease and mortality. Most studies have focussed on urban or traffic-related pollution, and less is known about the impacts from bushfire smoke on cardiovascular autonomic function, although it is associated with increased sudden cardiac death and mortality. We sought to investigate its instantaneous and short-term impacts on heart rate variability (HRV). METHODS: Twenty-four (24)-hour Holter electrocardiography (ECG) was repeated twice (during bushfire [Phase 1] and then clean air [Phase 2]) in 32 participants from two Australian towns (Warburton and Traralgon, Victoria) surrounding planned burning areas. This was compared with 10 control participants in another town (Maffra, Victoria) with two clean air assessments during the same periods. The primary HRV parameters assessed were those assessing overall HRV (Standard Deviation of Normal-to-Normal intervals [SDNN]), long-term HRV (Standard Deviation of the Average of Normal Sinus-to-Normal Sinus intervals for each 5-minutes [SDANN]), low frequency [LF]) and short-term HRV (Root Mean Square of Successive Differences between N-N intervals [RMSSD], High Frequency [HF], LF:HF ratio). Average concentrations of particulate matter <2.5 µm in diameter (PM2.5) were measured at fixed site monitors in each location. RESULTS: Mean PM2.5 levels were significantly elevated during bushfire exposure in Warburton (96.5±57.7 µg/m3 vs 4.0±1.9 µg/m3, p<0.001) and Traralgon (12.6±4.9 µg/m3 vs 3.4±3.1 µg/m3, p<0.001), while it remained low in the control town, Maffra, in each phase (4.3±3.2 µg/m3 and 3.9±3.6 µg/m3, p=0.70). Although SDANN remained stable in controls, the exposed cohort showed significant worsening in SDANN during bushfire smoke exposure by 9.6±25.7ms (p=0.039). In univariable analysis, smoke exposure was significantly associated with higher ΔSDNN and ΔSDANN (p=0.03, p=0.01 exposed vs control). The association remained significant in ΔSDANN after adjusting for age, sex and cigarette smoking (p=0.02) and of borderline significance in ΔSDNN (p=0.06). CONCLUSIONS: Exposure to the bushfire smoke was independently associated with reduced overall and long-term HRV. Our findings suggest that imbalance in cardiac autonomic function is a key mechanism of adverse cardiovascular effects of bushfire smoke.

Potential Biological Mediators of Myocardial and Vascular Complications of Air Pollution-A State-of-the-Art Review.

Ambient air pollution is recognised globally as a significant contributor to the burden of cardiovascular diseases. The evidence from both human and animal studies supporting the cardiovascular impact of exposure to air pollution has grown substantially, implicating numerous pathophysiological pathways and related signalling mediators. In this review, we summarise the list of activated mediators for each pathway that lead to myocardial and vascular injury in response to air pollutants. We performed a systematic search of multiple databases, including articles between 1990 and Jan 2022, summarising the evidence for activated pathways in response to each significant air pollutant. Particulate matter <2.5 µm (PM2.5) was the most studied pollutant, followed by particulate matter between 2.5 µm-10 µm (PM10), nitrogen dioxide (NO2) and ozone (O3). Key pathogenic pathways that emerged included activation of systemic and local inflammation, oxidative stress, endothelial dysfunction, and autonomic dysfunction. We looked at how potential mediators of each of these pathways were linked to both cardiovascular disease and air pollution and included the overlapping mediators. This review illustrates the complex relationship between air pollution and cardiovascular diseases, and discusses challenges in moving beyond associations, towards understanding causal contributions of specific pathways and markers that may inform us regarding an individual's exposure, response, and likely risk.

Short-Term Exposure to Sulfur Dioxide and Nitrogen Monoxide and Risk of Out-of-Hospital Cardiac Arrest.

