Unmet needs in valvular heart disease.

Valvular heart disease (VHD) is the next epidemic in the cardiovascular field, affecting millions of people worldwide and having a major impact on health care systems. With aging of the population, the incidence and prevalence of VHD will continue to increase. However, VHD has not received the attention it deserves from both the public and policymakers. Despite important advances in the pathophysiology, natural history, management, and treatment of VHD including the development of transcatheter therapies, VHD remains underdiagnosed, identified late, and often undertreated with inequality in access to care and treatment options, and there is no medication that can prevent disease progression. The present review article discusses these gaps in the management of VHD and potential actions to undertake to improve the outcome of patients with VHD.

Trends in aortic valve replacement for aortic stenosis: a French nationwide study.

AIMS: Transcatheter aortic valve replacement (TAVR) as an alternative to surgical aortic valve replacement (SAVR) has profoundly changed the management of patients with aortic valve stenosis (AS). Large unbiased nationwide data regarding TAVR implementation, impact on SAVR and their respective outcomes are scarce. METHODS AND RESULTS: Based on a French administrative hospital-discharge database, we collected data on all consecutive aortic valve replacements (AVRs) performed in France for AS between 2007 and 2019 [106 253 isolated SAVR (49%), 46 514 combined SAVR (21%), and 65 651 TAVR (30%)]. The number of AVR linearly increased between 2007 and 2019 (from 10 892 to 23 109, P for trend < 0.0001) due to a marked increase in TAVR (from 253 to 13 030, P for trend < 0.0001), while SAVR increased up to 2013 and then declined (10 892 in 2007, 12 699 in 2013, and 10 079 in 2019). The Charlson index decreased linearly for TAVR, but in two steps for SAVR (2011 and 2017). In-hospital mortality rates of both SAVR and TAVR declined (both P for trend < 0.0001) and were similar or lower for TAVR than for isolated SAVR in patients 75 years or above in the last 3 years (2017-19). Complication rates of TAVR also declined but permanent pacemaker rates remained high and length of stay substantial (16.7% and median 6 days, respectively, in 2017-19). CONCLUSION: The number of AVR has doubled in a decade and TAVR has become the dominant form of AVR in 2018. The improvement in patient profiles seems to have anticipated the demonstrated benefit of TAVR in intermediate and low-risk patients. In patients 75 years or older, TAVR should be considered as the first option. We also highlight two important areas for improvement, the high permanent pacemaker rates, and the long length of stay even in the contemporary era. Our results may have major implications for clinical practice and policymakers.

Trends in aortic valve replacement for aortic stenosis: a French nationwide study.

AIMS: Transcatheter aortic valve replacement (TAVR) as an alternative to surgical aortic valve replacement (SAVR) has profoundly changed the management of patients with aortic valve stenosis (AS). Large unbiased nationwide data regarding TAVR implementation, impact on SAVR and their respective outcomes are scarce. METHODS AND RESULTS: Based on a French administrative hospital-discharge database, we collected data on all consecutive aortic valve replacements (AVRs) performed in France for AS between 2007 and 2019 [106 253 isolated SAVR (49%), 46 514 combined SAVR (21%), and 65 651 TAVR (30%)]. The number of AVR linearly increased between 2007 and 2019 (from 10 892 to 23 109, P for trend < 0.0001) due to a marked increase in TAVR (from 253 to 13 030, P for trend < 0.0001), while SAVR increased up to 2013 and then declined (10 892 in 2007, 12 699 in 2013, and 10 079 in 2019). The Charlson index decreased linearly for TAVR, but in two steps for SAVR (2011 and 2017). In-hospital mortality rates of both SAVR and TAVR declined (both P for trend < 0.0001) and were similar or lower for TAVR than for isolated SAVR in patients 75 years or above in the last 3 years (2017-19). Complication rates of TAVR also declined but permanent pacemaker rates remained high and length of stay substantial (16.7% and median 6 days, respectively, in 2017-19). CONCLUSION: The number of AVR has doubled in a decade and TAVR has become the dominant form of AVR in 2018. The improvement in patient profiles seems to have anticipated the demonstrated benefit of TAVR in intermediate and low-risk patients. In patients 75 years or older, TAVR should be considered as the first option. We also highlight two important areas for improvement, the high permanent pacemaker rates, and the long length of stay even in the contemporary era. Our results may have major implications for clinical practice and policymakers.

