The Prognostic Value of Left Atrial Global Longitudinal Strain and Left Atrial Phasic Volumes in Patients Undergoing Transcatheter Valve Implantation for Severe Aortic Stenosis.

INTRODUCTION: The changes and the prognostic implications of left atrial (LA) volumes (LAV), LA function, and vascular load in patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) are less known. METHODS: We enrolled 150 symptomatic patients (mean age 82 ± 8 years, 58% female, and pre-TAVI aortic valve area 0.40 ± 0.19 cm/m2) with severe AS who underwent 2D transthoracic echocardiography and 2D speckle tracking echocardiography at average 21 ± 35 days before and 171 ± 217 days after TAVI. The end point was a composite of new onset of atrial fibrillation, hospitalization for heart failure and all-cause death (major adverse cardiac events [MACE]). RESULTS: After TAVI, indexed maximal LA volume and minimum volume of the LA decreased by 2.1 ± 10 mL/m2 and 1.6 ± 7 mL/m2 (p = 0.032 and p = 0.011, respectively), LA function index increased by 6.8 ± 11 units (p < 0.001), and LA stiffness decreased by 0.38 ± 2.0 (p = 0.05). No other changes in the LA phasic volumes, emptying fractions, and vascular load were noted. Post-TAVI, both left atrial and ventricular global peak longitudinal strain improved by about 6% (p = 0.01 and 0.02, respectively). MACE was reached by 37 (25%) patients after a median follow-up period of 172 days (interquartile range, 20-727). In multivariable models, MACE was associated with both pre- and post-TAVI LA global peak longitudinal strain (hazard ratio [HR] 0.75, CI 0.59-0.97; and HR 0.77, CI 0.60-1.00, per 5 percentage point units, respectively), pre-TAVI LV global endocardial longitudinal strain (HR 1.37, CI 1.02-1.83 per 5 percentage point units), and with most of the LA phasic volumes. CONCLUSION: Within 6 months after TAVI, there is reverse LA remodeling and an improvement in LA reservoir function. Pre- and post-TAVI indices of LA function and volume remain independently associated with MACE. Larger studies enrolling a greater diversity of patients may provide sufficient evidence for the utilization of these imaging biomarkers in clinical practice.

The Association between Aortic Valve Weight, Echocardiographic Indices, and All-Cause Death in 1,046 Patients Undergoing Surgical Aortic Valve Replacement for Aortic Stenosis.

BACKGROUND: Aortic valve weight (AVW), a flow independent measure of aortic stenosis (AS) severity, is reported to have heterogeneous associations with the echocardiographic variables used for AS evaluation. Controversy exists regarding its impact on survival after aortic valve replacement (AVR). OBJECTIVE: We sought to determine the association between AVW with echocardiographic measures of AS severity and all-cause mortality after surgical AVR. METHODS: One thousand and forty-sixconsecutive patients underwent surgical AVR for AS, the excised valves were weighed, and an echocardiogram was done before surgery. RESULTS: Males had heavier valves than females, for both absolute and body surface are (BSA)-indexed values (2.78 ± 1.23 vs. 2.08 ± 0.68 g, p < 0.001; and 1.38 ± 0.61 vs. 1.19 ± 0.41 g/m2, p < 0.001, respectively). In a restricted cohort of 634 patients with isolated severe AS and normal ejection fraction, the correlations of AVW with echocardiographic variables of AS were modest, the strongest being with the dimensionless index (r = -0.27 and -0.26 for male and female, both p < 0.01). Stratified by stroke volume index and mean gradient (MG), no associations were found in the low-gradient groups (i.e., MG <40 mmHg). At a median follow-up of 3.5 years, there were only 244 deaths in the entire cohort. Mortality was not related to AVW, except in females who displayed an inverse relationship (HR = 0.67; 95% CI 0.47-0.95) only when it was analyzed as a continuous variable. CONCLUSIONS: The weak correlation between AVW with the echocardiographic indices of AS may reflect its complex pathophysiology, heterogeneous hemodynamics, and possible pitfalls in the current echocardiographic methods used in clinical practice. The prognostic value of AVW after AVR warrants further evaluation.

The Utility of Flow Rate Compared with Left Ventricular Stroke Volume Index in the Hemodynamic Classification of Severe Aortic Stenosis with Preserved Ejection Fraction.

