Artificial Intelligence Assessment of Biological Age From Transthoracic Echocardiography: Discrepancies with Chronologic Age Predict Significant Excess Mortality.

BACKGROUND: Age and sex can be estimated using artificial intelligence on the basis of various sources. The aims of this study were to test whether convolutional neural networks could be trained to estimate age and predict sex using standard transthoracic echocardiography and to evaluate the prognostic implications. METHODS: The algorithm was trained on 76,342 patients, validated in 22,825 patients, and tested in 20,960 patients. It was then externally validated using data from a different hospital (n = 556). Finally, a prospective cohort of handheld point-of-care ultrasound devices (n = 319; ClinicalTrials.gov identifier NCT05455541) was used to confirm the findings. A multivariate Cox regression model was used to investigate the association between age estimation and chronologic age with overall survival. RESULTS: The mean absolute error in age estimation was 4.9 years, with a Pearson correlation coefficient of 0.922. The probabilistic value of sex had an overall accuracy of 96.1% and an area under the curve of 0.993. External validation and prospective study cohorts yielded consistent results. Finally, survival analysis demonstrated that age prediction ≥5 years vs chronologic age was associated with an independent 34% increased risk for death during follow-up (P < .001). CONCLUSIONS: Applying artificial intelligence to standard transthoracic echocardiography allows the prediction of sex and the estimation of age. Machine-based estimation is an independent predictor of overall survival and, with further evaluation, can be used for risk stratification and estimation of biological age.

Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter-defibrillators and long-term mechanical support. For others, more evidence is still needed before large-scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device-provided therapy and also device-guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care.

Pseudo-discordance mimicking low-flow low-gradient aortic stenosis in transcatheter aortic valve replacement patients with severe symptomatic aortic stenosis.

BACKGROUND: While the combination of a small aortic valve area (AVA) and low mean gradient is frequently labeled 'low-flow low-gradient aortic stenosis (AS)', there are two potential causes for this finding: underestimation of mean gradient and underestimation of AVA. METHODS: In order to investigate the prevalence and causes of discordant echocardiographic findings in symptomatic patients with AS and normal left ventricular (LV) function, we evaluated 72 symptomatic patients with AS and normal LV function by comparing Doppler, invasive, computed tomography (CT) LV outflow tract (LVOT) area, and calcium score (CaSc). RESULTS: Thirty-six patients had discordant echocardiographic findings (mean gradient < 40 mmHg, AVA ≤ 1 cm²). Of those, 19 had discordant invasive measurements (true discordant [TD]) and 17 concordant (false discordant [FD]): In 12 of the FD the mean gradient was > 30 mmHg; technical pitfalls were found in 10 patients (no reliable right parasternal Doppler in 6). LVOT area by echocardiography or CT could not differentiate between concordants and discordants nor between TD and FD (p = NS). CaSc was similar in concordants and FD (p = 0.3), and it was higher in true concordants than in TD (p = 0.005). CaSc positive predictive value for the correct diagnosis of severe AS was 95% for concordants and 93% for discordants. CONCLUSIONS: Discordant echocardiographic findings are commonly found in patients with symptomatic AS. Underestimation of the true mean gradient due to technical difficulties is an important cause of these discrepant findings. LVOT area by echocardiography or CT cannot differentiate between TD and FD. In the absence of a reliable and compete multi-window Doppler evaluation, patients should undergo CaSc assessment.

Repair with annuloplasty only of balanced bileaflet mitral valve prolapse with severe regurgitation.

OBJECTIVES: Repair of severe mitral valve and mitral regurgitation (MR) in patients with degenerative bileaflet pathology can be challenging. Initial results with a ring-only repair (ROR) approach have shown promising results, but long-term outcomes in larger series are lacking. We report on outcomes of ROR in severe MR secondary to bileaflet prolapse, including Barlow's disease. METHODS: Eighty patients with degenerative multi-segment bileaflet disease underwent ROR for severe MR with a predominantly central regurgitant jet indicating balanced bileaflet prolapse. The main outcome measure of this study was long-term recurrent MR probability. Secondary outcomes were late mortality, reoperation and in-hospital complications. RESULTS: The mean age was 53 ± 15 years and 54% were males. The mean ejection fraction was 59.2 ± 6.6, 24% and 40% had atrial fibrillation. Barlow's disease was found in 77% of the patients. Minimally invasive surgery was performed in 15 patients (19%). There were no perioperative mortalities or cerebrovascular events in the entire cohort. Post-repair mild outflow tract obstruction (systolic anterior motion) was observed in 4 patients (5%) after ROR. In a mean follow-up of 60 ± 48 months, there was 1 case of death. At follow-up, there was 1 (1%) reoperation due to recurrent MR, and 4 patients who had recurrent moderate or more MR. The 10-year freedom from recurrent MR was 97%. None had severe MR at the latest follow-up. CONCLUSIONS: In patients with severe MR and a central regurgitant jet secondary to balanced multi-segment bileaflet mitral valve prolapse, ROR is a simple and efficient approach providing excellent long-term results without a substantial risk of systolic anterior motion.

