bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of atrial fibrillation in clinical outcomes of low gradient aortic stenosis
Authors: Kolluri N , Oguz D , Scott C G , Crestanello J A , Nkomo V T
Published: October 2022

Introduction

Aortic stenosis (AS) is the most common significant valvular heart disease in developed countries. A significant portion of the AS populations have low-gradient AS (LGAS), defined as aortic valve area ≤1.0 cm2 and a trans-aortic mean systolic gradient and peak velocity <40 mmHg and <4 m/s, respectively. LGAS has been shown previously to have worse mortality compared to high-gradient AS (HGAS). Atrial fibrillation (AF) is associated with LGAS and AF has been associated with worse outcomes compared to sinus rhythm (SR) in HGAS. The prognostic impact of AF in LGAS is not well described in previous literature.

Hypothesis

AF will be associated with worse clinical outcomes compared to SR in patients with LGAS.

Methods

3400 patients diagnosed with LGAS from 2010–2020 were retrospectively identified and analyzed. Their electrical rhythm was analyzed at the time of their echocardiographic diagnosis of LGAS and patients were split into 3 separate groups: SR (n=2036), SR with history of AF (n=519), and AF (n=845). After adjustment for age, sex, and Charlson Comorbidity Index (CCI), primary endpoints of overall mortality and cardiac mortality were assessed for patients.

Results

Compared to those with SR, patients with AF and history of AF had significantly higher overall mortality (HR 1.52, p<0.0001 and HR 1.22, p=0.004, respectively) and cardiac mortality (HR 2.05, p<0.0001 and HR 1.37, p=0.03, respectfully) (Figure 1). On further sub group analysis, AF seemed to be most importantly associated with mortality and cardiac mortality in patients with preserved ejection fraction (EF >50%, normal flow LGAS) compared to those patients with reduced EF (classical low-flow LGAS), where there was no statistically significant difference in outcomes between AF and SR (Figure 2).

Conclusions

Atrial fibrillation, compared to sinus rhythm, is associated with worse overall mortality and cardiac mortality in patients with LGAS and preserved EF. Specifically, this association was strongest in patients with preserved EF >50%. Given these findings, the presence of AF should be factored into clinical decision making regarding LGAS management given the higher risk of age, sex, and CCI adjusted overall and cardiac mortality. Further research needs to be done to see if earlier aortic valve intervention in these patients would improve mortality compared to their SR counterparts.

Funding Acknowledgement

Type of funding sources: None.
Clinical characteristics, echocardiographic features and long-term outcomes of patients with ischaemic versus non-ischaemic left ventricular thrombus
Authors: Goh F Q , Sim J J L , Ling R R , Neo V S Q , Ng E S T , Leow A S T , Tan B Y Q , Kong W K F , Sharma V K , Poh K K , Wong R C , Yeo L L L , Chai P , Yeo T C , Sia C H
Published: October 2022

Background

Left ventricular thrombus (LVT) may develop in patients following myocardial infarction (MI), as well as in ischaemic and non-ischaemic cardiomyopathies, and may result in acute ischaemic stroke. Smaller studies comparing LVT associated with ischaemic and non-ischaemic aetiologies only reported 1-year outcomes or focused on specific subpopulations. We aimed to compare the clinical and echocardiographic characteristics and longer-term outcomes in a large population of patients with ischaemic versus non-ischaemic LVT.

Methods

This was a retrospective study of 552 consecutive patients with echocardiographically-identified LVT from March 2011 to January 2021 at a tertiary centre. Ischaemic LVT included LVT associated with MI and ischaemic cardiomyopathy. Non-ischaemic LVT included cases without evidence of ischaemia. Echocardiographic images were interpreted by trained cardiologists. We studied thrombus resolution as well as 5-year rates of ischaemic stroke and all-cause mortality.

Results

Of the 552 patients, mean age was 59.9 years and 84.4% were male. 492 patients had ischaemic LVT and 60 patients had non-ischaemic LVT. Ischaemic LVT was associated with older age (60.4 versus 55.3 years), male sex (86.8% versus 65.0%), smoking (49.2% versus 25.0%) and hyperlipidaemia (54.3% versus 28.3%). Left ventricular ejection fraction (LVEF) was lower in non-ischaemic LVT (28.9% versus 31.9%). LVEF ≤35% was associated with increased mortality in ischaemic LVT (HR 2.11, 95% CI 1.32–3.38). Rates of thrombus resolution, stroke and all-cause mortality were similar in the 2 groups. Anticoagulation was associated with a lower risk of stroke in ischaemic LVT (HR 0.32, 95% CI 0.16–0.66) and lower mortality in both ischaemic (HR 0.44, 95% CI 0.26–0.72) and non-ischaemic LVT (HR 0.14, 95% CI 0.03–0.61).

Conclusion

Patients with ischaemic LVT were more often older, male, smokers and had cardiovascular co-morbidities compared to those with non-ischaemic LVT. Thrombus resolution, stroke and all-cause mortality rates were similar in both groups. Anticoagulation was associated with lower mortality but this needs to be investigated in future prospective studies.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): CHS was supported by the National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Faculty Scheme
Systemic proinflammatory-profibrotic response in aortic stenosis patients with diabetes and its relationship with myocardial remodeling and clinical outcome
Authors: Lee H J , Park C S , Lee S , Park J B , Kim H K , Park S J , Kim Y J , Lee S P
Published: October 2022

Background

It is unclear whether and how diabetes mellitus may aggravate myocardial fibrosis and remodeling in the pressure-overloaded heart. We investigated the impact of diabetes on the prognosis of aortic stenosis (AS) patients and its underlying mechanisms using comprehensive noninvasive imaging studies and plasma proteomics.