OBJECTIVES: To substitute the stroke volume index (SVi) with flow rate (FR) in the hemodynamic classification of severe aortic stenosis (AS) with preserved ejection fraction (EF), in order to evaluate its prognostic value. METHODS: A total of 529 patients (78.8 ± 9.8 years old, 44.1% males) with isolated severe AS (aortic valve area, AVA < 1 cm2), EF ≥50%, in sinus rhythm, who underwent transthoracic echocardiography, were stratified by FR (≥/< 200 mL/s) and mean pressure gradient (MG) (≥/< 40 mm Hg): FRnormal/MGhigh, FRlow/MGhigh, FRnormal/MGlow, and FRlow/MGlow. RESULTS: Aortic valve replacement was more frequently performed in the FRnormal/MGhigh than in the FRlow/MGlow group (69.3 vs. 47%, respectively, p < 0.0001), yielding a similar survival benefit across all four groups. Over a median follow-up of 51 ± 29 months, there were 249 deaths. In highly adjusted models, the FRlow/MGlow group had a higher all-cause mortality (HR = 1.7, 95% CI: 1.1-2.6, p = 0.02) than patients with FRnormal/MGhigh. FR had a stronger association with AVA than SVi (r = 0.51 vs. 0.41, respectively, p = 0.0002), and a similar predictive value for death (AUC = 0.57 and 0.58, respectively, p = 0.88). CONCLUSIONS: The FRlow/MGlow subset of AS is associated with the worst prognosis, and FR is not superior to SVi in the hemodynamic classification of severe AS.

Fibrosis-related biomarkers and risk of total and cause-specific mortality: the cardiovascular health study.

Fibrosis has been implicated in diverse diseases of the liver, kidney, lungs, and heart, but its importance as a risk factor for mortality remains unconfirmed. We determined the prospective associations of 2 complementary biomarkers of fibrosis, transforming growth factor-ß (TGF-ß) and procollagen type III N-terminal propeptide (PIIINP), with total and cause-specific mortality risks among community-living older adults in the Cardiovascular Health Study (1996-2010). We measured circulating TGF-ß and PIIINP levels in plasma samples collected in 1996 and ascertained the number of deaths through 2010. Both TGF-ß and PIIINP were associated with elevated risks of total and pulmonary mortality after adjustment for sociodemographic, clinical, and biochemical risk factors. For total mortality, the hazard ratios per doubling of TGF-ß and PIIINP were 1.09 (95% confidence interval (CI): 1.01, 1.17; P = 0.02) and 1.14 (CI: 1.03, 1.27; P = 0.01), respectively. The corresponding hazard ratios for pulmonary mortality were 1.27 (CI: 1.01, 1.60; P = 0.04) for TGF-ß and 1.52 (CI: 1.11, 2.10; P = 0.01) for PIIINP. Associations of TGF-ß and PIIINP with total and pulmonary mortality were strongest among individuals with higher C-reactive protein concentrations (P for interaction < 0.05). Our findings provide some of the first large-scale prospective evidence that circulating biomarkers of fibrosis measured late in life are associated with death.

Clinical and echocardiographic correlates of mortality in medically treated patients with severe isolated aortic stenosis and normal left ventricular ejection fraction.

BACKGROUND: Many symptomatic patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF) are denied surgery and have a grim prognosis with medical management. METHODS AND RESULTS: Between 2003 and 2012, among 550 patients with severe isolated AS and preserved LVEF on transthoracic echocardiography, 241 did not undergo aortic valve replacement (mean age, 83.2±7.6 years; 54% female; aortic valve area index, 0.40±0.13cm(2)/m(2); mean LVEF, 64.8±7.6%) and 67% presented with cardiac symptoms. At a mean follow-up of 25.5±25.1 months, 134 patients (56%) had died. Survival at 1, 5 and 9.5 years was 71%, 28% at 12%, respectively. Median survival was 36.3 months (95% confidence interval [CI]: 27.2-42.4 months). In unadjusted analyses, age, heart failure, hypertension, renal insufficiency, left atrial size, pulmonary artery systolic pressure (PASP), relative wall thickness and LV mass/LV end diastolic volume ratio were associated with mortality. On multivariate analysis adjusted for all significant univariate predictors, age ≥78 years, history of hypertension, left atrial diameter ≥40mm and PASP ≥42mmHg gave a joint area under the curve of 0.80 (95% CI: 0.73-0.86) for mortality. CONCLUSIONS: In medically treated patients with severe isolated AS and preserved LVEF, older age, history of hypertension, and echo-Doppler variables reflecting LV diastolic dysfunction are independent predictors of death.

