Early outcomes following integration of computed tomography (CT) coronary angiography service in an established cardiology practice in disease management.

BACKGROUND: Computed tomography coronary angiography (CTCA) is an established modality for the diagnosis and assessment of cardiovascular disease. However, price and space pressure have mostly necessitated outsourcing CTCA to external radiology providers. Advara HeartCare has recently integrated CT services within local clinical networks across Australia. This study examined the benefits of the presence (integrated) or absence (pre-integrated) of this "in-house" CTCA service in real-world clinical practice. METHODS: De-identified patient data from electronic medical records were used to create an Advara HeartCare CTCA database. Data analysis included clinical history, demographics, CTCA procedure, and 30-day outcomes post-CTCA from two age-matched cohorts: integrated (n â€‹= â€‹495) and pre-integrated (n â€‹= â€‹456). RESULTS: Data capture was more comprehensive and standardised across the integrated cohort. There was a 21% increase in referrals for CTCA from cardiologists observed for the integration cohort vs. pre-integration [n â€‹= â€‹332 (72.8%) pre-integration vs. n â€‹= â€‹465 (93.9%) post-integration, p â€‹< â€‹0.0001] with a parallel increase in diagnostic assessments including blood tests [n â€‹= â€‹209 (45.8%) vs. n â€‹= â€‹387 (78.1%), respectively, p â€‹< â€‹0.0001]. The integrated cohort received lower total dose length product [Median 212 (interquartile range 136-418) mGy∗cm vs. 244 (141.5, 339.3) mGy∗cm, p â€‹= â€‹0.004] during the CTCA procedure. 30-days after CTCA scan, there was a significantly higher use of lipid-lowering therapies in the integrated cohort [n â€‹= â€‹133 (50.5%) vs. n â€‹= â€‹179 (60.6%), p â€‹= â€‹0.04], along with a significant decrease in the number of stress echocardiograms performed [n â€‹= â€‹14 (10.6%) vs. n â€‹= â€‹5 (11.6%), p â€‹= â€‹0.01]. CONCLUSION: Integrated CTCA has salient benefits in patient management, including increased pathology tests, statin usage, and decreased post-CTCA stress echocardiography utilisation. Our ongoing work will examine the effect of integration on cardiovascular outcomes.

Comorbidities and Symptom Status in Moderate and Severe Aortic Stenosis: A Multicenter Clinical Cohort Study.

Background: Symptoms associated with severe aortic stenosis (AS) are used to guide management. Objectives: The purpose of this study was to examine the pattern of symptoms, comorbidities, and cardiac damage in moderate and severe AS. Methods: A total of 846,198 echocardiographic investigations from 330,940 individuals aged >18 years were selected for the most recent echocardiogram, moderate or severe AS (mean gradient 20.0-39.9 mm Hg, aortic valve peak gradient 3.0-3.9 m/s and aortic valve area >1.0 cm2; or ≥ 40.0 mm Hg, ≥4.0 m/s or ≤1.0 cm2, respectively), and a cardiologist consultation. Natural Language Processing was applied to letters to extract comorbidities, dyspnea, chest pain, and syncope. Patients with prior aortic valve replacement were excluded. Results: 2,213 patients (0.7% overall, 32.8% females) had moderate and 3,416 (1.0%, 47.3% females) had severe AS. Comorbidities were common, including hypertension, (56.6% moderate AS, 53.1% severe AS, P = 0.01), coronary disease (46.0% and 46.8%, respectively, P = 0.58) and atrial fibrillation (29.6% and 34.8%, respectively, P < 0.001). Symptoms were also common in both moderate (n = 915, 41.3%) and severe (n = 1,630, 47.7%) AS (P < 0.001). Comorbidities were more likely in symptomatic vs asymptomatic patients (P < 0.001). Dyspnea was more likely in severe AS, whereas angina and syncope were similar in moderate vs severe AS. In multivariable analysis, only dyspnea was associated with severe (vs moderate) AS (OR: 1.73, 95% CI: 1.41-2.13, P < 0.001). In both adjusted and unadjusted models, the degree of cardiac damage did not relate to presence of any symptoms but was associated with AS severity. Conclusions: Dyspnea is common in both moderate and severe AS, is associated with comorbidities and is not related to the degree of cardiac damage. Symptom-guided management decisions in AS may need revision.