BACKGROUND & AIMS: Over the past decades, particulate matter (PM), especially fine PM <2.5 µm in aerodynamic diameter (PM2.5) has been a major research focus. However, the air pollutant is a mixture of gases or vapour-phase compounds, such as carbon monoxide (C), nitrogen oxides (NOx), photochemical oxidants (Ox), and sulfur dioxide (SO2). Little is known about their cardiovascular effect, individually or in combination with PM. Thus, we aimed to determine the associations between the incidence of acute cardiac events and both gaseous and PM using a case-crossover design. METHODS: Cardiovascular cases were identified through the Gunma Prefectural Ambulance Activity Database in Japan in 2015 (1,512 out-of-hospital cardiac arrest [OHCA] and 1,002 heart failures from 53,006 ambulance cases). Air quality data from the nearest station was for day of the arrest (lag0) and 1-2 days before the arrest (lag1, lag2) and the moving average across days 0-1 (lag0-1). Conditional logistic regression was used for unadjusted and adjusted analysis for temperature and humidity. RESULTS: Independent associations of OHCA were daily concentrations of SO2 at lag1 (OR 1.173, 95%CI 1.004, 1.370; p=0.044) and lag0-1 (OR 1.203, 95%CI 1.015, 1.425; p=0.033); and daily NO concentrations at lag2 (OR 1.039, 95%CI 1.007, 1.072; p=0.016). The incidence of heart failure was significantly associated with daily concentrations of Ox on the day of the event in univariable model but not after adjustment for temperature and humidity. No associations were found for other pollutants. CONCLUSIONS: Short-term exposure to SO2 and NO are associated with an increased risk of OHCA.

A Systematic Review of Frailty Scores Used in Heart Failure Patients.

BACKGROUND: Frailty is a complex, multi-dimensional syndrome commonly observed in patients with heart failure (HF). The presence of frailty in patients living with HF is strongly associated with increased vulnerability to adverse events, including falls, hospitalisation, and increased mortality. Several scoring systems have been developed to assess the presence of frailty in patients with HF. These scoring systems vary in their complexity and applicability; however, they provide the physician with a more comprehensive understanding of the biological, functional, and psychosocial needs of these patients. OBJECTIVES: To assess the clinical applicability of frailty tools in HF patients and their prognostic value, specifically relating to outcomes such as mortality, readmissions, and clinical deterioration. METHODS: A literature search using six electronic databases (PubMed, Scopus, Embase, MEDLINE, Cochrane and Web of Science) was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Key search Medical Subject Headings (MeSH) terms combined "Frailty" AND "Heart failure". Studies were included if they assessed frailty using systematically defined criteria in a HF population. The PRISMA guidelines were used to include all relevant articles based on titles and abstracts. Full text articles were screened based on abstract relevance. A systematic narrative review of the literature was conducted on the final list of full text articles. RESULTS: An initial search yielded 8,066 articles. Following the removal of duplicates, title, and abstract searches, the remaining 154 articles underwent full text review, with 31 articles accepted for final qualitative synthesis. The two most utilised frailty scores were the Fried Frailty Phenotype (n=10) and the Barthel Index (n=8). The frailty scores provide prognostic data on multiple outcomes including mortality, increased hospitalisation, and functional decline. CONCLUSION: At the present time there is no universally applied frailty measure in a HF population. Choice of frailty score should be guided by physician experience and clinical setting, as well as tailored to a patient's functional, biological, and psychosocial circumstances. A push to adopt a single universal scoring system may help to ensure that frailty is assessed in all patients who live with HF.

Rationale and Design of the Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT): A Pilot Study.