Methods

Severe AS patients undergoing both echocardiography and cardiovascular magnetic resonance (CMR) (n=253 of which 66 had diabetes) comprised the imaging cohort. The degree of replacement and diffuse interstitial fibrosis by late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) was quantified using CMR. Plasma samples were analyzed with the multiplex proximity extension assay for 92 proteomic biomarkers in a separate biomarker cohort of severe AS patients (n=100 of which 27 had diabetes).

Results

In the imaging cohort, diabetic patients were older (70.4±6.8 vs. 66.7±10.1 years) and had a higher prevalence of ischemic heart disease (28.8% vs. 9.1%), with more advanced ventricular diastolic dysfunction. On CMR, diabetic patients had increased replacement and diffuse interstitial fibrosis (LGE% 0.3 [0.0–1.6] versus 0.0 [0.0–0.5], p=0.009; ECV% 27.9 [25.7–30.1] versus 26.7 [24.9–28.5], p=0.025) (Figure 1).

Plasma proteomics analysis of the biomarker cohort revealed that 9 proteins (E-selectin, interleukin-1 receptor type 1, interleukin-1 receptor type 2, galectin-4, intercellular adhesion molecule 2, integrin beta-2, galectin-3, growth differentiation factor 15, and cathepsin D) are significantly elevated in diabetic AS patients (Figure 2). Pathway over-representation analyses of the plasma proteomics with Gene Ontology terms indicated that pathways related to inflammatory response and extracellular matrix components were enriched, suggesting that diabetes is associated with systemic effects that evoke proinflammatory and profibrotic response to the pressure-overloaded myocardium.

During follow-up (median 6.3 years [IQR 5.2–7.2]) of the imaging cohort, 232 patients received aortic valve replacement (AVR) with 53 unexpected heart failure admissions or death. Diabetes was a significant predictor of heart failure and death, independent of clinical covariates and AVR (hazard ratio 1.88, 95% confidence interval 1.06–3.31, p=0.030).

Conclusion

Plasma proteomic analyses indicate that diabetes potentiates the systemic proinflammatory and profibrotic milieu in AS patients. These systemic biological changes underlie the increase of myocardial fibrosis, diastolic dysfunction, and worse clinical outcomes in severe AS patients with concomitant diabetes.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): National Research Foundation of Korea
Association of left ventricular myocardial work with all-cause mortality after transcatheter aortic valve implantation
Authors: Nussbaum S , Anwer S , Erhart L , Zurcher D , Walther A L , Winkler N , Rumpf P M , Tsiourantani G , Tanner F C
Published: October 2022

Introduction

Echocardiography is an important modality for peri-interventional assessment of patients undergoing transcatheter aortic valve implantation (TAVI). Left ventricular (LV) global longitudinal strain measures ventricular deformation at end-systole, while myocardial work parameters determine LV deformation throughout the cardiac cycle and correct for afterload.

Aims

To evaluate LV deformation by myocardial work efficiency (GWE) and index (GWI) in early post-TAVI echocardiography and explore its association with all-cause mortality.

Methods

We analyzed 144 patients with severe aortic stenosis and an echocardiography study within two weeks after TAVI. All echocardiographic analyses were performed using GE EchoPac v2.6. Follow-up data was obtained from medical records until September 2021. All-cause mortality was the primary endpoint.

Results

During a median follow-up duration of 625 [IQR: 511.0–769.8] days, 25 (17.5%) patients died. No significant differences in the baseline characteristics were found between non-survivors and survivors. GWE (Figure 1A) and GWI (Figure 1B) were significantly lower among non-survivors than survivors. Both myocardial work parameters differentiated non-survivors from survivors with a cut-off value of −85% for GWE and 990 mmHg% for MWI (Figure 2; both p<0.001).

Conclusions

In this study, GWE and GWI were lower among non-survivors than survivors and were associated with an increased risk of all-cause mortality after TAVI.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss Heart Foundation
Phenotyping patients with aortic stenosis using cluster analysis to determine mortality and suitability for transcatheter aortic valve replacement
Authors: Sen J , Pires D , De Sa A , Ascher D , Wahi S , Marwick T
Published: October 2022

Background

Current classification of aortic stenosis (AS) is based on guideline-recommended echocardiographic criteria. Heterogeneity of patients with AS is increasingly recognised. Clinical and demographic factors in addition to echocardiographic parameters can determine those who may derive the greatest benefit from transcatheter aortic valvular replacement (TAVR) and influence patient outcomes.

Purpose

Our study aims to define distinct AS echocardiographic and clinical phenotypes and to accurately identify patients most likely to die or benefit from TAVR.

Methods

Patients diagnosed with at least mild AS between 2009 and 2021 (pre-TAVR) from a multicentre echocardiographic database at a quaternary referral centre included. Unsupervised clustering analysis was performed using K-means, partitioning around medoids, density-based spatial clustering, hierarchical clustering algorithms on 56 demographic, echocardiographic and clinical variables. Associations between AS clusters and clinical outcomes (all-cause mortality, cardiovascular death, AS-related death), and effect of TAVR on clinical outcomes were assessed using Cox proportional hazards models.

Results

Four AS clusters were identified amongst 2,456 patients with median follow up of 4.7 years (median age: 77 years, male: 66%).

