Predictors of embolism and death in left-sided infective endocarditis: the European Society of Cardiology EURObservational Research Programme European Infective Endocarditis registry.

BACKGROUND AND AIMS: Even though vegetation size in infective endocarditis (IE) has been associated with embolic events (EEs) and mortality risk, it is unclear whether vegetation size associated with these potential outcomes is different in left-sided IE (LSIE). This study aimed to seek assessing the vegetation cut-off size as predictor of EE or 30-day mortality for LSIE and to determine risk predictors of these outcomes. METHODS: The European Society of Cardiology EURObservational Research Programme European Infective Endocarditis is a prospective, multicentre registry including patients with definite or possible IE throughout 2016-18. Cox multivariable logistic regression analysis was performed to assess variables associated with EE or 30-day mortality. RESULTS: There were 2171 patients with LSIE (women 31.5%). Among these affected patients, 459 (21.1%) had a new EE or died in 30 days. The cut-off value of vegetation size for predicting EEs or 30-day mortality was >10 mm [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.13-1.69, P = .0015]. Other adjusted predictors of risk of EE or death were as follows: EE on admission (HR 1.89, 95% CI 1.54-2.33, P < .0001), history of heart failure (HR 1.53, 95% CI 1.21-1.93, P = .0004), creatinine >2 mg/dL (HR 1.59, 95% CI 1.25-2.03, P = .0002), Staphylococcus aureus (HR 1.36, 95% CI 1.08-1.70, P = .008), congestive heart failure (HR 1.40, 95% CI 1.12-1.75, P = .003), presence of haemorrhagic stroke (HR 4.57, 95% CI 3.08-6.79, P < .0001), alcohol abuse (HR 1.45, 95% CI 1.04-2.03, P = .03), presence of cardiogenic shock (HR 2.07, 95% CI 1.29-3.34, P = .003), and not performing left surgery (HR 1.30 95% CI 1.05-1.61, P = .016) (C-statistic = .68). CONCLUSIONS: Prognosis after LSIE is determined by multiple factors, including vegetation size.

OUTSMART HF: A Randomized Controlled Trial of Routine Versus Selective Cardiac Magnetic Resonance for Patients With Nonischemic Heart Failure (IMAGE-HF 1B).

BACKGROUND: Cardiac magnetic resonance (CMR) is a recommended imaging test for patients with heart failure (HF); however, there is a lack of evidence showing incremental benefit over transthoracic echocardiography. Our primary hypothesis was that routine use of CMR will yield more specific diagnoses in nonischemic HF. Our secondary hypothesis was that routine use of CMR will improve patient outcomes. METHODS: Patients with nonischemic HF were randomized to routine versus selective CMR. Patients in the routine strategy underwent echocardiography and CMR, whereas those assigned to selective use underwent echocardiography with or without CMR according to the clinical presentation. HF causes was classified from the imaging data as well as by the treating physician at 3 months (primary outcome). Clinical events were collected for 12 months. RESULTS: A total of 500 patients (344 male) with mean age 59±13 years were randomized. The routine and selective CMR strategies had similar rates of specific HF causes at 3 months clinical follow-up (44% versus 50%, respectively; P=0.22). At image interpretation, rates of specific HF causes were also not different between routine and selective CMR (34% versus 30%, respectively; P=0.34). However, 24% of patients in the selective group underwent a nonprotocol CMR. Patients with specific HF causes had more clinical events than those with nonspecific caused on the basis of imaging classification (19% versus 12%, respectively; P=0.02), but not on clinical assessment (15% versus 14%, respectively; P=0.49). CONCLUSIONS: In patients with nonischemic HF, routine CMR does not yield more specific HF causes on clinical assessment. Patients with specific HF causes from imaging had worse outcomes, whereas HF causes defined clinically did not. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01281384.

Echocardiography in the Assessment of Patients with Rheumatologic Diseases.

Cardiovascular disease is an important extra-articular manifestation of rheumatologic diseases leading to considerable mortality and morbidity. Echocardiography emerges as a useful non-invasive technique for the screening and evaluation of cardiac involvement in these patients. With the technological advancement in echocardiographic techniques, we have gained a greater appreciation of the prevalence and nature of the cardiac involvement in these patients, as detection of subclinical disease is increasingly feasible. This review discusses cardiac involvement in patients with rheumatoid arthritis, systemic lupus erythematosus, anti-phospholipid antibody syndrome, systemic sclerosis and ankylosing spondylitis, and the role of different echocardiographic modalities in their evaluation.

