5-Year Outcomes of Trans Carotid Transcatheter Aortic Valve Replacement.

BACKGROUND: Trans-carotid Transcatheter Aortic Valve Replacement (TC-TAVR) has emerged as an alternative TAVR access. However, scarce data on long-term outcomes following TC-TAVR exist. This study aimed to evaluate 5-year clinical outcomes post-TC-TAVR. METHODS: One hundred ten consecutive patients who underwent TC-TAVR and completed the 5-year after the procedure were included. Baseline, procedural, and follow-up data were collected prospectively in a dedicated database. The primary endpoint was the incidence of a composite of all-cause mortality, stroke, and repeat hospitalization. Echocardiography results, New York Heart Association (NYHA) class, and quality of life (QOL) assessed with the EuroQol visual analogue scale (EQ-VAS) were examined over the 5-year follow-up. RESULTS: The median age was 77 (72-82.2) years, 42.3% were women, and the median STS risk score was 5.02% (3.4-7.5%). The incidence of the composite endpoint was 54.5%. Death from any cause occurred in 45.6% of cases (11.9 per 100 patients-years), stroke in 8.2% (1.9 per 100 patient-years), disabling stroke in 2.7% (0.7 per 100 patient-years), and rehospitalization in 27.2%. The improvements in valve hemodynamics, NYHA class, and EQ-VAS following the procedure persisted at the 5-year follow-up (p<.001). Bioprosthetic valve failure occurred in 0.9%. CONCLUSIONS: About half of the moderate-to-high-risk patients undergoing TC-TAVR survived with no major cardiovascular events at 5-year follow-up. The yearly incidence of strokes was low, and early improvements in valve hemodynamics, functional status and QOL persisted at 5 years. These results suggest the long-term safety and efficacy of TC-TAVR, and would support this approach as an alternative to surgery in non-transfemoral candidates.

Sensor-guided transcatheter aortic valve replacement.

OBJECTIVES: The SavvyWire(OpSens Medical) is a support wire for transcatheter aortic valve replacement (TAVR) procedures that, in addition to its dedicated left ventricle (LV) pacing capabilities, has a distal pressure sensor that measures live transvalvular hemodynamics during the procedure. We aimed to determine the safety, efficacy, and functionality of the SavvyWire during TAVR procedures in an all-comer population. METHODS: We performed a multicentric, prospective, observational, single-arm, all-comers registry of patients with symptomatic, severe aortic stenosis undergoing TAVR in 3 Canadian centers. Data were collected in a dedicated database, and pre-specified questionnaires were fulfilled by the heart team implanters after each procedure. RESULTS: A total of 60 patients were included (mean age: 78.6 ± 7.2 years; 51% women; mean Society of Thoracic Surgeons score: 2.2 ± 1.6%). TAVR was performed through a transfemoral approach in 90% of cases, and balloon- and self-expandable valves were used in 73% and 27% of patients, respectively. There were no cases of LV perforation, guidewire deformation, significant loss of capture, or major software malfunction. The rate of successful delivery of the TAVR system was 100%, and effective LV pacing was achieved in 98% of patients. The pre-TAVR mean gradient was 39 ± 14 mm Hg while the final post-TAVR gradient was 8 ± 5 mm Hg; the mean aortic systolic pressure during rapid pacing was 54 ± 12 mm Hg. In 97% of the TAVR procedures, SavvyWire's functionality was reported to be better or similar to other TAVR workhorse support wires. CONCLUSIONS: SavvyWire was safe, effective, and functional for live transvalvular hemodynamic evaluation and rapid pacing during TAVR procedures. More studies with larger sample sizes and comparison against different wires and gradient measurement methods are warranted.

Incidence, Predictors, and Prognostic Impact of Bleeding Events After TAVR According to VARC-3 Criteria.

