Novel echocardiographic pixel intensity quantification method for differentiating transthyretin cardiac amyloidosis from light chain cardiac amyloidosis and other phenocopies.

AIMS: Differentiating cardiac amyloidosis (CA) subtypes is important considering the significantly different therapies for transthyretin (ATTR)-CA and light chain (AL)-CA. Therefore, an echocardiographic method to distinguish ATTR-CA from AL-CA would provide significant value. We assessed a novel echocardiographic pixel intensity method to quantify myocardial calcification to differentiate ATTR-CA from phenocopies of CA and from AL-CA, specifically. METHODS AND RESULTS: 167 patients with ATTR-CA (n=53), AL-CA (n=32), hypertrophic cardiomyopathy (n=37), and advanced chronic kidney disease (n=45) were retrospectively evaluated. The septal reflectivity ratio (SRR) was measured as the average pixel intensity of the visible anterior septal wall divided by the average pixel intensity of the visible posterior lateral wall. SRR and other myocardial strain-based echocardiographic measures were evaluated with receiver operator characteristic analysis to evaluate accuracy in distinguishing ATTR-CA from AL-CA and other forms of left ventricular hypertrophy. Mean septal reflectivity ratio (SRR) was significantly higher in the ATTR-CA cohort compared to the other cohorts (p <0.001). SRR demonstrated the largest AUC (0.91, p<0.0001) for distinguishing ATTR from all other cohorts and specifically for distinguishing ATTR-CA from AL-CA (AUC=0.90, p<0.0001, specificity 96%, sensitivity 63%). There was excellent inter- and intra-operator reproducibility with an ICC of 0.91 (p <0.001) and 0.89 (p <0.001), respectively. CONCLUSION: The SRR is a reproducible and robust parameter for differentiating ATTR-CA from other phenocopies of CA and specifically ATTR-CA from AL-CA.

Cardiac Structural and Functional Remodeling After Transcatheter Mitral Valve in Valve Implantation: Early Changes and Prognostic Significance.

Background: Transcatheter mitral valve-in-valve (MViV) replacement has emerged as an alternative to redo mitral valve (MV) surgery for the management of failed bioprosthetic MVs. The degree of cardiac remodeling assessed by echocardiography has been shown to have prognostic implications in degenerative mitral regurgitation patients undergoing MV surgery. The impact of transcatheter MViV in patients with degenerative bioprosthetic MV failure on cardiac remodeling and its associated prognosis remains undescribed. Objectives: The aim of this study is to describe the early anatomic and functional changes of the left-sided chambers and right ventricle by echocardiography posttranscatheter MViV intervention and their impact on mortality outcomes. Additionally, we sought to analyze the outcome of heart failure in bioprosthetic MV failure patients undergoing transcatheter MViV replacement. Methods: We analyzed consecutive patients undergoing MViV intervention for symptomatic bioprosthetic MV failure. Echocardiograms before intervention and within 100 days postintervention were analyzed. A chart review was performed to obtain baseline characteristics, follow-up visits, 30-day heart failure and 1-year all-cause mortality outcomes. Results: A total of 62 patients (mean age 69 ± 13 years, 61% male) were included in the study. Most patients were undergoing MViV intervention for prosthetic mitral stenosis n = 48 (77.4%) and the rest for mitral regurgitation or mixed disease. Compared with baseline, significant reductions were observed in median left atrial volume (LAV; 103 [81-129] ml vs. 95.2 [74.5-117.5] ml, p < 0.01) and mean (SD) left atrial conduit strain (9.1% ± 5.2% vs. 10.8% ± 4.8%, p = 0.039) within 100 days postintervention. Early reduction in right ventricular free wall global longitudinal strain and fractional area change also occurred postintervention. No significant change in left ventricular chamber dimensions or ejection fraction was observed. During the 1-year follow up period, 5 (8%) patients died. While baseline LAV was not associated with 1-year all-cause mortality (OR 0.98 CI 0.95-1.01; p = 0.27), a change in LAV in the follow up period was associated with all-cause mortality at 1 year (OR 1.06 CI 1.01-1.12; p = 0.023). At 30 days postintervention, 65% of patients had an improvement in their New York Heart Association functional class. Conclusion: In this retrospective study of patients undergoing transcatheter MViV intervention for failed bioprosthetic MVs, early reverse remodeling of the left atrium occurs within 100 days postintervention and reduction in LAV is associated with reduced all-cause mortality at 1 year. In addition, there is significant improvement in heart failure symptoms at 30 days following intervention but further investigation into the longitudinal remodeling changes and long-term outcomes is needed.

