Diagnostic Pitfall and Clinical Characteristics of Variant Versus Wild-Type Transthyretin Amyloid Cardiomyopathy in Asian Population: The Korean Nationwide Cohort Study.

BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) with clinical phenotypes that vary across regions and genotypes. We sought to characterize the clinical characteristics of ATTR-CM in Asia. METHODS: Data from a nationwide cohort of patients with ATTR-CM from six major tertiary centres in South Korea were analysed between 2010 and 2021. All patients underwent clinical evaluation, biochemical laboratory tests, echocardiography, and transthyretin (TTR) genotyping at the time of diagnosis. The study population comprised 105 Asian ATTR-CM patients (mean age: 69 years; male: 65.7%, wild-type ATTR-CM: 41.9%). RESULTS: Among our cohort, 18% of the patients had a mean left ventricular (LV) wall thickness < 12 mm. The diagnosis of ATTR-CM increased notably during the study period (8 [7.6%] during 2010-2013 vs. 22 [21.0%] during 2014-2017 vs. 75 [71.4%] during 2018-2021). Although the duration between symptom onset and diagnosis did not differ, the proportion of patients with HF presenting mild symptoms increased during the study period (25% NYHA class I/II between 2010-2013 to 77% between 2018-2021). In contrast to other international registry data, male predominance was less prominent in wild-type ATTR-CM (68.2%). The distribution of TTR variants was also different from Western countries and from Japan. Asp38Ala was the most common mutation. CONCLUSION: A nationwide cohort of ATTR-CM exhibited less male predominance, a proportion of patients without increased LV wall thickness, and distinct characteristics of genetic mutations, compared to cohorts in other parts of the world. Our results highlight the ethnic variation in ATTR-CM and may contribute to improving the screening process for ATTR-CM in the Asian population.

Two decade trends in cardiovascular disease outcomes and cardiovascular risk factors among US veterans living with HIV.

Coomprhensive data on temporal trends in cardiovascular disease (CVD) risk factors and outcomes in people living with HIV are limited. Using retrospective data on 50,284 US Veterans living with HIV (VLWH) who received care in the VA from 2001 to 2019, we calculated the prevalence and incidence estimates of CVD risk factors and outcomes, as well as the average annual percent changes (AAPC) in the estimates. The mean age of the Veterans increased from 47.8 (9.1) years to 58.0 (12.4) years during the study period. The population remained predominantly (>95%) male and majority Black (∼50%). The prevalence of the CVD outcomes increased progressively over the study period: coronary artery disease (3.9%-18.7%), peripheral artery disease (2.3%, 10.3%), ischemic cerebrovascular disease (1.1%-9.9%), and heart failure (2.4%-10.5%). There was a progressive increase in risk factor burden, except for smoking which declined after 2015. The AAPC in prevalence was statistically significant for the CVD outcomes and risk factors. When adjusted for age, the predicted prevalence of CVD risk factors and outcomes showed comparable (but attenuated) trends. There was generally a comparable (but attenuated) trend in incidence of CVD outcomes, procedures, and risk factors over the study period. The use of statins increased from 10.6% (2001) to 40.8% (2019). Antiretroviral therapy usage increased from 77.7% (2001) to 85.0% (2019). In conclusion, in a retrospective analysis of large-scale VA data we found the burden and incidence of several CVD risk factors and outcomes have increased among VLWH over the past 20 years.

Aortic Valve Calcification Is Associated with Future Cognitive Impairment.

BACKGROUND: While an association between atherosclerosis and dementia has been identified, few studies have assessed the longitudinal relationship between aortic valve calcification (AVC) and cognitive impairment (CI). OBJECTIVE: We sought to determine whether AVC derived from lung cancer screening CT (LCSCT) was associated with CI in a moderate-to-high atherosclerotic risk cohort. METHODS: This was a single site, retrospective analysis of 1401 U.S. veterans (65 years [IQI: 61, 68] years; 97%male) who underwent quantification of AVC from LCSCT indicated for smoking history. The primary outcome was new diagnosis of CI identified by objective testing (Mini-Mental Status Exam or Montreal Cognitive Assessment) or by ICD coding. Time-to-event analysis was carried out using AVC as a continuous variable. RESULTS: Over 5 years, 110 patients (8%) were diagnosed with CI. AVC was associated with new diagnosis of CI using 3 Models for adjustment: 1) age (HR: 1.104; CI: 1.023-1.191; p = 0.011); 2) Model 1 plus hypertension, hyperlipidemia, diabetes, CKD stage 3 or higher (glomerular filtration rate < 60 mL/min) and CAD (HR: 1.097; CI: 1.014-1.186; p = 0.020); and 3) Model 2 plus CVA (HR: 1.094; CI: 1.011-1.182; p = 0.024). Sensitivity analysis demonstrated that the association between AVC and new diagnosis of CI remained significant upon exclusion of severe AVC (HR: 1.100 [1.013-1.194]; p = 0.023). Subgroup analysis demonstrated that this association remained significant when including education in the multivariate analysis (HR: 1.127 [1.030-1.233]; p = 0.009). CONCLUSION: This is the first study demonstrating that among mostly male individuals who underwent LCSCT, quantified aortic valve calcification is associated with new diagnosis of CI.