Secondary chordal resection with septal myectomy for treatment of symptomatic obstructive hypertrophic cardiomyopathy.

OBJECTIVES: Left ventricular outflow tract obstruction causes symptoms of heart failure in most patients with hypertrophic cardiomyopathy. Resection of the secondary mitral valve (MV) chordae has recently been shown to move the MV apparatus posteriorly, thereby eradicating the outflow gradient. The aim of this study was to evaluate whether secondary chordal resection concomitant to septal myectomy improves outcomes. METHODS: Between 2005 and 2020, a total of 165 patients underwent septal myectomy without MV repair or replacement in our Medical Center. Secondary MV chordal resection was performed in 60 patients, and their outcomes were compared with those of the remaining 105 patients who did not undergo chordal resection (controls). Mean age was 61 ± 13 and 58 ± 16 years, respectively (P = 0.205). RESULTS: There were no in-hospital deaths throughout the entire cohort. Of those patients who underwent secondary chordal resection, New York Heart Association functional class decreased from 3 (interquartile range 2-3) preoperatively to 1 (interquartile range 1-2) postoperatively (P < 0.001), and resting outflow gradient decreased from 91 ± 39 mmHg to 13 ± 8 mmHg (86% change, P < 0.001). Compared with controls, patients who underwent secondary chordal resection had a significant lower resting outflow gradient at follow-up (14 ± 7 mmHg vs 21 ± 15 mmHg, P = 0.002). The rate of moderate or more than moderate mitral regurgitation at 5 years was 2% in the secondary chordal resection group and 5% in the controls (hazard ratio 1.05, confidence interval 0.11-10.32; P = 0.965). CONCLUSIONS: In this observational study, we report that secondary chordal resection concomitant to septal myectomy for left ventricular outflow tract obstruction is safe, relieves heart failure symptoms and reduces left ventricular outflow tract gradient in appropriately selected patients.

Short membranous septum length in bicuspid aortic valve stenosis increases the risk of conduction disturbances.

BACKGROUND: Distinct anatomical features predispose bicuspid AS patients to conduction disturbances after TAVR. This study sought to evaluate whether the incidence of permanent pacemaker implantation (PPMI) and left bundle branch block (LBBB) in patients with bicuspid aortic stenosis (AS) following transcatheter aortic valve replacement (TAVR) is related to an anatomical association between bicuspid AS and short membranous septal (MS) length. METHODS: Sixty-seven consecutive patients with bicuspid AS from a Bicuspid AS TAVR multicenter registry and 67 propensity-matched patients with tricuspid AS underwent computed tomography before TAVR. RESULTS: MS length was significantly shorter in bicuspid AS compared with tricuspid AS (6.2 ± 2.5 mm vs. 8.4 ± 2.7 mm, respectively; p < 0.001). In patients with bicuspid AS, MS length and aortic valve calcification were the most powerful pre-procedural independent predictors of PPMI or LBBB (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.15 to 1.55, p = 0.003 and OR: 1.92, 95% CI: 1.1 to 3.34, p = 0.022, respectively). When taking into account pre- and post-procedural parameters, aortic valve calcification and the difference between MS length and implantation depth were the most powerful independent predictors of PPMI or LBBB in patients with bicuspid AS (OR: 1.82, 95%: 1.1 to 3.1, p = 0.027; OR: 1.25, 95% CI: 1.10 to 1.38, p = 0.003). CONCLUSION: MS length, which was significantly shorter in bicuspid AS compared with tricuspid AS, aortic valve calcification, and device implantation deeper than MS length predict PPMI or LBBB in bicuspid AS after TAVR.