BACKGROUND: Cancer therapeutics-related cardiac dysfunction (CTRCD) is a well-recognised complication of cancer treatment. Treatment of CTRCD involves cardioprotective therapy (CPT) which can lead to a recovery of CTRCD with normalisation of the left ventricular ejection fraction (LVEF). As a result, there are potentially millions of cancer survivors with recovered CTRCD on CPT. Cardioprotective therapy can be associated with an undesirable long-term pill burden, financial costs, and side effects. Cancer survivorship is anticipated to increase significantly by the end of this decade. To date, there is no evidence of the safety of stopping CPT in this setting. This study seeks to evaluate the hypothesis that ceasing cardioprotective medication is a feasible and safe option without significant impact on LVEF in low-risk patients who have recovered from CTRCD. METHODS AND ANALYSIS: We will perform a multicentre prospective open-label randomised controlled trial with blinded endpoint (PROBE) of supervised CPT cessation compared to continuing CPT (control). The primary study end point is the change in LVEF by cardiac magnetic resonance imaging at 6 months of enrolment between the two groups. Secondary end points include changes in quality-of-life questionnaires, other cardiac imaging parameters, and recurrence of heart failure. CONCLUSION: Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT) is one of the first studies currently underway to evaluate the safety of ceasing CPT in recovered CTRCD. The results will inform clinical practice in this evidence-free zone.

Role of Myocardial Strain Imaging in Cancer Therapy-Related Cardiac Dysfunction.

PURPOSE OF REVIEW: This review aims to provide a contemporary perspective on the role of myocardial strain imaging in the management of patients on cardiotoxic therapy. RECENT FINDINGS: Risk/benefit evaluation of cardiotoxic cancer treatment remains challenging, weighing life-saving cancer therapy with fatal cardiac dysfunction potentially caused by cancer therapy. The serial change in left ventricular ejection fraction (LVEF) was conventionally used for the detection of cancer therapy-related cardiac dysfunction (CTRCD). Peak systolic global longitudinal strain (GLS) by speckle-tracking echocardiography has turned into a vital pre- and post-chemotherapy assessment for the early detection of cardiotoxicity. Complexity in cardiotoxic therapy regimen, different definition of CTRCD by LVEF, variations in GLS values, timings, and variable cutoffs make it challenging to standardize the protocol for the detection of CTRCD. GLS > 15% relative reduction from baseline has been widely used. Evidence suggests that GLS could predict early subclinical LV dysfunction, and initiation of cardioprotective therapy led to less decline of LV function. Most of the studies used an echocardiographic endpoint, and the impact of GLS on the long-term clinical outcome is not established. GLS has emerged as a reliable measure to identify early subclinical LV dysfunction by detecting myocardial deformation in patients on cardiotoxic chemotherapy. To date, a significant decline in GLS suggests the initiation of cardioprotective therapy with close monitoring. Interruption of prognostically important cardiotoxic chemotherapies requires a multidisciplinary team approach guided mainly by LVEF and other clinical factors. Further randomized control trials with hard clinical endpoints and longer follow-ups may help to determine the role of GLS in CTRCD.

The Effect of Obesity on Echocardiographic Image Quality.

BACKGROUND: Increased body mass index (BMI) may reduce transthoracic echocardiogram (TTE) image quality, resulting in increased requirements for ultrasound enhancing agents (UEA), as recommended by the American Society of Echocardiography (ASE), and a greater incidence of non-diagnostic studies. METHODS: Over a 5-month period 1,108 TTEs were analysed as to (1) whether they could answer the clinical question posed by the ordering physician (i.e. were diagnostic vs non diagnostic), and (2) whether they required UEAs according to the ASE guidelines. Patient characteristics were gathered from the medical record. RESULTS: 12.9% of TTEs were non-diagnostic (21.0% of TTEs in the obese population [BMI≥30 kg/m2] vs 7.8% in the non-obese [p<0.001]). Predictors of a non-diagnostic study were BMI (OR 1.09, [95% CI 1.06-1.11], p<0.0001), male gender (OR 1.54, [1.06-2.25], p=0.02), and inpatient status (OR 1.75, [1.20-2.55], p=0.004). Obesity (BMI≥30) was strongly associated with non-diagnostic studies (OR 3.22, [2.23-4.51], p<0.001). Factors associated with increased requirement of UEAs were BMI (OR 1.10, [1.08-1.12], p<0.0001), age (OR 1.02, [1.01-1.03], p<0.0001) and inpatient status (OR 1.7, [1.29-2.24], p<0.05). Obesity (BMI>30) was strongly associated with contrast requirement (OR 3.16, [2.43-4.10], p<0.0001). CONCLUSIONS: Body mass index, male gender and inpatient status were associated with an increased incidence of non-diagnostic studies. Body mass index, age and inpatient status were associated with an increased requirement for UEAs.