Cluster 1 (n=542) had the lowest aortic valvular area (AVA, mean 0.89 cm2), highest peak velocity (Vmax) (4.3 m/s), mean gradient (45 mmHg), and the most bicuspid valves (12.7%). Cluster 2 (n=827) had 50% women, mostly in sinus rhythm and less severe echo findings. Cluster 3 (n=592) had predominantly males (85%) with a mean AVA of 1.65 cm2 and the most cardiovascular risk factors (hypertension, diabetes, hyperlipidaemia, stable angina, acute coronary syndrome, and atherosclerosis). Cluster 4 (n=495) had the highest left atrial size (mean 32 cm2), the most atrial fibrillation (82%), heart failure (80%), rheumatic heart disease (26%) and chronic kidney disease (55.8%), but only moderate AS (AVA 1.3 cm2, Vmax 3 m/s). All-cause mortality was highest in Cluster 4 (Hazard ratio (HR) 1.57, 95% CI: 1.33–1.85) and AS-related death was highest in Cluster 1 (HR 3.96, 95% CI: 2.61–5.99, Figure 1A). TAVR reduced AS-related death in only Cluster 1 (HR 0.22, 95% CI: 0.05–0.88, p=0.033, Figure 1B).

Conclusions

We demonstrated that phenotypic classification via a combination of demographics, echocardiography and comorbidities can significantly improve management of AS. This personalised approach can be implemented to identify patients most likely to die and most likely to benefit from TAVR.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): National Heart Foundation of Australia (ID: 102578)National Health and Medical Research Council of Australia (ID: 1191044)
To compare efficacy and safety of direct oral anticoagulants in patients with concurrent atrial fibrillation and bioprosthetic heart valve repair or replacement: a systematic review and meta-analysis
Authors: Kaur A , Dhaliwal A , Khandait H , Konje S , Bhatia K , Sohal S , Turagam M , Gwon Y , Mamas M , Dominguez A , Bhatt D , Velagapudi P
Published: October 2022

Background

Use of direct oral anticoagulants (DOACs) is contraindicated in patients with mechanical valves. However data on their use in patients with atrial fibrillation (AF) and bioprosthetic valves (BV) is still limited.

Purpose

To assess the safety and efficacy of DOACs versus Vitamin K antagonist (VKA) in patients with AF after BV repair or replacement.

Methods

We performed a comprehensive review of electronic databases (PubMed, Embase, Scopus, Cochrane) using MeSH terms and keywords for DOACs, AF and BVs from inception through December 2021. Randomized clinical trials (RCT) or observational studies that reported clinical outcomes comparing DOACs versus VKA in patients with AF and BVs were eligible for inclusion. Ten articles were reviewed for full text. Primary outcome was a composite of all cause stroke or systemic embolic event.

Secondary outcomes included major bleeding and all-cause mortality. Subgroup analysis stratified by study design was performed. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using Mantel-Haenszel method with DerSimonian-Laird estimator for tau2 for random effects model.

Interstudy heterogeneity was assessed using the Higgins I 2 value. All statistical analysis was performed using RevMan 5.4.1 software.

Results

Ten studies (5 RCTs, 5 observational studies) with a total of 5,333 patients (DOACs n=2434; VKA n=2899) were included. Aortic, mitral and mixed BV repair or replacement were 74.2%, 25.6% and 0.02% respectively. The mean age was 72.6±11.9 years. The mean follow-up was 15.7±12.9 months. Type of DOACs included apixaban (n=553, 22.7%), rivaroxaban (n=893, 36.7%), dabigatran (n=151, 6.2%) and edoxaban (n=837, 34.4%). There was no significant difference in primary outcome of stroke or systemic embolic event (RR: 0.79; CI: 0.56–1.11; p>0.05; I2=12%) or secondary outcomes of major bleeding (RR: 0.84; CI: 0.64–1.11; p>0.05; I2=45%), and all-cause mortality (RR: 0.84; CI: 0.64–1.11; p>0.05; I2=29%) between DOACs compared with VKA.

Conclusion

In patients with AF and BV, DOACs are non-inferior to VKA for risk of stroke or systemic embolism, major bleeding, and all-cause mortality. Thus, DOACs can serve as a viable alternative to VKAs which have a narrow therapeutic index, multiple drug interactions, and require frequent monitoring.

Funding Acknowledgement

Type of funding sources: None.
Comparing direct oral anticoagulants versus vitamin K antagonist in patients with atrial fibrillation after transcatheter aortic valve replacement: an updated meta-analysis
Authors: Dhaliwal A , Kaur A , Konje S , Bhatia K , Sohal S , Rawal H , Turagam M , Gwon Y , Mamas M , Dominguez A , Bhatt D , Velagapudi P
Published: October 2022

Background

Oral anticoagulation therapy is indicated for patients undergoing transcatheter aortic valve replacement (TAVR) with concomitant or new onset atrial fibrillation (AF). However the data on optimal anticoagulation regimen in this population remains unclear.

Purpose

To compare efficacy and safety outcomes of direct oral anticoagulants (DOACs) versus Vitamin K antagonists (VKA) in patients with AF post TAVR.

Methods

We searched electronic databases (PubMed, Embase, Scopus, Cochrane) from inception to February28th, 2022 using MeSH terms and keywords for DOACs, AF or TAVR. Primary outcome of interest was all-cause stroke or systemic embolic event. Secondary safety outcomes were major bleeding and all-cause mortality. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effects model. Interstudy heterogeneity was assessed using the Higgins I 2 value. All statistical analysis were performed using RevMan 5.4.1 software.