Outcomes of Degenerative Mitral Valve Repair Surgery for Anterior, Posterior, and Bileaflet Pathology.

BACKGROUND: Degenerative mitral valve disease involving anterior leaflet pathology is considered less favorable regarding durability of surgical repair than isolated posterior leaflet disease. We aimed to compare the outcomes of patients undergoing mitral valve repair for anterior, posterior, and bileaflet pathologies, and to investigate predictors for repair failure. METHODS: Of the 760 consecutive patients with degenerative leaflet disease who underwent mitral valve repair, 485 (64%) had posterior, 223 (29%) had bileaflet, and 52 (7%) had anterior leaflet pathology. Mean age was 58 ± 12, 54 ± 14, and 58 ± 17 years, respectively (P = .001). Mean follow-up was 67 ± 47 months. RESULTS: There was no in-hospital or 30-day mortality. Freedom from reoperation was 97%, 95%, and 92%, respectively, and there were 25 (5%), 9 (4%), and 1 (2%) late deaths in the posterior, bileaflet, and anterior groups, respectively (not significant). Late echocardiography revealed that 94%, 97%, and 96% of patients (posterior, bileaflet, and anterior groups respectively) were free from moderate-severe or severe mitral regurgitation (P = .375). Postoperative residual mild mitral regurgitation emerged as the strongest predictor for recurrent mitral regurgitation (grade 3/4) at follow-up (hazard ratio = 2.36; 95% confidence interval, 1.30-4.29; P = .005). Unlike patients with excess mitral tissue, among patients with fibroelastic deficiency or those who underwent major leaflet resection, the use of larger ring annuloplasty was associated with recurrent mitral regurgitation (hazard ratio = 1.31/ring size increment; P < .001). CONCLUSIONS: Mitral valve repair can be achieved with excellent early and intermediate results across all valve pathologies. Further studies are required to determine the potential long-term impact of the underlying pathology on the rate of recurrent mitral regurgitation.

Rationale and design of the EACVI AFib Echo Europe Registry for assessing relationships of echocardiographic parameters with clinical thrombo-embolic and bleeding risk profile in non-valvular atrial fibrillation.

The European Society of Cardiology (ESC) guidelines for management of atrial fibrillation (AF) recommend the use of CHA2DS2VASc risk score for assessment of thromboembolic (TE) risk, whereas the stratification of bleeding risk should be obtained by HAS-Bleed to balance the most appropriate anticoagulation (OAC) therapy. However, men with CHA2DS2VASc score = 1 and women with CHA2DS2VASc = 2, who are at intermediate TE risk, represent a grey zone where guidelines do not provide a definite OAC indication. Accordingly, implementation of risk stratification with echocardiography could be extremely useful. Both prospective and cross-sectional studies on transthoracic echocardiography (TTE) prediction of TE events and studies utilizing transoesophageal echocardiographic parameters as surrogate markers of TE events makes sustainable the hypothesis that echocardiography could improve TE prediction in non-valvular AF. Moreover, considering the close association of AF and stroke, all echo-Doppler parameters that have shown to predict AF onset and recurrence could be useful also to predict TE events in this clinical setting. Accordingly, EACVI AFib Echo Europe Registry has been designed as an observational, cross-sectional study, with the aim of evaluating: (i) left atrial (LA) size and function together with left ventricular geometry, systolic and diastolic functions in paroxysmal, persistent, and permanent AF; (ii) relationships of structural/functional parameters with clinical TE and bleeding risk profile. By the AFib Echo Europe Registry, we expect to collect data on echocardiographic phenotype of patients with AF. The large data set accumulated will be useful to test the level of agreement of different echocardiographic measurements with the available risk scores.

Echo-Doppler estimation of left ventricular filling pressure: results of the multicentre EACVI Euro-Filling study.

