Adult Congenital Heart Disease Care in Canada: Has Quality of Care Improved in the Last Decade?

BACKGROUND: Patients with adult congenital heart disease (ACHD) are at increased risk of comorbidity and death compared with the age-matched population. Specialized care is shown to improve survival. The purpose of this study was to analyze current measures of quality of care in Canada compared with those published by our group in 2012. METHODS: A survey focusing on structure and process measures of care quality in 2020 was sent to 15 ACHD centres registered with the Canadian Adult Congenital Heart Network. For each domain of quality, comparisons were made with those published in 2012. RESULTS: In Canada, 36,708 patients with ACHD received specialized care between 2019 and 2020. Ninety-five cardiologists were affiliated with ACHD centres. The median number of patients per ACHD clinic was 2000 (interquartile range [IQR]: 1050, 2875). Compared with the 2012 results, this represents a 68% increase in patients with ACHD but only a 19% increase in ACHD cardiologists. Compared with 2012, all procedural volumes increased with cardiac surgeries, increasing by 12% and percutaneous intervention by 22%. Wait time for nonurgent consults and interventions all exceeded national recommendations by an average of 7 months and had increased compared with 2012 by an additional 2 months. Variability in resources were noted across provincial regions. CONCLUSIONS: Over the past 10 years, ACHD care gaps have persisted, and personnel and infrastructure have not kept pace with estimates of ACHD population growth. Strategies are needed to improve and reduce disparity in ACHD care relative to training, staffing, and access to improved care for Canadians with ACHD.

The Impact of the COVID-19 Pandemic Restrictions on the Provision of Adult Congenital Heart Disease Care Across Canada: A National Survey.

Background: The COVID-19 pandemic significantly impacted health care access across Canada with the reduction in in-person evaluations. The aim of the study was to examine the effects of the COVID-19 pandemic on access to health care services among the Canadian population with adult congenital heart disease (ACHD). Methods: All Canadian adult congenital heart affiliated centres were contacted and asked to collect data on outpatient clinic and procedural volumes for the 2019 and 2020 calendar years. A survey was sent detailing questions on clinic and procedural volumes and wait times before and after pandemic restrictions. Descriptive statistics were used with the Student t-test to compare groups. Results: In 2019, there were 19,326 ACHD clinic visits across Canada and only 296 (1.5%) virtual clinic visits. However, during the first year of the pandemic, there were 20,532 clinic visits and 11,412 (56%) virtual visits (P < 0.0001). There were no differences in procedural volumes (electrophysiology, cardiac surgery, and percutaneous intervention) between 2019 and 2020. The mean estimated wait times (months) before the pandemic vs the pandemic were as follows: nonurgent consult 5.4 ± 2.6 vs 6.6 ± 4.2 (P = 0.65), ACHD surgery 6.0 ± 3.5 vs 7.0 ± 4.6 (P = 0.47), electrophysiology procedures 6.3 ± 3.3 vs 5.7 ± 3.3 (P = 0.72), and percutaneous intervention 4.6 ± 3.9 vs 4.4 ± 2.3 (P = 0.74). Conclusions: During the pandemic and restrictions of social distancing, the use of virtual clinic visits helped to maintain continuity in ACHD clinical care, with 56% of ACHD visits being virtual. The procedural volumes and wait times for consultation and percutaneous and surgical interventions were not delayed.

Contexte: La pandémie de COVID-19 a eu des répercussions sur l'accès aux soins de santé partout au Canada, y compris une diminution des évaluations en personne. La présente étude visait à évaluer l'effet de la pandémie de COVID-19 sur l'accès aux soins de santé chez les adultes atteints de cardiopathie congénitale. Méthodologie: Nous avons communiqué avec tous les centres canadiens de prise en charge de la cardiopathie congénitale chez l'adulte et nous leur avons demandé de recueillir des données sur les consultations externes et le volume des interventions pour les années 2019 et 2020. Un sondage détaillé leur a été transmis sur les volumes de consultations et d'interventions et sur les temps d'attentes avant et après la mise en place de restrictions liées à la pandémie. Les groupes ont été comparés lors d'une analyse statistique descriptive utilisant le test t de Student. Résultats: En 2019, 19 326 consultations pour cause de cardiopathie congénitale chez l'vadulte ont été enregistrées au Canada, dont seulement 296 (1,5 %) ont eu lieu en mode virtuel. Au cours de la première année de la pandémie, 20 532 consultations ont été relevées; 11 412 (56 %) ont été menées virtuellement (p < 0,0001). Aucune différence n'a été observée dans le volume d'interventions (interventions en électrophysiologie, interventions chirurgicales et interventions percutanées) entre 2019 et 2020. Les temps d'attente moyens estimés en mois, avant et pendant la pandémie, étaient les suivants : consultations non urgentes, 5,4 ± 2,6 vs 6,6 ± 4,2 (p = 0,65); interventions chirurgicales, 6,0 ± 3,5 vs 7,0 ± 4,6 (p = 0,47); interventions en électrophysiologie, 6,3 ± 3,3 vs 5,7 ± 3,3 (p = 0,72); et interventions percutanées, 4,6 ± 3,9 vs 4,4 ± 2,3 (p = 0,74). Conclusion: Au cours de la pandémie et de la période où les restrictions de distanciation sociale étaient en vigueur, le recours aux consultations virtuelles dans les cliniques a contribué à la continuité des soins offerts aux adultes atteints de cardiopathie congénitale, puisque 56 % des visites se sont déroulées virtuellement. Le volume d'interventions n'a pas été touché et les temps d'attentes pour les consultations, les interventions percutanées et les interventions chirurgicales ne se sont pas allongés.