BACKGROUND: The updated Valve Academic Research Consortium (VARC) definition for bleeding events after transcatheter aortic valve replacement (TAVR) lacks of clinical validation. OBJECTIVES: The aim of this study was to determine the incidence, predictors, and clinical impact of bleeding events following TAVR as defined by recent VARC-3 criteria. METHODS: A total of 2,384 consecutive patients with severe symptomatic aortic stenosis undergoing TAVR were included. Early (at index hospitalization) and late (after hospital discharge) bleeding complications were defined according to VARC-3 criteria as type 1, 2, 3, or 4. Baseline, procedural, and follow-up (24 [IQR: 12-43] months) data were prospectively collected. RESULTS: Bleeding events occurred in 761 patients (31.9%): types 1, 2, 3, and 4 in 169 (22.2%), 399 (52.4%), 149 (19.6%), and 44 (5.8%) patients, respectively. The primary vascular access site and gastrointestinal locations were the most common bleeding sources among early and late bleeding events, respectively. Female sex, thoracotomy access, larger (14-F) sheath use, and dual antiplatelet therapy determined an increased risk of early bleeding events (P < 0.02 for all). The use of the radial artery for secondary access was associated with a significant risk reduction of early bleeding (P < 0.001). Type 2 and type 3 events were associated with an increased mortality risk at 30-day (HR: 2.94 [95% CI: 1.43-6.03; P = 0.003] and HR: 4.91 [95% CI: 2.19-11.03; P < 0.001], respectively) and 1-year (HR: 1.86 [95% CI: 1.28-2.69; P = 0.001] and HR: 2.28 [95% CI: 1.41-3.66; P = 0.001], respectively) follow-up. A similar prognostic pattern was observed when applying VARC-2 criteria but with a much lower global incidence of early bleeding events (19% vs 27%; P < 0.001). CONCLUSIONS: Bleeding events after TAVR were associated with poorer short- and long-term survival. The magnitude of this correlation was proportional to bleeding severity defined according to VARC-3 criteria. Further studies on bleeding prevention following TAVR are warranted to improve procedural safety and patient prognosis.

Myocardial Injury After Transcatheter Aortic Valve Replacement According to VARC-3 Criteria.

BACKGROUND: The Valve Academic Research Consortium (VARC)-3 definition for myocardial injury after transcatheter aortic valve replacement (TAVR) lacks of clinical validation. OBJECTIVES: This study sought to determine the incidence, predictors, and clinical impact of periprocedural myocardial injury (PPMI) following TAVR as defined by recent VARC-3 criteria. METHODS: We included 1,394 consecutive patients who underwent TAVR with a new-generation transcatheter heart valve. High-sensitivity troponin levels were assessed at baseline and within 24 hours after the procedure. PPMI was defined according to VARC-3 criteria as an increase ≥70 times in troponin levels (vs ≥15 times according to the VARC-2 definition). Baseline, procedural, and follow-up data were prospectively collected. RESULTS: PPMI was diagnosed in 193 (14.0%) patients. Female sex and peripheral artery disease were independent predictors of PPMI (P < 0.01 for both). PPMI was associated with a higher risk of mortality at 30-day (HR: 2.69, 95% CI: 1.50-4.82; P = 0.001) and 1-year (for all-cause mortality, HR: 1.54; 95% CI: 1.04-2.27; P = 0.032; for cardiovascular mortality, HR: 3.04; 95% CI: 1.68-5.50; P < 0.001) follow-up. PPMI according to VARC-2 criteria had no impact on mortality. CONCLUSIONS: About 1 out of 10 patients undergoing TAVR in the contemporary era had PPMI as defined by recent VARC-3 criteria, and baseline factors like female sex and peripheral artery disease determined an increased risk. PPMI had a negative impact on early and late survival. Further studies on the prevention of PPMI post-TAVR and implementing measures to improve outcomes in PPMI patients are warranted.

Rationale and Design of the Rivaroxaban Post-Transradial Access for the Prevention of Radial Artery Occlusion Trial (CAPITAL-RAPTOR).

INTRODUCTION: Transradial access (TRA) has rapidly emerged as the preferred vascular access site for coronary angiography and percutaneous coronary intervention. Radial artery occlusion (RAO) remains as an important complication of TRA as it precludes future ipsilateral transradial procedures. While intraprocedural anticoagulation has been studied extensively, the definitive role of postprocedural anticoagulation has not yet been established. METHODS AND ANALYSIS: The Rivaroxaban Post-Transradial Access for the Prevention of Radial Artery Occlusion trial is a multicentre, prospective, randomised, open-label, blinded-endpoint design study investigating the efficacy and safety of rivaroxaban to reduce the incidence of RAO. Eligible patients will undergo randomisation to receive either rivaroxaban 15 mg once daily for 7 days or to no additional postprocedural anticoagulation. Doppler ultrasound to assess radial artery patency will be performed at 30 days. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ottawa Health Science Network Research Ethics Board (approval number 20180319-01H). The study results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03630055.

