Prognostic Implications and Alterations in Left Atrial Deformation Following Transcatheter Aortic Valve Implantation.

AIMS: To evaluate the prognostic implications of left atrial reservoir strain-defined diastolic dysfunction (LARS-DD) grade in patients undergoing TAVI for severe aortic stenosis (AS) and to determine if post-TAVI LARS was more closely associated with new-onset atrial fibrillation than pre-TAVI LARS. METHODS AND RESULTS: Pre-TAVI LARS-DD was evaluated by speckle-tracking echocardiography and was assigned as grade 0 to 1 (LARS≥24%), grade 2 (LARS≥19 to <24%) and grade 3 (LARS<19%). Patients were followed-up for the primary endpoint of all-cause mortality from the date of TAVI. For the secondary endpoint, patients with pre- and post-TAVI LARS measurements and no history of atrial fibrillation were evaluated for the occurrence of new-onset atrial fibrillation. A total of 601 patients (median age 81 [76-85] years, 53% male) were included. Overall, 169 patients (28%) were LARS-DD grade 0/1, 96 patients (16%) were LARS-DD grade 2 and 336 (56%) were LARS-DD grade 3. Over a median follow-up of 40 (IQR 26-58) months, a total of 258 (43%) patients died. In a comprehensive multivariable Cox regression model, LARS-DD grade was independently associated with all-cause mortality (adjusted HR 1.28 per one-grade increase, 95%CI 1.07-1.53, P=0.007). For the secondary endpoint of new-onset atrial fibrillation, a total of 285 patients were evaluated. Post-TAVI LARS (SDHR 1.14 per 1%<20%, 95%CI 1.05-1.23, P=0.0009), but not pre-TAVI LARS (P=0.93) was independently associated with new-onset atrial fibrillation. CONCLUSIONS: Increasing LARS-DD grade was independently associated with long-term post-TAVI survival in patients with severe AS. Post-TAVI LARS was closely related to the occurrence of new-onset atrial fibrillation.

Changes in Global Longitudinal Strain after TAVI: Additional Prognostic Value over Cardiac Damage in Patients with Severe Aortic Stenosis.

Background: Previous studies demonstrated the prognostic value of baseline cardiac damage staging as well as left ventricular global longitudinal strain (LVGLS) in patients undergoing transcatheter aortic valve implantation (TAVI). The aim of the present study was to evaluate the changes in cardiac damage stage and LVGLS after TAVI and to investigate their prognostic values when integrated into the follow-up assessment. Methods: Patients with severe aortic stenosis undergoing TAVI were hierarchically classified into cardiac damage stages based on echocardiographic criteria before TAVI and at a 6-month follow-up. At the same time, LVGLS was measured. The staging system included stage 0 = no signs of cardiac damage; stage 1 = LV damage; stage 2 = mitral or left atrial damage; stage 3 = pulmonary vasculature or tricuspid damage; and stage 4 = right ventricular damage. The primary endpoint was all-cause mortality. Results: A total of 620 patients were included. At follow-up, LVGLS significantly improved, and the improvement was similar among each baseline cardiac damage stage. Follow-up LVGLS values were divided into quintiles, and each quintile was integrated into the cardiac damage staging, leading to a reclassification of 308 (50%) patients. At the time of a median follow-up at 48 (IQR 31-71) months starting from the 6-month follow-up after TAVI, 262 (38%) patients had died. A multivariable Cox regression model showed that LVGLS-integrated cardiac damage staging at follow-up had an incremental prognostic value over the baseline assessment (HR per 1-stage increase 1.384; 95% CI 1.152-1.663; p < 0.001). Conclusions: The integration of LVGLS with conventional echocardiographic parameters of cardiac damage at a 6-month follow-up after TAVI can improve patient risk-stratification.

Pulmonary congestion assessed by lung ultrasound in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation: Prevalence and prognostic implications.