Doppler Echocardiographic Phenotypes in Suspected 'Severe' Aortic Stenosis: Matrix-Based Approach to Diagnosis and Management.

BACKGROUND: Among patients with suspected severe aortic stenosis (AS), Doppler echocardiographic (DE) data are often discordant, and further analysis is required for accurate diagnosis and optimal management. In this study, an automated matrix-based approach was applied to an echocardiographic database of patients with AS that identified 5 discrete echocardiographic data patterns, 1 concordant and 4 discordant, each reflecting a particular pathophysiology/measurement error that guides further workup and management. METHODS: A primary/discovery cohort of consecutive echocardiographic studies with at least 1 DE parameter of severe AS and analogous data from an independent secondary/validation cohort were retrospectively analyzed. Parameter thresholds for inclusion were aortic valve area (AVA) <1.0 cm2, transaortic mean gradient (MG) ≥ 40 mmHg, and/or transaortic peak velocity (PV) ≥ 4.0 m/sec. Doppler velocity index (DVI) was also determined. Logic provided by an in-line SQL query embedded within the database was used to assign each patient to 1 of 5 discrete matrix patterns, each reflecting 1 or more specific pathophysiologies. Feasibility of automated pattern-driven triage of discordant cases was also evaluated. RESULTS: In both cohorts, data from each patient fitted only 1 data pattern. Of the 4,643 primary cohort patients, 39% had concordant parameters for severe AS and DVI <0.30 (pattern 1); 35% had AVA < 1.0 cm2, MG < 40 mm Hg, PV < 4 m/sec, DVI < 0.30 (pattern 2); 9% had MG ≥ 40 mmHg and/or PV ≥ 4 m/sec, DVI > 0.30 (pattern 3); 10% had AVA < 1.0 cm2, MG < 40 mmHg, PV < 4 m/sec, DVI >0.30 (pattern 4); and 7% had MG > 40 mmHg and/or PV ≥ 4 m/sec, AVA > 1.0 cm2, DVI < 0.30 (pattern 5). Findings were validated among the 387 secondary cohort patients in whom pattern distribution was remarkably similar. CONCLUSIONS: Matrix-based pattern recognition permits automated in-line identification of specific pathophysiology and/or measurement error among patients with suspected severe AS and discordant DE data.

Female Patient Presenting With Increasing Pedal Edema.

This case report discusses a diagnosis of congenital bicuspid-tricuspid valve in a female patient in their 20s with a history of heart transplant.

Reverse Remodeling Effects of Sacubitril-Valsartan: Structural and Functional Optimization in Stage C Heart Failure.

Sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor, reduces all-cause mortality and the rate of heart failure hospitalizations in patients with heart failure with reduced ejection fraction. This study aimed to elucidate the benefits of initiating sacubitril-valsartan on ventricular remodeling in patients previously optimized on guideline-directed medical therapy. In this prospective, single-arm longitudinal study, 40 patients with heart failure with reduced ejection fraction who were optimized on guideline-directed medical therapy were transitioned to sacubitril-valsartan. The primary end point was the change in left ventricular (LV) volume at 1 year as assessed by 3-dimensional transthoracic echocardiography. Other echocardiographic end points included change in LV-function and change in right ventricular (RV) size and function. The mean age was 55 ± 12 years, and 63% were male. At 1 year, LV end-diastolic volume decreased from 242 ± 71 to 157 ± 57 ml (p <0.001) with a corresponding increase in LV ejection fraction from 32 ± 7% to 44 ± 9% (p <0.001). RV end-diastolic volume decreased from 151 ± 51 to 105 ±45 ml (p <0.001). Although RV ejection fraction did not change (51 ± 8 vs 51 ± 10; p = 0.35), RV global longitudinal strain improved from -14.9 ± 3.4 % to -19.3 ± 4.3% (p <0.001). When added to standard medical therapy for heart failure, sacubitril-valsartan induces significant remodeling of both the right and left ventricles as assessed by 3-dimensional echocardiography.

The physical origin of aneurysm growth, dissection, and rupture.

Rupture of aortic aneurysms is by far the most fatal heart disease, with a mortality rate exceeding 80%. There are no reliable clinical protocols to predict growth, dissection, and rupture because the fundamental physics driving aneurysm progression is unknown. Here, via in-vitro experiments, we show that a blood-wall, fluttering instability manifests in synthetic arteries under pulsatile forcing. We establish a phase space to prove that the transition from stable flow to unstable aortic flutter is accurately predicted by a flutter instability parameter derived from first principles. Time resolved strain maps of the evolving system reveal the dynamical characteristics of aortic flutter that drive aneurysm progression. We show that low level instability can trigger permanent aortic growth, even in the absence of material remodeling. Sufficiently large flutter beyond a secondary threshold localizes strain in the walls to the length scale clinically observed in aortic dissection. Lastly, significant physical flutter beyond a tertiary threshold can ultimately induce aneurysm rupture via failure modes reported from necropsy. Resolving the fundamental physics of aneurysm progression directly leads to clinical protocols that forecast growth as well as intercept dissection and rupture by pinpointing their physical origin.