Angina in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

INTRODUCTION AND OBJECTIVES: To evaluate the prevalence, clinical characteristics, and outcomes of patients with angina undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis. METHODS: A total of 1687 consecutive patients with severe aortic stenosis undergoing TAVR at our center were included and classified according to patient-reported angina symptoms prior to the TAVR procedure. Baseline, procedural and follow-up data were collected in a dedicated database. RESULTS: A total of 497 patients (29%) had angina prior to the TAVR procedure. Patients with angina at baseline showed a worse New York Heart Association (NYHA) functional class (NYHA class> II: 69% vs 63%; P=.017), a higher rate of coronary artery disease (74% vs 56%; P <.001), and a lower rate of complete revascularization (70% vs 79%; P <.001). Angina at baseline had no impact on all-cause mortality (HR, 1.02; 95%CI, 0.71-1.48; P=.898) and cardiovascular mortality (HR, 1.2; 95%CI, 0.69-2.11; P=.517) at 1 year. However, persistent angina at 30 days post-TAVR was associated with increased all-cause mortality (HR, 4.86; 95%CI, 1.71-13.8; P=.003) and cardiovascular mortality (HR, 20.7; 95%CI, 3.50-122.6; P=.001) at 1-year follow-up. CONCLUSIONS: More than one-fourth of patients with severe aortic stenosis undergoing TAVR had angina prior to the procedure. Angina at baseline did not appear to be a sign of a more advanced valvular disease and had no prognostic impact; however, persistent angina at 30 days post-TAVR was associated with worse clinical outcomes.

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).

Chest Pain Evaluation: Diagnostic Testing.

Chest pain/discomfort (CP) is a common symptom and can be a diagnostic dilemma for many clinicians. The misdiagnosis of an acute or progressive chronic cardiac etiology may carry a significant risk of morbidity and mortality. This review summarizes the different options and modalities for establishing the diagnosis and severity of coronary artery disease. An effective test selection algorithm should be individually tailored to each patient to maximize diagnostic accuracy in a timely fashion, determine short- and long-term prognosis, and permit implementation of evidence-based treatments in a cost-effective manner. Through collaboration, a decision algorithm was developed (www.chowmd.ca/cadtesting) that could be adopted widely into clinical practice.

La douleur ou la gêne thoracique sont des symptômes fréquents qui peuvent poser un dilemme diagnostique pour de nombreux médecins. Les erreurs de diagnostic d'une cause aiguë ou chronique progressive d'origine cardiaque peuvent d'ailleurs entraîner un risque considérable de morbidité et de mortalité. La présente synthèse porte sur les différentes options et modalités d'établissement du diagnostic et de la gravité d'une coronaropathie. Un algorithme efficace pour le choix des tests doit être adapté à chaque patient afin de maximiser l'exactitude diagnostique dans les plus brefs délais, de déterminer le pronostic à court et à long terme, et de permettre une mise en œuvre de traitements fondés sur des données probantes tout en tenant compte des coûts. Un algorithme décisionnel a donc été conjointement mis au point (www.chowmd.ca/cadtesting) et pourrait être largement adopté dans la pratique clinique.

Association Between Right Ventricular Dysfunction and Adverse Outcomes in Peripartum Cardiomyopathy: Insights From the BRO-HF Quebec Cohort Study.

Background: Peripartum cardiomyopathy (PPCM) is associated with severe morbidity and mortality, and the significance of right ventricular (RV) involvement is unclear. We sought to determine whether RV systolic dysfunction or dilatation is associated with adverse clinical outcomes in women with PPCM. Methods: We conducted a multicentre retrospective cohort study examining the association between echocardiographic RV systolic dysfunction or dilatation at the time of PPCM diagnosis and clinical outcomes. Clinical endpoints of interest were the need for mechanical support, recovery of left ventricular ejection fraction at follow-up, and a combined endpoint of hospitalization for heart failure, cardiac transplant, or death. Results: A total of 67 women, median age 30 years (interquartile range: 7), were diagnosed with PPCM between 1994 and 2015 in 17 participating centres. Twin pregnancies occurred in 11%; 62% of women were multiparous; and 24% had preeclampsia. RV systolic function was impaired in 18 (27%) and dilated in 8 (12%). Seven women required ventricular assistance, and 8 experienced the composite outcome during follow-up (25 [interquartile range 61] months). RV dysfunction was associated with the need for mechanical support (odds ratio 10.10 (95% confidence interval: 1.86-54.81), P = 0.007), but neither RV dysfunction nor dilatation was associated with left ventricular ejection fraction recovery, the need for cardiac transplant, heart failure hospitalization, or death. Conclusions: RV dysfunction is associated with the need for mechanical support in women with PPCM. These findings may improve risk stratification of complications and clinical management.

