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The Journal of Invasive Cardiology Feb 2024The SavvyWire(OpSens Medical) is a support wire for transcatheter aortic valve replacement (TAVR) procedures that, in addition to its dedicated left ventricle (LV)... (Observational Study)
Observational Study
OBJECTIVES
The SavvyWire(OpSens Medical) is a support wire for transcatheter aortic valve replacement (TAVR) procedures that, in addition to its dedicated left ventricle (LV) pacing capabilities, has a distal pressure sensor that measures live transvalvular hemodynamics during the procedure. We aimed to determine the safety, efficacy, and functionality of the SavvyWire during TAVR procedures in an all-comer population.
METHODS
We performed a multicentric, prospective, observational, single-arm, all-comers registry of patients with symptomatic, severe aortic stenosis undergoing TAVR in 3 Canadian centers. Data were collected in a dedicated database, and pre-specified questionnaires were fulfilled by the heart team implanters after each procedure.
RESULTS
A total of 60 patients were included (mean age: 78.6 ± 7.2 years; 51% women; mean Society of Thoracic Surgeons score: 2.2 ± 1.6%). TAVR was performed through a transfemoral approach in 90% of cases, and balloon- and self-expandable valves were used in 73% and 27% of patients, respectively. There were no cases of LV perforation, guidewire deformation, significant loss of capture, or major software malfunction. The rate of successful delivery of the TAVR system was 100%, and effective LV pacing was achieved in 98% of patients. The pre-TAVR mean gradient was 39 ± 14 mm Hg while the final post-TAVR gradient was 8 ± 5 mm Hg; the mean aortic systolic pressure during rapid pacing was 54 ± 12 mm Hg. In 97% of the TAVR procedures, SavvyWire's functionality was reported to be better or similar to other TAVR workhorse support wires.
CONCLUSIONS
SavvyWire was safe, effective, and functional for live transvalvular hemodynamic evaluation and rapid pacing during TAVR procedures. More studies with larger sample sizes and comparison against different wires and gradient measurement methods are warranted.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Aortic Valve; Aortic Valve Stenosis; Canada; Heart Valve Prosthesis; Hemodynamics; Prospective Studies; Prosthesis Design; Risk Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 38335504
DOI: 10.25270/jic/23.00242 -
The Journal of Invasive Cardiology Jul 2023A 76-year-old female with severe symptomatic aortic stenosis underwent cardiac CT angiography imaging. Severe calcification of the ascending aorta (porcelain aorta)...
A 76-year-old female with severe symptomatic aortic stenosis underwent cardiac CT angiography imaging. Severe calcification of the ascending aorta (porcelain aorta) (Figures 1A and 1B) precluded surgical aortic valve replacement. The aortic annular area, perimeter, and diameter were 372 mm2, 68.5 mm, and 20 mm, respectively. Transcatheter aortic valve replacement (TAVR) was performed with direct implantation of a 23 mm Sapien S3 valve (Edwards Lifesciences). The valve was delivered via the right femoral artery and a pigtail catheter was delivered to the aortic root via the left femoral artery. The balloon ruptured during valve implantation (Video).
Topics: Female; Humans; Aged; Transcatheter Aortic Valve Replacement; Aortic Valve Stenosis; Aortic Valve; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Treatment Outcome; Prosthesis Design
PubMed: 37769616
DOI: No ID Found -
Biology of Sex Differences Oct 2023Aortic stenosis (AS) is characterized by inflammation, fibrosis, osteogenesis and angiogenesis. Men and women develop these mechanisms differently. Galectin-3 (Gal-3) is...
BACKGROUND
Aortic stenosis (AS) is characterized by inflammation, fibrosis, osteogenesis and angiogenesis. Men and women develop these mechanisms differently. Galectin-3 (Gal-3) is a pro-inflammatory and pro-osteogenic lectin in AS. In this work, we aim to analyse a potential sex-differential role of Gal-3 in AS.
METHODS
226 patients (61.50% men) with severe AS undergoing surgical aortic valve (AV) replacement were recruited. In AVs, Gal-3 expression and its relationship with inflammatory, osteogenic and angiogenic markers was assessed. Valve interstitial cells (VICs) were primary cultured to perform in vitro experiments.