Results

We identified five eligible studies (1RCT, 4 observational) including 3694 patients (DOAC n=1581, VKA n=2113). The mean age was 81.4±0.9 years. The mean follow-up was 12.4±14.3 months. Type of DOACs included apixaban (n=394, 24.9%), rivaroxaban (n=354, 22.4%), dabigatran (n=119, 7.5%) and edoxaban (n=714, 45.2%).There was no significant difference in primary outcome of stroke or systemic embolic event (RR: 0.93; CI: 0.65–1.33; p>0.05; I2=5%), or in secondary outcomes of major bleeding (RR: 1.02; CI: 0.78–1.34; p>0.05; I2=44%) and all-cause mortality (RR: 0.87; CI: 0.59–1.27; p>0.05; I2=56%) between DOACs and VKA groups.

Conclusion

This meta-analysis shows anticoagulation therapy with DOACs has similar safety and efficacy outcomes compared to VKA in patients with AF undergoing TAVR.

Funding Acknowledgement

Type of funding sources: None.
Do valve type and post-ballooning affect transprosthetic gradients in patients undergoing transcatheter aortic valve-in-valve procedure?
Authors: Fusini L , Muratori M , Tamborini G , Gripari P , Ghulam Ali S , Cefalu' C , Fabbiocchi F , Galli S , Roberto M , Agrifoglio M , Pontone G , Bartorelli A L , Pepi M
Published: October 2022

Introduction

Valve-in-Valve transcatheter aortic valve implantation (ViV-TAVI) is an appealing treatment option for patients with degenerated aortic bioprosthetic valves. However, high post-procedural transprosthetic gradients are very common after ViV-TAVI than after TAVI for native-valve aortic stenosis.

Aim

We sought to evaluate transprosthetic gradients (ΔP) and hemodynamic outcome in patients undergoing ViV-TAVI according to valve type and balloon post-dilation (balloon-expandable vs self-expandable with and without post-dilation).

Material and methods

We retrospectively analyzed 111 patients undergoing ViV-TAVI. A balloon-expandable valve was used in 35 patients (32%, Group 1), a self-expandable valve in 76 cases of which 39 (35%, Group 2) without balloon post-dilation and 37 (33%, Group 3) with balloon post-dilation. A comprehensive transthoracic echocardiography (TTE) was performed in all patients at baseline, at discharge and at 6-months follow-up.

Results

Successful ViV-TAVI was performed in 110 patients (99%). Baseline peak and mean ΔP, left ventricular volumes, ejection fraction, and pulmonary artery systolic pressure were similar among groups. A significant improvement in all echocardiographic parameters was observed in all groups over time (Table 1). In particular, a significant reduction in postprocedural gradients was observed at discharge and at 6-months follow-up compared to baseline in all groups. Immediately after ViV-TAVI procedure, the lowest value of mean ΔP was observed in Group 3 (12±7 mmHg) compared to both Group 1 (20±9 mmHg) and Group 2 (17±8 mmHg, p=0.001). This result was confirmed at 6-months follow-up (p=0.012). Rate of small valve size (≤23 mm) implanted was similar among groups (Group 1: 78%, Group 2: 60%, Group 3: 62%, p=0.123). Similar 1-year all-cause mortality was observed among groups (9%, 13%, 0%, respectively, p=0.135).

Conclusions

In patients with failed surgical aortic prosthesis, ViV-TAVI is an effective option and is associated with sustained improved hemodynamics in all patients. Anyway, the choice of prosthetic valve type and implantation technique are relevant on residual transprosthetic gradients and should be taken into account for a better long-term outcome.

Funding Acknowledgement

Type of funding sources: None.
Yield of echocardiographic screening of first-degree relatives of children with bicuspid aortic valve
Authors: Norsk J , Sillesen A S , Raja A A , Paerregaard M , Dannesbo S , Hansson V M , Kock T , Voegg R O B , Vejlstrup N , Iversen K , Bundgaard H
Published: October 2022

Background

Bicuspid aortic valve (BAV) is the most common congenital heart defect, affecting 0.8% of new-borns. BAV is associated with valve dysfunction, as well as an increased risk of aortopathy. The prevalence of BAV in first-degree relatives of symptomatic BAV patients, is reported to be 5–10%. First-degree relatives also have an increased risk of aortic dilatation, independently of aortic valve morphology.

Purpose

The purpose of the study was to determine the prevalence of BAV, associated valve dysfunction and aortopathy in first-degree relatives to children diagnosed with BAV neonatally in a population-based study.

Methods

Between April 2016 and October 2018 all expecting parents at three major maternity centres were offered inclusion in a large-scale population study with focus on congenital heart disease (N≥25,000). A total of 197 children, in 196 families, were diagnosed with BAV. All first-degree relatives, including half-siblings, were offered inclusion in the follow-up study with standardized transthoracic echocardiography. Adults were also examined with transoesophageal echocardiography. Aorta diameters were measured at the AV annulus, sinuses of Valsalva, sino-tubolare junction and in the proximal ascending aorta. Aortic dilatation in children were defined as any aortic root or ascending aorta diameter ≥2 standard deviations (SD) from the expected mean, calculated as z-score using formulas from the Paediatric Heart Network Echocardiogram Database. In adults, aortic dilatation was defined as aortic root and/or ascending aorta diameters indexed to body surface area (BSA) exceeding normal reference values established by the European Association of Cardiovascular Imaging.