Introduction: La cardiomyopathie du péripartum (CMP-PP) est associée à la morbidité grave et à la mortalité, mais on ignore l'importance de l'atteinte ventriculaire droite (VD). Nous avons cherché à déterminer si la dysfonction systolique ou la dilatation VD sont associées aux résultats cliniques défavorables chez les femmes atteintes de CMP-PP. Méthodes: Nous avons mené une étude de cohorte rétrospective multicentrique sur l'association entre la dysfonction systolique ou la dilatation VD à l'échographie au moment du diagnostic de CMP-PP et les résultats cliniques. Les critères cliniques d'intérêt étaient la nécessité d'une assistance mécanique, la récupération de la fraction d'éjection ventriculaire gauche (FEVG) au suivi et un critère combiné d'hospitalisation liée à l'insuffisance cardiaque (IC), la transplantation cardiaque ou la mort. Résultats: Un total de 67 femmes, dont l'âge médian était de 30 ans (écart interquartile [EI] : 7), ont reçu un diagnostic de CMP-PP entre 1994 et 2015 dans 17 centres participants. Les grossesses gémellaires sont survenues chez 11 % ; 62 % de femmes étaient multipares ; et 24 % souffraient de prééclampsie. La fonction systolique VD était compromise chez 18 (27 %) femmes et le VD, dilaté, chez huit (12 %) femmes. Sept femmes ont eu besoin d'une assistance ventriculaire, et huit ont subi le critère composite durant le suivi (25 [EI : 61] mois). La dysfonction VD a été associée à la nécessité d'une assistance mécanique (rapport de cotes 10,10 [intervalle de confiance à 95 % : 1,86-54,81], P = 0,007), mais ni la dysfonction ni la dilatation VD n'ont été associées à la récupération de la FEVG, à la nécessité d'une transplantation cardiaque, à une hospitalisation liée à l'IC ou à la mort. Conclusions: La dysfonction VD est associée à la nécessité d'une assistance mécanique chez les femmes atteintes de CMP-PP. Ces conclusions peuvent permettre d'améliorer la stratification des risques de complications et la prise en charge clinique.

Modifiable Risk Factors and Residual Risk Following Coronary Revascularization: Insights From a Regionalized Dedicated Follow-Up Clinic.

OBJECTIVE: To ensure compliance with optimal secondary prevention strategies and document the residual risk of patients following revascularization, we established a postrevascularization clinic for risk-factor optimization at 1 year, with outcomes recorded in a web-based registry. Although coronary revascularization can reduce ischemia, medical treatment of coronary artery disease (CAD) remains the cornerstone of ongoing risk reduction. While standardized referral pathways and protocols for revascularization are prevalent and well studied, post-revascularization care is often less formalized. PATIENTS AND METHODS: The University of Ottawa Heart Institute is a tertiary-care center providing coronary revascularization services. From 2015 to 2019, data were prospectively recorded in the CAPITAL revascularization registry, and patient-level procedural, clinical, and outcome data are collected in the year following revascularization. Major adverse cardiovascular event (MACE) was defined as death, myocardial infarction, unplanned revascularization, or cerebrovascular accident. Kaplan-Meier curves were generated to evaluate time-to-event data for clinical outcomes by risk-factor management, and comparisons were performed using log-rank tests and reported by hazard ratio (HR) and 95% confidence intervals (CIs). RESULTS: A cohort of 4147 patients completed 1-year follow-up after revascularization procedure that included 3462 undergoing percutaneous coronary intervention (PCI), 589 undergoing coronary artery bypass graft (CABG), and 96 undergoing both PCI and CABG. In the year following revascularization (median follow-up 13.3 months-interquartile range [IQR]: 11.9-16.5) 11% of patients experienced MACE, with female patients being disproportionately at risk. Moreover, 47.7% of patients had ≥2 risk factors (diabetes, dyslipidemia, overweight, active smoker) at the time of follow-up, with 45.0% of patients with diabetes failing to achieve target hemoglobin (Hb) A1c, 54.8% of smokers continuing to smoke, and 27.1% of patients failing to achieve guideline-directed lipid targets. CONCLUSION: Patients who have undergone revascularization procedures remain at elevated risk for MACE, and inadequately controlled risk factors are prevalent in follow-up. This highlights the need for aggressive secondary prevention strategies and implementation of programs to optimize postrevascularization care.