Transfemoral tricuspid valve replacement and one-year outcomes: the TRISCEND study.

BACKGROUND AND AIMS: For patients with symptomatic, severe tricuspid regurgitation (TR), early results of transcatheter tricuspid valve (TV) intervention studies have shown significant improvements in functional status and quality of life associated with right-heart reverse remodelling. Longer-term follow-up is needed to confirm sustained improvements in these outcomes. METHODS: The prospective, single-arm, multicentre TRISCEND study enrolled 176 patients to evaluate the safety and performance of transcatheter TV replacement in patients with ≥moderate, symptomatic TR despite medical therapy. Major adverse events, reduction in TR grade and haemodynamic outcomes by echocardiography, and clinical, functional, and quality-of-life parameters are reported to one year. RESULTS: Enrolled patients were 71.0% female, mean age 78.7 years, 88.0% ≥ severe TR, and 75.4% New York Heart Association classes III-IV. Tricuspid regurgitation was reduced to ≤mild in 97.6% (P < .001), with increases in stroke volume (10.5 ± 16.8 mL, P < .001) and cardiac output (0.6 ± 1.2 L/min, P < .001). New York Heart Association class I or II was achieved in 93.3% (P < .001), Kansas City Cardiomyopathy Questionnaire score increased by 25.7 points (P < .001), and six-minute walk distance increased by 56.2 m (P < .001). All-cause mortality was 9.1%, and 10.2% of patients were hospitalized for heart failure. CONCLUSIONS: In an elderly, highly comorbid population with ≥moderate TR, patients receiving transfemoral EVOQUE transcatheter TV replacement had sustained TR reduction, significant increases in stroke volume and cardiac output, and high survival and low hospitalization rates with improved clinical, functional, and quality-of-life outcomes to one year. Funded by Edwards Lifesciences, TRISCEND ClinicalTrials.gov number, NCT04221490.

Determinants of Aortic Stenosis Progression in Bicuspid and Tricuspid Aortic Valves.

Background: Bicuspid aortic valve (BAV) is associated with a faster progression of aortic stenosis (AS). Whether the determinants of AS progression are the same or different in patients with BAV vs tricuspid aortic valve (TAV) is unknown. The aim of this study was to identify the factors associated with the progression of AS in patients with BAV vs patients with TAV. Methods: Patients with AS were prospectively recruited in the Metabolic Determinants of the Progression of Aortic Stenosis (PROGRESSA) study (ClinicalTrials.gov Identifier: NCT01679431). The haemodynamic progression rate of AS was assessed by the annualized progression rate of peak aortic jet velocity (Vpeak). Univariable and multivariable linear regression analyses were used to identify the factors associated with a faster progression of AS in patients with BAV vs patients with TAV. Results: There were 79 patients with BAV and 208 patients with TAV. The baseline severity of AS was similar between the 2 groups of patients as well as the annualized progression rate of AS. In patients with BAV, obesity (ß = 0.25, P = 0.04), diabetes (ß = 0.26, P = 0.02), and BAV with right-noncoronary cusp fusion (ß = 0.29, P = 0.01) were found to be independently associated with a faster progression of AS, whereas in patients with TAV, AS baseline severity (baseline Vpeak, ß = 0.14, P = 0.04) and chronic kidney disease (ß = 0.16, P = 0.02) were significantly associated with AS progression. Conclusion: Factors associated with progression rate of AS are different in BAV and TAV. The main factors associated with a faster progression of AS appear to be obesity, diabetes, right-noncoronary cusp fusion in patients with BAV vs chronic kidney disease in patients with TAV.