Associations between respiratory and vascular function in early childhood.

BACKGROUND AND OBJECTIVE: The link between respiratory and vascular health is well documented in adult populations. Impaired lung function is consistently associated with thicker arteries and higher incidence of cardiovascular disease. However, there are limited data on this relationship in young children and the studies that exist have focussed on populations at high risk of cardiorespiratory morbidity. We determined if an association exists between respiratory and cardiovascular function in young children and, if so, whether it is confounded by known cardiorespiratory risk factors. METHODS: Respiratory and vascular data from a prospective cohort study established to evaluate the health implications 3 years after coal mine fire smoke exposure in children aged 3-5 years were used. Respiratory function was measured using the forced oscillation technique and included resistance at 5 Hz (R5 ), reactance at 5 Hz (X5 ) and area under the reactance curve (AX). Vascular health was measured by carotid intima-media thickness (ultrasound) and pulse wave velocity (arterial tonometry). Regression analyses were used to examine the relationship between the respiratory Z-scores and cardiovascular measures. Subsequent analyses were adjusted for potential confounding by maternal smoking during pregnancy, maternal education and exposure to fine particulate matter <2.5 µm in aerodynamic diameter (PM2.5 ). RESULTS: Peripheral lung function (X5 and AX), but not respiratory system resistance (R5 ), was associated with vascular function. Adjustment for maternal smoking, maternal education and early life exposure to PM2.5 had minimal effect on these associations. CONCLUSION: These observations suggest that peripheral lung stiffness is associated with vascular stiffness and that this relationship is established early in life.

Two-Dimensional Strain is more Precise than Conventional Measures of Left Ventricular Systolic Function in Pediatric Patients.

Ejection fraction (EF) and fractional shortening (FS) are standard methods of quantifying left ventricular (LV) systolic function. 2D global longitudinal strain (2D GLS) is a well-established, but underutilized method for LV function quantification. The aim of this study was to assess precision of GLS compared to EF & FS in pediatrics. Echocardiograms were prospectively analyzed by 2 blinded observers. FS, EF, and GLS were calculated following standard methods. Bland-Altman was applied to assess agreement. Intraclass correlation coefficient (ICC) was used to measure reliability. Coefficient of variation was used to demonstrate relative variability between methods. 103 pediatric echos were evaluated for inter-observer reproducibility, and 15 patients for intra-observer reproducibility. GLS had higher inter-observer agreement and reliability (bias 7%, 95% LOA - 3.4 to + 3.5, ICC 0.86 CI 0.80-0.90) compared to EF (bias 27%, 95% LOA - 18.9 to + 19.5; ICC 0.25 CI 0.07-0.43) and FS (bias 12%, 95% LOA - 11.9 to + 12.2; ICC 0.53 CI 0.38-0.66). GLS also had higher intra-observer agreement (bias 4%, 95% LOA - 3.6 to + 3.7; ICC 0.87 CI 0.66-0.96) compared to EF (bias 11%, 95% LOA - 14.9 to + 15.1; ICC 0.26 CI - 0.28-0.67) and FS (bias 12%, 95% LOA - 12.2 to + 12.5; ICC 0.38 CI - 0.15-0.74). GLS is a more precise method for quantifying LV function in pediatrics, with lower variability compared to EF and FS. GLS provides a more reliable evaluation of LV systolic function and should be utilized more widely in pediatrics.

Patient Risk Factors for Bioprosthetic Aortic Valve Degeneration: A Systematic Review and Meta-Analysis.