Characteristics and Outcomes of Patients Who Are Denied From a Percutaneous Edge-to-Edge Mitral Valve Repair After Being Referred to a Transcatheter Mitral Valve Program: Impact of a Dedicated Multidisciplinary Mitral Heart Team Approach.

BACKGROUND: Many patients referred for a MitraClip intervention are finally refused for this intervention, and data are very scarce on their outcomes. Our study sought to determine the characteristics and outcomes of patients who are referred to a mitral valve clinic and are finally denied from a percutaneous mitral edge-to-edge repair. METHODS: A total of 210 patients referred to our clinic for severe mitral regurgitation were retrospectively analyzed. Fifty-seven patients underwent a MitraClip procedure. For exploratory purposes, a propensity-matched cohort comparing the patients accepted for a MitraClip procedure and those refused for any mitral intervention was analyzed. RESULTS: Among the 153 patients who were refused for MitraClip, 46% had functional MR, 42% had degenerative MR, and 11% had mixed disease. Reasons for denial included unfavorable anatomy, patient refusal, mitral valve surgery referral, cardiac resynchronization therapy, other advanced heart failure therapies, and palliative care. After a mean follow-up of 13 months, 50% were in New York Heart Association class I or II, 63% had less than severe MR, and mortality rate was 29%. In the propensity-matched cohort, there was no difference in symptoms improvement, but there was less overall mortality (P=.01), cardiovascular mortality (P<.01) and severe MR (P<.01) in the MitraClip group. CONCLUSIONS: A multidisciplinary heart team evaluation for complex MR patients can be useful not solely for selecting the ideal MitraClip eligible patients, but also to select the best treatment strategy in each individualized context.

Transvalvular Flow, Sex, and Survival After Valve Replacement Surgery in Patients With Severe Aortic Stenosis.

BACKGROUND: The respective impacts of transvalvular flow, gradient, sex, and their interactions on mortality in patients with severe aortic stenosis undergoing surgical aortic valve replacement (AVR) are unknown. OBJECTIVES: This study sought to compare the impact of pre-operative flow-gradient patterns on mortality after AVR and to examine whether there are sex differences. METHODS: This study analyzed clinical, echocardiographic, and outcome data prospectively collected in 1,490 patients (544 women [37%]), with severe aortic stenosis and preserved left ventricular ejection fraction who underwent AVR. RESULTS: In this cohort, 601 patients (40%) had normal flow (NF) with high gradient (HG), 405 (27%) NF with low gradient (LG), 246 (17%) paradoxical low flow (LF)/HG, and 238 (16%) LF/LG. During a median follow-up of 2.42 years (interquartile range: 1.04 to 4.29 years), 167 patients died. Patients with LF/HG exhibited the highest mortality after AVR (hazard ratio [HR]: 2.01; 95% confidence interval [CI]: 1.33 to 3.03; p < 0.01), which remained significant after multivariate adjustment (HR: 1.96; 95% CI: 1.29 to 2.98; p < 0.01). Both LF/LG and NF/LG patients had comparable outcome to NF/HG (p ≥ 0.47). Optimal thresholds of stroke volume index were obtained for men (40 ml/m2) and women (32 ml/m2). Using these sex-specific cutpoints, paradoxical LF was independently associated with increased mortality in both women (adjusted HR: 2.05; 95% CI: 1.21 to 3.47; p < 0.01) and men (adjusted HR: 1.54; 95% CI: 1.02 to 2.32; p = 0.042), whereas guidelines' threshold (35 ml/m2) does not. CONCLUSIONS: Paradoxical LF/HG was associated with higher mortality following AVR, suggesting that a reduced flow is a marker of disease severity even in patients with HG aortic stenosis. Early surgical AVR (i.e., before gradient attains 40 mm Hg) might be preferable in these patients. Furthermore, the use of sex-specific thresholds (<40 ml/m2 for men and <32 ml/m2 for women) to define low-flow outperforms the guidelines' threshold of 35 ml/m2 in risk stratification after AVR.