RESULTS
Proteomic analysis revealed that intracellular Gal-3 was over-expressed in VICs of male AS patients. Gal-3 secretion was also higher in men's VICs as compared to women's. In human AVs, Gal-3 protein levels were significantly higher in men, with stronger immunostaining in VICs with myofibroblastic phenotype and valve endothelial cells. Gal-3 levels in AVs were positively correlated with inflammatory markers in both sexes. Gal-3 expression was also positively correlated with osteogenic markers mainly in men AVs, and with angiogenic molecules only in this sex. In vitro, Gal-3 treatment induced expression of inflammatory, osteogenic and angiogenic markers in male's VICs, while it only upregulated inflammatory and osteogenic molecules in women-derived cells. Gal-3 blockade with pharmacological inhibitors (modified citrus pectin and G3P-01) prevented the upregulation of inflammatory, osteogenic and angiogenic molecules.
CONCLUSIONS
Gal-3 plays a sex-differential role in the setting of AS, and it could be a new sex-specific therapeutic target controlling pathological features of AS in VICs.
Topics: Female; Humans; Male; Aortic Valve; Aortic Valve Stenosis; Endothelial Cells; Galectin 3; Proteomics
PubMed: 37875993
DOI: 10.1186/s13293-023-00556-1 -
ESC Heart Failure Aug 2023There is evidence to suggest that the subtype of aortic stenosis (AS), the degree of myocardial fibrosis (MF), and level of aortic valve calcification (AVC) are...
AIMS
There is evidence to suggest that the subtype of aortic stenosis (AS), the degree of myocardial fibrosis (MF), and level of aortic valve calcification (AVC) are associated with adverse cardiac outcome in AS. Because little is known about their respective contribution, we sought to investigate their relative importance and interplay as well as their association with adverse cardiac events following transcatheter aortic valve replacement (TAVR).
METHODS AND RESULTS
One hundred consecutive patients with severe AS and indication for TAVR were prospectively enrolled between January 2017 and October 2018. Patients underwent transthoracic echocardiography, multidetector computed tomography, and left ventricular endomyocardial biopsies at the time of TAVR. The final study cohort consisted of 92 patients with a completed study protocol, 39 (42.4%) of whom showed a normal ejection fraction (EF) high-gradient (NEFHG) AS, 13 (14.1%) a low EF high-gradient (LEFHG) AS, 25 (27.2%) a low EF low-gradient (LEFLG) AS, and 15 (16.3%) a paradoxical low-flow, low-gradient (PLFLG) AS. The high-gradient phenotypes (NEFHG and LEFHG) showed the largest amount of AVC (807 ± 421 and 813 ± 281 mm , respectively) as compared with the low-gradient phenotypes (LEFLG and PLFLG; 503 ± 326 and 555 ± 594 mm , respectively, P < 0.05). Conversely, MF was most prevalent in low-output phenotypes (LEFLG > LEFHG > PLFLG > NEFHG, P < 0.05). This was paralleled by a greater cardiovascular (CV) mortality within 600 days after TAVR (LEFLG 28% > PLFLG 26.7% > LEFHG 15.4% > NEFHG 2.5%; P = 0.023). In patients with a high MF burden, a higher AVC was associated with a lower mortality following TAVR (P = 0.045, hazard ratio 0.261, 95% confidence interval 0.07-0.97).
CONCLUSIONS
MF is associated with adverse CV outcome following TAVR, which is most prevalent in low EF situations. In the presence of large MF burden, patients with large AVC have better outcome following TAVR. Conversely, worse outcome in large MF and relatively little AVC may be explained by a relative prominence of an underlying cardiomyopathy. The better survival rates in large AVC patients following TAVR indicate TAVR induced relief of severe AS-associated pressure overload with subsequently improved outcome.
Topics: Humans; Aortic Valve; Transcatheter Aortic Valve Replacement; Treatment Outcome; Aortic Valve Stenosis; Fibrosis; Cardiomyopathies
PubMed: 37060191
DOI: 10.1002/ehf2.14307 -
Cardiovascular Diabetology Jan 2024Remnant cholesterol (RC) is implicated in the risk of cardiovascular disease. However, comprehensive population-based studies elucidating its association with aortic...