Contexte: La bicuspidie valvulaire aortique (BVA) est associée à une progression plus rapide de la sténose aortique (SA). On ignore toutefois si les facteurs en cause dans la progression de la SA sont les mêmes chez les patients qui présentent une BVA et chez ceux qui présentent une valve aortique tricuspide. Le but de cette étude était de déterminer les facteurs associés à la progression de la SA chez les patients présentant une BVA par rapport à ceux ayant une valve aortique tricuspide. Méthodologie: Des patients présentant une SA ont été recrutés dans l'étude PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis), une étude prospective sur les déterminants métaboliques de la progression de la SA (ClinicalTrials.gov : NCT01679431). Pour calculer le taux de progression hémodynamique de la SA, on a utilisé les mesures annualisées de la vélocité maximale du jet transaortique (Vmax). Des analyses de régression linéaire univariées et multivariées ont permis de mettre en évidence les facteurs associés à une progression plus rapide de la SA en présence d'une BVA par rapport à une valve aortique tricuspide. Résultats: Parmi les patients évalués, 79 présentaient une BVA et 208, une valve aortique tricuspide. La gravité de la SA au départ était comparable entre les deux groupes de patients, tout comme le taux de progression annualisé de la SA. Chez les patients avec BVA, l'obésité (ß = 0,25, P = 0,04), le diabète (ß = 0,26, P = 0,02) et la BVA avec fusion des feuillets coronaire droit et non coronaire (ß = 0,29, P = 0,01) ont été associés de manière indépendante à une progression plus rapide de la SA, tandis que chez les patients ayant une valve tricuspide, la gravité de la SA au départ (Vmax initiale, ß = 0,14, P = 0,04) et la présence d'une néphropathie chronique (ß = 0,16, P = 0,02) ont été significativement associées à une progression de la SA. Conclusion: Les facteurs associés au taux de progression de la SA sont différents selon qu'il y a ou non présence d'une BVA. Les principaux facteurs associés à une progression plus rapide de la SA semblent être l'obésité, le diabète et la fusion des feuillets coronaire droit et non coronaire pour la BVA, tandis que la néphropathie chronique serait le facteur aggravant chez les patients présentant une valve aortique tricuspide.

Transcatheter tricuspid valve interventions: Current devices and associated evidence.

Tricuspid regurgitation (TR) is a common finding in patients with chronic cardiopathy, and often a marker of an advanced disease. Being silent or with symptoms intertwined with the primitive left heart disease, TR has often been neglected, leading to the late referral of patients with advanced right-heart failure. Hence, isolated tricuspid surgery has been associated with high morbidity and mortality rates, the worse of all valve interventions, and medical management has been limited to symptomatic treatment. In this context, percutaneous therapies for severe TR have gained traction, addressing the unmet therapeutic gap for a less invasive disease-modifying management. The aim of this review is to provide an updated overview on transcatheter tricuspid valve interventions, focusing on devices' characteristics, associated evidence, and future perspectives.

Left ventricular asymmetric remodeling and subclinical left ventricular dysfunction in patients with calcific aortic valve stenosis - Results from a subanalysis of the PROGRESSA study.

BACKGROUND: LV asymmetric remodeling (LVAR) is a feature commonly found in AS patients and it is presumed to be mainly related to the severity of valve stenosis. The aim of this study was to determine the associated factors and impact on left ventricular (LV) systolic function of LVAR in patients with mild and moderate aortic valve stenosis (AS). METHODS: Clinical, Doppler-echocardiographic and computed-tomographic data of 155 AS patients with preserved LV ejection fraction (≥50%) prospectively recruited in the PROGRESSA study (NCT01679431) were analyzed. LVAR was defined as a septal wall thickness ≥ 13 mm and a ratio of septal/posterior wall thickness > 1.5. LV global longitudinal strain (LV-GLS) was available in 129 patients. Plasma levels of N-terminal natriuretic B-type peptides (Nt-proBNP) were also measured. RESULTS: Mean age was 63 ± 15 years (70% men). LVAR was present in 21% (n = 33) of patients. A series of nested multivariate analysis revealed that age was the only factor associated with LVAR (all p ≤ 0.03). Additionally, these patients had higher baseline Nt-proBNP ratio (median [25-75 percentiles]: 1.04 [0.66-2.41] vs. 0.65 [0.33-1.19], p = 0.02), and significantly reduced LV-GLS (17.9[16.6-19.5] vs. 19.3[17.4-20.7] |%|, p = 0.04). A 1:1 matched analysis showed a significant association of LVAR with reduced LV-GLS (17.9[16.6-19.5] vs. 19.8[18.1-20.7] |%|, p = 0.02) and elevated Nt-proBNP (134[86-348] vs. 83[50-179]pg/ml, p = 0.03). Multivariable analysis also revealed that LVAR remains significantly associated with reduced LV-GLS (p = 0.03) and elevated Nt-proBNP (p = 0.001). LVAR was significantly associated with increased risk of major adverse cardiac events and death (Hazard ratio [95% confidence interval]: 2.32[1.28-4.22], p = 0.006). CONCLUSIONS: LVAR was found in ~20% of patients with mild or moderate AS and was not related to the degree of AS severity or concomitant comorbidities, but rather to older age. LVAR was significantly associated with reduced LV longitudinal systolic function, increased Nt-proBNP levels, and higher risk of major adverse events and death. These findings provide support for closer clinical and echocardiographic surveillance of patients harboring this adverse LV remodeling feature.