Absence of left ventricular hypertrophy in severe isolated aortic stenosis and preserved left ventricular systolic function.

BACKGROUND AND AIM OF THE STUDY: Recent evidence challenges the paradigm that left ventricular hypertrophy (LVH) is required to preserve left ventricular systolic performance in severe aortic stenosis (AS). The study aims were to determine the clinical, echocardiographic and prognostic implications in a cohort of patients with symptomatic severe AS, a preserved left ventricular ejection fraction (LVEF), and an absence of LVH. METHODS: Echocardiographic, clinical, aortic valve replacement (AVR)-related and all-cause death data were analyzed in 512 patients (253 males, 259 females; mean age 78.4 +/- 10.3 years) with severe AS and a preserved LVEF. Of these patients, 21% were enrolled prospectively, and the mean follow up was 40.4 +/- 32.5 months. RESULTS: By using the American Society of Echocardiography equation for left ventricular mass calculation, LVH was shown to be present in 330 patients (63%) and absent from 182 (36%). Typically, patients without LVH had a larger body surface area, were more often male, had a larger aortic valve area index (AVAi), and had similar LVEFs and rates of AVR as compared to those with LVH. A total of 59 deaths (32.4%) occurred among patients without LVH, and 134 (40.6%) among those with LVH (p = 0.07). When the left ventricular mass index (LVMi) was analyzed as a continuous variable, in both unadjusted and adjusted models for demographics, clinical characteristics, medications, AVAi, LVEF, and systemic vascular resistance, no association was found between LVMi and survival (p = 0.26). However, only patients with a normal LVMi and relative wall thickness had a survival benefit when compared to those with any pattern of abnormal left ventricular geometry (p = 0.01). CONCLUSION: LVH was absent in more than one-third of patients with severe AS, and was not associated with worse outcomes. A normal left ventricular geometry was associated with lower mortality rates, while AVR was associated with prolonged survival, regardless of LVMi. Mechanisms other than compensatory hypertrophy appear capable of offsetting the adverse effects of afterload excess in AS.

Association of thyroid dysfunction in individuals ≥ 65 years of age with subclinical cardiac abnormalities.

CONTEXT: The relationship between thyroid dysfunction and measures of myocardial disease in older individuals remains to be defined. OBJECTIVE: To evaluate the impact of thyroid dysfunction on structure and function of the left-heart chambers and blood markers of cardiac disease. DESIGN: Cross-sectional analysis. SETTING: The Cardiovascular Health Study, a community-based cohort of older individuals recruited from four urban areas in the United States. PATIENTS: Of 3163 participants studied, 2477 were euthyroid, 465 had subclinical hypothyroidism (SCH), 47 overt hypothyroidism (OH), 45 endogenous (endo) subclinical hyperthyroidism (endo-SCT), and 129 had exogenous (exo) SCT due to thyroid hormone supplementation. INTERVENTIONS: Clinical evaluation, blood sampling and biomarker measurement, 2-dimensional and speckle-tracking echocardiography. MAIN OUTCOME MEASURE(S): Left heart myocardial deformation, circulating biomarkers of diastolic overload (NT-proBNP), fibrosis (sST2, gal-3), and cardiomyocyte injury (hs-cTnT). RESULTS: SCH was associated with higher NT-proBNP (beta = 0.17, p = 0.004), whereas OH was associated with higher hs-cTnT (beta = 0.29, p = 0.005). There were also suggestive associations of SCH with higher sST2, as well as endo-SCT with higher gal-3 and lower (worse) left atrial reservoir strain. Left ventricular longitudinal strain and end-diastolic strain rate did not differ significantly from euthyroid participants in SCH, OH, or exo-SCT. CONCLUSIONS: In this free-living elderly cohort, subclinical and overt hypothyroidism were associated with abnormalities of blood biomarkers consistent with diastolic overload and myocardial necrosis respectively, whereas subclinical hyperthyroidism tended to be associated with myocardial fibrosis and decreased left atrial strain. Our findings could represent stage B heart failure and illuminate distinct aspects of the pathobiology of heart disease related to thyroid gland dysfunction with potential clinical implications.

A machine learning-derived risk score to predict left ventricular diastolic dysfunction from clinical cardiovascular magnetic resonance imaging.