Aortic valve calcification predicts all-cause mortality independent of coronary calcification and severe stenosis.

BACKGROUND AND AIMS: Calcific aortic valve disease is highly prevalent in patients with significant smoking history and is a marker of atherosclerosis. The aim of this study was to define the prognostic value of aortic valve calcification (AVC) derived from low dose, lung cancer screening computed tomography (LCSCT) for all-cause mortality in this higher risk population. METHODS: This is a single site, retrospective analysis of 1529 moderate-to-high atherosclerotic cardiovascular risk U.S. veterans (65 years [IQI: 61, 68] years; 96% male), who underwent clinically indicated LCSCT. CTs were scored for aortic valve calcification (AVC) and coronary artery calcification (CAC). The primary endpoint was all-cause mortality and secondary endpoints were nonfatal myocardial infarction (MI) and nonfatal cerebrovascular accident (CVA). RESULTS: Over 4-year follow-up, 227 patients (15%) died, 112 patients (7%) had nonfatal MI, and 52 patients (3%) had nonfatal CVA. AVC was predictive of all-cause mortality (HR per 100: 1.041 [1.030-1.052], p < 0.001), and this association remained significant after multivariate adjustment for traditional atherosclerotic risk factors, including CAC (1.021 [1.007-1.036], p = 0.003). After excluding patients with severe aortic stenosis (AS) or severe AVC (≥1274 AU in women and ≥2065 AU in men), in a subset of 765 patients who had echocardiograms, this association remained significant after multivariate analysis (HR per 100: 1.052 [1.010-1.095], p = 0.014). Despite controlling for CAC in the models, AVC was still associated with MI (HR per 100: 1.021 [1.004-1.039], p = 0.017) and with CVA (HR per 100: 1.027 [1.002-1.051], p = 0.032). CONCLUSIONS: Scoring AVC derived from LCSCT is predictive of mortality, nonfatal MI, and nonfatal CVA in patients at known risk for cardiovascular disease, independent of coronary calcification or severe aortic valve stenosis.

Home-Based Cardiac Rehabilitation Alone and Hybrid With Center-Based Cardiac Rehabilitation in Heart Failure: A Systematic Review and Meta-Analysis.

Background Center-based cardiac rehabilitation (CBCR) has been shown to improve outcomes in patients with heart failure (HF). Home-based cardiac rehabilitation (HBCR) can be an alternative to increase access for patients who cannot participate in CBCR. Hybrid cardiac rehabilitation (CR) combines short-term CBCR with HBCR, potentially allowing both flexibility and rigor. However, recent data comparing these initiatives have not been synthesized. Methods and Results We performed a meta-analysis to compare functional capacity and health-related quality of life (hr-QOL) outcomes in HF for (1) HBCR and usual care, (2) hybrid CR and usual care, and (3) HBCR and CBCR. A systematic search in 5 standard databases for randomized controlled trials was performed through January 31, 2019. Summary estimates were pooled using fixed- or random-effects (when I2>50%) meta-analyses. Standardized mean differences (95% CI) were used for distinct hr-QOL tools. We identified 31 randomized controlled trials with a total of 1791 HF participants. Among 18 studies that compared HBCR and usual care, participants in HBCR had improvement of peak oxygen uptake (2.39 mL/kg per minute; 95% CI, 0.28-4.49) and hr-QOL (16 studies; standardized mean difference: 0.38; 95% CI, 0.19-0.57). Nine RCTs that compared hybrid CR with usual care showed that hybrid CR had greater improvements in peak oxygen uptake (9.72 mL/kg per minute; 95% CI, 5.12-14.33) but not in hr-QOL (2 studies; standardized mean difference: 0.67; 95% CI, -0.20 to 1.54). Five studies comparing HBCR with CBCR showed similar improvements in functional capacity (0.0 mL/kg per minute; 95% CI, -1.93 to 1.92) and hr-QOL (4 studies; standardized mean difference: 0.11; 95% CI, -0.12 to 0.34). Conclusions HBCR and hybrid CR significantly improved functional capacity, but only HBCR improved hr-QOL over usual care. However, both are potential alternatives for patients who are not suitable for CBCR.

Association of tobacco use and cessation with coronary atherosclerosis.