Genetic Variation in LPA, Calcific Aortic Valve Stenosis in Patients Undergoing Cardiac Surgery, and Familial Risk of Aortic Valve Microcalcification.

Importance: Genetic variants at the LPA locus are associated with both calcific aortic valve stenosis (CAVS) and coronary artery disease (CAD). Whether these variants are associated with CAVS in patients with CAD vs those without CAD is unknown. Objective: To study the associations of LPA variants with CAVS in a cohort of patients undergoing heart surgery and LPA with CAVS in patients with CAD vs those without CAD and to determine whether first-degree relatives of patients with CAVS and high lipoprotein(a) (Lp[a]) levels showed evidence of aortic valve microcalcification. Design, Setting, and Participants: This genetic association study included patients undergoing cardiac surgery from the Genome-Wide Association Study on Calcific Aortic Valve Stenosis in Quebec (QUEBEC-CAVS) study and patients with CAD, patients without CAD, and control participants from 6 genetic association studies: the UK Biobank, the European Prospective Investigation of Cancer (EPIC)-Norfolk, and Genetic Epidemiology Research on Aging (GERA) studies and 3 French cohorts. In addition, a family study included first-degree relatives of patients with CAVS. Data were collected from January 1993 to September 2018, and analysis was completed from September 2017 to September 2018. Exposures: Case-control studies. Main Outcomes and Measures: Presence of CAVS according to a weighted genetic risk score based on 3 common Lp(a)-raising variants and aortic valve microcalcification, defined as the mean tissue to background ratio of 1.25 or more, measured by fluorine 18-labeled sodium fluoride positron emission tomography/computed tomography. Results: This study included 1009 individuals undergoing cardiac surgery and 1017 control participants in the QUEBEC-CAVS cohort; 3258 individuals with CAVS and CAD, 41 100 controls with CAD, 2069 individuals with CAVS without CAD, and 380 075 control participants without CAD in the UK Biobank, EPIC-Norfolk, and GERA studies and 3 French cohorts combined; and 33 first-degree relatives of 17 patients with CAVS and high Lp(a) levels (≥60 mg/dL) and 23 control participants with normal Lp(a) levels (<60 mg/dL). In the QUEBEC-CAVS study, each SD increase of the genetic risk score was associated with a higher risk of CAVS (odds ratio [OR], 1.35 [95% CI, 1.10-1.66]; P = .003). Each SD increase of the genetic risk score was associated with a higher risk of CAVS in patients with CAD (OR, 1.30 [95% CI, 1.20-1.42]; P < .001) and without CAD (OR, 1.33 [95% CI, 1.14-1.55]; P < .001). The percentage of individuals with a tissue to background ratio of 1.25 or more or CAVS was higher in first-degree relatives of patients with CAVS and high Lp(a) (16 of 33 [49%]) than control participants (3 of 23 [13%]; P = .006). Conclusions and Relevance: In this study, a genetically elevated Lp(a) level was associated with CAVS independently of the presence of CAD. These findings support further research on the potential usefulness of Lp(a) cascade screening in CAVS.

Lipoprotein(a), Oxidized Phospholipids, and Aortic Valve Microcalcification Assessed by 18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography.