Introduction: The evaluation of left ventricular diastolic dysfunction (LVDD) by clinical cardiac magnetic resonance (CMR) remains a challenge. We aimed to train and evaluate a machine-learning (ML) algorithm for the assessment of LVDD by clinical CMR variables and to investigate its prognostic value for predicting hospitalized heart failure and all-cause mortality. Methods: LVDD was characterized by echocardiography following the ASE guidelines. Eight demographic and nineteen common clinical CMR variables including delayed enhancement were used to train Random Forest models with a Bayesian optimizer. The model was evaluated using bootstrap and five-fold cross-validation. Area under the ROC curve (AUC) was utilized to evaluate the model performance. An ML risk score was used to stratify the risk of heart failure hospitalization and all-cause mortality. Results: A total of 606 consecutive patients underwent CMR and echocardiography within 7 days for cardiovascular disease evaluation. LVDD was present in 303 subjects by echocardiography. The performance of the ML algorithm was good using the CMR variables alone with an AUC of 0.868 (95% CI: 0.811-0.917), which was improved by combining with demographic data yielding an AUC 0.895 (95% CI: 0.845-0.939). The algorithm performed well in an independent validation cohort with AUC 0.810 (0.731-0.874). Subjects with higher ML scores (>0.4121) were associated with increased adjusted hazard ratio for a composite outcome than subjects with lower ML scores (1.72, 95% confidence interval 1.09-2.71). Discussion: An ML algorithm using variables derived from clinical CMR is effective in identifying patients with LVDD and providing prognostication for adverse clinical outcomes.

Left Ventricular Mass, Myocardial Structure, and Function in Severe Aortic Stenosis: an Echocardiographic and Cardiac Magnetic Resonance Imaging Study.

In severe aortic stenosis (AS), there are conflicting data on the prognostic implications of left ventricular (LV) hypertrophy (LVH). We aimed to characterize the LV geometry, myocardial matrix structural changes, and prognostic stratification using cardiac magnetic resonance imaging (CMR) and echocardiography in subjects with severe AS with and without LVH. Consecutive patients who had severe isolated AS and sufficient quality echocardiography and CMR within 6 months of each other were evaluated for LVH, cardiac structure, morphology, and late gadolinium-enhancement imaging. Kaplan-Meier curves, linear models, and proportional hazards models were used for prognostic stratification. There were 93 patients enrolled (mean age 74 ± 11 years, 48% female), of whom 38 (41%) had a normal LV mass index (LVMI), 41 (44%) had LVH defined at CMR by LVMI >2 SD higher than normal, and 14 (15% of the total) with >4 SD higher than the reference LVMI (severely elevated). The Society of Thoracic Surgeons scores were similar among the LVMI groups. Compared with those with normal LVMI, patients with LVH had higher LV end-diastolic and end-systolic volumes, increased late gadolinium-enhancement burden, and lower LV ejection fraction. Most notably, CMR feature-tracking global radial strain, 2-dimensional speckle-tracking echocardiography global longitudinal strain, and left atrial reservoir function were significantly worse. On the survival analyses, LVMI was not associated with a composite of all-cause mortality and/or heart failure hospitalization. In conclusion, compared with normal LVMI, elevated LVMI was not associated with a higher risk of adverse outcomes.

The Associations of Aortic Valve Sclerosis, Aortic Annular Increased Reflectivity, and Mitral Annular Calcification with Subsequent Aortic Stenosis in Older Individuals: Findings from the Cardiovascular Health Study.

BACKGROUND: Although aortic valve sclerosis (AVS) is well described as preceding aortic stenosis (AS), the associations of AS with antecedent mitral annular calcification (MAC) and aortic annular increased reflectivity (AAIR) have not been characterized. In a population-based prospective study, the authors evaluated whether MAC, AAIR, and AVS are associated with the risk for incident AS. METHODS: Among participants of the Cardiovascular Health Study free of AS at the 1994-1995 visit, the presence of MAC, AAIR, AVS, and the combination of all three was evaluated in 3,041 participants. Cox proportional-hazards regression was used to assess the association between the presence of calcification and the incidence of moderate or severe AS in three nested models adjusting for factors associated with atherosclerosis and inflammation both relevant to the pathogenesis of AS. RESULTS: Over a median follow-up period of 11.5 years (interquartile range, 6.7-17.0 years), 110 cases of incident moderate or severe AS were ascertained. Strong positive associations with incident moderate or severe AS were found for all calcification sites after adjustment for the main model covariates: AAIR (hazard ratio [HR], 2.90; 95% CI, 1.95-4.32; P < .0005), AVS (HR, 2.20; 95% CI, 1.44-3.37; P < .0005), MAC (HR, 1.67; 95% CI, 1.14-2.45; P = .008), and the combination of all three (HR, 2.50; 95% CI, 1.65-3.78; P < .0005). In a secondary analysis, the risk for AS increased with the number of sites at which calcification was present. CONCLUSIONS: In a large cohort of community-dwelling elderly individuals, there were strong associations between each of AAIR, AVS, MAC, and the combination of the three and incident moderate or severe AS. The novel finding that AAIR had a particularly strong association with incident AS, even after adjusting for other calcification sites, suggests its value in identifying individuals at risk for AS and potential inclusion in routine assessment by transthoracic echocardiography.