Metabolic activity of the left and right atria are differentially altered in patients with atrial fibrillation and LV dysfunction.

BACKGROUND: Alterations in atrial metabolism may play a role in the perpetuation of atrial fibrillation (AF). This study sought to compare 18F-fluorodeoxyglucose (FDG) uptake on PET, in patients with LV dysfunction versus those without AF. METHODS: Seventy-two patients who underwent myocardial viability assessment were evaluated. AF patients (36) had persistent or permanent AF based on history and ECG. Patients without AF (36) were matched to AF patients based on sex, diabetes, age, and LVEF. Maximum and mean FDG Standard Uptake Values (SUV) in the left atrial (LA) wall and right atrial (RA) wall were measured. Tissue-to-blood ratios (TBR) were calculated as atrial wall to blood-pool activity. Atrial volumes were measured by echocardiography. RESULTS: Maximum and mean FDG SUV and TBRs were significantly increased in the RA (but not the LA) of patients with AF compared to those without (P < 0.01). When accounting for changes in atrial volume, the presence of AF remained a significant predictor of higher RAMAX, but not RAMEAN FDG uptake. CONCLUSION: In patients with LV dysfunction from ischemic cardiomyopathy, LA and RA glucose metabolism are differentially altered in those with persistent atrial fibrillation. Further investigations should elucidate the temporal relationship between AF and glucose metabolic changes, as a potential target for therapy.

Increased myocardial oxygen consumption rates are associated with maladaptive right ventricular remodeling and decreased event-free survival in heart failure patients.

BACKGROUND: Reduced left ventricular (LV) function is associated with increased myocardial oxygen consumption rate (MVO2) and altered sympathetic activity, the role of which is not well described in right ventricular (RV) dysfunction. METHODS AND RESULTS: 33 patients with left heart failure were assessed for RV function/size using echocardiography. Positron emission tomography (PET) was used to measure 11C-acetate clearance rate (kmono), 11C-hydroxyephedrine (11C-HED) standardized uptake value (SUV), and retention rate. RV MVO2 was estimated from kmono. 11C-HED SUV and retention indicated sympathetic neuronal function. A composite clinical endpoint was defined as unplanned cardiac hospitalization within 5 years. Patients with (n = 10) or without (n = 23) RV dysfunction were comparable in terms of sex (male: 70.0 vs 69.5%), LV ejection fraction (39.6 ± 9.0 vs 38.6 ± 9.4%), and systemic hypertension (70.0 vs 78.3%). RV dysfunction patients were older (70.9 ± 13.5 vs 59.4 ± 11.5 years; P = .03) and had a higher prevalence of pulmonary hypertension (60.0% vs 13.0%; P = .01). RV dysfunction was associated with increased RV MVO2 (.106 ± .042 vs .068 ± .031 mL/min/g; P = .02) and decreased 11C-HED SUV and retention (6.05 ± .53 vs 7.40 ± 1.39 g/mL (P < .001) and .08 ± .02 vs .11 ± .03 mL/min/g (P < .001), respectively). Patients with an RV MVO2 above the median had a shorter event-free survival (hazard ratio = 5.47; P = .01). Patients who died within the 5-year follow-up period showed a trend (not statistically significant) for higher RV MVO2 (.120 ± .026 vs .074 ± .038 mL/min/g; P = .05). CONCLUSIONS: RV dysfunction is associated with increased oxygen consumption (also characterized by a higher risk for cardiac events) and impaired RV sympathetic function.

Reliable quantification of myocardial sympathetic innervation and regional denervation using [11C]meta-hydroxyephedrine PET.