AIMS: The present Euro-Filling report aimed at comparing the diagnostic accuracy of the 2009 and 2016 echocardiographic grading algorithms for predicting invasively measured left ventricular filling pressure (LVFP). METHOD AND RESULTS: A total of 159 patients who underwent simultaneous evaluation of echo estimates of LVFP and invasive measurements of LV end-diastolic pressure (LVEDP) were enrolled at nine EACVI centres. Thirty-nine (25%) patients had a reduced LV ejection fraction (<50%), 77 (64%) were in NYHA ≥ II, and 85 (53%) had coronary artery disease. Sixty-four (40%) patients had elevated LVEDP (≥15 mmHg). Taken individually, all echocardiographic Doppler estimates of LVFP (E/A, E/e', left atrial volume, tricuspid regurgitation jet velocity) were marginally correlated with LVEDP. By using the 2016 recommendations, 65% of patients with normal non-invasive estimate of LVFP had normal LVEDP, while 79% of those with elevated non-invasive LVFP had elevated invasive LVEDP. By using 2009 recommendations, 68% of the patients with normal non-invasive LVFP had normal LVEDP, while 55% of those with elevated non-invasive LVFP had elevated LVEDP. The 2016 recommendations (sensitivity 75%, specificity 74%, positive predictive value 39%, negative predictive value 93%, AUC 0.78) identified slightly better patients with elevated invasive LVEDP (≥ 15 mmHg) as compared with the 2009 recommendations (sensitivity 43%, specificity 75%, positive predictive value 49%, negative predictive value 71%, AUC 0.68). CONCLUSION: The present Euro-Filling study demonstrates that the new 2016 recommendations for assessing LVFP non-invasively are fairly reliable and clinically useful, as well as superior to the 2009 recommendations in estimating invasive LVEDP.

Shifting Perceptions of Risk and Reward: Use of Anticoagulation in Patients With Acute Brain Ischemia and Atrial Fibrillation: Nine-Year Data From a National Acute Stroke Registry (National Acute Stroke Israeli Survey [NASIS]).

BACKGROUND AND PURPOSE: Despite overwhelming evidence for the benefits of anticoagulation in patients with brain ischemia and atrial fibrillation, vast underuse has been reported. METHODS: Use of anticoagulation for secondary stroke prevention was assessed in the National Acute Stroke Israeli Survey registry (NASIS) of hospitalized patients with atrial fibrillation and acute brain ischemia. Logistic regression analysis was performed to evaluate the effects of clinical covariates on anticoagulation therapy at discharge, and anticoagulation use over time was assessed in subgroups of patients with identified barriers to anticoagulation utilization. RESULTS: There were 1254 survivors of acute brain ischemia with atrial fibrillation (mean age 77.2±10.6 years; 57.7% female). Between 2004 and 2013, the proportion of patients discharged on anticoagulation increased from 55% to 76.2%, and among those without perceived contraindications from 70% to 96% (P<0.0001). Older age, greater stroke severity, earlier registry period, and presence of contraindications were independent predictors of withholding therapy. Increased anticoagulation use over the years was observed even in patients with barriers to anticoagulation use, including patients with potential contraindications (P<0.001). CONCLUSIONS: In survivors of acute brain ischemia with atrial fibrillation, we observed a substantial increase in anticoagulation utilization within less than a decade. This change was mainly driven by greater utilization of anticoagulation in subgroups with traditional clinical barriers to anticoagulation use, indicating a shift in physicians' perceptions of the risk-benefit ratio of anticoagulation.

Rational and design of EuroCRT: an international observational study on multi-modality imaging and cardiac resynchronization therapy.

AIMS: Assessment of left ventricular (LV) volumes and ejection fraction (LVEF) with cardiac imaging is important in the selection of patients for cardiac resynchronization therapy (CRT). Several observational studies have explored the role of imaging-derived LV dyssynchrony parameters to predict the response to CRT, but have yielded inconsistent results, precluding the inclusion of imaging-derived LV dyssynchrony parameters in current guidelines for selection of patients for CRT. METHODS: The EuroCRT is a large European multicentre prospective observational study led by the European Association of Cardiovascular Imaging. We aim to explore if combing the value of cardiac magnetic resonance (CMR) and echocardiography could be beneficial for selecting heart failure patients for CRT in terms of improvement in long-term survival, clinical symptoms, LV function, and volumes. Speckle tracking echocardiography will be used to assess LV dyssynchrony and wasted cardiac work whereas myocardial scar will be assessed with late gadolinium contrast enhanced CMR. All data will be measured in core laboratories. The study will be conducted in European centres with known expertise in both CRT and multimodality cardiac imaging.

Sex differences in aortic root and vascular anatomy in patients undergoing transcatheter aortic valve implantation: A computed-tomographic study.