Validation of two-dimensional methods for left atrial volume measurement: a comparison of echocardiography with cardiac computed tomography.

BACKGROUND: Left atrial volume (LAVol) is an important predictor of cardiovascular outcomes. Different formulas are applied to calculate LAVol using two-dimensional transthoracic echocardiography (2DTTE) with variable reference values. The objective of the study was to evaluate the accuracy of methods to calculate LAVol by 2DTTE or cardiac computed tomography (CT). METHODS AND RESULTS: Overall 177 consecutive patients who underwent both a 2DTTE and retrospective electrocardiogram (ECG)-gated coronary CT angiography (CTA) within 15 days were included for this study. LA volume measurements were calculated by 2DTTE and 2DCT using the biplane area-length, biplane Simpson's, prolate-ellipsoid-1 and prolate-ellipsoid-2 methods. These results were compared with those measured by CT using a volumetric method. There was very good correlation between the CT and echocardiographic measures for LAVol, but significant underestimation of the echocardiographic methods when compared to the reference standard (33.5%, 39.1%, 48.1%, and 53.2% for the biplane area-length, biplane Simpson's, prolate-ellipsoid-1, and prolate-ellipsoid-2 methods, respectively). The biplane area-length method using 2DTTE had the closest volume estimation of all echocardiographic methods to the reference standard (67.6 ± 25.5 mL vs. 106 ± 35.5 mL, r = 0.712). Similarly, the biplane area-length method using CT most accurately predicted LAVol (103.3 ± 36.0 mL, r = 0.965). CONCLUSIONS: Compared to CT, 2DTTE provides reasonable assessment of LAVol, although all measurement methods underestimate LAVol. For both 2DTTE and CT, the biplane area-length method appears to provide the most accurate 2D estimate of LAVol.

Tricuspid regurgitation following implantation of a pacemaker/cardioverter-defibrillator.

Tricuspid regurgitation due to permanent pacemaker/defibrillator lead implantation (LITR) has been described more than 3 decades ago, but has come into attention recently due to the dramatic increase in the use of these devices. This entity has not been well defined and its impact on the patient and the health care system is largely unknown. This complication can have important implications. First, the presence and severity of tricuspid regurgitation in general is associated with reduced patient survival, and in the severe cases may require corrective surgery. Second, with the increasing age of the population and the expanding indications of these devices, one expects to encounter many more cases of LITR in the future. Third, this is an iatrogenic complication and therefore potentially preventable. This review discusses the prevalence, mechanisms, and risk factors of LITR as well as the management and potential strategies to prevent its occurrence.

Arterial Age and Early Vascular Aging, But Not Chronological Age, Are Associated With Faster Thoracic Aortic Aneurysm Growth.

Background Aneurysm size is an imperfect risk assessment tool for those with thoracic aortic aneurysm (TAA). Assessing arterial age may help TAA risk stratification, as it better reflects aortic health. We sought to evaluate arterial age as a predictor of faster TAA growth, independently of chronological age. Methods and Results We examined 137 patients with TAA. Arterial age was estimated according to validated equations, using patients' blood pressure and carotid-femoral pulse wave velocity. Aneurysm growth was determined prospectively from available imaging studies. Multivariable linear regression assessed the association of chronological age and arterial age with TAA growth, and multivariable logistic regression assessed associations of chronological and arterial age with the presence of accelerated aneurysm growth (defined as growth>median in the sample). Mean±SD chronological and arterial ages were 62.2±11.3 and 54.2±24.5 years, respectively. Mean baseline TAA size and follow-up time were 45.9±4.0 mm and 4.5±1.9 years, respectively. Median (interquartile range) TAA growth was 0.31 (0.14-0.52) mm/year. Older arterial age (ß±SE for 1 year: 0.004±0.001, P<0.0001) was independently associated with faster TAA growth, while chronological age was not (P=0.083). In logistic regression, each 5-year increase in arterial age was associated with a 23% increase in the odds of accelerated TAA growth (95% CI, 1.085-1.394; P=0.001). Conclusions Arterial age is independently associated with accelerated aneurysm expansion, while chronological age is not. Our results highlight that a noninvasive and inexpensive assessment of arterial age can potentially be useful for TAA risk stratification and disease monitoring as compared with the current clinical standard (chronological age).

Aortic Stenosis Progression: A Systematic Review and Meta-Analysis.