Transcatheter Interventions for Tricuspid Valve Disease: What to Do and Who to Do It On.

Tricuspid valve disease, and particularly the management of severe tricuspid regurgitation (TR), has gained momentum in recent years. Although it is well known that this frequent condition is associated with poor clinical outcomes, these patients have been classically managed medically, leading to end-stage right ventricular heart failure. Moreover, late referral to surgery has contributed to a high rate of periprocedural complications and in-hospital surgical mortality. Thus, the development of a less invasive catheter-based therapy would be of high clinical relevance in this context. Several transcatheter tricuspid valve intervention (TTVI) devices have been developed in recent years. The particular characteristics of the tricuspid valve (large noncalcific annulus, presence of chief surrounding structures such as the conduction system or the right coronary artery) make multimodality imaging (eg, transesophageal echocardiography, computed tomography) key in the preprocedural assessment of TTVI. According to their mechanism of action and therapeutic target, TTVI includes transcatheter repair either with coaptation or annuloplasty systems, caval valve devices, and transcatheter tricuspid valve replacement. The initial TTVI experience showed that most procedures were well tolerated, with high procedural success and low in-hospital and early mortality. Also, most TTVI recipients improved their functional status and recent data suggest improved outcomes compared with medical management. However, the rate of significant residual TR after transcatheter tricuspid valve repair remains high and very scarce data exist on longer term (beyond 6-12 months) outcomes. The present review provides an overview regarding the framework of chronic TR and TTVI therapeutic options, and describes the updated current evidence in this challenging field.

Risk prediction models for heart failure admissions in adults with congenital heart disease.

BACKGROUND: Heart failure (HF) is the leading cause of death in adult patients with congenital heart disease (ACHD). No risk prediction model exists for HF hospitalization (HFH) for ACHD patients. We aimed to develop a clinically relevant one-year risk prediction system to identify ACHD patients at high risk for HFH. METHODS: Data source was the Quebec CHD Database. A retrospective cohort including all ACHD patients aged 18-64 (1995-2010) was constructed for assessing the cumulative risk of HFH adjusting for competing risk of death. To identify one-year predictors of incident HFH, multivariable logistic regressions were employed to a nested case-control sample of all ACHD patients aged 18-64 in 2009. The final model was used to create a risk score system based on adjusted odds ratios. RESULTS: The cohort included 29,991 ACHD patients followed for 648,457 person-years. The cumulative HFH risk by age 65 was 12.58%. The case-control sample comprised 26,420 subjects, of whom 189 had HFHs. Significant one-year predictors were age ≥ 50, male sex, CHD lesion severity, recent 12-month HFH history, pulmonary arterial hypertension, chronic kidney disease, coronary artery disease, systemic arterial hypertension, and diabetes mellitus. The created risk score ranged from 0 to 19. The corresponding HFH risk rose rapidly beyond a score of 8. The risk scoring system demonstrated excellent prediction performance. CONCLUSIONS: One eighth of ACHD population experienced HFH before age 65. Age, sex, CHD lesion severity, recent 12-month HFH history, and comorbidities constructed a risk prediction model that successfully identified patients at high risk for HFH.

Effect of Regional Upper Septal Hypertrophy on Echocardiographic Assessment of Left Ventricular Mass and Remodeling in Aortic Stenosis.