BACKGROUND: Very little data exist on the impact of sex on aortic and arterial anatomy as relevant for transcatheter aortic valve implantation (TAVI). OBJECTIVE: To investigate whether patients with severe aortic stenosis (AS) referred for TAVI display sex-specific differences in aortic root and ilio-femoral artery size. METHODS: In 506 patients referred for pre-procedural CT evaluation before TAVI we performed a detailed assessment of aortic root anatomy: size of the annulus and the sinus of Valsalva (SoV), diameter of the sino-tubular junction (STJ), and distance of the coronary artery ostia to the aortic annulus plane; we also determined the dimensions of aorta, subclavian, and ilio-femoral arteries. RESULTS: Women had significantly smaller aortic root dimensions (annulus mean diameter: 22.9 ± 2.2 mm vs. 25.7 ± 2.7 mm, SoV mean diameter: 31.8 ± 4.2 mm vs. 36.3 ± 3.8 mm, STJ mean diameter: 26.3 ± 3.4 mm vs. 29.8 ± 4.2 mm) and lower left and right coronary artery ostia take-off (12.3 ± 2.4 vs. 14.1 ± 2.9 mm; 14.8 ± 2.6 vs. 17.1 ± 3.2 mm, respectively) than men (P < 0.001 for all), even after adjustment for their smaller body surface area (BSA) and height. Dimensions of the ascending aorta, subclavian and ilio-femoral arteries were also significantly smaller in women, but not when adjusted for BSA. CONCLUSIONS: Women with severe AS had smaller aortic root dimensions even after correcting for their smaller body size and height, reflecting a sex-specific difference. In contrast, sex-related differences in aortic, subclavian, and ilio-femoral dimensions were fully explained by the smaller BSA of women.

Exercise Dynamics in Secondary Mitral Regurgitation: Pathophysiology and Therapeutic Implications.

Secondary mitral valve regurgitation (MR) remains a challenging problem in the diagnostic workup and treatment of patients with heart failure. Although secondary MR is characteristically dynamic in nature and sensitive to changes in ventricular geometry and loading, current therapy is mainly focused on resting conditions. An exercise-induced increase in secondary MR, however, is associated with impaired exercise capacity and increased mortality. In an era where a multitude of percutaneous solutions are emerging for the treatment of patients with heart failure, it becomes important to address the dynamic component of secondary MR during exercise as well. A critical reappraisal of the underlying disease mechanisms, in particular the dynamic component during exercise, is of timely importance. This review summarizes the pathophysiological mechanisms involved in the dynamic deterioration of secondary MR during exercise, its functional and prognostic impact, and the way current treatment options affect the dynamic lesion and exercise hemodynamics in general.

Short- and Long-Term Prognostic Implications of Jugular Venous Distension in Patients Hospitalized With Acute Heart Failure.

The present study was designed to assess the role of jugular venous distension (JVD) as a predictor of short- and long-term mortality in a "real-life" setting. The independent association between the presence of admission JVD and the 30-day, 1- and 10-year mortality was assessed among 2,212 patients hospitalized with acute heart failure (HF) who were enrolled in the Heart Failure Survey in Israel (2003). Independent predictors of JVD finding in study patients included: the presence of significant hyponatremia (odds ratio [OR] 1.48; p = 0.03), reduced left ventricular ejection fraction ([LVEF] OR 1.24; p = 0.03), anemia (OR 1.3; p = 0.01), New York Heart Association III to IV (OR 1.34; p <0.01) and age >75 years (OR 1.32; p = 0.01). The presence of JVD versus its absence at the time of HF hospitalization was associated with increased 30-day mortality (7.2% vs 4.9%, respectively; p = 0.02), 1-year (33% vs 28%, respectively; p <0.001), and greater 10-year mortality (91.8% vs 87.2%, respectively; p <0.001). Consistently, interaction term analysis demonstrated that the presence of JVD at the time of the index HF hospitalization was independently associated with a significant increased risk for 10-year mortality, with a more pronounced effect among younger patients, patients with reduced LVEF, preserved renal function, and chronic HF. In conclusion, in patients admitted with HF, JVD is associated with specific risk factors and is independently associated with increased risk of both short- and long-term mortality. These findings can be used for improved risk assessment and management of this high-risk population.