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).

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.

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).

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.

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.

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.

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.

Thoracic Aortic Aneurysm Growth in Bicuspid Aortic Valve Patients: Role of Aortic Stiffness and Pulsatile Hemodynamics.

Background Bicuspid aortic valve ( BAV ) is the most common congenital cardiac abnormality. A thoracic aortic aneurysm ( TAA ) is present in ≈50% of BAV patients, who also have an 8-fold higher risk of aortic dissection than the general population. Because the health of the aorta is directly reflected in its stiffness and pulsatile hemodynamics, we hypothesized that measures of aortic stiffness and arterial load would be associated with TAA growth in BAV . Methods and Results Twenty-nine unoperated participants with TAA due to BAV who had serial imaging were recruited. Aortic stiffness and steady and pulsatile arterial load were evaluated with validated methods that integrate arterial tonometry with echocardiography. TAA growth was assessed retrospectively based on available imaging, blinded to hemodynamic status. Multivariable linear regression assessed associations of aortic stiffness and hemodynamic variables with TAA growth, adjusting for potential confounders. Overall, 66% of participants were men. Mean±SD for age, baseline aneurysm size, growth rate, and follow-up time were 57.2±8.3 years, 46.9±3.6 mm, 0.75±0.81 mm/y, and 2.9±3.3 years, respectively. We found that greater aortic stiffness (ß± SE for carotid-femoral pulse wave velocity: 0.30±0.13. P=0.03) and aortic characteristic impedance (ß± SE : 0.46±0.18, P=0.02), as well as lower total arterial and proximal aortic compliance (ß± SE : -0.44±0.21, P=0.05, and -0.63±0.16, P=0.001, respectively) were independently associated with faster aneurysm growth. Conclusions In patients with TAA due to BAV , measures of greater aortic stiffness and pulsatile arterial load indicate an association with accelerated aneurysm expansion. Assessing arterial hemodynamics may be useful for risk stratification and disease monitoring in TAA patients with BAV .

Lead-Specific Features Predisposing to the Development of Tricuspid Regurgitation After Endocardial Lead Implantation.

BACKGROUND: Endocardial lead in the right ventricle is recognized as a cause for tricuspid regurgitation (TR), but the mechanism remains elusive. We sought to evaluate lead-specific features on the development of TR after endocardial lead implantation. METHODS: This was a prospective single-center study. The patients underwent 2-dimensional echocardiograms before endocardial lead implantation and at follow-up visits at 4 to 6 weeks, 6 months, and 12 months. We assessed the position of the endocardial lead at the tricuspid annulus by 3-dimensional echocardiography, the tricuspid leaflet interference by the endocardial lead by both 2- and 3-dimensional echocardiography, and the degree of lead slack radiologically. Patient characteristics and lead-related factors were evaluated in the prediction of new or worse TR by univariable and multivariable analyses. RESULTS: New or increased TR was detected in 38 of 128 patients at the 12-month follow-up. The postero-septal commissure was the most common lead position, and tricuspid leaflet interference detected in 21 patients was associated with a noncommissural lead position. The implantation of an implantable cardioverter defibrillator lead was not associated with new TR compared with the implantation of a pacemaker lead. Tricuspid leaflet interference (P < 0.0001), but not lead position or lead slack, was the only lead-specific factor associated with the development of TR. CONCLUSION: After right ventricle endocardial lead implantation, leaflet interference determined by echocardiography, but not the nature of the lead, the lead position at the tricuspid annulus, and the radiological lead slack, predicted TR development at 1 year postimplantation.

CONTEXTE: Il est établi que la présence d'une sonde endocavitaire dans le ventricule droit est une cause de régurgitation tricuspide (RT), mais le mécanisme en cause n'est pas encore bien compris. Nous avons tenté d'évaluer la corrélation entre certaines caractéristiques des sondes et l'apparition d'une RT secondaire à l'implantation d'une sonde endocavitaire. MÉTHODOLOGIE: Il s'agit d'une étude prospective menée dans un seul centre. Une échocardiographie bidimensionnelle a été réalisée avant la mise en place d'une sonde endocavitaire, ainsi qu'aux visites de suivi menées 4 à 6 semaines, 6 mois et 12 mois après l'intervention. Nous avons évalué la position de la sonde endocavitaire par rapport à l'anneau tricuspidien par échocardiographie tridimensionnelle, l'interférence de la sonde avec la valve tricuspide par échocardiographie bidimensionnelle et tridimensionnelle, et le degré de liberté de mouvement de la sonde par radiographie. Les caractéristiques des patients et les facteurs liés à la sonde ont été pris en compte dans la prédiction du risque de RT nouvelle ou d'aggravation d'une RT existante au moyen d'analyses univariées et multivariées. RÉSULTATS: Une RT nouvelle ou aggravée a été détectée au suivi à 12 mois chez 38 des 128 patients. Dans la plupart des cas, la sonde se trouvait à la commissure postéroseptale; chez 21 patients, une interférence avec la valve tricuspide a été détectée alors que la sonde ne se trouvait pas à la commissure. La mise en place d'une sonde de défibrillateur implantable n'a pas été associée à l'apparition d'une RT, comparativement à l'implantation d'une sonde de stimulateur cardiaque. L'interférence avec la valve tricuspide (p < 0,0001) était le seul facteur lié à la sonde associé à l'apparition d'une RT; aucun lien n'a été établi avec la position et le degré de liberté de mouvement de la sonde. CONCLUSION: Après la mise en place d'une sonde endocavitaire dans le ventricule droit, l'interférence avec la valve tricuspide établie par échocardiographie permettait de prédire l'apparition d'une RT dans l'année suivant la mise en place de la sonde sans égard au type de sonde, à sa position par rapport à l'anneau tricuspidien ou à la liberté de mouvement détectée par radiographie.