BACKGROUND: Aortic valve stenosis is a progressive disorder with variable progression rates. The factors affecting aortic stenosis (AS) progression remain largely unknown. OBJECTIVES: This systematic review and meta-analysis sought to determine AS progression rates and to assess the impact of baseline AS severity and sex on disease progression. METHODS: The authors searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 1, 2020, for prospective studies evaluating the progression of AS with the use of echocardiography (mean gradient [MG], peak velocity [PV], peak gradient [PG], or aortic valve area [AVA]) or computed tomography (calcium score [AVC]). Random-effects meta-analysis was performed to evaluate the rate of AS progression for each parameter stratified by baseline severity, and meta-regression was performed to determine the impact of baseline severity and of sex on AS progression rate. RESULTS: A total of 24 studies including 5,450 patients (40% female) met inclusion criteria. The pooled annualized progression of MG was +4.10 mm Hg (95% CI: 2.80-5.41 mm Hg), AVA -0.08 cm2 (95% CI: 0.06-0.10 cm2), PV +0.19 m/s (95% CI: 0.13-0.24 m/s), PG +7.86 mm Hg (95% CI: 4.98-10.75 mm Hg), and AVC +158.5 AU (95% CI: 55.0-261.9 AU). Increasing baseline severity of AS was predictive of higher rates of progression for MG (P < 0.001), PV (P = 0.001), and AVC (P < 0.001), but not AVA (P = 0.34) or PG (P = 0.21). Only 4 studies reported AS progression stratified by sex, with only PV and AVC having 3 studies to perform a meta-analysis. No difference between sex was observed for PV (P = 0.397) or AVC (P = 0.572), but the level of confidence was low. CONCLUSIONS: This study provides progression rates for both hemodynamic and anatomic parameters of AS and shows that increasing hemodynamic and anatomic baseline severity is associated with faster AS progression. More studies are needed to determine if sex differences affect AS progression. (Aortic Valve Stenosis Progression Rate: A Systematic Review and Meta-Analysis; CRD42021207726).

EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease.

The introduction of devices for transcatheter aortic valve implantation, mitral repair, and closure of prosthetic paravalvular leaks has led to a greatly expanded armamentarium of catheter-based approaches to patients with regurgitant as well as stenotic valvular disease. Echocardiography plays an essential role in identifying patients suitable for these interventions and in providing intra-procedural monitoring. Moreover, echocardiography is the primary modality for post-procedure follow-up. The echocardiographic assessment of patients undergoing transcatheter interventions places demands on echocardiographers that differ from those of the routine evaluation of patients with native or prosthetic valvular disease. Consequently, the European Association of Echocardiography in partnership with the American Society of Echocardiography has developed the recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. It is intended that this document will serve as a reference for echocardiographers participating in any or all stages of new transcatheter treatments for patients with valvular heart disease.

Left atrial-left ventricular angle, a new measure of left atrial and left ventricular remodeling.

We assessed the left atrial-left ventricular (LA-LV) long axis angulation value as a new measure of LA remodeling, and studied its predictors, its effect on two-dimensional LA volume (2D LAVol) estimation, and optimization techniques for 2D LAVol values. Retrospective electrocardiogram-gated coronary computed tomographic angiograms of 164 consecutive patients were reviewed. The LA-LV angle was measured in reconstructed 3-chamber views, and its predictors were determined. The LAVol measured by the area-length method after image optimization along the LV long axis (AL) and the LA long axis (AC-AL), was compared with that measured by the three-dimensional (3D)-volumetric method. LAVol calculation was modified to minimize differences from the 3D values. LA-LV angles ranged from 0° to 63°. In the univariate analysis, decreasing angulation was significantly associated with increasing LV end-diastolic volume (LVEDV), mitral regurgitation grade, LV and LA anteroposterior dimensions, and decreasing LV ejection fraction (LVEF). On multivariate analysis, increasing LVEDV, MR, and LA anteroposterior dimension inversely correlated with angulation; LVEF was positively correlated. The AL and 3D methods significantly differed only for patients with angles ≤ 29.9°. Conversely, LAVol was overestimated for all angules by AC-AL. Modification of AL LAVol using a regression equation, or by substituting the shortest with the longest and average LA lengths in patients with angles ≤ 29.9° and 30-39.9°, respectively neutralized the difference. The LA-LV angle is a new measure of LA and LV remodeling predicted by LV size and function, MR, and LA-anteroposterior dimension. AL formula modifications based on angulation in LV-optimized views better correlate with the 3D method than LA-view modification.

Central Hypertension in Patients With Thoracic Aortic Aneurysms: Prevalence and Association With Aneurysm Size and Growth.