BACKGROUND: Transthoracic echocardiography (TTE) is the reference method for evaluation of aortic stenosis (AS), and it is extensively used to quantitate left ventricular (LV) mass and volumes. Regional upper septal hypertrophy (USH) or septal bulge is a frequent finding in patients with AS and may lead to overestimation of LV mass when using linear measurements. The objective of this study was to compare estimates of LV mass obtained by two-dimensional transthoracic echocardiographic LV dimensions measured at different levels of the LV cavity with those obtained by cardiovascular magnetic resonance (CMR). METHODS: One hundred six patients (mean age, 63 ± 15 years; 68% men) with AS were included in this subanalysis of the PROGRESSA study. Two-dimensional transthoracic echocardiographic measurements of LV dimensions were obtained at the basal level (BL; as recommended in guidelines), immediately below the septal bulge (BSB), and at a midventricular level (ML). Regional USH was defined as a basal interventricular septal thickness ≥ 13 mm and >1.3 times the thickness of the septal wall at the ML. Agreement between transthoracic echocardiographic and CMR measures was evaluated using Bland-Altman analysis. RESULTS: The distribution of AS severity was mild in 23%, moderate in 57%, and severe in 20% of patients. Regional USH was present in 28 patients (26%). In the whole cohort, two-dimensional TTE overestimated LV mass (bias: BL, +60 ± 31 g; BSB, +59 ± 32 g; ML, +54 ± 32 g; P = .02). The biplane Simpson method slightly but significantly underestimated LV end-diastolic volume (bias -10 ± 20 mL, P < .001) compared with CMR. Overestimation of LV mass was more marked in patients with USH when measuring at the BL and was significantly lower when measuring LV dimensions at the ML (P < .025 vs BL and BSB). CONCLUSIONS: Two-dimensional TTE systematically overestimated LV mass and underestimated LV volumes compared with CMR. However, the bias between TTE and CMR was less important when measuring at the ML. Measurements at the BL as suggested in guidelines should be avoided, and measurements at the ML should be preferred in patients with AS, especially in those with USH.

Early Multinational Experience of Transcatheter Tricuspid Valve Replacement for Treating Severe Tricuspid Regurgitation.

OBJECTIVES: The aim of this registry was to evaluate the feasibility and safety of transcatheter tricuspid valve implantation (TTVI) in patients with extreme surgical risk. BACKGROUND: Isolated tricuspid regurgitation (TR) surgery is associated with high in-hospital mortality. METHODS: Thirty consecutive patients (mean age 75 ± 10 years; 56% women) from 10 institutions, with symptomatic functional TR, had institutional and notified body approval for compassionate use of the GATE TTVI system. Baseline, discharge, and 30-day follow-up echocardiographic data and procedural, in-hospital, and follow-up clinical outcomes were collected. RESULTS: At baseline, all patients had multiple comorbidities, severe or greater TR, and reduced baseline right ventricular function. Technical success was achieved in 26 of 30 patients (87%). Device malpositioning occurred in 4 patients, with conversion to open heart surgery in 2 (5%). Of those who received the device, 100% had reductions in TR of ≥1, and 75% experienced reductions of ≥2 grades, resulting in 18 of 24 of patients (76%) with mild or less TR at discharge. All patients had mild or less central TR. There was continued improvement in TR grade between discharge and 30 days in 15 of 19 patients (79%). In-hospital mortality was 10%. At mean follow-up of 127 ± 82 days, 4 patients (13%) had died. Of patients alive at follow-up, 62% were in New York Heart Association functional class I or II, with no late device-related adverse events. CONCLUSIONS: Compassionate treatment of severe, symptomatic functional TR using a first-generation TTVI device is associated with significant reduction in TR and improvement in functional status with acceptable in-hospital mortality. Further studies are needed to determine the appropriate patient population and long-term outcomes with TTVI therapy.

Transcatheter Tricuspid Valve Intervention: Coaptation Devices.

Transcatheter tricuspid valve intervention (TTVI) has recently emerged as an alternative for the treatment of severe tricuspid regurgitation (TR). Multiple percutaneous devices have been developed in the last decade with promising early results. Among them, the coaptation devices are designed to reduce TR severity by valve leaflet plication or occupying the regurgitant orifice with a spacer. To date, the MitraClip/TriClip devices (Abbott, Santa Clara, CA, USA), the PASCAL system (Edwards Lifesciencies, Irvine, CA, USA), and the FORMA device (Edwards Lifesciencies, Irvine, CA, USA) have been used as coaptation devices for treating severe TR. The present document aimed to review the clinical evidence on coaptation devices in the field of TTVI, describing its design characteristics, main procedural steps, and early and mid-term outcomes.

Estimation of Stroke Volume and Aortic Valve Area in Patients with Aortic Stenosis: A Comparison of Echocardiography versus Cardiovascular Magnetic Resonance.