The choice of valve type for aortic valve replacement surgery is sometimes challenging. The main risk for bioprostheses is structural valve degeneration (SVD); however, little is known about what the most important risk factors are. We conducted a systematic review and meta-analysis to identify the risk factors and estimate their pooled effect sizes to aid the prosthesis choice for replacement. We followed PRISMA guidelines and systematically searched three electronic databases (PubMed, Scopus, and Web of Science) using appropriate key terms: 'aortic valve', 'bioprosthesis', 'degeneration', 'durability', 'prosthesis failure', etc. Hazard ratio (HR) and odds ratio (OR) and associated 95% confidence intervals (CI) were extracted. Pooled risk estimates were calculated using a random-effects model. Twenty-nine (29) observational studies were included with a total of 25,490 patients, 981 of whom developed SVD over a mean follow-up time of 18.5 years. Four (4) factors influencing bioprosthetic SVD were identified: increasing age was a protective factor (per 1-yr increase, HR: 0.91 [95% CI 0.89, 0.94], p<0.0001), whereas increased body surface area (HR 1.77 [1.04, 3.01], p=0.034), patient-prosthesis mismatch (HR 1.95 [1.56, 2.43], p<0.001), and smoking (HR 2.28 [1.37, 3.79], p=0.0015) were risk factors for SVD. We found younger age, patient-prosthesis mismatch, body surface area, and smoking, as risk factors for aortic SVD, which should be considered for valve selection. This study generates a further hypothesis that accelerated flow across the valve is a shared key component in the pathophysiology of SVD, thus future research should consider other high cardiac output states.

Influence of Risk on Reduction of Readmission and Death by Disease Management Programs in Heart Failure.

OBJECTIVE: Disease management programs (DMPs) may reduce short-term readmission or death after heart failure (HF) hospitalization. We sought to determine if targeting of DMP to the highest-risk patients could improve efficiency. METHODS AND RESULTS: Patients (n = 412) admitted with HF were randomized to usual care or an intensive DMP including optimizing intravascular volume status at discharge, increased self-care education, exercise guidance, closer home surveillance, and increased intensity of HF nurse follow-up. Both treatment groups were similar in demographics, medication use, Charlson comorbidity index, ejection fraction, and left ventricular and atrial volumes. Readmission or death occurred in 74/197 (37%) usual care and 50/215 (23%) DMP patients within 30 days (relative risk [RR] 0.62, 95% confidence interval [CI] 0.46-0.84), and 113/197 (57%) usual care and 78/215 (36%) DMP patients within 90 days, (RR 0.63, 9%% CI 0.51-0.78). The predicted risk of death and readmission (estimated from our previously developed risk score) was similar between treatment groups (mean predicted risk 38.6 ± 22.2% vs 39.4 ± 21.9%; P = .73) and similar across categories of predicted risk between the treatment groups. For 30-day readmission or death, patients from the 2 highest risk quintiles showed a benefit from intervention, and there was an interaction between intervention and predicted risk (P = .02). For 90-day readmission or death, most patients-other than those in the lowest-risk quintile-benefited from the intervention. CONCLUSIONS: Use of a risk score may permit targeting of DMP to reduce HF admission. Intensive DMP may reduce short-term readmission or death, particularly in high-risk patients.

Feasibility and Normal Ranges of Arterial Intima-Media Thickness and Stiffness in 2-Year-Old Children: A Pilot Study.

INTRODUCTION: In adults, noninvasive assessments of vascular function have been established. However, little is known about the applicability and reference values of these techniques among children < 6 years old and none ≤ 2. We aimed to determine the feasibility of conducting noninvasive vascular assessments in 2-year-old children and the normal range of results in this age group. METHODS: Carotid intima-media thickness (cIMT) and abdominal aorta IMT (aaIMT), pulse wave velocity (PWV), arterial diameter change, stiffness index (ß), and distensibility were assessed in 2-year-old children. IMT was assessed using an automatic contour detection. RESULTS: The proportion of successful measurements was 72% (42/58) with cIMT 64%, aaIMT 67%, and PWV 43%. Average far wall cIMT was 0.51 mm and 0.40 for aaIMT. Mean PWV was 4.15 m/s, with relatively wider range in stiffness index and distensibility. Common carotid arteries had a higher mean distensibility of 4.58%/10 mmHg compared with 2.98%/10 mmHg for the abdominal aorta. The number of data points automatically detected at far wall cIMT was higher than that in aaIMT (left cIMT: 244 ± 13 and right: 240 ± 23 vs. abdominal 185 ± 63, p < 0.001). Better and more consistent quality was achieved for cIMT than aaIMT measurements. PWV measurement was only feasible in cooperative children with efficient distractions. CONCLUSIONS: Noninvasive methods for early detection of cardiovascular risks were feasible in at least two-thirds of 2-year-old children. Given the greater feasibility and image quality, cIMT is a preferable option for assessing vascular health in young children.