BACKGROUND: Hypertension (HTN) has the greatest population-attributable risk for aortic dissection and is highly prevalent among patients with thoracic aortic aneurysms (TAAs). Although HTN is diagnosed based on brachial blood pressure (bBP), central HTN (central systolic blood pressure [cSBP] ≥130 mm Hg) is of interest as it better reflects blood pressure (BP) in the aorta. We aimed to (i) evaluate the prevalence of central HTN among TAA patients without a diagnosis of HTN, and (ii) assess associations of bBP vs. central blood pressure (cBP) with aneurysm size and growth. METHODS: One hundred and five unoperated subjects with TAAs were recruited. With validated methodology, cBP was assessed with applanation tonometry. Aneurysm size was assessed at baseline and follow-up using imaging modalities. Aneurysm growth rate was calculated in mm/year. Multivariable linear regression adjusted for potential confounders assessed associations of bBP and cBP with aneurysm size and growth. RESULTS: Seventy-seven percent of participants were men and 49% carried a diagnosis of HTN. Among participants without diagnosis of HTN, 15% had central HTN despite normal bBP ("occult central HTN"). In these patients, higher central systolic BP (cSBP) and central pulse pressure (cPP) were independently associated with larger aneurysm size (ß ± SE = 0.28 ± 0.11, P = 0.014 and cPP = 0.30 ± 0.11, P = 0.010, respectively) and future aneurysm growth (ß ± SE = 0.022 ± 0.008, P = 0.013 and 0.024 ± 0.009, P = 0.008, respectively) while bBP was not (P > 0.05). CONCLUSIONS: In patients with TAAs without a diagnosis of HTN, central HTN is prevalent, and higher cBP is associated with larger aneurysms and faster aneurysm growth.

Clinical profile and outcome of recurrent infective endocarditis.

AIMS: Purpose of this study is to compare the clinical course and outcome of patients with recurrent versus first-episode infective endocarditis (IE). METHODS: Patients with recurrent and first-episode IE enrolled in the EUROpean ENDOcarditis (EURO-ENDO) registry including 156 centres were identified and compared using propensity score matching. Recurrent IE was classified as relapse when IE occurred ≤6 months after a previous episode or reinfection when IE occurred >6 months after the prior episode. RESULTS: 3106 patients were enrolled: 2839 (91.4%) patients with first-episode IE (mean age 59.4 (±18.1); 68.3% male) and 267 (8.6%) patients with recurrent IE (mean age 58.1 (±17.7); 74.9% male). Among patients with recurrent IE, 13.2% were intravenous drug users (IVDUs), 66.4% had a repaired or replaced valve with the tricuspid valve being more frequently involved compared with patients with first-episode IE (20.3% vs 14.1%; p=0.012). In patients with a first episode of IE, the aortic valve was more frequently involved (45.6% vs 39.5%; p=0.061). Recurrent relapse and reinfection were 20.6% and 79.4%, respectively. Staphylococcus aureus was the microorganism most frequently observed in both groups (p=0.207). There were no differences in in-hospital and post-hospitalisation mortality between recurrent and first-episode IE. In patients with recurrent IE, in-hospital mortality was higher in IVDU patients. Independent predictors of poorer in-hospital and 1-year outcome, including the occurrence of cardiogenic and septic shock, valvular disease severity and failure to undertake surgery when indicated, were similar for recurrent and first-episode IE. CONCLUSIONS: In-hospital and 1-year mortality was similar in patients with recurrent and first-episode IE who shared similar predictors of poor outcome.

Effect of Lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial.

BACKGROUND: Aortic stenosis (AS) is an active process with similarities to atherosclerosis. The objective of this study was to assess the effect of cholesterol lowering with rosuvastatin on the progression of AS. METHODS AND RESULTS: This was a randomized, double-blind, placebo-controlled trial in asymptomatic patients with mild to moderate AS and no clinical indications for cholesterol lowering. The patients were randomized to receive either placebo or rosuvastatin 40 mg daily. A total of 269 patients were randomized: 134 patients to rosuvastatin 40 mg daily and 135 patients to placebo. Annual echocardiograms were performed to assess AS progression, which was the primary outcome; the median follow-up was 3.5 years. The peak AS gradient increased in patients receiving rosuvastatin from a baseline of 40.8+/-11.1 to 57.8+/-22.7 mm Hg at the end of follow-up and in patients with placebo from 41.6+/-10.9 mm Hg at baseline to 54.8+/-19.8 mm Hg at the end of follow-up. The annualized increase in the peak AS gradient was 6.3+/-6.9 mm Hg in the rosuvastatin group and 6.1+/-8.2 mm Hg in the placebo group (P=0.83). Treatment with rosuvastatin was not associated with a reduction in AS progression in any of the predefined subgroups. CONCLUSIONS: Cholesterol lowering with rosuvastatin 40 mg did not reduce the progression of AS in patients with mild to moderate AS; thus, statins should not be used for the sole purpose of reducing the progression of AS. Clinical Trial Registration Information- URL: http://www.controlled-trials.com/. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN 32424163.