Genesis of improved quality in imaging through a national Australian echocardiography registry.

BACKGROUND: Despite rapid technological advances and growth, quality in imaging has not received the focus seen elsewhere in cardiovascular medicine, resulting in significant gaps between guidelines and practice. Contemporary echocardiography practice requires comprehensive real-time data collection to allow dynamic auditing and benchmarking of key performance indices. The American College of Cardiology (ACC) proposed additional data standardisation, structured reporting identifying key data elements and imaging registries. In the absence of an Australian echocardiography registry, we developed a national clinical quality registry (GenesisCare Cardiovascular Outcomes Echo Registry). We hypothesised that measurement and local reporting of data would improve compliance of echo studies with quality guidelines and hence their clinical value. METHODS AND RESULTS: We prospectively collected data on 4 099 281 echocardiographic studies entered directly into a central electronic database from 63 laboratories across four Australian states between 2010 and 2021. Real-time auditing of key data elements and introduction of quality improvement pathways were performed to maximise completeness and uniformity of data acquisition and reporting. We compared completeness of key data element acquisition (AV peak velocity, left ventricular ejection fraction, E/e', LA area, rhythm, RVSP) by time and state using de-identified data. Key performance outcomes benchmarked against the aggregated study cohort and international standards were reported to individual sites to drive quality improvement. Between 2010 and 2014 there were significant improvements in data completeness (72.0%+/-26.8% vs 86.8%+/-13.5%, p=0.02), which were maintained to 2020. In addition, interstate variability fell for both EF and E/e' (p<0.002). CONCLUSIONS: This large-scale collaboration provides a platform for the development of major quality improvement initiatives in echocardiography. Introduction of local quality assurance programmes via a unified national data set significantly improved the completeness of reporting of key echo quality measures. This in turn significantly improved the quality of, and reduced the interstate variability of, echo data. Developing a centralised database allowed rapid adoption nationally of local quality improvements.

CardiSort: a convolutional neural network for cross vendor automated sorting of cardiac MR images.

OBJECTIVES: To develop an image-based automatic deep learning method to classify cardiac MR images by sequence type and imaging plane for improved clinical post-processing efficiency. METHODS: Multivendor cardiac MRI studies were retrospectively collected from 4 centres and 3 vendors. A two-head convolutional neural network ('CardiSort') was trained to classify 35 sequences by imaging sequence (n = 17) and plane (n = 10). Single vendor training (SVT) on single-centre images (n = 234 patients) and multivendor training (MVT) with multicentre images (n = 434 patients, 3 centres) were performed. Model accuracy and F1 scores on a hold-out test set were calculated, with ground truth labels by an expert radiologist. External validation of MVT (MVTexternal) was performed on data from 3 previously unseen magnet systems from 2 vendors (n = 80 patients). RESULTS: Model sequence/plane/overall accuracy and F1-scores were 85.2%/93.2%/81.8% and 0.82 for SVT and 96.1%/97.9%/94.3% and 0.94 MVT on the hold-out test set. MVTexternal yielded sequence/plane/combined accuracy and F1-scores of 92.7%/93.0%/86.6% and 0.86. There was high accuracy for common sequences and conventional cardiac planes. Poor accuracy was observed for underrepresented classes and sequences where there was greater variability in acquisition parameters across centres, such as perfusion imaging. CONCLUSIONS: A deep learning network was developed on multivendor data to classify MRI studies into component sequences and planes, with external validation. With refinement, it has potential to improve workflow by enabling automated sequence selection, an important first step in completely automated post-processing pipelines. KEY POINTS: • Deep learning can be applied for consistent and efficient classification of cardiac MR image types. • A multicentre, multivendor study using a deep learning algorithm (CardiSort) showed high classification accuracy on a hold-out test set with good generalisation to images from previously unseen magnet systems. • CardiSort has potential to improve clinical workflows, as a vital first step in developing fully automated post-processing pipelines.