Relation of Cigarette Smoking and Heart Failure in Adults ≥65 Years of Age (From the Cardiovascular Health Study).

Cigarette smoking is associated with adverse cardiac outcomes, including incident heart failure (HF). However, key components of potential pathways from smoking to HF have not been evaluated in older adults. In a community-based study, we studied cross-sectional associations of smoking with blood and imaging biomarkers reflecting mechanisms of cardiac disease. Serial nested, multivariable Cox models were used to determine associations of smoking with HF, and to assess the influence of biochemical and functional (cardiac strain) phenotypes on these associations. Compared with never smokers, smokers had higher levels of inflammation (C-reactive protein and interleukin-6), cardiomyocyte injury (cardiac troponin T [hscTnT]), myocardial "stress"/fibrosis (soluble suppression of tumorigenicity 2 [sST2], galectin 3), and worse left ventricle systolic and diastolic function. In models adjusting for age, gender, and race (DEMO) and for clinical factors potentially in the causal pathway (CLIN), smoking exposures were associated with C-reactive protein and interleukin-6, sST2, hscTnT, and with N-terminal pro-brain natriuretic protein (in Whites). In DEMO adjusted models, the cumulative burden of smoking was associated with worse left ventricle systolic strain. Current smoking and former smoking were associated with HF in DEMO models (hazard ratio 1.41, 95% confidence interval 1.22 to 1.64 and hazard ratio 1.14, 95% confidence interval 1.03 to 1.25, respectively), and with current smoking after CLIN adjustment. Adjustment for time-varying myocardial infarction, inflammation, cardiac strain, hscTnT, sST2, and galectin 3 did not materially alter the associations. Smoking was associated with HF with preserved and decreased ejection fraction. In conclusion, in older adults, smoking is associated with multiple blood and imaging biomarker measures of pathophysiology previously linked to HF, and to incident HF even after adjustment for clinical intermediates.

Association between depressive symptoms and fibrosis markers: the Cardiovascular Health Study.

OBJECTIVE: Fibrosis plays an important role in heart failure (HF) and other diseases that occur more frequently with increasing age. Depression is associated with an increased risk of heart failure and other age-related diseases. This study examined the association between depressive symptoms and fibrosis markers in adults aged 65 years and above. METHODS: Fibrosis markers and depressive symptoms were assessed in 870 participants (age=80.9+/-5.9 yrs, 49% women) using a case-control design based on heart failure status (307 HF patients and 563 age- and sex-matched controls, of whom 284 with CVD risk factors (hypertension, diabetes mellitus, or hypercholesterolemia) and 279 controls without these CVD risk factors). Fibrosis markers were procollagen type I (PIP), type I collagen (CITP), and procollagen type III (PIIINP). Inflammation markers included C-reactive protein, white blood cell counts and fibrinogen. Depression was assessed using the Center for Epidemiological Studies-Depression (CES-D) scale using a previously validated cut-off point for depression (CES-D > or = 8). Covariates included demographic and clinical variables. RESULTS: Depression was associated with higher levels of PIP (median=411.0, inter-quartile range (IQR)=324.4-472.7 ng/mL vs. 387.6, IQR=342.0-512.5 ng/mL, p=0.006) and CITP (4.99, IQR=3.53-6.85 vs. 4.53, IQR=3.26-6.22 microg/L, p=0.024), but not PIIIINP (4.07, IQR=2.75-5.54 microg/L vs. 3.58, IQR=2.71-5.01 microg/L, p=0.29) compared to individuals without depression. Inflammation markers were also elevated in depressed participants (CRP, p=0.014; WBC, p=0.075; fibrinogen, p=0.074), but these inflammation markers did not account for the relationship between depression and fibrosis markers. CONCLUSIONS: Depression is associated with elevated fibrosis markers and may therefore adversely affect heart failure and other age-related diseases in which extra-cellular matrix formation plays a pathophysiological role.