BACKGROUND: In aortic stenosis, accurate measurement of left ventricular stroke volume (SV) is essential for the calculation of aortic valve area (AVA) and the assessment of flow status. Current American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines suggest that measurements of left ventricular outflow tract diameter (LVOTd) at different levels (at the annulus vs 5 or 10 mm below) yield similar measures of SV and AVA. The aim of this study was to assess the effect of the location of LVOTd measurement on the accuracy of SV and AVA measured on transthoracic echocardiography (TTE) compared with cardiovascular magnetic resonance (CMR). METHODS: One hundred six patients with aortic stenosis underwent both TTE and CMR. SV was estimated on TTE using the continuity equation with LVOTd measurements at four locations: at the annulus and 2, 5, and 10 mm below annulus. SV was also determined on CMR using phase contrast acquired in the aorta (SVCMR-PC), and a hybrid AVACMR-PC was calculated by dividing SVCMR-PC by the transthoracic echocardiographic Doppler aortic velocity-time integral. Comparison between methods was made using Bland-Altman analysis. RESULTS: Compared with the referent method of phase-contrast CMR for the estimation of SVCMR-PC and AVACMR-PC (SVCMR-PC 83 ± 16 mL, AVACMR-PC 1.27 ± 0.35 cm2), the best agreement was obtained by measuring LVOTd at the annulus or 2 mm below (P = NS), whereas measuring 5 and 10 mm below the annulus resulted in significant underestimation of SV and AVA by up to 15.9 ± 17.3 mL and 0.24 ± 0.28 cm2, respectively (P < .01 for all). Accuracy for classification of low flow was best at the annulus (86%) and 2 mm below (82%), whereas measuring 5 and 10 mm below the annulus significantly underperformed (69% and 61%, respectively, P < .001). CONCLUSIONS: Measuring LVOTd at the annulus or very close to it provides the most accurate measures of SV and AVA, whereas measuring LVOTd 5 or 10 mm below significantly underestimates these parameters and leads to significant overestimation of the severity of aortic stenosis and prevalence of low-flow status.

Effect of bicuspid aortic valve phenotype on progression of aortic stenosis.

AIMS: To compare the progression of aortic stenosis (AS) in patients with bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV). METHODS AND RESULTS: One hundred and forty-one patients with mild-to-moderate AS, recruited prospectively in the PROGRESSA study, were included in this sub-analysis. Baseline clinical, Doppler echocardiography and multidetector computed tomography characteristics were compared between BAV (n = 32) and TAV (n = 109) patients. The 2-year haemodynamic [i.e. peak aortic jet velocity (Vpeak) and mean transvalvular gradient (MG)] and anatomic [i.e. aortic valve calcification density (AVCd) and aortic valve calcification density ratio (AVCd ratio)] progression of AS were compared between the two valve phenotypes. The 2-year progression rate of Vpeak was: 16 (-0 to 40) vs. 17 (3-35) cm/s, P = 0.95; of MG was: 1.8 (-0.7 to 5.8) vs. 2.6 (0.4-4.8) mmHg, P = 0.56; of AVCd was 32 (2-109) vs. 52 (25-85) AU/cm2, P = 0.15; and of AVCd ratio was: 0.08 (0.01-0.23) vs. 0.12 (0.06-0.18), P = 0.16 in patients with BAV vs. TAV. In univariable analyses, BAV was not associated with AS progression (all, P ≥ 0.26). However, with further adjustment for age, AS baseline severity, and several risk factors (i.e. sex, history of hypertension, creatinine level, diabetes, metabolic syndrome), BAV was independently associated with faster haemodynamic (Vpeak: ß = 0.31, P = 0.02) and anatomic (AVCd: ß = 0.26, P = 0.03 and AVCd ratio: ß = 0.26, P = 0.03) progression of AS. CONCLUSION: In patients with mild-to-moderate AS, patients with BAV have faster haemodynamic and anatomic progression of AS when compared to TAV patients with similar age and risk profile. This study highlights the importance and necessity to closely monitor patients with BAV and to adequately control and treat their risk factors. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov Unique identifier: NCT01679431.

Sex-Related Differences in the Extent of Myocardial Fibrosis in Patients With Aortic Valve Stenosis.