BACKGROUND
Remnant cholesterol (RC) is implicated in the risk of cardiovascular disease. However, comprehensive population-based studies elucidating its association with aortic valve calcium (AVC) progression are limited, rendering its precise role in AVC ambiguous.
METHODS
From the Multi-Ethnic Study of Atherosclerosis database, we included 5597 individuals (61.8 ± 10.1 years and 47.5% men) without atherosclerotic cardiovascular disease at baseline for analysis. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), as estimated by the Martin/Hopkins equation. Using the adjusted Cox regression analyses, we examined the relationships between RC levels and AVC progression. Furthermore, we conducted discordance analyses to evaluate the relative AVC risk in RC versus LDL-C discordant/concordant groups.
RESULTS
During a median follow-up of 2.4 ± 0.9 years, 568 (10.1%) participants exhibited AVC progression. After adjusting for traditional cardiovascular risk factors, the HRs (95% CIs) for AVC progression comparing the second, third, and fourth quartiles of RC levels with the first quartile were 1.195 (0.925-1.545), 1.322 (1.028-1.701) and 1.546 (1.188-2.012), respectively. Notably, the discordant high RC/low LDL-C group demonstrated a significantly elevated risk of AVC progression compared to the concordant low RC/LDL-C group based on their medians (HR, 1.528 [95% CI 1.201-1.943]). This pattern persisted when clinical LDL-C threshold was set at 100 and 130 mg/dL. The association was consistently observed across various sensitivity analyses.
CONCLUSIONS
In atherosclerotic cardiovascular disease-free individuals, elevated RC is identified as a residual risk for AVC progression, independent of traditional cardiovascular risk factors. The causal relationship of RC to AVC and the potential for targeted RC reduction in primary prevention require deeper exploration.
Topics: Male; Humans; Female; Calcium; Cholesterol, LDL; Aortic Valve; Cardiovascular Diseases; Cholesterol; Hypercholesterolemia; Atherosclerosis
PubMed: 38195550
DOI: 10.1186/s12933-023-02081-2 -
BMC Medicine Jul 2023Calcific aortic valve disease (CAVD) is the most prevalent valvular disease and has high morbidity and mortality. CAVD is characterized by complex pathophysiological...
BACKGROUND
Calcific aortic valve disease (CAVD) is the most prevalent valvular disease and has high morbidity and mortality. CAVD is characterized by complex pathophysiological processes, including inflammation-induced osteoblastic differentiation in aortic valve interstitial cells (AVICs). Novel anti-CAVD agents are urgently needed. Protein tyrosine phosphatase nonreceptor type 22 (PTPN22), an intracellular nonreceptor-like protein tyrosine phosphatase, is involved in several chronic inflammatory diseases, including rheumatoid arthritis and diabetes. However, it is unclear whether PTPN22 is involved in the pathogenesis of CAVD.
METHODS
We obtained the aortic valve tissue from human and cultured AVICs from aortic valve. We established CAVD mice model by wire injury. Transcriptome sequencing, western bolt, qPCR, and immunofluorescence were performed to elucidate the molecular mechanisms.
RESULTS
Here, we determined that PTPN22 expression was upregulated in calcific aortic valve tissue, AVICs treated with osteogenic medium, and a mouse model of CAVD. In vitro, overexpression of PTPN22 induced osteogenic responses, whereas siRNA-mediated PTPN22 knockdown abolished osteogenic responses and mitochondrial stress in the presence of osteogenic medium. In vivo, PTPN22 ablation ameliorated aortic valve lesions in a wire injury-induced CAVD mouse model, validating the pathogenic role of PTPN22 in CAVD. Additionally, we discovered a novel compound, 13-hydroxypiericidin A 10-O-α-D-glucose (1 → 6)-β-D-glucoside (S18), in a marine-derived Streptomyces strain that bound to PTPN22 with high affinity and acted as a novel inhibitor. Incubation with S18 suppressed osteogenic responses and mitochondrial stress in human AVICs induced by osteogenic medium. In mice with aortic valve injury, S18 administration markedly alleviated aortic valve lesions.