PURPOSE: Cardiac sympathetic nervous system (SNS) dysfunction is associated with poor prognosis in chronic heart failure patients. This study characterized the reproducibility and repeatability of [11C]meta-hydroxyephedrine (HED) positron emission tomography (PET) quantification of cardiac SNS innervation, regional denervation, and myocardial blood flow (MBF). METHODS: Dynamic HED PET-CT scans were performed 47 ± 22 days apart in 20 patients with stable heart failure and reduced ejection fraction. Three observers, blinded to clinical data, used FlowQuant® to evaluate the test-retest repeatability and inter- and intra-observer reproducibility of HED tracer uptake and clearance rates to measure global (LV-mean) retention index (RI), volume of distribution (VT), and MBF. Values were also compared with and without regional partial-volume correction. Regional denervation was quantified as %LV defect size of values < 75% of the LV-maximum. Test-retest repeatability and observer reproducibility were evaluated using intra-class-correlation (ICC) and Bland-Altman coefficient of repeatability (NPC). RESULTS: Intra- and inter-observer correlations of both VT and RI were excellent (ICC = 0.93-0.99). Observer reproducibility (NPC = 3-13%) was lower than test-retest repeatability (NPC = 12-61%). Both regional (%LV defect size) and global (LV-mean) measures of sympathetic innervation were more repeatable using the simple RI model compared to VT (NPC = 12% vs. 19% and 30% vs. 54%). Using either model, quantification of regional denervation (defect size) was consistently more reliable than the global LV-mean values of RI or VT. Regional partial-volume correction degraded repeatability of both the global and regional VT measures by 2-12%. Test-retest repeatability of MBF estimation was relatively poor (NPC = 30-61%) compared with the RI. CONCLUSIONS: Quantitative measures of global and regional SNS innervation were most repeatable using the simple RI method of analysis compared with the more complex VT. Observer variability was significantly lower than the test-retest repeatability using a highly automated analysis program. These results support the use of the simple RI method for reliable analysis of HED PET images in clinical research studies for future evaluation of new therapies and for risk stratification in patients with heart failure.

The echocardiographic assessment of the right ventricle in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia compared with athletes and matched controls.

BACKGROUND: There are discrepancies in the quantitative echocardiographic criteria for the right ventricle (RV) between the revised task force criteria (TFC) for Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) and the guidelines for RV assessment endorsed by American Society of Echocardiography (ASE). Importantly, these criteria do not take into account potential adaptation of the RV to exercise. The goal of this study was to compare the revised TFC quantitative echocardiographic parameters in patients with ARVC/D, athletes and matched controls. METHODS: Echocardiographic parameters of the RV were retrospectively collected in patients who fulfilled the TFC for ARVC/D, an age- matched, sex-matched, and body surface area-matched control population, and athletes (defined as individuals who exercised for more than 7 hours per week). Patients with structural heart disease were excluded in the control and athlete groups. RESULTS: Twenty patients with ARVC/D, 11 athletes and 20 matched controls were included. There was no significant difference between ARVC/D patients and athletes with the exception of the parasternal long axis right ventricular outflow tract diameter. All parameters were significantly different between ARVC/D patients and the control group. Furthermore, when subjects were categorized into meeting 1 major revised TFC/abnormal ASE criteria or not, only ASE criteria were able to differentiate ARVC/D from control population. Both were unable to differentiate ARVC/D from athletes. CONCLUSIONS: Right ventricle quantitative echocardiographic criteria in the revised TFC are not specific for ARVC/D. Care should be taken in applying these criteria in athletes.

Repeatable and reproducible measurements of myocardial oxidative metabolism, blood flow and external efficiency using 11C-acetate PET.

BACKGROUND: Non-invasive approaches to investigate myocardial efficiency can help track the progression of heart failure (HF). This study evaluates the repeatability and reproducibility of 11C-acetate positron emission tomography (PET) imaging of oxidative metabolism. METHODS AND RESULTS: Dynamic 11C-acetate PET scans were performed at baseline and followup (47 ± 22 days apart) in 20 patients with stable HF with reduced ejection fraction. Two observers blinded to patients' clinical data used FlowQuant® to evaluate test-retest repeatability, as well as intra- and inter-observer reproducibility of 11C-acetate tracer uptake and clearance rates, for the measurement of myocardial oxygen consumption (MVO2), myocardial external efficiency (MEE), work metabolic index (WMI), and myocardial blood flow. Reproducibility and repeatability were evaluated using intra-class-correlation (ICC) and Bland-Altman coefficient-of-repeatability (CR). Test-retest correlations and repeatability were better for MEE and WMI compared to MVO2. All intra- and inter-observer correlations were excellent (ICC = 0.95-0.99) and the reproducibility values (CR = 3%-6%) were significantly lower than the test-retest repeatability values (22%-54%, P < 0.001). Repeatability was improved for all parameters using a newer PET-computed tomography (CT) scanner compared to older PET-only instrumentation. CONCLUSION: 11C-acetate PET measurements of WMI and MEE exhibited excellent test-retest repeatability and operator reproducibility. Newer PET-CT scanners may be preferred for longitudinal tracking of cardiac efficiency.