Factor Xa Inhibition for the Treatment of Venous Thromboembolism Associated With Cancer: A Meta-Analysis of the Randomised Controlled Trials.

BACKGROUND: Venous thromboembolism (VTE) is a common cause of morbidity and mortality in cancer patients. Until recently, guidelines recommended the use of low-molecular weight heparin (LMWH) as standard of care for VTE in patients with cancer. Despite the proven efficacy of direct oral anticoagulants (DOACs) for treatment of VTE, there is equipoise supporting their use in cancer patients. METHODS: A systematic review of PubMed, Medline and EMBASE identified four randomised controlled trials (RCTs) in patients with cancer and VTE comparing a factor Xa inhibitor (FXaI) to LMWH. A meta-analysis was performed with a primary outcome of VTE recurrence and key secondary outcomes of major bleeding, clinically relevant non-major bleeding (CRNMB) and gastrointestinal (GI) bleeding. RESULTS: Four RCTs with 2,907 patients were included. 1,451 patients were randomised to FXaI and 1,456 to LMWH. VTE recurrence was lower in the FXaI group (RR 0.62, 95%CI 0.44-0.87; p=0.01; I2=24.90), with an absolute risk difference of -4% equating to a number needed to treat of 25 for prevention of recurrent VTE with FXaI. No significant difference in major bleeding was noted between groups (RR 1.33, 95%CI 0.84-2.11; p=0.23). Rates of GI bleeding (RR 1.87, 95%CI 1.06-3.29; p=0.03) and CRNMB (RR 1.57, 95%CI 1.11-2.23; p=0.01) were greater with FXaIs. CONCLUSION: In patients with cancer and VTE, the rate of VTE recurrence was significantly lower with FXaI than with LMWH without an increased risk of major bleeding. Our data supports the use of FXaIs as the standard of care for the treatment of VTE in this population.

SMARTphone Based Cardiovascular Risk Reduction in BREAST Cancer Patients (SMART-BREAST): A Randomised Controlled Trial Protocol.

INTRODUCTION: Breast cancer survivors are at greater risk for cardiovascular-related mortality compared to women without breast cancer. Accordingly, attention to reducing the risk of cardiovascular disease must be a priority in the long-term management of these patients. With the exponential rise in cancer survivors, there is a need for innovative cardio-oncology programs. This paper describes the study design of a randomised controlled trial assessing the effectiveness of a smartphone-based cardiovascular risk reduction program in improving physical activity and cardiovascular health in patients undergoing treatment for breast cancer. METHODS AND ANALYSIS: The aim of this study is to assess the efficacy and usability of a smartphone-based model of care for exercise promotion, cardiovascular risk reduction and community engagement in women undergoing treatment for breast cancer. This will be achieved by testing our personalised smartphone application "BreastMate", as an adjunct to standard care in a single-blinded, parallel, randomised controlled trial. The primary outcome of the trial is change in exercise capacity, as measured by the 6-minute walk test distance at 12 months compared to baseline. Secondary endpoints include improvements in cardiovascular risk factor status and quality of life, received dose intensity of chemotherapy and major adverse cardiovascular events. ETHICS: Multicentre ethical approval has been granted by the Austin Hospital (HREC/47081/Austin/2018). DISSEMINATION OF RESULTS: The analysed results will be published in a peer reviewed journal on completion of the clinical trial. REGISTRATION DETAILS: SMART-BREAST has been prospectively registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR12620000007932).

Transcatheter aortic valve replacement in patients with a history of cancer: Periprocedural and long-term outcomes.