Results

In total, 352 first-degree relatives (242 adults [35.3 years SD 5.5] and 110 children [4.5 years, SD 3.5] were included. BAV was diagnosed in 24 relatives (6.8%). BAV could not be conclusively ruled out in 52 relatives (14.8%), who are awaiting further examination with transoesophageal echocardiography. Dilatation of the aortic root was observed in 8 adult relatives and in 17 children (7.1%). Aortic valve regurgitation was observed in 23 relatives (6.5%). In total 58 relatives (16.2%) were diagnosed with either BAV, dilated aorta, or aortic regurgitation.

Conclusion

One in fifteen first-degree relatives to children diagnosed with BAV neonatally, also had BAV, corresponding to >8 fold increase in prevalence compared with the background population. One in six relatives had BAV, dilated aorta, or aortic regurgitation. These findings are of importance for family-screening programs of BAV.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Danish Children's Heart Association
Impact of percutaneous mitral valve clipping on right ventricular functions
Authors: Rifaie O A A , Abulatta R M , Naem H M , Alamoodi O M , Nosseir I M , Alkhashab K M , Ragab T M
Published: October 2022

Background

Percutaneous mitral valve clipping (PMVC) is being used successfully in the management of severe functional mitral regurgitation (MR) in patients with high surgical risk. However, the impact of (PMVC) on right ventricular volumes and functions is not clear.

Aim

The aim of the present study was to assess the impact of (PMVC) (on both short and intermediate terms) on right ventricular (RV) volumes and functions using trans-thoracic echocardiography.

Methods

The study population included 37 patients with severe (MR), and congestive heart failurewho wereat high surgical risk. The mean age was 61±14 years, 9 (24.3%)were males. (PMVC) was successfully done for all patients.All had clinical and echocardiographic follow up at 6 and 12-months post (PMVC).

Results

MR showed significant improvement after (PMVC). MRwas less than grade II in 29 (78%)of patients at 6 months and persisted at 12 months (P=0.0001). Similarly, tricuspid regurgitation (TR) showed marked improvement. Severe (TR) was seen in 29 patients (78%) before), but decreased to 7 patients (18.9%) after (PMVC) (P=0.004). Left ventricular ejection fraction (LVEF) improved from 32.63±13.35% at base line to 36.31±13.28% at 6 months (P=0.003). This was maintained at 12 months (35.38±91%) Table 1 shows the changes in RV end diastolic volume (RVDV); RV end systolic volume (RVSV) RV ejection fraction (RVEF), Tricuspid annulus plane systolic excursion (TAPSE), RV longitudinal systolic function by tissue Doppler imaging (TDI) as well as peak systolic pulmonary artery pressure (PASP).

Conclusion

(PMVC) induced a significant reverse remodeling of RV by decreasing both (RVDV) and (RVSV). Moreover, it improved longitudinal RV systolic function as well as (RVEF). This was maintained up to one year follow up.

Funding Acknowledgement

Type of funding sources: None.
Extent and determinants of pulmonary hypertension unmasked by handgrip exercise in patients with mitral regurgitation
Authors: Spieker M , Sidabras J , Lagarden H , Veulemans V , Horn P , Akhyari P , Kelm M , Westenfeld R
Published: October 2022

Background

Pulmonary hypertension (PH) is an established prognosticator in patients with mitral regurgitation (MR). However, a substantial proportion of patients with MR presents without PH at rest but may develop PH during exercise. Previous studies already demonstrated the prevalence and prognostic impact of PH during bicycle exercise. Until now, there are no data on exercise PH assessed by handgrip exercise.

Purpose

To assess prevalence and predictors of exercise-induced PH during handgrip exercise in patients with MR.

Methods

We prospectively included patients with MR and at least mild severity that underwent echocardiography at rest and during three minutes of handgrip exercise according to a standardized protocol. PH was defined by systolic pulmonary artery pressure (SPAP) >50 mmHg.

Results

The final patient cohort included 371 patients with primary and secondary MR. Mean age was 74±11 years, 48% were female and 59% had atrial fibrillation. Median NT-proBNP was 2017 (845–4976) ng/l. Thirty-eight percent of patients had primary MR, while 62% presented with secondary MR. At rest, MR severity was graded as mild in 56% of patients, moderate in 32% and severe in 12%. Mean SPAP at rest was 40±12 mmHg, and 63 patients (17%) revealed PH at rest (SPAP >50 mmHg). Handgrip exercise leads to an increase in SPAP by 7±12 mmHg. Thus, during exercise 137 patients (37%) exhibited SPAP >50 mmHg. Together, 110 patients (32%) of those patients without PH at rest, showed PH during handgrip exercise. Left- (OR 1.021 (1.010 to 1.033); p<0.001), and right atrial volume index (OR 1.020 (1.009 to 1.035); p<0.001), RV fractional area change (OR 0.972 (0.949 to 0.994); p=0.013), tricuspid regurgitation (OR 1.863 (1.434 to 2.445); p<0.001) and SPAP at rest (OR 1.131 (1.100 to 1.167); p<0.001) were the predictors of exercise PH. Moreover, there was a linear correlation between the change in MR severity assessed by effective regurgitant orifice area (r=0.359; p<0.001) and regurgitation volume (r=0.370; p<0.001) and the change in SPAP. Patients with exercise PH and patients with PH at rest were more symptomatic according to NYHA functional class than patients without PH (p=0.008) (Fig. 1).