Echocardiography and Cardio-Oncology.

Owing to the ongoing increase in cancer survivors because of the remarkable and continuous progress in cancer management, a paradigm shift is occurring from cancer as a 'terminal illness' to a 'chronic condition' with cardiovascular risks. This also affects cardiology practice with increased cardiovascular morbidity and mortality rates among patients with cancer due to direct and/or indirect side effects of anticancer treatment. Thus, cardio-oncology has emerged as a new cardiology subspecialty, which focusses on risk stratification, prevention, diagnosis, treatment, and follow-up of cardiovascular disease related to cancer treatment. This review summarises echocardiographic evaluation of cardiac dysfunction and heart failure as they are the most concerning cardiovascular complications of cancer therapy and worsen its morbidity and mortality. This review covers cardiac function assessment and proposed cut-off values before/during/after cancer chemotherapy. The goal of this review is to aid clinicians to manage the patients with cancer sufficiently by connecting the existing knowledge in clinical cardiology with novel information from current advances in cardio-oncology.

Accuracy of blinded clinician interpretation of single-lead smartphone electrocardiograms and a proposed clinical workflow.

Despite the appeal of smartphone-based electrocardiograms (ECGs) for arrhythmia screening, a paucity of data exists on the accuracy of primary care physicians' and cardiologists' interpretation of tracings compared with the device's automated diagnosis. Using 408 ECGs in 51 patients, we demonstrate a variable accuracy in clinician interpretation of smartphone-based ECGs, with only cardiologists demonstrating satisfactory agreement when referenced against a 12-lead ECG. Combining the device automated diagnostic algorithm with cardiologist interpretation of only uninterpretable traces yielded excellent results and provides an efficient, cost-effective workflow for the utilization of a smartphone-based ECG in clinical practice.

Association of depression with evolution of heart failure in patients with type 2 diabetes mellitus.

BACKGROUND: Depression is a prevalent, independent predictor of mortality in patients with heart failure (HF). Depression is also common in type 2 diabetes mellitus (T2DM), which is itself an important risk factor for HF. However, association of depression with incident HF in T2DM is undefined. The aim of the present study was to evaluate the predictive value of depression in predicting incident HF in a community-based cohort of asymptomatic patients with T2DM. METHODS: We prospectively recruited 274 asymptomatic T2DM patients ≥ 65 years (age 71 ± 4 year, 56% men) with preserved EF and no ischemic heart disease from a community-based population. The Patient Health Questionnaire 9 (PHQ-9) was used to detect depression, and LV dysfunction was sought with a comprehensive echocardiogram, including LV hypertrophy (LVH) and subclinical diastolic function (E/e'). Over a median follow-up of 1.5 years (range 0.5-3), 20 patients were lost to follow-up and 254 individuals were followed for outcomes. RESULTS: At baseline, depression was present in 9.5%, LVH was identified in 26% and reduced E/e' in 11%. Over a median follow-up of 1.5 years, 37 of 245 patients developed new-onset HF and 3 died, giving an event rate of 107/1000 person-years. In a competing-risks regression analysis, depression (adjusted HR 2.54, 95% CI 1.18-5.46; p = 0.017) was associated with incident HF and had incremental predictive power to clinical, biochemical and echocardiographic variables. CONCLUSION: Depression is prevalent in asymptomatic elderly patients with T2DM, and depression independently and incrementally predicts incident HF.