Transcatheter Aortic Valve Implantation (TAVI) for Native Aortic Valve Regurgitation　- A Systematic Review.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become the standard of care for management of high-risk patients with aortic stenosis. Limited data is available regarding the performance of TAVI in patients with native aortic valve regurgitation (NAVR).Methods and Results:We performed a systematic review from 2002 to 2016. The primary outcome was device success as per VARC-2 criteria. Secondary endpoints included procedural complications, and 30-day and 1-year mortality rates. A total of 175 patients were included from 31 studies. Device success was reported in 86.3% of patients - with device failure driven by moderate aortic regurgitation (AR ≥3+) and/or need for a second device. Procedural complications were rare, with no procedural deaths, myocardial infarctions or annular ruptures reported. Procedural safety was acceptable with a low 30-day incidence of stroke (1.5%). The 30-day and 1-year overall mortality rates were 9.6% and 20.0% (cardiovascular death, 3.8% and 10.1%, respectively). Patients receiving 2nd-generation valves demonstrated similar safety profiles with greater device success compared with 1st-generation valves (96.2% vs. 78.4%). This was driven by the higher incidence of second-valve implantation (23.4% vs. 1.7%) and significant paravalvular leak (8.3% vs. 0.0%). CONCLUSIONS: TAVI demonstrates acceptable safety and efficacy in high-risk patients with severe NAVR. Second-generation valves may afford a similar safety profile with improved device success. Dedicated studies are needed to definitively establish the efficacy of TAVI in this population.

Right Heart Function During and After Community-Acquired Pneumonia in Adults.

BACKGROUND: New-onset or worsening heart failure is the most common extra-pulmonary complication of community-acquired pneumonia (CAP) during the first 30 days after diagnosis. METHODS: We evaluated the changes in the right ventricular function amongst adult CAP survivors from the time of acute infection to its resolution. We performed comprehensive transthoracic echocardiographic examinations to assess right heart function during the acute illness and the convalescent period (4 to 6 weeks after hospital discharge). RESULTS: Twenty-six patients underwent acute measurements, of which convalescent measurements were completed in 19 subjects. There was no significant change in any of the right heart function parameters from the acute to convalescent stage of CAP. CONCLUSIONS: Our results suggest that right ventricular function does not meaningfully change in the transition from the acute to convalescent stage of CAP in non-critically ill adult CAP survivors.

Appropriate Use Criteria for Cardiac Computed Tomography: Impact on Diagnostic Utility.

BACKGROUND: Appropriate Use Criteria (AUC) guidelines for cardiac computed tomography (CCT) were developed to limit testing to reasonable clinical settings. However, significant testing is still done for inappropriate indications. This study investigates the impact of AUC on evaluability of CCT to determine if inappropriate tests result in a greater proportion of nondiagnostic results. METHODS: Investigators reviewed the medical records of 2417 consecutive patients who underwent CCT at the University of Ottawa Heart Institute. We applied the 2010 AUC and classified them as appropriate, inappropriate, or uncertain. Unclassifiable tests, as well as those with uncertain appropriateness, were excluded from the final analysis. Cardiac computed tomography results were classified as diagnostic if (1) all coronary segments were visualized, evaluable, and without obstructive stenosis; or (2) obstructive coronary artery disease with greater than 50% diameter stenosis in at least 1 coronary artery. All other test results were considered nondiagnostic. RESULTS: Of the 1984 patients included in the final analysis, 1522 patients (76.7%) had indications that were appropriate, whereas the remaining 462 (23.3%) were inappropriate. Inappropriate tests resulted in a higher rate of nondiagnostic results compared with appropriate CCT (9.0% vs 6.2%, P = 0.034). Inappropriate tests also had significantly more studies with nonevaluable segments than appropriate tests (24.5% vs 16.4%, P < 0.001) and were more likely to reveal obstructive coronary disease than appropriate CCT (50.5% vs 32.7%, P < 0.001). CONCLUSIONS: Cardiac computed tomography done for inappropriate indications may be associated with lower diagnostic yield and could impact future downstream resource utilization and health care costs.