BACKGROUND: Lipoprotein(a) (Lp[a]) is the preferential lipoprotein carrier of oxidized phospholipids (OxPLs) and a well-established genetic risk factor for calcific aortic valve stenosis (CAVS). Whether Lp(a) predicts aortic valve microcalcification in individuals without CAVS is unknown. Our objective was to estimate the prevalence of elevated Lp(a) and OxPL levels in patients with CAVS and to determine if individuals with elevated Lp(a) but without CAVS have higher aortic valve microcalcification. METHODS: We recruited 214 patients with CAVS from Montreal and 174 patients with CAVS and 108 controls from Québec City, Canada. In a second group of individuals with high (≥75 nmol/L, n = 27) or low (<75 nmol/L, n = 28) Lp(a) levels, 18F-sodium fluoride positron emission tomography/computed tomography was performed to determine the difference in mean tissue-to-background ratio (TBR) of the aortic valve. RESULTS: Patients with CAVS had 62.0% higher Lp(a) (median = 28.7, interquartile range [8.2-116.6] vs 10.9 [3.6-28.8] nmol/L, P < 0.0001), 50% higher OxPL-apolipoprotein-B (2.2 [1.3-6.0] vs 1.1 [0.7-2.6] nmol/L, P < 0.0001), and 69.9% higher OxPL-apolipoprotein(a) (7.3 [1.8-28.4] vs 2.2 [0.8-8.4] nmol/L, P < 0.0001) levels compared with individuals without CAVS (all P < 0.0001). Individuals without CAVS but elevated Lp(a) had 40% higher mean TBR compared with individuals with low Lp(a) levels (mean TBR = 1.25 ± 0.23 vs 1.15 ± 0.11, P = 0.02). CONCLUSIONS: Elevated Lp(a) and OxPL levels are associated with prevalent CAVS in patients studied in an echocardiography laboratory setting. In individuals with elevated Lp(a), evidence of aortic valve microcalcification by 18F-sodium fluoride positron emission tomography/computed tomography is present before the development of clinically manifested CAVS.

CONTEXTE: La lipoprotéine(a) (Lp[a]), la principale lipoprotéine assurant le transport des phospholipides oxydés (PLOx), est un facteur de risque génétique bien établi de la sténose aortique calcifiante (SAC). On ignore si la présence de Lp(a) est un facteur prédictif de la microcalcification de la valve aortique chez les individus non atteints de SAC. Notre objectif était d'estimer la prévalence de taux élevés de Lp(a) et de PLOx chez des patients atteints de SAC et de déterminer si la microcalcification de la valve aortique est plus marquée chez les individus affichant des taux élevés de Lp(a) en l'absence de SAC. MÉTHODOLOGIE: Nous avons recruté 214 patients atteints de SAC à Montréal et 174 patients atteints de SAC et 108 patients témoins à Québec (Canada). Dans un second groupe de patients présentant des taux de Lp(a) élevés (≥ 75 nmol/l, n = 27) ou faibles (< 75 nmol/l, n = 28), une tomographie par émission de positons au fluorure de sodium marqué au 18F a été réalisée en vue de comparer la valeur moyenne du rapport signal/bruit (RSB) de la valve aortique. RÉSULTATS: Les patients atteints de SAC présentaient des taux de Lp(a) plus élevés de 62,0 % (médiane = 28,7, intervalle interquartile [de 8,2 à 116,6] vs 10,9 [de 3,6 à 28,8] nmol/l, p < 0,0001), des taux de OxPL-apolipoprotéine-B plus élevés de 50 % (2,2 [de 1,3 à 6,0] vs 1,1 [de 0,7 à 2,6] nmol/l, p < 0,0001) et des taux de PLOx-apolipoprotéine(a) plus élevés de 69,9 % (7,3 [de 1,8 à 28,4] vs 2,2 [de 0,8 à 8,4] nmol/l, p < 0,0001) comparativement aux patients non atteints de SAC (toutes les valeurs p < 0,0001). Les patients non atteints de SAC mais présentant des taux élevés de Lp(a) avaient un RSB moyen supérieur de 40 % à celui des individus affichant un faible taux de Lp(a) (RSB moyen = 1,25 ± 0,23 vs 1,15 ± 0,11, p = 0,02). CONCLUSIONS: Des taux élevés de Lp(a) et de PLOx sont associés à la prévalence de la SAC chez des patients étudiés par échocardiographie. Chez les individus présentant un taux élevé de Lp(a), les signes d'une microcalcification de la valve aortique, décelés par tomographie par émission de positons au fluorure de sodium marqué au 18F /tomodensitométrie sont présents avant l'apparition des manifestations cliniques de la SAC.

The effect of bromocriptine on left ventricular functional recovery in peripartum cardiomyopathy: insights from the BRO-HF retrospective cohort study.