The Association between Left Ventricular Diastolic Dysfunction and Myocardial Scar and Their Collective Impact on All-Cause Mortality.

BACKGROUND: Left ventricular diastolic dysfunction (DD) and myocardial scar are important contributors to cardiovascular morbidity and mortality. The aim of this study was to test the hypothesis that myocardial scar is a substrate of DD and that collectively they contribute to increased risk for all-cause mortality. METHODS: The study included 607 consecutive patients who underwent echocardiography and cardiac magnetic resonance imaging within 1 week. DD was assessed by echocardiography according to the contemporary guidelines and myocardial scar by late gadolinium enhancement (LGE). All-cause mortality was the main outcome. RESULTS: Scar prevalence was significantly higher comparing no DD with mild and advanced DD (25%, 61%, and 80%, respectively; P < .001), and scar burden was greater by semiquantitative LGE scores (1.4 ± 3.4, 4.8 ± 6.3, and 6.8 ± 8.8, respectively; P < .001). After 10 years of follow-up, 50 patients (8.2%) had died. The mortality incidence was significantly higher comparing no DD with mild and advanced DD (2.5, 17.3, and 55.7 deaths per 1,000 person-years, respectively; P < .001). It was also higher in patients with higher LGE scores (4.3, 22.7, and 35.2 deaths per 1,000 person-years in groups with LGE scores of 0, 1-6, and ≥7, respectively; P < .001). The risk for death was higher among patients with both DD and scar. The additive interaction of DD and scar for mortality was significant (P < .001). In the multivariate Cox proportional-hazards analysis, DD and scar were associated with mortality (P < .001). CONCLUSIONS: There is a strong link between the echocardiographic findings of DD and the morphologic changes of myocardial tissue. DD assessed according to contemporary guidelines effectively differentiates mortality risk. The additive interaction of DD and scar on mortality risk highlights the pivotal role of myocardial tissue characterization in patients with DD.

Reduced cardiac function is associated with cardiac injury and mortality risk in hospitalized COVID-19 Patients.

BACKGROUND: Cardiac injury is common in COVID-19 patients and is associated with increased mortality. However, it remains unclear if reduced cardiac function is associated with cardiac injury, and additionally if mortality risk is increased among those with reduced cardiac function in COVID-19 patients. HYPOTHESIS: The aim of this study was to assess cardiac function among COVID-19 patients with and without biomarkers of cardiac injury and to determine the mortality risk associated with reduced cardiac function. METHODS/RESULTS: This retrospective cohort study analyzed 143 consecutive COVID-19 patients who had an echocardiogram during hospitalization between March 1, 2020 and May 5, 2020. The mean age was 67 ± 16 years. Cardiac troponin-I was available in 131 patients and an increased value (>0.03 ng/dL) was found in 59 patients (45%). Reduced cardiac function, which included reduced left or right ventricular systolic function, was found in 40 patients (28%). Reduced cardiac function was found in 18% of patients without troponin-I elevation, 42% with mild troponin increase (0.04-5.00 ng/dL) and 67% with significant troponin increase (>5 ng/dL). Reduced cardiac function was also present in more than half of the patients on mechanical ventilation or those deceased. The in-hospital mortality of this cohort was 28% (N = 40). Using logistic regression analysis, we found that reduced cardiac function was associated with increased mortality with adjusted odds ratio (95% confidence interval) of 2.65 (1.18 to 5.96). CONCLUSIONS: Reduced cardiac function is highly prevalent among hospitalized COVID-19 patients with biomarkers of myocardial injury and is independently associated with mortality.

Severe isolated aortic stenosis with normal left ventricular systolic function and low transvalvular gradients: pathophysiologic and prognostic insights.

