Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

BACKGROUND: Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. METHODS: In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. RESULTS: During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. CONCLUSIONS: Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. REGISTRATION: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

Assessment of the Severity of Aortic Regurgitation by Noninvasive Imaging : Non-invasive MMI for AR.

PURPOSE OF THE REVIEW: The role of multimodality imaging in the evaluation of patients with aortic regurgitation is summarized in this review. RECENT FINDINGS: The etiology (mechanism) of the aortic regurgitation and the severity of aortic regurgitation and hemodynamic consequences are key in the decision making of patients with severe aortic regurgitation. While echocardiography remains as the leading technique to assess all these parameters, other imaging techniques have become essential for the accurate assessment of aortic regurgitation severity and the timing of aortic intervention. The anatomic suitability of transcatheter aortic valve implantation in inoperable patients with severe aortic regurgitation is usually assessed with computed tomography. Aortic regurgitation is a prevalent disease with various pathophysiological mechanisms that need a personalized treatment. The evaluation of the mechanism and severity of aortic regurgitation can be initially performed with echocardiography. Three-dimensional techniques, including echocardiography, have become very relevant for accurate assessment of the regurgitation severity and its hemodynamic consequences. Assessment of myocardial tissue characteristics with cardiac magnetic resonance is key in the risk stratification of patients and in the timing of aortic intervention. Computed tomography is important in the assessment of aortic dimensions and selection of patients for transcatheter aortic valve implantation.

Prevalence and factors associated with atrial mitral and tricuspid regurgitation in patients with atrial fibrillation.

BACKGROUND: This study aimed to examine the prevalence of atrial tricuspid regurgitation (ATR) and atrial mitral regurgitation (AMR) in the setting of atrial fibrillation (AFib) and identify variables related to the severity of both types of regurgitation. METHODS: Cross-sectional study evaluating data from transthoracic echocardiograms performed during 2019. We included patients with AFib during the examination, and without primary valve disease or other significant heart disease. RESULTS: Four-hundred and thirty-two patients fulfilled the inclusion criteria (mean age 77.5±9.2 years, 49.1% women). We observed significant ATR in 14.8%, and significant AMR in 1.4% of patients. ATR and AMR severities were equal in 49.3% of patients, and 41% displayed greater ATR severity. ATR prevalence was significantly greater among women (23.1% vs 6.8%, p < 0.001), but AMR prevalence was similar between genders (1.9% vs .9%, p = 0.443). Variables related to greater ATR severity were: female sex (OR: 2.61, 95%CI: 1.60-4.24), left atrial (LA) volume (OR: 3.58, 95%CI: 1.50-8.55), systolic pulmonary artery pressure (OR: 1.10, 95%CI: 1.07-1.13), and moderate AMR (OR: 2.21, 95%CI: 1.22-4.00). Variables related to greater AMR severity were female sex (OR: 1.96, 95%CI: 1.24-3.09), LA volume (OR: 11.68, 95%CI: 5.29-25.80), and body mass index (OR: .94, 95%CI: .90-.98). CONCLUSIONS: In the context of AFib, ATR was more prevalent than AMR and prevailed in women. LA enlargement was associated with higher degrees of both AMR and ATR. Pulmonary hypertension was also independently associated with ATR, as well as greater AMR severity, suggesting possible adaptive changes in leaflets that might modify the atrial regurgitation incidence.

High-sensitivity troponin T in asymptomatic severe aortic stenosis.

Background: In asymptomatic severe aortic stenosis (ASAS), treatment decisions are made on an individual basis, and case management presents a clinical conundrum. Methods: We prospectively phenotyped consecutive patients with ASAS using echocardiography, exercise echocardiography, cardiac MRI and biomarkers (NT-proBNP, high-sensitivity troponin T (hs-TnT) and ST2) (n = 58). The primary endpoint was a composite of cardiovascular death, new-onset symptoms, cardiac hospitalization, guideline-driven indication for valve replacement and cardiovascular death at 12 months. Results: During the first year, 46.6% patients met primary endpoint. In multivariable analysis, aortic regurgitation ≥2 (p = 0.01) and hs-TnT (p = 0.007) were the only independent predictors of the primary endpoint. The best cutoff value was identified as hs-TnT >10ng/L, which was associated with a ∼10-fold greater risk of the primary endpoint (HR, 9.62; 95% CI, 2.27-40.8; p = 0.002). A baseline predictive model including age, sex and variables showing p < 0.10 in univariable analyses showed an area under the curve (AUC) of 0.79(0.66-0.91). Incorporation of hs-TnT into this model increased the AUC to 0.90(0.81-0.98) (p = 0.03). Patient reclassification with the model including hs-TnT yielded an NRI of 1.28(0.46-1.78), corresponding to 43% adequately reclassified patients. Conclusions: In patients with ASAS, hs-TnT >10ng/L was associated with high risk of events within 12 months. Including hs-TnT in routine ASAS management markedly improved prediction metrics.