CONCLUSION
PTPN22 plays an essential role in the progression of CAVD, and inhibition of PTPN22 with S18 is a novel option for the further development of potent anti-CAVD drugs. Therapeutic inhibition of PTPN22 retards aortic valve calcification through modulating mitochondrial dysfunction in AVICs.
Topics: Humans; Animals; Mice; Aortic Valve; Phosphoric Monoester Hydrolases; Aortic Valve Stenosis; Cells, Cultured; Protein Tyrosine Phosphatase, Non-Receptor Type 22
PubMed: 37443055
DOI: 10.1186/s12916-023-02888-6 -
European Heart Journal Nov 2023Early diagnosis of aortic stenosis (AS) is critical to prevent morbidity and mortality but requires skilled examination with Doppler imaging. This study reports the...
BACKGROUND AND AIMS
Early diagnosis of aortic stenosis (AS) is critical to prevent morbidity and mortality but requires skilled examination with Doppler imaging. This study reports the development and validation of a novel deep learning model that relies on two-dimensional (2D) parasternal long axis videos from transthoracic echocardiography without Doppler imaging to identify severe AS, suitable for point-of-care ultrasonography.
METHODS AND RESULTS
In a training set of 5257 studies (17 570 videos) from 2016 to 2020 [Yale-New Haven Hospital (YNHH), Connecticut], an ensemble of three-dimensional convolutional neural networks was developed to detect severe AS, leveraging self-supervised contrastive pretraining for label-efficient model development. This deep learning model was validated in a temporally distinct set of 2040 consecutive studies from 2021 from YNHH as well as two geographically distinct cohorts of 4226 and 3072 studies, from California and other hospitals in New England, respectively. The deep learning model achieved an area under the receiver operating characteristic curve (AUROC) of 0.978 (95% CI: 0.966, 0.988) for detecting severe AS in the temporally distinct test set, maintaining its diagnostic performance in geographically distinct cohorts [0.952 AUROC (95% CI: 0.941, 0.963) in California and 0.942 AUROC (95% CI: 0.909, 0.966) in New England]. The model was interpretable with saliency maps identifying the aortic valve, mitral annulus, and left atrium as the predictive regions. Among non-severe AS cases, predicted probabilities were associated with worse quantitative metrics of AS suggesting an association with various stages of AS severity.
CONCLUSION
This study developed and externally validated an automated approach for severe AS detection using single-view 2D echocardiography, with potential utility for point-of-care screening.
Topics: Humans; Deep Learning; Echocardiography; Aortic Valve Stenosis; Aortic Valve; Ultrasonography
PubMed: 37611002
DOI: 10.1093/eurheartj/ehad456 -
Scientific Reports Sep 2023Pressure recovery (PR) is essential part of the post stenotic fluid mechanics and depends on the ratio of EOA/A, the effective aortic valve orifice area (EOA) and aortic...
Pressure recovery (PR) is essential part of the post stenotic fluid mechanics and depends on the ratio of EOA/A, the effective aortic valve orifice area (EOA) and aortic cross-sectional area (A). In patients with advanced ascending aortic aneurysm and mildly diseased aortic valves, the effect of A on pressure recovery and corresponding functional aortic valve opening area (ELCO) was evaluated before and after valve-sparing surgery (Dacron graft implantation). 66 Patients with ascending aortic aneurysm (mean aortic diameter 57 +/- 10 mm) and aortic valve-sparing surgery (32 reimplantation technique (David), 34 remodeling technique (Yacoub)) were routinely investigated by Doppler echocardiography. Dacron graft with a diameter between 26 and 34 mm were implanted. EOA was significantly declined after surgery (3.4 +/- 0.8 vs. 2.6 +/- 0.9cm; p < 0.001). Insertion of Dacron prosthesis resulted in a significant reduction of A (26.7 +/- 10.2 vs. 6.8 +/- 1.1cm; p < 0.001) with increased ratio of EOA/A (0.14 +/- 0.05 vs. 0.40 +/- 0.1; p < 0.001) and pressure recovery index (PRI; 0.24 +/- 0.08 vs. 0.44 +/- 0.06; p < 0.0001). Despite reduction of EOA, ELCO (= EOA corrected for PR) increased from 4.0 +/- 1.1 to 5.0 +/- 3.1cm (p < 0.01) with reduction in transvalvular LV stroke work (1005 +/- 814 to 351 +/- 407 mmHg × ml, p < 0.001) after surgery. These effects were significantly better in patients with Yacoub technique than with the David operation. The hemodynamic findings demonstrate a valve-vessel interaction almost entirely caused by a marked reduction in the ascending A with significant PR gain. The greater hemodynamic benefit of the Yacoub technique due to higher EOA values compared to the David technique was evident and may be of clinical relevance.