BACKGROUND: A history of cancer is incorporated into the surgical risk assessment of patients undergoing surgical aortic valve replacement through the Society for Thoracic Surgeons score. However, the prognostic significance of cancer in patients treated with transcatheter aortic valve replacement (TAVR) is unclear. As the cancer survivorship population increases, it is imperative to establish the efficacy and safety of TAVR in patients with severe symptomatic aortic stenosis (AS) and a history of malignancy. OBJECTIVES: The primary goal of this study was to assess the periprocedural outcomes and long-term mortality in patients with a history of cancer undergoing TAVR. METHODS: A systematic review of PubMed, MEDLINE, and EMBASE was conducted to identify studies reporting outcomes in patients with a history of malignancy undergoing TAVR. A meta-analysis was performed using a random-effects model with a primary outcome of all-cause mortality and cardiac mortality at the longest follow-up. On secondary analyses, procedural safety was assessed. RESULTS: A total of 13 observational studies with 10,916 patients were identified in the systematic review. Seven studies including 6,323 patients were included in the quantitative analysis. Short-term mortality (relative risk [RR] 0.61, 95%CI 0.36-1.01; p = .06) and long-term all-cause mortality (RR 1.24, 95%CI 0.95-1.63; p = .11) were not significantly different when comparing patients with and without a history of cancer. No significant difference in the rate of periprocedural complications including stroke, bleeding, acute kidney injury, and pacemaker implantation was noted. CONCLUSION: In patients with severe AS undergoing TAVR, a history of cancer was not associated with adverse short or long-term survival. Based on these findings, TAVR should be considered in all patients with severe symptomatic AS, irrespective of their history of malignancy.

Nivolumab resulting in persistently elevated troponin levels despite clinical remission of myocarditis and myositis in a patient with malignant pleural mesothelioma: case report.

Malignant pleural mesothelioma (MPM) remains a deadly disease with limited therapeutic options beyond platinum/pemetrexed chemotherapy. Immune checkpoint inhibitors have demonstrated modest benefit in the second to later-line settings. An MPM patient from our institute developed myocarditis and myositis after 2 cycles of second-line nivolumab. Despite immunosuppression with corticosteroids and mycophenolate mofetil, there was ongoing rise in troponin levels which remained elevated for months. The patient developed an impressive but brief response following cessation of nivolumab. Myocarditis and myositis are rare complications of immune checkpoint inhibitors. Clinicians should be aware of these possible complications as myocarditis can result in mortality.

The effects of sublingual nitroglycerin administration in coronary computed tomography angiography.

PURPOSE: The purpose of our study was to compare coronary luminal diameters in patients undergoing coronary computed tomography angiography (CCTA) performed with different sublingual nitroglycerin (NTG) spray regimens. MATERIALS AND METHODS: We retrospectively reviewed CCTA studies performed in two historical groups (Group 1, single dose nitroglycerin 2 min prior to CCTA, and Group 2, single dose 10 min prior), and a current protocol group (Group 3, single dose at 2 and 10 min prior). Thirty patients were evaluated per group. Two blinded readers measured coronary luminal diameters with comparison of diameter measurements. A third blinded reader assessed image quality of coronary artery segments. RESULTS: Significant group-level differences in median luminal diameters were identified. Higher median diameters (95% CI) across all segments of 0.40 mm (0.20, 0.60) for Group 2 versus 1 and 0.50 mm (0.30, 0.70) for Group 3 versus 1 were recorded (both P < 0.001). No significant differences in median luminal diameters were found between Groups 2 and 3. No significant differences in image quality were found among the groups apart from higher image quality for the distal LAD for both Groups 2 and 3 compared to Group 1. CONCLUSION: Sublingual nitroglycerin spray administered as a single dose at 10 minute dilates coronary arteries more than when only administered at 2 min prior to CCTA. Combined two doses at 10 and 2 min prior to CCTA do not yield further dilatation of coronary arteries.

Plasma ACE2 Activity Predicts Mortality in Aortic Stenosis and Is Associated With Severe Myocardial Fibrosis.