Effect of rosuvastatin on C-reactive protein and progression of aortic stenosis.

BACKGROUND: Elevated C-reactive protein (CRP) is a common finding in patients with aortic stenosis (AS) and may be associated with rapid AS progression and worse outcome. The purpose of the study was to examine the role of high-sensitivity CRP and its interaction with rosuvastatin on the progression of AS. METHODS: We measured CRP at baseline, 1 year, and end of follow-up in 260 patients with a median follow-up of 3.5 years. Analyses were performed based on baseline CRP tertiles and baseline CRP >3 and ≤3 mg/L. RESULTS: After adjustment for baseline characteristics, higher CRP levels were associated with age, female gender, body mass index, and lower high-density lipoprotein cholesterol levels but not with AS severity. Treatment with rosuvastatin led to a persistent decrease in CRP at 1 year and end of follow-up. Progression of AS was detected in patients in all 3 CRP tertiles, and rosuvastatin treatment had no impact on progression in all 3 tertiles. Similar findings were observed using CRP >3 mg/L as the cutpoint. Multiple linear regression showed that baseline AS velocity (P < .001), but not CRP, was the only predictor of progression of AS; age (P = .05) and baseline AS velocity (P < .001), but not CRP and rosuvastatin treatment, were predictors of outcome events. CONCLUSION: C-reactive protein does not predict severity, progression, and prognosis in patients with mild to moderate AS. Treatment with rosuvastatin reduces CRP levels but has no effect on the progression and clinical events of AS.

EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease.

The introduction of devices for transcatheter aortic valve implantation, mitral repair, and closure of prosthetic paravalvular leaks has led to a greatly expanded armamentarium of catheter-based approaches to patients with regurgitant as well as stenotic valvular disease. Echocardiography plays an essential role in identifying patients suitable for these interventions and in providing intra-procedural monitoring. Moreover, echocardiography is the primary modality for post-procedure follow-up. The echocardiographic assessment of patients undergoing transcatheter interventions places demands on echocardiographers that differ from those of the routine evaluation of patients with native or prosthetic valvular disease. Consequently, the European Association of Echocardiography in partnership with the American Society of Echocardiography has developed the recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. It is intended that this document will serve as a reference for echocardiographers participating in any or all stages of new transcatheter treatments for patients with valvular heart disease.

Single vs Serial Assessments of Arterial Hemodynamics to Predict Thoracic Aortic Aneurysm Expansion.

BACKGROUND: Thoracic aortic aneurysm (TAA) is a highly morbid disease. We have previously shown that baseline hemodynamic measures reflecting aortic function are associated with future TAA expansion. However, whether serial arterial hemodynamic assessment further improves TAA growth assessment remains unknown. Therefore, we aimed to compare single vs serial arterial hemodynamic assessments in the evaluation of future TAA growth. METHODS: Eighty-six unoperated participants with TAA underwent noninvasive arterial hemodynamic assessment using arterial tonometry and echocardiography at baseline and after 1 year. Aortic diameter was measured serially with the use of standard imaging modalities. Stepwise multivariable linear regression was used to assess associations of baseline and 1-year change (Δ) in arterial hemodynamic measures with TAA growth. RESULTS: Mean age was 62.7 ± 11.0 years; 79% were male. Mean aneurysm growth was 0.48 ± 0.54 mm/year after a follow-up of 2.96 ± 1.03 years. Yearly changes in arterial hemodynamic measures ranged from -3.2% to +4.2%. Linear regression results showed that while baseline arterial hemodynamic measures were independently associated with aneurysm growth (carotid-femoral pulse wave velocity: ß ± SE = 0.038 ± 0.013; aortic characteristic impedance: ß ± SE = 0.002 ± 0.001; proximal aortic compliance: ß ± SE = -0.011 ± 0.006; forward pressure wave amplitude: ß ± SE 0.009 ± 0.002; reflected pressure wave amplitude: ß ± SE = 0.017 ± 0.006; P < 0.05 for each), the 1-year Δ in these measures did not incrementally add to aneurysm growth assessment (P > 0.05 for each Δ). CONCLUSIONS: Although baseline measures of aortic function independently predict TAA expansion, 1-year changes in these measures do not improve this prediction. Thus, for TAA risk assessment purposes, a baseline assessment of aortic function may suffice, which simplifies its use for potential predictive algorithms.