Conclusion(s)

In patients with primary and secondary MR, handgrip echocardiography unmasks exercise PH in every third patient without PH at rest. Bi-atrial dilatation, right ventricular function, tricuspid regurgitation and SPAP at rest were predictors of exercise PH, while changes in MR severity during handgrip exercise correlate with changes in pulmonary pressures.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by the Forschungskommission of the Medical Faculty of the Heinrich Heine University Düsseldorf to Maximilian Spieker for a Clinician Scientist Track.
Supervised learning-derived tailored risk-stratification in patients with severe secondary mitral regurgitation
Authors: Heitzinger G , Spinka G , Prausmueller S , Pavo N , Dannenberg V , Dona C , Kammerlander A , Nitsche C , Kastl S , Strunk G , Huelsmann M , Rosenhek R , Hengstenberg C , Bartko P E , Goliasch G
Published: October 2022

Background

Mitral regurgitation secondary to heart failure (sMR) has considerable impact on quality of life, heart failure (HF) rehospitalizations and mortality. A diverse burden of comorbidities suggests multifaceted aspects of individual risks. This risk-spectrum has never been studied but is essential to understand disease trajectories.

Objectives

To provide a comprehensive and structured decision-tree-like approach to risk-stratification in patients with severe sMR.

Methods

This large-scale, long-term observational study included 1317 patients with severe sMR from the entire HF spectrum (preserved, mid-range and reduced ejection fraction). Primary endpoint was all-cause mortality and survival tree analysis, a supervised learning technique, was applied to identify patient subgroups with excessive risk of mortality (Figure 1).

Results

Eight distinct subgroups that differed significantly in long-term survival were identified (Figure 2). Subgroup 7, characterized by younger age (≤66), higher hemoglobin (>12.7 g/dl) and higher albumin levels (>40.6 g/l) had the best survival. In contrast, subgroup 5 displayed a 20-fold risk of mortality (HR 95% CI: 20.38 ([0.78–38.52]), P<0.001) and presented with older age (>68 years) and low serum albumin (≤40.6 g/l) and higher NT-proBNP levels (≥9750 pg/ml). Results were consistent in internal and temporal validation.

Conclusion

Supervised machine learning reveals an unexpected heterogeneity in the sMR risk-spectrum, indicating the clinical challenges tied to severe sMR. A decision-tree-like model can guide through the risk spectrum and provide tailored risk-stratification. This structured approach provides the foundation to generate hypotheses towards improved therapeutic strategies and optimized patient care.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund
Ventricular arrhythmias and sudden cardiac death caused by mitral valve prolapse: should we operate and when?
Authors: Cameron J , Sutherland N , Han H C , Raman J , Lim H
Published: October 2022

Background

Several autopsy and observational studies have investigated the link between mitral valve prolapse (MVP) and sudden cardiac death (SCD) due to the well accepted yet rare occurrence of complex ventricular arrhythmia (VA) in this cohort. Few studies however have investigated whether arrhythmia burden and more importantly SCD are reduced following surgical correction of MVP.

Purpose

To investigate the impact of mitral valve surgery (MVS) (replacement or repair) on VA and SCD in patients with MVP.

Methods

A systematic review of the current literature was conducted using an electronic search of the PubMed database in October 2021. Studies were included if subjects had undergone mitral valve (MV) repair or replacement with documented rates of arrythmias/SCD pre- and post-intervention. Small patient numbers in individual reports precluded formal meta-analysis and results were reported on a per study basis.

Results

19 identified studies (10 cohort studies, nine case studies) comprised 1322 patients with a pooled mean age of 63.4 years and 38.9% were female. 748 of the 1322 patients underwent MVS: 263 MV repair, 18 MV replacement (one with leaflet and papillary muscle excision), two MV repair with Maze procedure, 177 percutaneous transcatheter MV repair, 45 annuloplasty with or without valve repair, and in 243 cases the surgical method was not specified.

Of the 10 included cohort studies, seven of the eight which investigated rates of VA post MVS concluded there was a significant reduction, while one reported the predisposition to arrythmia persisted after relieving the abnormal mechanical effects of non-ischaemic MR (75% due to MVP). One study reported a reduction in SCD post MVS. Each of the nine included case studies showed a reduction in VA post MVS. One study showed mitral annular disjunction (MAD) was independently associated with a higher risk of arrhythmic events, this link persisting with time dependent MVS although reduced compared to medical management.

Conclusions

The underlying mechanisms for VA and SCD associated with MVP are not completely understood, and guidelines for the surgical correction of MVP based on arrhythmic and SCD risk are lacking. This systematic review illustrates a possible reduction in VA following MVS. Further identification of patients at risk of SCD, and potential use of risk stratification algorithms, would allow for consideration of earlier management and appropriate use of implantable cardioverter-defibrillators (ICD) placement / MVS with an expected survival benefit.

Funding Acknowledgement

Type of funding sources: None.
Prognostic significance of mean transmitral pressure gradient in degenerative non-rheumatic mitral valve: insights from a vast echocardiographic database
Authors: Massalha E , Klempfner R , Maor E , Beigel R , Kuperstein R , Matetzky S , Beinart R , Segev A , Guetta V , Fefer P
Published: October 2022

Background

The incidence and prevalence of senile, non-rheumatic mitral valve disease are increasing and there is a renewed interest in new transcatheter structural cardiac interventions intended to treat that valvular disorder. While the severity of rheumatic mitral valve disease can be accurately assessed by echocardiography using various parameters, including mean transmitral pressure gradient, these methods have been questioned for quantifying senile mitral valve disorder and their prognostic significance is still unknown.