AIMS: Lung ultrasound (LUS) is a sensitive tool to assess pulmonary congestion (PC). Few data are available on LUS-PC evaluation in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the prevalence and prognostic impact of LUS-PC in patients with severe AS before and after TAVI. METHODS AND RESULTS: We designed a single-centre prospective study in patients referred for TAVI for severe AS (ClinicalTrials.gov identification number: NCT05024942). All patients underwent echocardiography and LUS (according to a simplified 8-zone scanning protocol) the day before and within 72 h after the procedure. The primary endpoint was the composite of all-cause mortality, hospitalization for heart failure and urgent medical visits for worsening dyspnoea at 12-month follow-up. A total of 127 patients were enrolled (mean age 81.1 ± 5.8 years; 54.3% female). Pre-TAVI LUS-PC was documented in 65 patients (51%). After TAVI, the prevalence of LUS-PC significantly decreased as compared to pre-TAVI evaluation, being documented in only 28 patients (22% vs. 51%, p < 0.001) with a median B-lines score of 4 (interquartile range [IQR] 0-11) versus 11 (IQR 6-19) pre-TAVI (p < 0.001). During a median follow-up of 12 (12-17) months, 25 patients (19.6%) met the composite endpoint. On multivariable Cox regression analysis, pre-TAVI LUS-PC was independently associated with cardiovascular events (hazard ratio 2.764, 95% confidence interval 1.114-6.857; p = 0.028). CONCLUSIONS: Lung ultrasonography reveals a high prevalence of PC in patients with severe AS undergoing TAVI, which is significantly reduced by the procedure. Pre-TAVI PC, measured by LUS, is an independent predictor of 1-year clinical outcome.

Early cardiac mechanics abnormalities in patients with mitochondrial diseases.

BACKGROUND: Evidence about early cardiac mechanics abnormalities in patients with mitochondrial diseases (MDs) before overt cardiomyopathy is limited. METHODS: In this prospective study, we performed a comparative analysis of conventional and speckle tracking echocardiographic parameters between patients with genetically identified MDs and no overt cardiomyopathy vs controls matched for age, sex and cardiovascular risk factors. The Newcastle mitochondrial disease adult scale (NMDAS) was calculated, using a threshold of > 21 as indicator of high disease severity. RESULTS: We enrolled 24 MDs patients (50 % males, mean age 47.2 ± 14.3 years), the most prevalent mutation was the MT-TL1 m.3243A>G (37.5 %). In MDs patients all dimensional echocardiographic parameters were similar to controls. Conversely, albeit normal, Tissue Doppler septal systolic (p = 0.002) and early diastolic velocities (p = 0.016) were significantly lower and E/e' ratio was higher (p = 0.032) in MDs. Moreover, LV-GLS was significantly reduced in MDs as compared to their counterparties (20.2 ± 1.6 vs 22.6 ± 1.5, p < 0.001). Similarly, LA reservoir and conduit strain were significantly lower in MDs (31.7 ± 7.0 vs 35.9 ± 6.6, p = 0.038; 19.7 ± 5.6 vs 23.1 ± 6.0, p = 0.049 respectively), while LA contractile strain was similar between the two groups. Lower values of LV-GLS were observed in patients with NMDAS > 21 vs patients with NMDAS ≤ 21 (19.0 ± 1.2 vs 21.0 ± 1.3, p = 0.001). CONCLUSIONS: In patients with MDs and no overt cardiomyopathy Tissue Doppler and speckle tracking analysis unveil worse LV systolic and diastolic function indices as compared to controls. Reduced LV-GLS values were found especially in those with worse disease burden.

Structural and functional abnormalities of left-sided cardiac chambers in Barlow's disease without significant mitral regurgitation.