BACKGROUND AND AIMS: The impact of tobacco use and cessation on atherogenesis remains unclear. We aimed to study the association of tobacco use and prior cessation with the presence, extent and severity of atherosclerosis on coronary computed tomographic angiography (CTA). METHODS: We examined 1798 consecutive symptomatic patients without known coronary artery disease (CAD) referred for CTA, stratified by smoking status (never, current [within 30 days], or former [>30 days before CTA]). Plaque severity (none, <50%, ≥50% stenosis), composition (non-calcified [NCP], partially calcified [PCP], or calcified plaque [CP]), and segment involvement score (SIS) were visually graded. Multivariate analysis was performed, adjusting for CAD risk factors and cholesterol lowering medication use. RESULTS: The median age of patients was 50 years [IQR:42-58] (61% male), with 74% never smokers, 12% current smokers, and 14% former smokers (median quit duration = 12 years [IQR:3-26]). Smoking exposure in former versus current smokers was 11 [IQR:5-25] and 10 [IQR:2-20] pack-years, respectively (p = 0.01). Compared to never smokers, current smokers demonstrated an increased odds ratio of all plaque types (adjusted OR: any NCP = 1.55 [95% CI 1.04-2.32], p = 0.03; any PCP = 1.61 [1.10-2.37], p = 0.02; any CP = 1.93 [1.32-2.81], p = 0.001), non-obstructive CAD (aOR = 1.47 [1.04, 2.07], p = 0.03), obstructive CAD (aOR = 1.81 [1.01-3.24], p = 0.047), and SIS > 4 (aOR = 1.60 [1.04-2.46], p = 0.03). Compared to current smoking, prior smoking cessation (≥12 years) was associated with a decreased odds ratio of any NCP (aOR = 0.42 [0.19-0.90], p = 0.03), CP (aOR = 0.43 [0.22-0.84], p = 0.02), and obstructive CAD (aOR = 0.40, [0.15-0.98], p = 0.048). CONCLUSIONS: Current smoking is independently associated with the presence and extent of coronary plaque, and a higher risk of non-obstructive and obstructive CAD compared to never smoking. Prior smoking cessation correlated with improvements in CTA-identified plaque measures.

Serum biomarkers in severe refractory cardiogenic shock.

OBJECTIVES: The aim of this study was to characterize levels of serum biomarkers in patients with severe refractory cardiogenic shock (SRCS) and to document temporal changes in these levels during restoration of circulation. BACKGROUND: Patients with SRCS have been challenging to study because of their rapidly changing clinical condition while undergoing multiple simultaneous interventions. METHODS: Twenty-one patients with SRCS received circulatory support via a percutaneously implanted ventricular assist device (PVAD). Serum samples obtained prior to PVAD support initiation, at 24 h of PVAD support, and at 7 days of PVAD support were assayed for B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), soluble tumor necrosis factor receptor-1 (sTNFR1), soluble Fas (sFas), soluble Fas ligand (sFasL), endothelin-1, and procollagen III N-terminal peptide (PIIINP). Baseline biomarker levels were qualitatively compared to reference values; levels at 24 h of PVAD support and at 7 days of PVAD support were compared to baseline using 2-tailed Wilcoxon matched pair signed rank tests with Bonferroni correction for multiple comparisons. RESULTS: These patients with SRCS had elevated serum levels of BNP, hsCRP, sTNFR1, endothelin-1, and PIIINP. Ventricular unloading and restoration of circulation via PVAD support in patients with SRCS were associated with reductions in serum BNP, sFas, and endothelin-1 levels and increases in serum sFasL and PIIINP levels. CONCLUSIONS: This study characterizes several important baseline serum biomarker levels in patients with SRCS and introduces a novel PVAD-based protocol with the potential to "reverse"-model the pathophysiology of cardiogenic shock.

An evidence-based guide for coronary calcium scoring in asymptomatic patients without coronary heart disease.

As public awareness and clinical use of CAC screening increases, physicians should, at a minimum, know the following information: 1) The presence of CAC indicates underlying CHD but does not predict luminal obstruction. 2) Non-contrast, prospectively ECG-gated cardiac EBCT and MDCT are sensitive, reproducible, rapid, and essentially equivalent imaging techniques commonly used to screen for CAC. 3) Currently, CAC screening is appropriate for all intermediate- risk patients and low-risk patients with a family history of premature CHD, and might be appropriate for all low-risk women. 4) The risks associated with CAC screening are a small but measurable excess risk of cancer and the risk of unnecessary downstream tests and procedures. 5) A CAC score of zero has a very high negative predictive value for CHD events. 6) Increasingly positive (non-zero) CAC scores are directly proportional to increased CHD event risk, and a CAC score >100 or greater than the 75th percentile indicates high risk. 7) Repeat screening to determine CAC progression or regression is not currently recommended.