Impact of a structured referral algorithm on the ability to monitor adherence to appropriate use criteria for transthoracic echocardiography.

BACKGROUND: Many free-form-text referral requisitions for transthoracic echocardiography (TTE) provide insufficient information to adequately evaluate their adherence to Appropriate Use Criteria (AUC). We developed a structured referral requisition algorithm based on requisition deficiencies identified retrospectively in a derivation cohort of 1303 TTE referrals and evaluated the performance of the algorithm in a consecutive series of cardiology outpatient referrals. METHODS: The validation cohort comprised 286 consecutive TTE outpatient cardiology referrals over a 2-week period. The relevant AUC indication was identified from information extracted from the free-form-text requisition. The structured referral algorithm was applied prospectively to the same cohort using information from the free-form-text requisition, electronic medical record and ordering clinicians. Referrals were classified as appropriate, uncertain, non-adherent (inappropriate) or unclassifiable based on the American College of Cardiology Foundation 2011 AUC. RESULTS: Only 28.7 % of free-form-text requisitions provided adequate information to identify the relevant AUC indication, as compared to 94.4 % of referrals using the structured referral algorithm (p < 0.001). The structured algorithm improved identification in the AUC categories of general evaluation of cardiac structure/function (100 % vs. 43.0 %, p < 0.001); valvular function (100 % vs. 23.0 %, p < 0.001); hypertension, heart failure or cardiomyopathy (100 % vs. 20.3 %, p < 0.001); and adult congenital heart disease (100 % vs. 0 %, p < 0.001). By applying the algorithm, the number of identifiable non-adherent studies increased from 2.6 to 10.4 % (p <0.001). CONCLUSIONS: Use of a structured TTE referral algorithm, as opposed to a free-form-text requisition, allowed the vast majority of referrals to be monitored for AUC adherence and facilitated the identification of potentially inappropriate referrals.

Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: a randomized study.

BACKGROUND: Heart failure with reduced ejection fraction and obstructive sleep apnea (OSA), 2 states of increased metabolic demand and sympathetic nervous system activation, often coexist. Continuous positive airway pressure (CPAP), which alleviates OSA, can improve ventricular function. It is unknown whether this is due to altered oxidative metabolism or presynaptic sympathetic nerve function. We hypothesized that short-term (6-8 weeks) CPAP in patients with OSA and heart failure with reduced ejection fraction would improve myocardial sympathetic nerve function and energetics. METHODS AND RESULTS: Forty-five patients with OSA and heart failure with reduced ejection fraction (left ventricular ejection fraction 35.8±9.7% [mean±SD]) were evaluated with the use of echocardiography and 11C-acetate and 11C-hydroxyephedrine positron emission tomography before and ≈6 to 8 weeks after randomization to receive short-term CPAP (n=22) or no CPAP (n=23). Work metabolic index, an estimate of myocardial efficiency, was calculated as follows: (stroke volume index×heart rate×systolic blood pressure÷Kmono), where Kmono is the monoexponential function fit to the myocardial 11C-acetate time-activity data, reflecting oxidative metabolism. Presynaptic sympathetic nerve function was measured with the use of the 11C-hydroxyephedrine retention index. CPAP significantly increased hydroxyephedrine retention versus no CPAP (Δretention: +0.012 [0.002, 0.021] versus -0.006 [-0.013, 0.005] min(-1); P=0.003). There was no significant change in work metabolic index between groups. However, in those with more severe OSA (apnea-hypopnea index>20 events per hour), CPAP significantly increased both work metabolic index and systolic blood pressure (P<0.05). CONCLUSIONS: In patients with heart failure with reduced ejection fraction and OSA, short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics. In those with more severe OSA, CPAP may improve cardiac efficiency. Further outcome-based investigation of the consequences of CPAP is warranted. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00756366.

Limitations of free-form-text diagnostic requisitions as a tool for evaluating adherence to appropriate use criteria for transthoracic echocardiography.