AIMS: This study aims to explore the presence of left ventricular (LV) and left atrial (LA) morphological and functional abnormalities in patients with Barlow's disease (BD) without significant mitral regurgitation (MR) and to investigate whether these abnormalities may predict MR progression. METHODS AND RESULTS: Consecutive patients with BD were retrospectively identified from two tertiary centres; those with MR graded from trivial to mild-to-moderate were selected and matched with healthy controls in a 1:1 ratio. Conventional and speckle-tracking echocardiographic data were collected. The development of moderate-to-severe or greater MR was evaluated on follow-up echocardiograms. Patients with BD (n = 231) showed increased LV dimensions and indexed LV mass (LVMi) in comparison with controls (P < 0.001); LV remodelling worsened with higher MR severity and was accompanied by an increased prevalence of eccentric LV hypertrophy (eLVH). Moreover, BD patients had larger LA volumes and more impaired LA reservoir strain vs. controls (P < 0.001), while LV strain was similar between the two groups. Multivariable linear regression analyses in the overall population identified BD and MR grade as independent predictors of remodelling markers (LV dimensions, LVMi, and LA volume) and BD as independent correlate of LA strain. MR progression was observed in 51 BD subjects (out of 170 patients with available follow-up). On Cox regression analysis, age, eLVH, mild-to-moderate MR, and mitral annular disjunction (MAD) emerged as independent predictors of MR progression. CONCLUSION: BD patients without significant MR show early LV and LA remodelling, together with reduced LA strain. MR progression was associated with eccentric LV remodelling, MAD, and MR severity.

Right Heart Remodeling and Outcomes in Patients With Tricuspid Regurgitation: A Literature Review and Meta-Analysis.

BACKGROUND: Functional tricuspid regurgitation (TR) can develop either because of right ventricular (RV) remodeling (ventricular functional TR) and/or right atrial dilation (atrial functional TR). OBJECTIVES: This meta-analysis aimed to investigate the association between right heart remodeling and long-term (>1 year) all-cause mortality in patients with significant TR (at least moderate, ≥2+). METHODS: MEDLINE, ISI Web of Science, and SCOPUS databases were searched. Studies reporting data on at least 1 RV functional parameter and long-term all-cause mortality in patients with significant TR were included. This study was designed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) requirements. RESULTS: Out of 8,902 studies, a total of 14 were included, enrolling 4,394 subjects. The duration of follow-up across the studies varied, ranging from a minimum of 15.5 months to a maximum of 73.2 months. Overall, long-term all-cause mortality was 31% (95% CI: 20%-41%; P ≤ 0.001). By means of meta-regression analyses, an inverse relation was found between tricuspid annular plane systolic excursion (11 studies enrolling 3,551 subjects, -6.3% [95% CI: -11.1% to -1.4%]; P = 0.011), RV fractional area change (9 studies, 2,975 subjects, -4.4% [95% CI: -5.9% to -2.9%]; P < 0.001), tricuspid annular dimension (7 studies, 2,986 subjects, -4.1% [95% CI: -7.6% to -0.5%]; P = 0.026), right atrial area (6 studies, 1,920 subjects, -1.9% [95% CI: -2.5% to -1.3%]; P < 0.001) and mortality. CONCLUSIONS: RV dysfunction parameters are associated to worse clinical outcomes in patients with TR, whereas right atrial dilatation is linked to a better prognostic outcome. Further studies are needed to unravel the pathophysiological differences within the functional TR spectrum. (Right heart remodeling and outcomes in patients with tricuspid regurgitation; CRD42023418667).

Incremental Value of Biventricular Strain in Patients with Severe Aortic Stenosis.