BACKGROUND AND AIM OF THE STUDY: A significant proportion of patients with severe valvular aortic stenosis (AS) and preserved left ventricular (LV) systolic function have low transvalvular gradients. The study aim was to determine the mechanisms and outcome of patients with this hemodynamic profile of AS. METHODS: Among 1,679 patients who underwent transthoracic echocardiography for the evaluation of AS at the authors' institution, 215 (105 females, 110 males; mean age: 77 +/- 10 years) had isolated AS (mean aortic valve area index 0.39 +/- 0.1 cm2/m2), normal sinus rhythm and normal LV ejection fraction. The mean follow up was 23 +/- 12 months, and the end-points were mortality, aortic valve replacement (AVR), or mortality or AVR. RESULTS: Forty-seven patients had a transvalvular mean gradient (MG) <30 mmHg (MG(low)) and 168 had MG > or = 30 mmHg (MG(high)). Compared to MG(high), the MG(low) group had a higher prevalence of hypertension, lower LV end-diastolic volume index (47 +/- 9 versus 56 +/- 12 ml/m2, p <0.0001), lower LV stroke vol-ume index (37 +/- 12 versus 41 +/- 11 ml/beat, p <0.0002), a lesser severity of stenosis (aortic valve area index 0.37 +/- 0.09 versus 0.46 +/- 0.09 cm2/m2, p <0.0001) and a higher systemic vascular resistance (2163 +/- 754 versus 1879 +/- 528 dyne cm s(-5). The LV end-diastolic volume index, systemic vascular resistance and energy loss index were predictors of MG <30 mmHg (OR = 0.30, 95% CI, 0.12, 0.62; OR = 3.05, 95% CI, 1.71, 6.26; and OR = 6.76, 95% CI, 3.44,15.38, respectively). MG <30 mmHg (MGhigh) was associated with almost 50% lower referral to surgery and a two-fold increase in preoperative mortality. CONCLUSION: In severe AS with a normal LV ejection fraction, MG <30 mmHg is related to a lesser severity of stenosis, a smaller LV volume, a lower flow rate and a higher systemic vascular resistance. Compared to the MG(high) group, these patients were less frequently referred to surgery and had a higher mortality.

Relation of the Myocardial Contraction Fraction, as Calculated from M-Mode Echocardiography, With Incident Heart Failure, Atherosclerotic Cardiovascular Disease and Mortality (Results from the Cardiovascular Health Study).

We evaluated the association between 2-dimensional (2D) echocardiography (echo)-determined myocardial contraction fraction (MCF) and adverse cardiovascular outcomes including incident heart failure (HF), atherosclerotic cardiovascular disease (ASCVD), and mortality. The MCF, the ratio of left ventricular (LV) stroke volume (SV) to myocardial volume (MV), is a volumetric measure of myocardial shortening that can distinguish pathologic from physiological hypertrophy. Using 2D echo-guided M-mode data from the Cardiovascular Health Study, we calculated MCF in subjects with LV ejection fraction (EF) ≥55% and used Cox models to evaluate its association with incident HF, ASCVD, and all-cause mortality after adjusting for clinical and echo parameters. We assessed whether log2(SV) and log2(MV) were consistent with the expected 1:-1 ratio used in the definition of MCF. Among 2,147 participants (age 72 ± 5 years), average MCF was 59 ± 13%. After controlling for clinical and echo variables, each 10% absolute increment in MCF was associated with lower risk of HF (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.82, 0.94), ASCVD (HR 0.90; 95% CI 0.85, 0.95), and death (HR 0.93; 95% CI 0.89, 0.97). Moreover, the MCF was still significantly associated with ASCVD and mortality, but not HF, after adjustment for percent-predicted LV mass. Significant departure from the 1:-1 ratio was not observed for ASCVD or death, but did occur for HF, driven by a stronger association for MV than SV. In conclusion, among older adults without CVD or low LV ejection fraction, 2D echo-guided M-mode-derived MCF was independently associated with lower risk of adverse cardiovascular outcomes, but this ratiometric index may not capture the full relation that is apparent when its components are modeled separately in the case of HF.

Relationship of bone mineral density with valvular and annular calcification in community-dwelling older people: The Cardiovascular Health Study.