OBJECTIVES: The aim of this study was to assess the effect of sex on myocardial fibrosis as assessed by using cardiac magnetic resonance (CMR) imaging in aortic stenosis (AS). BACKGROUND: Previous studies reported sex-related differences in the left ventricular (LV) remodeling response to pressure overload in AS. However, there are very few data regarding the effect of sex on myocardial fibrosis, a key marker of LV decompensation and adverse cardiac events in AS. METHODS: A total of 249 patients (mean age 66 ± 13 years; 30% women) with at least mild AS were recruited from 2 prospective observational cohort studies and underwent comprehensive Doppler echocardiography and CMR examinations. On CMR, T1 mapping was used to quantify extracellular volume (ECV) fraction as a marker of diffuse fibrosis, and late gadolinium enhancement (LGE) was used to assess focal fibrosis. RESULTS: There was no difference in age between women and men (age 66 ± 15 years vs 66 ± 12 years; p = 0.78). However, women presented with a better cardiovascular risk profile than men with less hypertension, dyslipidemia, diabetes, and coronary artery disease (all, p ≤ 0.10). As expected, LV mass index measured by CMR imaging was smaller in women than in men (p < 0.0001). Despite fewer comorbidities, women presented with larger ECV fraction (median: 29.0% [25th to 75th percentiles: 27.4% to 30.6%] vs. 26.8% [25th to 75th percentiles: 25.1% to 28.7%]; p < 0.0001) and similar LGE (median: 4.5% [25th-75th percentiles: 2.3% to 7.0%] vs. 2.8% [25th-75th percentiles: 0.6% to 6.8%]; p = 0.20) than men. In multivariable analysis, female sex remained an independent determinant of higher ECV fraction and LGE (all, p ≤ 0.05). CONCLUSIONS: Women have greater diffuse and focal myocardial fibrosis independent of the degree of AS severity. These findings further emphasize the sex-related differences in LV remodeling response to pressure overload.

Transcatheter innovations in tricuspid regurgitation: FORMA device.

Transcatheter tricuspid valve interventions (TTVIs) have arisen in recent years as an alternative treatment of tricuspid regurgitation (TR) in high risk patients. TTVIs can be classified as annuloplasty devices, caval valve implantation (CAVI), tricuspid valve replacement and coaptation devices. The FORMA repair system (Edwards Lifesciences, Irvine, CA, USA) aims to improve the coaptation of tricuspid leaflets by occupying the regurgitant orifice with a balloon spacer, which reduces the regurgitant orifice area. After the first-in-human reported case back in 2015, data from 18 patients treated under compassionate clinical use conditions and from 29 patients under the US early feasibility (EFS) trial have been published. The two studies included very high-risk surgical patients (Euroscore II >8 in both cohorts). Implantation success was achieved in 16 (89%) and 27 (93%) of patients, respectively. In the US EFS trial, results at 30 days showed improvements in New York Heart Association (NYHA) functional class (NYHA class ≥ III in 28% vs 84% at baseline, p =0.0002), 6-minute walking test (increase by 21 m, p =0.012) and in the Kansas City Cardiomyopathy Questionnaire (increase by 29 points, p < 0001). In addition, the Core Lab evaluation at 30 days showed statistically significant reductions in TR severity grading in the 25 available patients. Regarding the compassionate cohort, 15 patients had available data at long-term follow-up (≥ 2 years). NYHA functional class ≥ III was reduced from 93% to 34% (p <0.001). However, two-thirds of the patients remained with significant TR at last available follow-up, and there were no significant changes in EROA (0.92 vs. 0.77 cm2; p = 0.516). In conclusion, this first experience with the FORMA device showed the feasibility of the procedure. Despite the magnitude of TR reduction was moderate at long-term, significant improvements in heart failure symptoms and quality of life were achieved.

Long-Term Outcomes of the FORMA Transcatheter Tricuspid Valve Repair System for the Treatment of Severe Tricuspid Regurgitation: Insights From the First-in-Human Experience.

OBJECTIVES: To evaluate the long-term (≥2 years) outcomes following transcatheter tricuspid valve repair (TTVr) with the FORMA Transcatheter Tricuspid Valve Repair System (Edwards Lifesciences, Irvine, California). BACKGROUND: Scarce data exist on long-term outcomes following TTVr. METHODS: This multicenter experience included patients with severe tricuspid regurgitation (TR) who underwent TTVr with the FORMA system at 4 centers under a compassionate clinical use program. Data were collected at baseline, 30 days, and 1 year, and yearly thereafter. RESULTS: Nineteen patients (76 ± 9 years of age, 74% women, mean EuroSCORE II [European System for Cardiac Operative Risk Evaluation] 9.2 ± 5.6%) with functional TR were included. Procedural success was achieved in 17 (89%) patients and there were no cases of 30-day mortality. At a median follow-up of 32 (interquartile range: 24 to 36) months, 4 (24%) patients had died (3 from terminal heart failure, 1 from sepsis) and 3 (18%) patients required rehospitalization for heart failure. There was 1 device-related thrombosis and 1 pulmonary embolism, both in the setting of subtherapeutic oral anticoagulation. Less than severe TR was observed at echocardiography in 67% of patients at the 2- to 3-year follow-up. Among 15 successfully implanted patients with at least 24-month follow-up, significant improvements in New York Heart Association functional class (p < 0.001), 6-min walk test (+54 m; p = 0.016) and Kansas City Cardiomyopathy Questionnaire score (+16 points; p = 0.016) were observed, compared with baseline. CONCLUSIONS: TTVr using the FORMA system showed favorable long-term safety profile in high-surgical-risk patients, with sustained functional improvement and acceptable TR reduction up to 3 years.