OBJECTIVES: This study investigated the relationship between plasma angiotensin-converting enzyme 2 (ACE2) activity levels and the severity of stenosis and myocardial remodeling in patients with aortic stenosis (AS) and determined if plasma ACE2 levels offered incremental prognostic usefulness to predict all-cause mortality. BACKGROUND: ACE2 is an integral membrane protein that degrades angiotensin II and has an emerging role as a circulating biomarker of cardiovascular disease. METHODS: Plasma ACE2 activity was measured in 127 patients with AS; a subgroup had myocardial tissue collected at the time of aortic valve replacement. RESULTS: The median plasma ACE2 activity was 34.0 pmol/ml/min, and levels correlated with increased valvular calcification (p = 0.023) and the left ventricular (LV) mass index (r = 0.34; p < 0.001). Patients with above-median plasma ACE2 had higher LV end-diastolic volume (57 ml/m2 vs. 48 ml/m2; p = 0.021). Over a median follow-up of 5 years, elevated plasma ACE2 activity was an independent predictor of all-cause mortality after adjustment for relevant clinical, imaging, and biochemical parameters (HR: 2.28; 95% CI: 1.03 to 5.06; p = 0.042), including brain natriuretic peptide activation (integrated discrimination improvement: 0.08; p < 0.001). In 22 patients with plasma and tissue, increased circulating ACE2 was associated with reduced myocardial ACE2 gene expression (0.7-fold; p = 0.033) and severe myocardial fibrosis (p = 0.027). CONCLUSIONS: In patients with AS, elevated plasma ACE2 was a marker of myocardial structural abnormalities and an independent predictor of mortality with incremental value over traditional prognostic markers. Loss of ACE2 from the myocardium was associated with increased fibrosis and higher circulating ACE2 levels.

Distribution and Prognostic Significance of Left Ventricular Global Longitudinal Strain in Asymptomatic Significant Aortic Stenosis: An Individual Participant Data Meta-Analysis.

OBJECTIVES: In this individual participant data meta-analysis on left ventricular global longitudinal strain (LVGLS), our objective was to: 1) describe its distribution; 2) identify the most predictive cutoff values; and 3) assess its impact on mortality in asymptomatic patients with significant aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF). BACKGROUND: The evidence supporting the prognostic role of LVGLS in asymptomatic patients with AS has been obtained from several relatively small studies. METHODS: A literature search was performed for studies published between 2005 and 2017 without language restriction according to the following criteria: "aortic stenosis" AND "longitudinal strain." The corresponding authors of selected studies were contacted and invited to share their data that we computerized in a specific database. The primary endpoint was all-cause mortality. RESULTS: Among the 10 studies included, 1,067 asymptomatic patients with significant AS and LVEF >50% were analyzed. The median of LVGLS was 16.2% (from 5.6% to 30.1%). There were 91 deaths reported during follow-up with median of 1.8 (0.9 to 2.8) years, resulting in a pooled crude mortality rate of 8.5%. The LVGLS performed well in the prediction of death (area under the curve: 0.68). The best cutoff value identified was LVGLS of 14.7% (sensitivity, 60%; specificity, 70%). Using random effects model, the risk of death for patients with LVGLS <14.7% is multiplied by >2.5 (hazard ratio: 2.62; 95% confidence interval: 1.66 to 4.13; p < 0.0001), without significant heterogeneity between studies (I2 = 18.3%; p = 0.275). The relationship between LVGLS and mortality remained significant in patients with LVEF ≥60% (p = 0.001). CONCLUSIONS: This individual participant data meta-analysis demonstrates that in asymptomatic patients with significant AS and normal LVEF, impaired LVGLS is associated with reduced survival. These data emphasize the potential usefulness of LVGLS for risk stratification and management of these patients.

Highly Accelerated Breath-Hold Noncontrast Electrocardiographically- and Pulse-Gated Balanced Steady-State Free Precession Magnetic Resonance Angiography of the Thoracic Aorta: Comparison With Electrocardiographically-Gated Computed Tomographic Angiography.

OBJECTIVE: The aim of this study was to evaluate agreement of measured thoracic aortic caliber in patients with aortic disease, using electrocardiographically-(ECG) and pulse-gated breath-hold noncontrast balanced steady-state free precession MRA (ECG-MRA, P-MRA) at 1.5 T, compared with ECG-gated computed tomographic angiography (CTA). METHODS: Thirty-one patients underwent ECG-MRA, P-MRA, and CTA. Two readers independently measured aortic caliber in 7 segments, with agreement between techniques and readers evaluated. Image quality was qualitatively assessed. RESULTS: There was overall excellent agreement among ECG-MRA, P-MRA, and CTA for measured aortic caliber (Lin's concordance correlation coefficient ≥0.94, all comparisons); however, lower concordance was noted at the annulus (Lin's concordance correlation coefficient <0.6) at segmental assessment. There was excellent interreader agreement for aortic caliber for all 3 techniques (intraclass correlation coefficient >0.94). Image quality was poorer for both MRA techniques compared with CTA, particularly at the aortic root. CONCLUSIONS: Electrocardiographically-gated MRA and P-MRA at 1.5 T achieve comparable thoracic aortic measurements to gated CTA in clinical patients, despite inferior image quality.