Aims

The current study aims to document the natural history of patients with elevated senile mean transmitral pressure gradient (MG) and assess its prognostic significance.

Methods

A vast institutional echocardiography database was retrospectively analyzed from 2009 to 2020 for all patients aged over 60 years with a detailed echocardiography report with valid measurement of transmitral gradients. Patients with rheumatic valvular disease or who underwent surgical or transcatheter valvular replacement/repair were excluded. All-cause mortality was set to be the primary outcome, and survival models utilizing univariable and adjusted multivariable analysis for various clinical and echocardiographic variables were applied.

Results

A total of 5524 patients consisted of the final cohort. They were stratified by the MG into three groups: MG <3 (2914 patients, 53%), 3≤MG<6 (2079 patients, 37.6%) and MG ≥6 mmHg (531 patients,9.6%). The mean age of the total cohort was 77.2±7.9 years; 60.5% were female, 33.3% with diabetes mellitus, 15.1% with chronic kidney disease, and 14.1% with ischemic heart disease. An Adjusted Cox proportional hazard regression model demonstrated that MG is independently associated with all-cause mortality (adjusted HR 1.04 per 1 mmHg increase, 95% CI 1.02–1.05, p<0.001). Moreover, an elevated MG was associated with a rise in all-cause mortality (HR of 1.15 and 1.4 for patients with 3≤MG<6 and MG ≥6 mmHg, respectively (Fig. 1).

Conclusion

The elevated mean transmitral gradient in senile non-rheumatic valves is an independent predictor for all-cause mortality. Interventions and prospective trials intended to mitigate that risk should be needed.

Funding Acknowledgement

Type of funding sources: None.
Cardiac myxoma embolic events: characterization and predictors
Authors: Lacerda Teixeira B , Grazina A , Castelo A , Ferreira V , Bras P , Branco Mano T , Gil R , Moura Branco L , Galrinho A , Timoteo A T , Rio P , Pinto E , Coelho P , Fragata J , Cruz Ferreira R
Published: October 2022

Introduction

Myxomas are the most common heart tumors. Although, myxomas are often diagnosed incidentally in asymptomatic patients, they are frequently associated with embolic events, becoming an important cause of morbidity and mortality. Whether some myxomas' characteristics predict more embolic risk is not well established.

Objectives

This analysis aims to describe the clinical and echocardiographic data in a long cohort of patients with cardiac myxomas and to establish potential predictors of embolic events int these patients.

Methods

Between 1990 and 2021, 88 patients were diagnosed with cardiac myxoma. 84 were included in this analysis. Baseline characteristics, echocardiographic findings and embolic events were noted retrospectively. A binary logistic regression analysis using SPSS statistics software, version 25.0 was performed to establish possible embolic predictors.

Results

84 patients (mean age 63.1±12.9 years old, 75% female) with cardiac myxoma (sporadic type in 100%) were analyzed (table 1). The majority were located in the left atrium (88.1%, n=74), followed by right atrium (10.7%, n=9) and right ventricle (1.2%, n=1). The average dimension (longer axis) was 36.8±17.4mm. 9.6% of the patients (n=8) had Atrial Fibrillation (AF) rhythm. 22.6% of the patients (n=19) experienced embolic events, the majority to the central nervous system (19.0%, n=6), followed by peripheric/limbs (2.4%, n=2), renal (1.2%, n=1) and coronary (1.2%, n=1). The presence of irregular borders (papillary, bosselated) was the only parameter independently associated with increased risk of embolic events, by 6 times (OR 6.78, 95% confidence interval of 2.14–21.51, p-value 0.001). Neither the presence of AF, myxoma dimensions, presence of calcifications, pediculated insertion, myxoma mobility or heterogeneous aspect predicted embolic events with statistical significance (table 2).

Conclusions

Cardiac myxomas are frequently associated with embolic events (22.6% in our population), posing an important cause of morbidity and mortality in these patients. Besides the presence of irregular borders, the other myxoma's characteristics did not consistently predict the occurrence of embolic events. This data supports the well-recognized fact that all cardiac myxomas have the potential to embolic events, and therefore, should be excised, although those with very irregular borders are at much higher risk of embolization.

Funding Acknowledgement

Type of funding sources: None.
Prognostic value of liver stiffness in patients with tricuspid regurgitation
Authors: Gwak S , Seo J W , Cho I S , Hong G R , Shim C Y
Published: October 2022

Background

It has been known that liver stiffness (LS) assessed by transient elastography is associated with right heart dysfunction and the severity of the tricuspid regurgitation. However, the predictive value of LS for adverse outcome in patients with tricuspid regurgitation (TR) is uncertain.

Objectives

The aim of this study was to identify the prognostic value of LS in patients with moderate or greater degree of TR.

Methods

A total of 257 patients with moderate or severe TR who underwent both echocardiography and liver transient elastography were retrospectively analysed. Patients who have congenital heart disease or chronic liver disease including, viral hepatitis, alcoholic liver disease, autoimmune hepatitis, hepatocellular carcinoma were excluded. Severe LS was defined as elevated kilopascal (kPa) ≥11 (High kPa). Primary outcome was defined as the composite of all-cause death and unplanned admission for heart failure.