(1) Background: Left ventricular global longitudinal (LVGLS) and right ventricular free wall strain (RVFWS) demonstrated separate prognostic values in patients with severe aortic stenosis (AS). However, studies evaluating the combined assessment of LVGLS and RVFWS have shown contradictory results. This study explored the prognostic value of combining LVGLS and RVFWS in a large group of severe AS patients referred for transcatheter aortic valve implantation. (2) Methods: Patients were classified into three groups: preserved (LVGLS ≥ 15% AND RVFWS > 20%), single-ventricle impaired (LVGLS < 15% OR RVFWS ≤ 20%), or biventricular-impaired strain group (LVGLS < 15% AND RVFWS ≤ 20%). The cut-off values were based on previously published data and spline analyses. The endpoint was all-cause mortality. (3) Results: Of the 712 patients included (age 80 ± 7 years, 53% men), 248 (35%) died. The single-ventricle impaired and biventricular-impaired (vs. preserved) strain groups showed significantly lower 5-year survival rates (68% and 55% vs. 77%, respectively, p < 0.001). Through multivariable analysis, single-ventricle impaired (HR 1.762; 95% CI: 1.114-2.788; p = 0.015) and biventricular-impaired strain groups (HR 1.920; 95% CI: 1.134-3.250; p = 0.015) were independently associated with all-cause mortality. These findings were confirmed with a sensitivity analysis in patients with preserved LV ejection fraction. (4) Conclusions: In patients with severe AS, biventricular strain allows better risk stratification, even if LV ejection fraction is preserved.

Left atrial structural and functional remodelling in Fabry disease and cardiac amyloidosis: A comparative analysis.

BACKGROUND: Fabry disease (FD) and transthyretin cardiac amyloidosis (TTR CA) are cardiomyopathies with hypertrophic phenotype that share several features, including left atrial (LA) enlargement and dysfunction, but direct comparative data are lacking. Aim of the present study was to perform a comparative analysis of LA remodelling between the two diseases. METHODS AND RESULTS: In this prospective study, a total of 114 patients (31 FD and 83 TTR CA) were included; all of them had left ventricular hypertrophy (LVH), defined as left ventricular (LV) wall thickness ≥ 12 mm. Despite similar degree of LVH, patients with TTR CA showed worse LV systolic and diastolic function. LA maximal volume index was not significantly different between the two groups (p = 0.084), while patients with TTR CA showed larger LA minimal volume index (p = 0.001). Moreover, all phases of LA mechanics were more impaired in the TTR CA group vs FD (reservoir: 6.9[4.2-15.5] vs 19.0[15.5-29.5], p < 0.001). After excluding patients with atrial fibrillation (AF), these differences remained clearly significant. In multivariable regression analyses, LA reservoir strain showed an independent correlation with TTR CA, controlling for demographic characteristics, AF and LV systolic and diastolic performance (p ≤ 0.001), whereas LV global longitudinal strain did not. Finally, among echocardiographic parameters, LA function demonstrated the highest accuracy in discriminating the two diseases. CONCLUSIONS: TTR CA is characterized by a more advanced LA structural and functional remodelling in comparison to patients with FD and similar degree of LVH. The association between TTR CA and LA dysfunction remains consistent after adjustment for potential confounders.

Association of right atrial strain and long-term outcome in severe secondary tricuspid regurgitation.

OBJECTIVE: Severe secondary tricuspid regurgitation (STR) causes significant right atrial (RA) volume overload, resulting in structural and functional RA-remodelling. This study evaluated whether patients with severe STR and reduced RA function, as assessed by RA-reservoir-strain (RASr), show lower long-term prognosis. METHODS: Consecutive patients, from a single centre, with first diagnosis of severe STR and RASr measure available, were included. Extensive echocardiographic analysis comprised measures of cardiac chamber size and function, assessed also by two-dimensional speckle-tracking strain analysis. Primary outcome was all-cause mortality, analysed from inclusion until death or last follow-up. The association of RASr with the outcome was evaluated by Cox regression analysis and Akaike information criterion. RESULTS: A total of 586 patients with severe STR (age 68±13 years; 52% male) were included. Patients presented with mild right ventricular (RV) dilatation (end-diastolic area 13.8±6.5 cm2/m2) and dysfunction (free-wall strain 16.2±7.2%), and with moderate-to-severe RA dilatation (max area 15.0±5.3 cm2/m2); the median value of RASr was 13%. In the overall population, 10-year overall survival was low (40%, 349 deaths), and was significantly lower in patients with lower RASr (defined by the median value): 36% (195 deaths) for RASr ≤13% compared with 45% (154 deaths) for RASr >13% (log-rank p=0.016). With a median follow-up of 6.6 years, RASr was independently associated with all-cause mortality (HR per 5% RASr increase:0.928; 95% CI 0.864 to 0.996; p=0.038), providing additional value over relevant clinical and echocardiographic covariates (including RA size and RV function/size). CONCLUSIONS: Patients with severe STR presented with significant RA remodelling, and lower RA function, as measured by RASr, was independently associated with all-cause mortality, potentially improving risk stratification in these patients.