BACKGROUND: Monitoring the adherence to Appropriateness Use Criteria (AUC) has been identified as an important component for the accreditation of echocardiography laboratories. Referral requisitions are a logical tool to rapidly determine the appropriateness of transthoracic echocardiography (TTE) referrals, however data is lacking. We investigated whether standard free-form-text TTE referral requisitions can be used to evaluate AUC adherence. METHODS: Consecutive TTE referral requisitions to the University of Ottawa Heart Institute echocardiography laboratory were reviewed over a four-week period. Indication on the requisition was matched with the relevant indication on the 2011 American College of Cardiology Foundation (ACCF) AUC. Requisitions that did not provide sufficient information to identify the relevant AUC indication were identified as inadequate. For inadequate requisitions, reason for the referral was clarified through medical records and referring physicians. RESULTS: Of the 1303 requisitions, 26.2% did not provide adequate information to determine adherence to AUC, despite a non-adherence (inappropriate) rate of only 6.1% in the referral population. Indication for referral, physician specialty, outpatient status, and prior echocardiogram were independent predictors of inadequate requisitions (p < 0.001, respectively). The most common reasons for inadequate requisitions were a failure to report: 1) change in clinical status, 2) date of a prior echocardiogram, and 3) type and/or severity of a valve lesion. Inclusion of this information would have decreased the inadequacy rate by 56%. CONCLUSION: In a large, academic echocardiography laboratory, over one quarter of free-form-text TTE requisitions are inadequate to evaluate AUC adherence. Structured requisition formats requiring AUC-relevant information are needed to facilitate the practical application of AUC in the echocardiography laboratory.

Granulocyte colony-stimulating factor therapy for stem cell mobilization following anterior wall myocardial infarction: the CAPITAL STEM MI randomized trial.

BACKGROUND: Small studies have yielded divergent results for administration of granulocyte colony-stimulating factor (G-CSF) after acute myocardial infarction. Adequately powered studies involving patients with at least moderate left ventricular dysfunction are lacking. METHODS: Patients with left ventricular ejection fraction less than 45% after anterior-wall myocardial infarction were treated with G-CSF (10 µg/kg daily for 4 days) or placebo. After initial randomization of 86 patients, 41 in the placebo group and 39 in the G-CSF group completed 6-month follow-up and underwent measurement of left ventricular ejection fraction by radionuclide angiography. RESULTS: Baseline and 6-week mean ejection fraction was similar for the G-CSF and placebo groups: 34.8% (95% confidence interval [CI] 32.6%-37.0%) v. 36.4% (95% CI 33.5%-39.2%) at baseline and 39.8% (95% CI 36.2%-43.4%) v. 43.1% (95% CI 39.2%-47.0%) at 6 weeks. However, G-CSF therapy was associated with a lower ejection fraction at 6 months relative to placebo (40.8% [95% CI 37.4%-44.2%] v. 46.0% [95% CI 42.7%-44.3%]). Both groups had improved left ventricular function, but change in left ventricular ejection fraction was lower in patients treated with G-CSF than in those who received placebo (5.7 [95% CI 3.4-8.1] percentage points v. 9.2 [95% CI 6.3-12.1] percentage points). One or more of a composite of several major adverse cardiac events occurred in 8 patients (19%) within each group, with similar rates of target-vessel revascularization. INTERPRETATION: In patients with moderate left ventricular dysfunction following anterior-wall infarction, G-CSF therapy was associated with a lower 6-month left ventricular ejection fraction but no increased risk of major adverse cardiac events. Future studies of G-CSF in patients with left ventricular dysfunction should be monitored closely for safety. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT00394498.

Edge-to-edge with partial band mitral valve repair compared to replacement and undersized restrictive annuloplasty for ischemic mitral regurgitation.