Associations between bone mineral density and aortic valvular, aortic annular, and mitral annular calcification were investigated in a cross-sectional analysis of a population-based cohort of 1497 older adults. Although there was no association between continuous bone mineral density and outcomes, a significant association between osteoporosis and aortic valvular calcification in men was found. INTRODUCTION: The process of cardiac calcification bears a resemblance to skeletal bone metabolism and its regulation. Experimental studies suggest that bone mineral density (BMD) and valvular calcification may be reciprocally related, but epidemiologic data are sparse. METHODS: We tested the hypothesis that BMD of the total hip and femoral neck measured by dual-energy X-ray absorptiometry (DXA) is inversely associated with prevalence of three echocardiographic measures of cardiac calcification in a cross-sectional analysis of 1497 older adults from the Cardiovascular Health Study. The adjusted association of BMD with aortic valve calcification (AVC), aortic annular calcification (AAC), and mitral annular calcification (MAC) was assessed with relative risk (RR) regression. RESULTS: Mean (SD) age was 76.2 (4.8) years; 58% were women. Cardiac calcification was highly prevalent in women and men: AVC, 59.5 and 71.0%; AAC 45.1 and 46.7%; MAC 42.8 and 39.5%, respectively. After limited and full adjustment for potential confounders, no statistically significant associations were detected between continuous BMD at either site and the three measures of calcification. Assessment of WHO BMD categories revealed a significant association between osteoporosis at the total hip and AVC in men (adjusted RR compared with normal BMD = 1.24 (1.01-1.53)). In graded sensitivity analyses, there were apparent inverse associations between femoral neck BMD and AVC with stenosis in men, and femoral neck BMD and moderate/severe MAC in women, but these were not significant. CONCLUSION: These findings support further investigation of the sex-specific relationships between low BMD and cardiac calcification, and whether processes linking the two could be targeted for therapeutic ends.

Clinical significance of calcification of the fibrous skeleton of the heart and aortosclerosis in community dwelling elderly. The Cardiovascular Health Study (CHS).

BACKGROUND: Mitral annular calcification (MAC), aortic annular calcification (AAC), and aortic valve sclerosis (AVS) are associated with aging, and MAC and AVS are markers of advanced atherosclerosis. No studies have examined the prevalence and the clinical relevance of all 3 forms of calcification in a single free-living elderly population. METHODS: We used 2-dimensional echocardiography to evaluate MAC, AAC, AVS and all 3 combined in 3929 participants, mean age 76 +/- 5 years, 60% women, in the Cardiovascular Health Study, a prospective community-based observational study designed to assess cardiovascular disease (CVD) risk factors and outcomes in elderly persons. RESULTS: Mitral annular calcification was found in 1640 (42 %) subjects, AAC in 1710 (44 %), AVS in 2114 (54 %), and all 3 combined in 662 (17 %). The participants with these findings were older than those without them, and those with MAC had worse cardiovascular, renal, metabolic, and functional profile than those with AAC and AVS. Age-, sex-, and race-adjusted logistic regression analysis found a significant association between the 3 calcification categories and CVD, the strongest being between the combined group with congestive heart failure (odds ratio 2.04, 95% CI 1.34-3.09). In highly adjusted models, only MAC was associated with CVD, and the strength of association was related to the severity of MAC. CONCLUSIONS: In free-living elderly, MAC, AAC, and AVS are highly prevalent and are associated with CVD. Mitral annular calcification in particular has strong association with CVD, and with an adverse biomedical profile.

Cardiovascular morbidity and mortality in community-dwelling elderly individuals with calcification of the fibrous skeleton of the base of the heart and aortosclerosis (The Cardiovascular Health Study).

In the elderly, mitral annular calcification (MAC) and aortic valve sclerosis (AVS) are associated with increased cardiovascular morbidity and mortality. Aortic annular calcification (AAC) commonly occurs with MAC. However, the prognostic value of AAC, singly or in combination with MAC and AVS, for incident cardiovascular disease and mortality is unknown. From the Cardiovascular Health Study, we analyzed 3,782 participants (76 +/- 5 years of age, 60% women) who had an echocardiogram at the 1994 to 1995 examination and who were prospectively followed for an average of 6.6 years (range 0.01 to 8.5). All 3 calcification categories were associated with incident congestive heart failure (MAC: hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.35 to 2.18, AAC: HR 1.62, 95% CI 1.28 to 2.06, and AVS: HR 1.50, 95% CI 1.19 to 1.89) and death. A stronger association with incident cardiovascular disease and mortality was observed with a larger number of calcification categories and with increased MAC severity. Moreover, in the participants with prevalent cardiovascular disease at echocardiographic examination (n = 1,054), MAC and AAC were still associated with cardiovascular mortality (MAC: HR 1.91, 95% CI 1.04 to 3.50; AAC: HR 2.11, 95% CI 1.16 to 3.85) even in fully adjusted models. In conclusion, MAC, AAC, and AVS are associated with a significant risk of incident congestive heart failure, cardiovascular and all-cause mortalities, and worse outcome in older patients with preexisting cardiovascular disease. Elderly patients with these findings represent a high-risk group and may require close medical attention.