Aortic Stiffness, Central Blood Pressure, and Pulsatile Arterial Load Predict Future Thoracic Aortic Aneurysm Expansion.

Thoracic aortic aneurysm is a disease associated with high morbidity and mortality. Clinically useful strategies for medical management of thoracic aortic aneurysm are critically needed. To address this need, we sought to determine the role of aortic stiffness and pulsatile arterial load on future aneurysm expansion. One hundred five consecutive, unoperated subjects with thoracic aortic aneurysm were recruited and prospectively followed. By combining arterial tonometry with echocardiography, we estimated measures of aortic stiffness, central blood pressure, steady, and pulsatile arterial load at baseline. Aneurysm size was measured at baseline and follow-up with imaging; growth was calculated in mm/y. Stepwise multivariable linear regression assessed associations of arterial stiffness and load measures with aneurysm growth after adjusting for potential confounders. Mean±SD age, baseline aneurysm size, and follow-up time were 62.6±11.4 years, 46.24±3.84 mm, and 2.92±1.01 years, respectively. Aneurysm growth rate was 0.43±0.37 mm/y. After correcting for multiple comparisons, higher central systolic (ß±SE: 0.026±0.009, P=0.007), and pulse pressures (ß±SE: 0.032±0.009, P=0.0002), carotid-femoral pulse wave velocity (ß±SE: 0.032±0.011, P=0.005), amplitudes of the forward (ß±SE: 0.044±0.012, P=0.0003) and reflected (ß±SE: 0.060±0.020, P=0.003) pressure waves, and lower total arterial compliance (ß±SE: -0.086±0.032, P=0.009) were independently associated with future aneurysm growth. Measures of aortic stiffness and pulsatile hemodynamics are independently associated with future thoracic aortic aneurysm growth and provide novel insights into disease activity. Our findings highlight the role of central hemodynamic assessment to tailor novel risk assessment and therapeutic strategies to patients with thoracic aortic aneurysm.

ApoCIII-Lp(a) complexes in conjunction with Lp(a)-OxPL predict rapid progression of aortic stenosis.

OBJECTIVE: This study assessed whether apolipoprotein CIII-lipoprotein(a) complexes (ApoCIII-Lp(a)) associate with progression of calcific aortic valve stenosis (AS). METHODS: Immunostaining for ApoC-III was performed in explanted aortic valve leaflets in 68 patients with leaflet pathological grades of 1-4. Assays measuring circulating levels of ApoCIII-Lp(a) complexes were measured in 218 patients with mild-moderate AS from the AS Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial. The progression rate of AS, measured as annualised changes in peak aortic jet velocity (Vpeak), and combined rates of aortic valve replacement (AVR) and cardiac death were determined. For further confirmation of the assay data, a proteomic analysis of purified Lp(a) was performed to confirm the presence of apoC-III on Lp(a). RESULTS: Immunohistochemically detected ApoC-III was prominent in all grades of leaflet lesion severity. Significant interactions were present between ApoCIII-Lp(a) and Lp(a), oxidised phospholipids on apolipoprotein B-100 (OxPL-apoB) or on apolipoprotein (a) (OxPL-apo(a)) with annualised Vpeak (all p<0.05). After multivariable adjustment, patients in the top tertile of both apoCIII-Lp(a) and Lp(a) had significantly higher annualised Vpeak (p<0.001) and risk of AVR/cardiac death (p=0.03). Similar results were noted with OxPL-apoB and OxPL-apo(a). There was no association between autotaxin (ATX) on ApoB and ATX on Lp(a) with faster progression of AS. Proteomic analysis of purified Lp(a) showed that apoC-III was prominently present on Lp(a). CONCLUSION: ApoC-III is present on Lp(a) and in aortic valve leaflets. Elevated levels of ApoCIII-Lp(a) complexes in conjunction with Lp(a), OxPL-apoB or OxPL-apo(a) identify patients with pre-existing mild-moderate AS who display rapid progression of AS and higher rates of AVR/cardiac death. TRIAL REGISTRATION: NCT00800800.