Staging Cardiac Damage in Patients With Asymptomatic Aortic Valve Stenosis.

BACKGROUND: The optimal timing of intervention in patients with asymptomatic severe aortic stenosis (AS) remains controversial. OBJECTIVES: This multicenter study sought to test and validate the prognostic value of the staging of cardiac damage in patients with asymptomatic moderate to severe AS. METHODS: This study retrospectively analyzed the clinical, Doppler echocardiographic, and outcome data that were prospectively collected in 735 asymptomatic patients (71 ± 14 years of age; 60% men) with at least moderate AS (aortic valve area <1.5 cm2) and preserved left ventricular ejection fraction (≥50%) followed in the heart valve clinics of 4 high-volume centers. Patients were classified according to the following staging classification: no cardiac damage associated with the valve stenosis (Stage 0), left ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2), pulmonary vasculature or tricuspid valve damage (Stage 3), or right ventricular damage or subclinical heart failure (Stage 4). The primary endpoint was all-cause mortality. RESULTS: At baseline, 89 (12%) patients were classified in Stage 0, 200 (27%) in Stage 1, 341 (46%) in Stage 2, and 105 (14%) in Stage 3 or 4. Median follow-up was 2.6 years (interquartile range: 1.1 to 5.2 years). There was a stepwise increase in mortality rates according to staging: 13% in Stage 0, 25% in Stage 1, 44% in Stage 2, and 58% in Stages 3 to 4 (p < 0.0001). The staging was significantly associated with excess mortality in multivariable analysis adjusted for aortic valve replacement as a time-dependent variable (hazard ratio: 1.31 per each increase in stage; 95% CI: 1.06 to 1.61; p = 0.01), and showed incremental value to several clinical variables (net reclassification index = 0.34; p = 0.003). CONCLUSIONS: The new staging system characterizing the extra-aortic valve cardiac damage provides incremental prognostic value in patients with asymptomatic moderate to severe AS. This staging classification may be helpful to identify asymptomatic AS patients who may benefit from elective aortic valve replacement.

Cardiac remodeling after six weeks of high-intensity interval training to exhaustion in endurance-trained men.

High-intensity interval training (HIIT) improves physical performance of endurance athletes, although studies examining its cardiovascular effects are sparse. We evaluated the impact of HIIT on blood pressure, heart rate, and cardiac cavities' size and function in endurance-trained adults. Seventeen endurance-trained men underwent 24-h ambulatory blood pressure monitoring and Doppler echocardiography at baseline and after 6 wk of HIIT. Participants were divided into 2 groups [85% maximal aerobic power (HIIT85), n = 8 and 115% maximal aerobic power (HIIT115), n = 9] to compare the impact of different HIIT intensities. Ambulatory blood pressure monitoring and cardiac chambers' size and function were similar between groups at baseline. HIIT reduced heart rate (55 ± 8 vs. 51 ± 7 beats/min; P = 0.003), systolic blood pressure (121 ± 11 vs. 118 ± 9 mmHg; P = 0.01), mean arterial pressure (90 ± 8 vs. 89 ± 6 mmHg; P = 0.03), and pulse pressure (52 ± 6 vs. 49 ± 5 mmHg; P = 0.01) irrespective of training intensity. Left atrium volumes increased after HIIT (maximal: 50 ± 14 vs. 54 ± 14 mL; P = 0.02; minimal: 15 ± 5 vs. 20 ± 8 mL; P = 0.01) in both groups. Right ventricle global longitudinal strain lowered after training in the HIIT85 group only (20 ± 4 vs. 17 ± 3%, P = 0.04). In endurance-trained men, 6 wk of HIIT reduced systolic blood pressure and mean arterial pressure and increased left atrium volumes irrespective of training intensity, whereas submaximal HIIT deteriorated right ventricle systolic function.NEW & NOTEWORTHY The novel findings of this study are that 6 wk of high-intensity interval training increases left atrial volumes irrespective of training intensity (85 or 115% maximal aerobic power), whereas the submaximal training decreases right ventricular systolic function in endurance-trained men. These results may help identify the exercise threshold for potential toxicity of intense exercise training for at-risk individuals and ideal exercise training regimens conferring optimal cardiovascular protection and adapted endurance training for athletes.