Clinical and prognostic implications of left ventricular dilatation in heart failure.

AIMS: To assess the agreement between left ventricular end-diastolic diameter index (LVEDDi) and volume index (LVEDVi) to define LV dilatation and to investigate the respective prognostic implications in patients with heart failure (HF). METHODS AND RESULTS: Patients with HF symptoms and LV ejection fraction (LVEF) < 50% undergoing cardiac magnetic resonance were evaluated retrospectively. LV dilatation was defined as LVEDDi or LVEDVi above the upper normal limit according to published reference values. Patients were followed up for the combined endpoint of cardiovascular death or HF hospitalization during 5 years. A total of 564 patients (median age 64 years; 79% men) were included. LVEDDi had a modest correlation with LVEDVi (r = 0.682, P < 0.001). LV dilatation was noted in 84% of patients using LVEDVi-based definition and in 73% using LVEDDi-based definition, whereas 20% of patients displayed discordant definitions of LV dilatation. During a median follow-up of 2.8 years, patients with both dilated LVEDDi and LVEDVi had the highest cumulative event rate (HR 3.00, 95% CI 1.15-7.81, P = 0.024). Both LVEDDi and LVEDVi were independently associated with the primary outcome (hazard ratio 3.29, 95%, P < 0.001 and 2.8, P = 0.009; respectively). CONCLUSION: The majority of patients with HF and LVEF < 50% present both increased LVEDDi and LVEDVi whereas 20% show discordant linear and volumetric definitions of LV dilatation. Patients with increased LVEDDi and LVEDVi have the worst clinical outcomes suggesting that the assessment of these two metrics is needed for better risk stratification.

Heart failure hospitalization following surgical or transcatheter aortic valve implantation in low-risk aortic stenosis.

AIMS: In low-risk patients with severe aortic stenosis (AS), sutureless surgical aortic valve replacement (SU-SAVR) may be an alternative to transcatheter aortic valve implantation (TAVI). The risk of heart failure hospitalization (HFH) after aortic valve replacement (AVR) in this population is incompletely characterized. This study aims to investigate the incidence, predictors, and outcomes of HFH in patients undergoing SU-SAVR versus TAVI. METHODS AND RESULTS: Patients referred for AVR between 2013 and 2020 at two centres were consecutively included. The decision for SU-SAVR or TAVI was determined by a multidisciplinary Heart Team. Cox regression and competing risk analysis were conducted to assess adverse events. Of 594 patients (mean age 77.5 ± 6.4, 59.8% male), 424 underwent SU-SAVR, while 170 underwent TAVI. Following a mean follow-up of 34.1 ± 23.1 months, HFH occurred in 112 (27.8%) SU-SAVR patients and in 8 (4.8%) TAVI patients (P < 0.001). The SU-SAVR cohort exhibited higher all-cause mortality (138 [32.5%] patients compared with 30 [17.6%] in the TAVI cohort [P < 0.001]). These differences remained significant after sensitivity analyses with 1:1 propensity score matching for baseline variables. SU-SAVR with HFH was associated with increased all-cause mortality (61.6% vs. 23.1%, P < 0.001). Independent associates of HFH in SU-SAVR patients included diabetes, atrial fibrillation, chronic obstructive pulmonary disease, lower glomerular filtration rate and lower left ventricular ejection fraction. SU-SAVR patients with HFH had a 12-month LVEF of 59.4 ± 12.7. CONCLUSIONS: In low-risk AS, SU-SAVR is associated with a higher risk of HFH and all-cause mortality compared to TAVI. In patients with severe AS candidate to SU-SAVR or TAVI, TAVI may be the preferred intervention.