Challenges and opportunities for early career medical professionals in cardiovascular magnetic resonance (CMR) imaging: a white paper from the Society for Cardiovascular Magnetic Resonance.

The early career professionals in the field of Cardiovascular Magnetic Resonance (CMR) face unique challenges and hurdles while establishing their careers in the field. The Society for Cardiovascular Magnetic Resonance (SCMR) has expanded the role of the early career section within the society to foster the careers of future CMR leaders. This paper aims to describe the obstacles and available opportunities for the early career CMR professionals worldwide. Societal opportunities and actions targeted at the professional advancement of the early career CMR imagers are needed to ensure continuous growth of CMR as an imaging modality globally.

Preservation of Circumferential and Radial Left Ventricular Function as a Mitigating Mechanism for Impaired Longitudinal Strain in Early Cardiac Amyloidosis.

BACKGROUND: In patients with cardiac amyloidosis (CA), left ventricular ejection fraction (LVEF) is frequently preserved, despite commonly reduced global longitudinal strain (GLS). We hypothesized that nonlongitudinal contraction may initially serve as a mitigating mechanism to maintain cardiac output and studied the relationship between global circumferential (GCS) and radial (GRS) strain with LVEF and extracellular volume (ECV), a marker of amyloid burden. METHODS: Patients with CA who underwent cardiac magnetic resonance (CMR; n = 140, 70.7 ± 11.5 years, 66% male) or echocardiography (n = 67, 71 ± 13 years, 66% male) and normal controls (CMR, n = 20; echocardiography, n = 45) were retrospectively identified, and GCS, GLS, and GRS were quantified using feature-tracking CMR or speckle-tracking echocardiography and compared between CA patients with preserved and reduced LVEF (CAHFpEF, CAHFrEF) and controls. The prevalence of impaired strain (magnitudes <2.5th percentile of the controls) was compared between CAHFpEF and CAHFrEF and between ECV quartiles. RESULTS: While echocardiography-derived GLS was impaired in both CAHFpEF (-13.4% ± 3.1%, P < .003) and CAHFrEF (-9.1% ± 3.2%, P < .003), compared with controls (-20.8% ± 2.4%), GCS was more impaired in CAHFrEF compared with both controls (-15.6% ± 5.0% vs -32.3% ± 3.3%, P < .003) and CAHFpEF (-30.4% ± 5.7%, P < .003) and did not differ between CAHFpEF and controls (P = .24). The prevalence of abnormal CMR-derived GCS (P < .0001) and GRS (P < .0001) but not GLS (P = .054) varied significantly across ECV quartiles. CONCLUSIONS: Among CA patients with preserved LVEF, preserved GCS and GRS, despite near-universally impaired GLS, may be explained by an initial predominantly subendocardial involvement, where mostly longitudinal fibers are located. If confirmed in future studies, these findings may facilitate identification of patients with early stages of CA, when treatments may be most effective.

Characterization of Screen Failures Among Patients Evaluated for Transcatheter Tricuspid Valve Repair (TriSelect-Study).

BACKGROUND: Transcatheter tricuspid valve repair (TTVr) has significantly expanded treatment options for tricuspid regurgitation (TR). However, a sizeable proportion of patients are still declined for TTVr and little is known about their clinical characteristics and cardiac morphology. OBJECTIVES: This study sought to characterize patients who screen fail for TTVr with respect to their clinical characteristics and cardiac morphology. METHODS: A total of 547 patients were evaluated for TTVr between January 2016 to December 2021 from 3 centers in the United States and Germany. Clinical records and echocardiographic studies were used to assess medical history and right ventricular (RV) and tricuspid valve (TV) characteristics. RESULTS: Median age was 80 (IQR: 74-83) years and 60.0% were female. Over half (58.1%) were accepted for TTVr. Of those who were deemed unsuitable for TTVr (41.9%), the most common exclusion reasons were anatomical criteria (56.8%). In the regression analysis, RV and right atrial size, TV coaptation gap, and tethering area were identified as independent screen failure predictors. Other rejection reasons included clinical futility (17.9%), low symptom burden (12.7%), and technical limitations (12.7%). Most of the excluded patients (71.6%) were managed conservatively with medical therapy, while a small number either proceeded to TV surgery (22.3%) or subsequently became eligible for transcatheter tricuspid valve replacement in later available clinical trials in the United States (6.1%). CONCLUSIONS: The majority of TTVr screen failure patients are excluded due to TV, right atrial, and RV enlargement. However, a significant proportion is excluded due to clinical futility. These identifiable anatomical and clinical characteristics emphasize the importance of earlier referral and intervention of TR and the need for continued innovation of Transcatheter tricuspid valve interventions.