Evaluation of Modified Look-Locker Inversion Recovery and Arrhythmia-Insensitive Rapid Cardiac T1 Mapping Pulse Sequences in Cardiomyopathy Patients.

OBJECTIVE: The aim of this study was to compare the performance of arrhythmia-insensitive rapid (AIR) and modified Look-Locker inversion recovery (MOLLI) T1 mapping in patients with cardiomyopathies. METHODS: In 58 patients referred for clinical cardiac magnetic resonance imaging at 1.5 T, we compared MOLLI and AIR native and postcontrast T1 measurements. Two readers independently analyzed myocardial and blood T1 values. Agreement between techniques, interreader agreement per technique, and intrascan agreement per technique were evaluated. RESULTS: The MOLLI and AIR T1 values were strongly correlated (r = 0.98); however, statistically significantly different T1 values were derived (bias 80 milliseconds, pooled data, P < 0.01). Both techniques demonstrated high repeatability (MOLLI, r = 1.00 and coefficient of repeatability [CR] = 72 milliseconds; AIR, r = 0.99 and CR = 184.2 milliseconds) and produced high interreader agreement (MOLLI, r = 1.00 and CR = 51.7 milliseconds; AIR, r = 0.99 and CR = 183.5 milliseconds). CONCLUSIONS: Arrhythmia-insensitive rapid and MOLLI sequences produced significantly different T1 values in a diverse patient cohort.

Right ventricular global longitudinal strain is an independent predictor of right ventricular function: a multimodality study of cardiac magnetic resonance imaging, real time three-dimensional echocardiography and speckle tracking echocardiography.

OBJECTIVES: Accurate assessment of right ventricular (RV) systolic function is important, as it is an established predictor of mortality in cardiac and respiratory diseases. We aimed to compare speckle tracking-derived longitudinal deformation measurements with traditional two-dimensional (2D) echocardiographic parameters, as well as real time three-dimensional echocardiography (RT3DE) and cardiac magnetic resonance imaging (CMR)-derived RV volumes and ejection fraction (EF). METHOD: Subjects referred for CMR also underwent echocardiography. On both RT3DE and CMR, we measured RV volumes and EF. On 2D echocardiography, we analyzed RV fractional area change, RV internal diastolic diameter, tricuspid annular plane systolic excursion, tricuspid annular tissue Doppler-derived velocity, myocardial performance index, and RV global longitudinal strain (RV GLS). RESULTS: Sixty subjects were recruited (mean age = 45 ± 10 years; 60% male). RV GLS (R = -0.69, P < 0.001) and RT3DE RVEF (R = 0.56, P < 0.001) correlated well with CMR RVEF. RT3DE RV end-diastolic (RVEDV) and end-systolic (RVESV) volumes also correlated with CMR RV volumes: RVEDV, R = 0.74, P < 0.001 and RVESV, R = 0.84, P < 0.001. In addition, RV GLS best predicted the presence of RV dysfunction, defined as RVEF <48% on CMR (hazard ratio = 7.0 [1.5-31.7], P < 0.01). On receiver operator characteristic analysis, a RV GLS of -20% was the most sensitive and specific predictor of RV dysfunction (AUC 0.8 [0.57-1.0], P < 0.02). CONCLUSION: RVEF and volumes estimated on RT3DE were closely correlated with CMR measurements. When compared to more traditional markers of RV systolic function and RT3DE, RVGLS produced the highest correlation with CMR RVEF and was a good predictor of RV dysfunction. RV GLS should be considered a complementary modality to RT3DE and CMR in the assessment of RV systolic function.