Clinical staging of Anderson-Fabry cardiomyopathy: An operative proposal.

As a slowly progressive form of hypertrophic cardiomyopathy (HCM), Anderson-Fabry disease (FD) resembles the phenotype of the most common sarcomeric forms, although significant differences in presentation and long-term progression may help determine the correct diagnosis. A variety of electrocardiographic and imaging features of FD cardiomyopathy have been described at different times in the course of the disease, and considerable discrepancies remain regarding the assessment of disease severity by individual physicians. Therefore, we here propose a practical staging of FD cardiomyopathy, in hopes it may represent the standard for cardiac evaluation and facilitate communication between specialized FD centres and primary care physicians. We identified 4 main stages of FD cardiomyopathy of increasing severity, based on available evidence from clinical and imaging studies: non-hypertrophic, hypertrophic - pre-fibrotic, hypertrophic - fibrotic, and overt dysfunction. Each stage is described and discussed in detail, following the principle that speaking a common language is critical when managing such complex patients in a multi-disciplinary and sometimes multi-centre setting.

Mitral regurgitation in atrial fibrillation: Is a simple repair enough to tackle a complex problem?

BACKGROUND: Clinical and echocardiographic results of valve repair for mitral regurgitation in the setting of atrial fibrillation are poorly studied. METHODS: Between January 2008 and December 2020, 89 patients underwent valve repair for mitral regurgitation in the setting of atrial fibrillation. Clinical and echocardiographic follow-up data were collected and studied. The primary composite endpoint consisted of all-cause mortality or hospitalization for heart failure. RESULTS: Valve repair with true-sized annuloplasty was performed in 83 (93 %) and restrictive annuloplasty in 6 (7 %) patients. Early mortality occurred in 3 (3 %) and residual mitral regurgitation in 1 (1 %) patient. During a median follow-up of 5.4 years (interquartile range 3.4-9.5), 25 patients died, 6 due to end-stage heart failure. Ten patients were hospitalized for heart failure. The estimated event-free survival rate at 10 years was 48.2 % (95 % CI 33.5 %-62.9 %). Recurrent mitral regurgitation was observed in 14 patients and most often caused by leaflet tethering. When analyzed as a time-dependent variable, recurrent regurgitation was related to the occurrence of the primary endpoint (hazard ratio 3.192, 95 % CI 1.219-8.359, p = 0.018). On exploratory sub-analyses, no recurrent regurgitation was observed after restrictive annuloplasty or in patients with paroxysmal atrial fibrillation. Moreover, recurrent regurgitation was observed more often when signs of left ventricular impairment were present preoperatively. CONCLUSIONS: Despite good initial results, recurrent regurgitation was a frequent observation after valve repair for mitral regurgitation in atrial fibrillation and had an effect on heart failure related morbidity and mortality. Refinements in the timing of surgery and surgical technique might help improve outcomes.

Valvular heart disease and cardiomyopathy: reappraisal of their interplay.

Cardiomyopathies and valvular heart diseases are typically considered distinct diagnostic categories with dedicated guidelines for their management. However, the interplay between these conditions is increasingly being recognized and they frequently coexist, as in the paradigmatic examples of dilated cardiomyopathy and hypertrophic cardiomyopathy, which are often complicated by the occurrence of mitral regurgitation. Moreover, cardiomyopathies and valvular heart diseases can have a shared aetiology because several genetic or acquired diseases can affect both the cardiac valves and the myocardium. In addition, the association between cardiomyopathies and valvular heart diseases has important prognostic and therapeutic implications. Therefore, a better understanding of their shared pathophysiological mechanisms, as well as of the prevalence and predisposing factors to their association, might lead to a different approach in the risk stratification and management of these diseases. In this Review, we discuss the different scenarios in which valvular heart diseases and cardiomyopathies coexist, highlighting the need for an improved classification and clustering of these diseases with potential repercussions in the clinical management and, particularly, personalized therapeutic approaches.