Multimodality imaging in aortic stenosis: new diagnostic and therapeutic frontiers.

The advent of transcatheter aortic valve implantation has revolutionized the treatment of calcific aortic valve stenosis. Elderly patients who were previously considered inoperable have currently an efficacious and safe therapy that provides better survival. In addition, current practice guidelines tend to recommend earlier intervention to avoid the irreversible consequences of long-lasting pressure overload caused by the stenotic aortic valve. Appropriate timing of the intervention relies significantly on imaging techniques that provide information on the severity of the aortic stenosis as well as on the hemodynamic consequences and cardiac remodeling. While left ventricular ejection fraction remains one of the main functional parameters for risk stratification in patients with severe aortic stenosis, advances in imaging techniques have provided new structural and functional parameters that allow the identification of patients who will benefit from intervention before the occurrence of symptoms or irreversible cardiac damage. Furthermore, ongoing research aiming to identify the medical therapies that can effectively halt the progression of aortic stenosis relies heavily on imaging endpoints, and new imaging techniques that characterize the metabolic activity of calcific aortic stenosis have been proposed to monitor the effects of these therapies. The present review provides an up-to-date overview of the imaging advances that characterizes the pathophysiology and that have changed the management paradigm of aortic stenosis.

Timing of cardiac magnetic resonance and diagnostic yield in patients with myocardial infarction with nonobstructive coronary arteries.

INTRODUCTION AND OBJECTIVES: The present study sought to establish the diagnostic yield of cardiovascular magnetic resonance (CMR) in a large cohort of patients admitted with myocardial infarction (MI) with nonobstructive coronary artery disease (MINOCA) based on the timing of referral to CMR. METHODS: Consecutive patients referred to CMR from January 2009 to February 2022 with a working diagnosis of MINOCA were retrospectively evaluated. Cine, T2-weighted, early, and late gadolinium-enhanced images were acquired and analyzed. The frequency of the underlying diagnosis and the association between timing of CMR and relative frequency of each diagnosis were assessed. RESULTS: We included 207 patients (median age 50 years, 60% men). Final diagnosis after CMR was achieved in 91% of the patients (myocarditis in 45%, MI in 20%, tako-tsubo cardiomyopathy in 19%, and other cardiomyopathies in 7%). The performance of CMR within 7 days of admission with MINOCA (median, 5 days; 117 patients) allowed a higher diagnostic yield compared with CMR performed later (median, 10 days; 88 patients) (96% vs 86%, P=.02). Although myocarditis was the most frequent diagnosis in both groups according to time to CMR, its frequency was higher among patients with a CMR performed within the first 7 days (53% vs 35%, P=.02). The frequency of other underlying diagnoses was not influenced by CMR timing. CONCLUSIONS: CMR led to an underlying diagnosis of MINOCA in 91% of patients and its diagnostic yield increased to 96% when CMR was performed within 7 days of admission. The most frequent diagnosis was myocarditis..

Changes in echocardiographic parameters over time in paradoxical low-flow low-gradient aortic stenosis.

AIMS: To assess the progression of the disease and evolution of the main echocardiographic variables for quantifying AS in patients with severe low-flow low-gradient (LFLG) AS compared to other severe AS subtypes. METHODS AND RESULTS: Longitudinal, observational, multicenter study including consecutive asymptomatic patients with severe AS (aortic valve area, AVA < 1.0 cm²) and normal left ventricle ejection fraction (LVEF ≥ 50%). Patients were classified according to baseline echocardiography into: HG (high gradient; mean gradient ≥ 40 mmHg), NFLG (normal-flow low-gradient; mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35mL/m2), or LFLG (mean gradient < 40 mmHg, SVi ≤ 35 mL/m²). AS progression was analyzed by comparing patients' baseline measurements and their last follow-up measurements or those taken prior to aortic valve replacement (AVR). Of the 903 included patients, 401 (44.4%) were HG, 405 (44.9%) NFLG, and 97 (10.7%) LFLG. Progression of the mean gradient in a linear mixed regression model was greater in low-gradient groups: LFLG vs. HG (regression coefficient 0.124, P = 0.005) and NFLG vs. HG (regression coefficient 0.068, P = 0.018). No differences were observed between the LFLG and NFLG groups (regression coefficient 0.056, P = 0.195). However, AVA reduction was slower in the LFLG group compared to the NFLG (P < 0.001). During follow-up, in conservatively-managed patients, 19.1% (n = 9) of LFLG patients evolved to having NFLG AS and 44.7% (n = 21) to having HG AS. In patients undergoing AVR, 58.0% (n = 29) of LFLG baseline patients received AVR with a HG AS. CONCLUSION: LFLG AS shows an intermediate AVA and gradient progression compared to NFLG and HG AS. The majority of patients initially classified as having LFLG AS changed over time to having other severe forms of AS, and most of them received AVR with a HG AS.

Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits.

Objectives: To determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS). Methods: A longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] < 1.0 cm2) and normal left ventricular ejection fraction (LVEF). Patients were classified as: high-gradient (HG, mean gradient ≥ 40 mmHg), normal-flow low-gradient (NFLG, mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2). Results: Of 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3-30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12-0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13-0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20-0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively. Conclusions: Paradoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.

Preload dependence of pulmonary haemodynamics and right ventricular performance.

AIMS: Systolic pulmonary artery pressure (SPAP) and right heart adaptation in relation to pre-existing preload are often disregarded. To determine volume-related changes in the pulmonary-right ventricle (RV) unit and the preload dependence of its components, we analysed pulmonary haemodynamics and right ventricular performance, taking advantage of the plasma volume removal associated to haemodialysis (HD). METHODS AND RESULTS: Fifty-three stable patients on chronic HD with LVEF > 50% and without heart failure were recruited (mean age 63.0 ± 12.4 years; 31.2% women; hypertension in 89% and diabetes in 53%) and evaluated just before and after HD (mean ultrafiltration volume 2.4 ± 0.7 l). SPAP from both times were available in 39 patients. After HD, SPAP decreased (42.2 ± 12.6 to 33.7 ± 11.6 mmHg, p < 0.001) without modification of non-invasive pulmonary vascular resistance (1.75 ± 0.44 to 1.75 ± 0.40 eWU, p = 0.94). Age and drop in the E/e' ratio were the variables associated with greater reduction in PASP (p = 0.022 and p = 0.049, respectively). A significant reduction of right chamber sizes was observed, along with a diminution in measures of RV contractility, excluding RV longitudinal strain. Functional tricuspid regurgitation (FTR) diminution was observed in 26% of patients, occurring in every case with more than mild FTR. On multivariate analyses, left atrial size was the only predictor of pulmonary hypertension (defined as SPAP > 40 mmHg) (OR 1.29 (1.07-1.56), p = 0.006). CONCLUSION: Rapid volemic changes may affect FTR grading, RV size and contractility, with RV longitudinal strain being less variable than conventional parameters. SPAP decreases after HD, and this reduction is related to age and greater diminution of the E/e' ratio.

Long-term antibiotic therapy in patients with surgery-indicated not undergoing surgery infective endocarditis.

BACKGROUND: To date, there is little information regarding management of patients with infective endocarditis (IE) that did not undergo an indicated surgery. Therefore, we aimed to evaluate prognosis of these patients treated with a long-term antibiotic treatment strategy, including oral long term suppressive antibiotic treatment in five referral centres with a multidisciplinary endocarditis team. METHODS: This retrospective, multicenter study retrieved individual patient-level data from five referral centres in Spain. Among a total of 1797, 32 consecutive patients with IE were examined (median age 72 years; 78% males) who had not undergone an indicated surgery, but received long-term antibiotic treatment (LTAT) and were followed by a multidisciplinary endocarditis team, between 2011 and 2019. Primary outcomes were infection relapse and mortality during follow-up. RESULTS: Among 32 patients, 21 had IE associated with prostheses. Of the latter, 8 had an ascending aorta prosthetic graft. In 24 patients, a switch to long-term oral suppressive antibiotic treatment (LOSAT) was considered. The median duration of LOSAT was 277 days. Four patients experienced a relapse during follow-up. One patient died within 60 days, and 12 patients died between 60 days and 3 years. However, only 4 deaths were related to IE. CONCLUSIONS: The present study results suggest that a LTAT strategy, including LOSAT, might be considered for patients with IE that cannot undergo an indicated surgery. After hospitalization, they should be followed by a multidisciplinary endocarditis team.