Results

One hundred forty-one patients had moderate TR and 116 patients had severe TR. One hundred twenty-eight (50%) patients had severe liver stiffness. During a follow-up period (median 637 days, IQR 1317), 116 (45.1%) primary outcomes occurred. In Kaplan-Meier analysis, patients who had severe TR with high kPa showed the worst outcome. Moreover, patients who had high kPa were associated with worse clinical outcome both moderate TR group and severe TR group than patients with low kPa. In multivariate Cox regression analysis, severe liver stiffness was independently associated with primary outcomes (HR=1.66, 95% CI: 1.28–2.16), p<0.001).

Conclusions

LS is independently associated with adverse clinical outcomes in both patients with moderate and severe TR. The degree of liver fibrosis measured by transient elastography may be a useful marker of cardiac hepatopathy related to TR, and this may contribute to predict the prognosis of TR.

Funding Acknowledgement

Type of funding sources: None.
Can a simple echocardiographic Doppler VTI based flow comparison between the RVOT and LVOT assist in identifying patients with a significant atrial septal defect?
Authors: Khav N , Cheng K , Ramkumar S , Nerlekar N , Mottram P , Nicholls S , Moir S
Published: October 2022

Background

Detection of haemodynamically significant shunting from atrial septal defect (ASD) can be identified by using the pulmonary-systemic flow ratio (Qp/Qs). However, calculation of Qp/Qs by echocardiography relies on geometric assumptions that outflow tracts are circular, suffers from squared linear measures, and accurate measurement of right ventricular outflow tract (RVOT) diameter is challenging. Whilst adults with ASD should have overt right ventricular dilatation, RV sizing on echocardiography is often subjective and underappreciated. We evaluated whether a dimensionless index of flow (VTI) differences between the RVOT and left ventricular outflow tract (LVOT) could assist in identifying patients with ASD, and compared it with relative atrial index (RAI), a parameter previously assessed in identifying atrial shunting.

Methods

Data from 64 consecutive patients who underwent ASD closure and had no concomitant lesions, were compared with 63 normal controls. RVOT VTI, LVOT VTI, LVOT diameter, and atrial areas were measured.

Results

Between controls and ASD patients, there was no difference in LVOT VTI or forward stroke volume, but ASD patients had significantly higher RVOT VTI. The RVOT-LVOT VTI ratio was 1:1 in controls and 1.5:1 in ASD patients. Area under the ROC curve analysis of RVOT-LVOT VTI ratio was 0.83, and a ratio of 1.1:1 predicted patients with ASD with 86% sensitivity and 73% specificity. In comparison, the area under the ROC curve analysis of RAI was 0.70, and an RAI of 1.05:1 predicted patients with ASD with 77% sensitivity and 44% specificity.

Conclusion

Calculation of the dimensionless RVOT-LVOT VTI ratio is simple, and may be a useful additional semi-quantitative tool to assist cardiologists and sonographers in detecting atrial shunting, particularly in patients with borderline or overt right heart dilatation, and identify who patients should undergo further evaluation.

Funding Acknowledgement

Type of funding sources: None.
the diagnostic value of left-anterior-descending artery velocity assessed by transthoracic Doppler echocardiography for microvascular dysfunction in stenotic left-anterior-descending artery
Authors: Hada M , Hoshino M , Sugiyama T , Misawa T , Nagamine T , Ueno H , Matsuda K , Sayama K , Yonetsu T , Sasano T , Kakuta T
Published: October 2022

Background

Index of microcirculatory resistance (IMR) has been used as a clinical measure of microvascular function. Transthoracic Doppler echocardiography (TDE) can provide information on the functional status of coronary artery circulation. This study aims to assess the diagnostic value of left-anterior-descending artery (LAD) flow velocity by TDE for microvascular dysfunction.

Methods

Consecutive patients who were scheduled for elective percutaneous coronary intervention (PCI) for LAD lesions were prospectively enrolled in the single tertiary-care center between April 2020 and July 2021. Pre-PCI LAD diastolic peak velocity (DPV) by TDE at rest and hyperemia were measured. By invasive coronary angiography, quantitative coronary angiography and invasive wire-based physiological indices including fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) were measured.

Results

A total of 104 patients were studied. Median FFR and IMR values were 0.70 (0.60–0.74) and 20.68 (14.92–31.69), respectively. No significant relationship was observed between FFR and IMR. The prevalence of microvascular dysfunction defined as IMR≥25 was 39.4%. Basal DPV was 25 (20–33) cm/sec, and hyperemic DPV was 51 (41–67) cm/sec. In lesions with IMR≥25, reference diameter (RD) was significantly greater [2.63 (2.22–3.19) mm vs 2.39 (2.09–2.66) mm, p=0.019], basal DPV was lower [26 (18–29) cm/sec vs 29 (22–37) cm/sec, p=0.022)] and hyperemic DPV was lower [49 (19–54) cm/sec vs 56 (42–70) cm/sec, p=0.023] compared to lesions with IMR<25. ROC analysis showed basal DPV and RD are significant predictors of IMR≥25 [basal DPV: AUC 0.633 (0.525–0.742), best cutoff 29cm/sec RD: AUC 0.636 (0.523–0.750), best cutoff 2.84mm]. Multivariable logistic regression analysis showed basal DPV<29cm/sec and RD>2.84mm are independent predictors for IMR≥25 [Odds ratio: 3.08 (1.22–7.78), p=0.017; odds ratio 4.40 (1.55–12.50), p=0.005].

Conclusion

Basal DPV by non-invasive pre-PCI TDE and reference diameter can predict lesions with coexisting microvascular dysfunction in LAD territory with functionally significant lesions without the need of vasodilator-induced hyperemia and a wire-based invasive physiological measurement.

Funding Acknowledgement

Type of funding sources: None.