AIMS: Bromocriptine is thought to facilitate left ventricular (LV) recovery in peripartum cardiomyopathy (PPCM) through inhibition of prolactin secretion. However, this potential therapeutic effect remains controversial and was incompletely studied in diverse populations. METHODS AND RESULTS: Consecutive women with new-onset PPCM (n = 76) between 1994 and 2015 in Quebec, Canada, were classified according to treatment (n = 8, 11%) vs. no treatment (n = 68, 89%) with bromocriptine. We assessed LV functional recovery at mid-term (6 months) and long-term (last follow-up) and compared outcomes among groups. Women treated with bromocriptine experienced better mid-term left ventricular ejection fraction (LVEF) recovery from 23 ± 10% at baseline to 55 ± 12% at 6 months, compared with a change from 30 ± 12% at baseline to 45 ± 13% at 6 months in women treated with standard medical therapy (P interaction < 0.01). At long-term, a similar positive association was found with bromocriptine (9% greater LVEF variation, P interaction < 0.01). In linear regressions adjusted for obstetrical, clinical, echocardiographic, and pharmacological variables, treatment with bromocriptine was associated with a greater improvement in LVEF [ß coefficient (standard error), 14.1 (4.4); P = 0.03]. However, there was no significant association between bromocriptine use and the combined occurrence of all-cause death and heart failure events (hazard ratio, 1.18; 95% confidence interval, 0.15 to 9.31), using univariable Cox regressions based over a cumulative follow-up period of 285 patient-years. CONCLUSIONS: In women newly diagnosed with PPCM, treatment with bromocriptine was independently associated with greater LV functional recovery.

Multimarker Approach to Identify Patients With Higher Mortality and Rehospitalization Rate After Surgical Aortic Valve Replacement for Aortic Stenosis.

OBJECTIVES: This study sought to evaluate whether a multimarker approach might identify patients with higher mortality and hospitalization rates after aortic valve replacement (AVR) for aortic stenosis (AS). BACKGROUND: The society valve guidelines include accepted triggers for AVR in patients with severe asymptomatic AS, but circulating biomarkers do not have a clear role. METHOD: From a prospective registry of patients undergoing cardiac surgery between 2000 and 2012, 665 treated with surgical AVR (441 isolated) were evaluated. Seven biomarkers were measured on blood samples obtained before AVR. Biomarker levels were adjusted to account for the influence of age, sex, body mass index, and renal function; the median was used to determine an elevated value. Endpoints included all-cause mortality and all-cause and cardiovascular hospitalizations. Mean follow-up was 10.7 years and 299 (45%) died. RESULTS: Patients with 0 to 1, 2 to 3, 4 to 6, and 7 biomarkers elevated had 5-year mortality of 10%, 12%, 24%, and 33%, respectively, and 10-year mortality of 24%, 35%, 58%, and 71%, respectively (log-rank p < 0.001). The association between an increasing number of elevated biomarkers and increased all-cause mortality was observed among those with minimal symptoms (New York Heart Association functional class I or II) and those with a low N-terminal pro-B-type natriuretic peptide (p < 0.01 for both). Compared with those with 0 to 1 biomarkers elevated, patients with 4 to 6 or 7 biomarkers elevated had an increased hazard of mortality after adjustment for clinical risk scores (p < 0.01) and a 2- to 3-fold higher rate of all-cause and cardiovascular rehospitalization after AVR. Similar findings were obtained when evaluating cardiovascular mortality. Among patients with no or minimal symptoms, 42% had ≥4 biomarkers elevated. CONCLUSIONS: Among patients with severe AS treated with surgical AVR, an increasing number of elevated biomarkers of cardiovascular stress was associated with higher all-cause and cardiovascular mortality and a higher rate of repeat hospitalization. A multimarker approach may be useful in the surveillance of asymptomatic patients with severe AS to optimize surgical timing.

Management of Coronary Disease in the Era of Transcatheter Aortic Valve Replacement: Comprehensive Review of the Literature.

Among the cohort of complex and multifaceted patients undergoing transcatheter aortic valve replacement (TAVR), the prevalence of coronary artery disease (CAD) ranges from 48% to 75%. However, optimal management of CAD in this setting has not been established. This article provides a comprehensive review of the literature to depict the actual knowledge on the subject of aortic stenosis and concomitant CAD. This article also aids heart teams in their decision-making process to appropriately manage these challenging patients with aortic stenosis and CAD. Upcoming randomized studies will clarify the influence of CAD, the best timing for percutaneous coronary intervention, and its impact on TAVR results.