Cardiorenal anemia syndrome as a prognosticator for death in heart failure.

Anemia and chronic kidney disease are common in patients with heart failure (HF) and are associated with adverse outcomes. We analyzed the effect of cardiorenal anemia (CRA) syndrome, defined as anemia (hemoglobin <130 g/L for men, <120 g/L for women) and stage 3 or greater chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73 m(2)), in outpatients with HF. Consecutive patients with HF were prospectively enrolled from 2000 to 2005 (n = 748). The baseline clinical characteristics, pathology test results, and medication use were compared between those with and without CRA syndrome. The primary end point was all-cause mortality. The mean follow-up was 2.5 ± 1.6 years, with a left ventricular ejection fraction <45% present in 70% of patients. Angiotensin-converting enzyme inhibitors, ß blockers, and spironolactone were used in 87%, 67%, and 37%, respectively. CRA syndrome was present in 224 patients (30%). These patients had greater all-cause mortality (51% vs 26%, p <0.001), older age (mean 77 ± 8 vs 67 ± 14 years, p <0.001), and greater rates of diabetes mellitus (35% vs 23%, p <0.001) and ischemic heart disease (50% vs 35%, p <0.001). The independent predictors of mortality were CRA syndrome (hazard ratio 2.0, 95% confidence interval 1.4 to 2.8, p <0.001), left ventricular systolic dysfunction per grade (hazard ratio 1.5, 95% confidence interval 1.3 to 1.8, p <0.001), the absence of a ß blocker (hazard ratio 1.6, 95% confidence interval 1.1 to 2.2, p = 0.005), New York Heart Association class per class (hazard ratio 1.5, 95% confidence interval 1.2 to 1.9, p <0.01), and age per decade (hazard ratio 1.6, 95% confidence interval 1.4 to 2.0, p <0.001). In conclusion, CRA syndrome was common in patients with HF and was an independent predictor of all-cause mortality. Consideration should be given to identifying CRA syndrome and modifying reversible factors.

Usefulness of the Charlson co-morbidity index to predict outcomes in patients >60 years old with aortic stenosis during 18 years of follow-up.

The present study assessed the effect of age and co-morbidity on the outcomes of mild, moderate, and severe aortic stenosis (AS) in patients aged >60 years during 18 years of follow-up. The outcomes evaluated were hemodynamic progression, a composite cardiac mortality or aortic valve replacement (AVR) end point, and all-cause mortality. Consecutive Department of Veterans Affairs patients (aged >60 years) with AS were prospectively enrolled from 1988 to 1994 and followed until 2008 (n = 239). The baseline demographic, co-morbidity, and echocardiographic parameters were recorded. At enrollment, the mean age was 74 ± 6 years, and 78% were men. The annualized mean aortic valve gradient progression was 4 ± 4, 6 ± 5, and 10 ± 8 mm Hg for mild, moderate, and severe AS, respectively (p <0.001). During a mean follow-up of 8 ± 5 years, 206 deaths (52% cardiac) and 91 AVRs were recorded. The AVR/cardiac mortality event rate at 1, 5, and 10 years was 2%, 26%, and 50% for mild AS, 13%, 63%, and 69% for moderate AS, and 66%, 95%, and 95% for severe AS (p <0.001). During the study period, 132 patients developed severe AS. The survival rate at 1, 5, and 10 years was 60 ± 7%, 14 ± 5%, and 5 ± 3% with conservative management and 98 ± 2%, 82 ± 4%, and 50 ± 5% after AVR, respectively (p <0.001). The independent predictors of all-cause mortality were the age-adjusted Charlson co-morbidity index (hazard ratio 1.24, p <0.001), AVR (hazard ratio 0.40, p <0.001), and grade of left ventricular dysfunction (hazard ratio 1.36, p = 0.01). In conclusion, the prognostic significance of AS is determined by the hemodynamic severity, left ventricular function, and the presence of symptoms, in the context of age and co-morbidities. The age-adjusted Charlson co-morbidity index provides crucial prognostic information to guide the surgical risk/benefit discussions for patients with severe AS.