Prognostic Implications of the Extent of Cardiac Damage in Patients With Fabry Disease.

BACKGROUND: There is limited evidence on the risk stratification of cardiovascular outcomes in patients with Fabry disease (FD). OBJECTIVES: This study sought to classify FD patients into disease stages, based on the extent of the cardiac damage evaluated by echocardiography, and to assess their prognostic impact in a multicenter cohort. METHODS: Patients with FD from 5 Italian referral centers were categorized into 4 stages: stage 0, no cardiac involvement; stage 1, left ventricular (LV) hypertrophy (LV maximal wall thickness >12 mm); stage 2, left atrium (LA) enlargement (LA volume index >34 mL/m2); stage 3, ventricular impairment (LV ejection fraction <50% or E/e' ≥15 or TAPSE <17 mm). The study endpoint was the composite of all-cause death, hospitalization for heart failure, new-onset atrial fibrillation, major bradyarrhythmias or tachyarrhythmias, and ischemic stroke. RESULTS: A total of 314 patients were included. Among them, 174 (56%) were classified as stage 0, 41 (13%) as stage 1, 57 (18%) as stage 2 and 42 (13%) as stage 3. A progressive increase in the composite event rate at 8 years was observed with worsening stages of cardiac damage (log-rank P < 0.001). On multivariable Cox regression analysis, the staging was independently associated with the risk of cardiovascular events (HR: 2.086 per 1-stage increase; 95% CI: 1.487-2.927; P < 0.001). Notably, cardiac staging demonstrated a stronger and additive prognostic value, as compared with the degree of LV hypertrophy. CONCLUSIONS: In FD patients, a novel staging classification of cardiac damage, evaluated by echocardiography, is strongly associated with cardiovascular outcomes and may be helpful to refine risk stratification.

Hemodynamic implications of mitral annular calcification in patients undergoing transcatheter aortic valve implantation for severe aortic stenosis.

PURPOSES: Predicting hemodynamic changes of stenotic mitral valve (MV) lesions with mitral annular calcification (MAC) following transcatheter aortic valve implantation (TAVI) may inform clinical decision-making. This study aimed to investigate the association between the MAC severity quantified by computed tomography (CT) and changes in mean transmitral gradient (mTMG), mitral valve area (MVA) and stroke volume index (SVi) following TAVI. METHODS AND RESULTS: A total of 708 patients (median age 81, 52% male) with severe aortic stenosis (AS) underwent pre-procedural CT and pre- and post-TAVI transthoracic echocardiography. According to the classification of MAC severity determined by CT, 299 (42.2%) patients had no MAC, 229 (32.3%) mild MAC, 102 (14.4%) moderate MAC, and 78 (11.0%) severe MAC. After adjusting for age and sex, there was no significant change in mTMG following TAVI (Δ mTMG = 0.07 mmHg, 95% CI -0.10 to 0.23, P = 0.92) for patients with no MAC. In contrast, patients with mild MAC (Δ mTMG = 0.21 mmHg, 95% CI 0.01 to 0.40, P = 0.018), moderate MAC (Δ mTMG = 0.31 mmHg, 95% CI 0.02 to 0.60, P = 0.019) and severe MAC (Δ mTMG = 0.43 mmHg, 95% CI 0.10 to 0.76, P = 0.0012) had significant increases in mTMG following TAVI, with greater changes associated with increasing MAC severity. In contrast, there was no significant change in MVA or SVi following TAVI. CONCLUSION: In patients with severe AS undergoing TAVI, MAC severity was associated with greater increases in post-procedural mTMG whereas MVA or SVi remained unchanged. MAC severity should be considered for potential subsequent MV interventions if TAVI does not improve symptoms.