Objective: Evidence supports replacement over repair for ischemic mitral regurgitation due to improved durability; however, the latter often involves an undersized ring annuloplasty that does not include edge-to-edge approximation. The objective of this study was to evaluate the outcomes of replacement, edge-to-edge leaflet approximation with mild-undersized annuloplasty and undersized ring annuloplasty for ischemic mitral regurgitation. Methods: This is a single-center retrospective study of patients undergoing mitral surgery for moderate-severe or greater ischemic mitral regurgitation, between 2004 and 2020, with mild-undersized annuloplasty, mitral valve replacement, or undersized restrictive annuloplasty (undersized ring annuloplasty). The primary outcome was all-cause mortality. Secondary outcomes included first recurrence of mitral regurgitation, heart failure hospitalization, and composite of valve-related events (bleeding, thromboembolism, endocarditis, and mitral valve reoperation). Results: There were 121, 93, and 78 patients in the mitral valve replacement, mild-undersized annuloplasty, and undersized restrictive annuloplasty groups, respectively, with a median follow-up of 3.1, 5.9, and 3.8 years, respectively. Both mitral valve replacement (hazard ratio, 1.87; 95% CI, 1.029-3.415) and undersized restrictive annuloplasty (hazard ratio, 2.73; 95% CI, 1.480-5.061) were associated with worse survival compared with mild-undersized annuloplasty. At 2 years, the rate of mild-moderate mitral regurgitation was greater in the mild-undersized annuloplasty group compared with the mitral valve replacement group (P = .001) but less than in the undersized restrictive annuloplasty group (P = .001). The rate of recurrent moderate or greater mitral regurgitation at 2 years was similar between mild-undersized annuloplasty and mitral valve replacement groups but significantly higher after undersized restrictive annuloplasty (P < .0001). Mitral valve replacement and undersized restrictive annuloplasty were associated with a significant increase in the incidence of first heart failure hospitalization compared with mild-undersized annuloplasty (P < .001 and P = .001, respectively). Mitral valve replacement was associated with an increased incidence of valve-related events compared with mild-undersized annuloplasty (P = .002). Conclusions: Surgical edge-to-edge approximation in addition to a mild-undersizing annuloplasty offers similar durability compared with replacement, with a lower rate of hospitalization for heart failure, and may confer a survival advantage.

Cost-effectiveness of population screening for aortic stenosis.

BACKGROUND AND AIMS: Aortic stenosis (AS) is a progressive disease predominantly affecting elderly patients that carries significant morbidity and mortality without aortic valve replacement, the only proven treatment. Our objective was to determine the cost-effectiveness of AS screening using transthoracic echocardiography (TTE) in a geriatric population from the perspective of the publicly funded healthcare system in Canada. METHODS: Markov models estimating the cost-effectiveness ratio (ICER) for AS screening with a one-time TTE were developed. The model included diagnosed and undiagnosed AS health states, hospitalizations, TAVR and post-TAVR health states. Primary analysis included screening at 70 and 80 years of age with intervention at symptom onset, with scenario analysis included for early intervention at the time of severe asymptomatic AS diagnosis. Monte Carlo simulation of 5000 replications was completed with a lifetime horizon and 1.5% discount for costs and outcomes. RESULTS: Screening for AS at the age of 70 years was associated with an ICER of $156,722 and screening at 80 years of age was associated with an ICER of $28,005, suggesting that screening at 80 years of age is cost-effective when willingness-to-pay per QALY is $50,000. Scenario analysis with early intervention was not cost-effective with an ICER of $142,157 at 70 years, and $124,651 at 80 years. CONCLUSION: Screening for AS at 80 years of age with a one-time TTE, in a Canadian population, improves quality of life and is cost-effective in a publicly funded healthcare system providing TAVR is reserved for symptomatic patients.

Impact of the coronavirus disease 2019 pandemic on aortic valve replacement and outcomes in France.

BACKGROUND: The coronavirus disease of 2019 (COVID-19) pandemic lockdowns limited access to medical care. The impact on surgical (SAVR) and transcatheter (TAVR) aortic valve replacement (AVR) has been poorly described. AIM: We sought to evaluate the impact of the COVID-19 pandemic on the number and modalities of AVR, patient demographics and in-hospital outcomes at the nationwide level. METHODS: Using the French nationwide administrative hospital discharge database, we compared projected numbers and proportions of AVR and hospital outcomes, obtained using linear regressions derived from 2015-2019 trends, with those observed in 2020. RESULTS: In 2020, 21,382 AVRs were performed (13,051 TAVRs, 5706 isolated SAVRs and 2625 SAVRs combined with other cardiac surgery). Compared with the 2020 projected number of AVRs (24,586, 95% confidence interval [CI] 23,525-25,646), TAVRs (14,866, 95% CI 14,164-15,568), isolated SAVRs (6652, 95% CI 6203-7100) and SAVRs combined with other cardiac surgery (3069, 95% CI 2822-3315), there were reductions of 13.0%, 12.2%, 14.2% and 14.5%, respectively. These trends were similar regardless of sex or age. In 2020, the mean age, Charlson Comorbidity Index and hospital admission duration continued to decline, and the proportion of females remained constant, following 2015-2019 trends. Overall, 2020 in-hospital mortality was higher than projected (2.0% observed vs. 1.7% projected; 95% CI 1.5-1.9%), with no increased pacemaker implantation, but more acute kidney injury and cerebrovascular accidents in some surgical subsets. CONCLUSIONS: During the COVID-19 pandemic, fewer TAVR and SAVR procedures were performed, with increased in-hospital mortality and periprocedural complications. Extended follow-up will be important to establish the long-term effect of the COVID-19 pandemic on patient management and outcomes.