Topics: Humans; Aortic Valve; Aorta, Thoracic; Polyethylene Terephthalates; Catheters; Aorta
PubMed: 37714924
DOI: 10.1038/s41598-023-42068-3 -
Journal of the American Heart... Aug 2023Background Prognostic implications of transcatheter aortic valve implantation (TAVI) in low-gradient (LG) aortic stenosis (AS) remain controversial. The authors...
Background Prognostic implications of transcatheter aortic valve implantation (TAVI) in low-gradient (LG) aortic stenosis (AS) remain controversial. The authors hypothesized that differences in cardiac functional recovery may solve this ongoing controversy. The aim was to evaluate clinical outcomes and the response of left ventricular (LV) function following TAVI in patients with LG AS. Methods and Results This multicenter retrospective study included 1742 patients with severe AS undergoing TAVI between January 2015 and March 2019. Patients were subdivided into low-flow (LF) LG, normal-flow (NF) LG, LF high-gradient, and NF high-gradient AS groups according to the mean gradient of the aortic valve (LG <40 mm Hg) and LV stroke volume index (LF <35 mL/m). Outcomes and changes in echocardiographic parameters after TAVI were compared between the groups. A total of 227 patients (13%) had reduced ejection fraction, and 486 patients (28%) had LG AS (LF-LG 143 [8%]; NF-LG 343 [20%]). During a median follow-up period of 747 days, 301 patients experienced a composite end point of cardiovascular death and rehospitalization for cardiovascular events, which was higher in the LF-LG and NF-LG groups than in the high-gradient groups. LG AS was independently associated with the primary outcome (hazard ratio, 1.69; <0.001). Among 1239 patients with follow-up echocardiography, LG AS showed less improvement in the LV mass index and LV end-diastolic volume compared with high-gradient AS after 1 year, while LV recovery was similar between the LF AS and NF AS groups. Conclusions LG AS was associated with poorer outcomes and LV recovery, regardless of flow status after TAVI. Careful evaluation of AS severity may be required in LG AS to provide TAVI within the appropriate time and advanced care afterward.
Topics: Humans; Transcatheter Aortic Valve Replacement; Retrospective Studies; Treatment Outcome; Aortic Valve Stenosis; Aortic Valve; Ventricular Function, Left; Stroke Volume; Heart Valve Prosthesis Implantation; Severity of Illness Index
PubMed: 37581389
DOI: 10.1161/JAHA.123.029717 -
Multimedia Manual of Cardiothoracic... Mar 2024Micro-invasive totally endoscopic aortic valve replacement surgery is a minimally invasive cardiac procedure that can be performed with the help of several techniques...
Micro-invasive totally endoscopic aortic valve replacement surgery is a minimally invasive cardiac procedure that can be performed with the help of several techniques and technologies that employ the latest innovations in instrumentation and technological advances in the field, thereby greatly limiting the overall invasiveness of the procedure. With the help of a 3-dimensional camera, long instruments, a very small thoracotomy and a soft-tissue retractor without any rib retractor, the aortic valve can be easily and safely accessed for replacement. The other main features of these techniques are extracorporeal circulation that is achieved through peripheral percutaneous cannulation of the femoral vessels, antegrade cardioplegia, the use of automated devices for suturing the valvular ring and the prosthetic suture cuff, namely the RAM device, the Sew-Easy device and the Cor-Knot Mini device. Additionally, an automated vascular closure device such as the MANTA device is later used to close the femoral artery following decannulation.
Topics: Humans; Aortic Valve; Catheters; Endoscopy; Femoral Artery; Lower Extremity
PubMed: 38530245
DOI: 10.1510/mmcts.2023.094