Secondary Mitral Regurgitation and Heart Failure: Current Advances in Diagnosis and Management.

The causes of mitral regurgitation (MR) can be broadly divided into primary and secondary causes. Although primary MR is caused by degenerative alterations of the mitral valve and the mitral valve apparatus, secondary (functional) MR is multifactorial and related to dilation of the left ventricle and/or mitral annulus commonly resulting in concomitant restriction of the leaflets. Therefore, the treatment of secondary MR (SMR) is complex and includes guideline directed heart failure therapy along with surgical and transcatheter approaches that have shown effectiveness in certain subgroups. This review aims to provide insight into current advances in diagnosis and management of SMR.

Assessment of Right Ventricle Function and Tricuspid Regurgitation in Heart Failure: Current Advances in Diagnosis and Imaging.

Right ventricular (RV) systolic dysfunction increases mortality among heart failure patients, and therefore, accurate diagnosis and monitoring is paramount. RV anatomy and function are complex, usually requiring a combination of imaging modalities to completely quantitate volumes and function. Tricuspid regurgitation usually occurs with RV dysfunction, and quantifying this valvular lesion also may require multiple imaging modalities. Echocardiography is the first-line imaging tool for identifying RV dysfunction, with cardiac MRI and cardiac computed tomography adding valuable additional information.

The Emerging Role of Artificial Intelligence in Valvular Heart Disease.

Valvular heart disease (VHD) is a morbid condition in which timely identification and evidence-based treatments can lead to improved outcomes. Artificial intelligence broadly refers to the ability for computers to perform tasks and problem solve like the human mind. Studies applying AI to VHD have used a variety of structured (eg, sociodemographic, clinical) and unstructured (eg, electrocardiogram, phonocardiogram, and echocardiograms) and machine learning modeling approaches. Additional researches in diverse populations, including prospective clinical trials, are needed to evaluate the effectiveness and value of AI-enabled medical technologies in clinical care for patients with VHD.

1-Year Outcomes of Transcatheter Tricuspid Valve Repair.

BACKGROUND: Surgical management of isolated tricuspid regurgitation (TR) is associated with high morbidity and mortality, thereby creating a significant need for a lower-risk transcatheter solution. OBJECTIVES: The single-arm, multicenter, prospective CLASP TR (Edwards PASCAL TrAnScatheter Valve RePair System in Tricuspid Regurgitation [CLASP TR] Early Feasibility Study) evaluated 1-year outcomes of the PASCAL transcatheter valve repair system (Edwards Lifesciences) to treat TR. METHODS: Study inclusion required a previous diagnosis of severe or greater TR and persistent symptoms despite medical treatment. An independent core laboratory evaluated echocardiographic results, and a clinical events committee adjudicated major adverse events. The study evaluated primary safety and performance outcomes, with echocardiographic, clinical, and functional endpoints. Study investigators report 1-year all-cause mortality and heart failure hospitalization rates. RESULTS: Sixty-five patients were enrolled: mean age of 77.4 years; 55.4% female; and 97.0% with severe to torrential TR. At 30 days, cardiovascular mortality was 3.1%, the stroke rate was 1.5%, and no device-related reinterventions were reported. Between 30 days and 1 year, there were an additional 3 cardiovascular deaths (4.8%), 2 strokes (3.2%), and 1 unplanned or emergency reintervention (1.6%). One-year postprocedure, TR severity significantly reduced (P < 0.001), with 31 of 36 (86.0%) patients achieving moderate or less TR; 100% had at least 1 TR grade reduction. Freedom from all-cause mortality and heart failure hospitalization by Kaplan-Meier analyses were 87.9% and 78.5%, respectively. Their New York Heart Association functional class significantly improved (P < 0.001) with 92% in class I or II, 6-minute walk distance increased by 94 m (P = 0.014), and overall Kansas City Cardiomyopathy Questionnaire scores improved by 18 points (P < 0.001). CONCLUSIONS: The PASCAL system demonstrated low complication and high survival rates, with significant and sustained improvements in TR, functional status, and quality of life at 1 year. (Edwards PASCAL TrAnScatheter Valve RePair System in Tricuspid Regurgitation [CLASP TR] Early Feasibility Study [CLASP TR EFS]; NCT03745313).