Aortic valve replacement for aortic stenosis: Influence of centre volume on TAVR adoption rates and outcomes in France.

BACKGROUND: Transcatheter (TAVR) has supplanted surgical (SAVR) aortic valve replacement (AVR). AIM: To evaluate whether adoption of this technology has varied according to centre volume at the nationwide level. METHODS: From an administrative hospital-discharge database, we collected data on all AVRs performed in France between 2007 and 2019. Centres were divided into terciles based on the annual number of SAVRs performed in 2007-2009 ("before TAVR era"). RESULTS: A total of 192,773 AVRs (134,662 SAVRs and 58,111 TAVRs) were performed in 47 centres. The annual number of AVRs and TAVRs increased significantly and linearly in low-volume (<152 SAVRs/year; median 106, interquartile range [IQR] 75-129), middle-volume (152-219 SAVRs/year; median 197, IQR 172-212) and high-volume (>219 SAVRs/year; median 303, IQR 268-513) terciles, but to a greater degree in the latter (+14, +16 and +24 AVRs/centre/year and +16, +19 and +31 TAVRs/centre/year, respectively; PANCOVA<0.001). Charlson Comorbidity Index and in-hospital death rates declined from 2010 to 2019 in all terciles (all Ptrend<0.05). In 2017-2019, after adjusting for age, sex and Charlson Comorbidity Index, there was a trend toward lower death rates in the high-volume tercile (P=0.06) for SAVR, whereas death rates were similar for TAVR irrespective of tercile (P=0.27). Similar results were obtained when terciles were defined based on number of interventions performed in the last instead of the first 3years. Importantly, even centres in the lowest-volume tercile performed a relatively high number of interventions (150 TAVRs/year/centre). CONCLUSIONS: In a centralized public healthcare system, the total number of AVRs increased linearly between 2007 and 2019, mostly due to an increase in TAVR, irrespective of centre volume. Progressive declines in patient risk profiles and death rates were observed in all terciles; in 2017-2019 death rates were similar in all terciles, although lower in high-volume centres for SAVR.

Computed Simulation of Transcatheter Edge-to-Edge Mitral Valve Repair - A Proof of Concept Study.

AIMS: As transcatheter mitral valve (MV) interventions are expanding and more device types and sizes become available, a tool supporting operators in preprocedural planning and the clinical decision-making process is highly desirable. We sought to develop a finite element (FE) computational simulation model to predict results of transcatheter edge-to-edge (TEER) interventions. METHODS AND RESULTS: We prospectively enrolled patients with secondary mitral regurgitation (MR) referred for a clinically indicated TEER. Three-dimensional (3D) transesophageal echocardiograms performed at the beginning of the procedure were used to perform the simulation. On the 3D dynamic model of the MV that was first obtained, we simulated the clip implantation using the same clip(s) type, size, number, and implantation location that was used during the intervention. The 3D model of the MV obtained after simulation of the clip implantation was compared to the clinical results obtained at the end of the intervention. We analyzed the degree and location of residual MR and the shape and area of the diastolic mitral valve area. We performed computational simulation on 5 patients. Overall, the simulated models predicted well the degree and location of the residual regurgitant orifice(s) but tended to underestimate the diastolic mitral orifice area. CONCLUSIONS: In this proof-of-concept study, we present preliminary results on our algorithm simulating clip implantation in 5 patients with functional MR. We show promising results regarding the feasibility and accuracy in terms of predicting residual MR and the need to improve the estimation of the diastolic mitral valve area.