Valvular Heart Disease: From Basic to Clinical Advances

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiovascular Medicine".

Deadline for manuscript submissions: closed (22 September 2023) | Viewed by 19166

Special Issue Editor

Icahn School of Medicine at Mount Sinai, New York, NY, USA
Interests: aortic stenosis; extracellular matrix proteins siganling; lipoproteins

Special Issue Information

Dear Colleagues,

Calcified aortic valve disease (CAVD) affects over six million Americans and is associated with changes in the mechanical properties of valve leaflets, resulting in impaired valvular blood flow. CAVD is a fibrocalcific disease with multifactorial risk factors related to the complex environment where the aortic valve (AV) resides. The valvular tissue microstructure, particularly the extracellular matrix (ECM), plays an important role in maintaining the normal mechanical behavior of the valve. It has been reported that the accumulation of proteoglycans promotes lipoprotein retention, such as oxidized LDL, which stimulates cell mineralization through the activation of an inflammatory response.

However, statins did not succeed in slowing down the progression of aortic stenosis. PCSK9 and Lp(a) seem to be better targets for lipid lowering in patients with aortic stenosis. In the Special Issue, we want to focus on the latest findings in valvular heart disease (native and prosthetic valve) from basic science to clinical research. We are also accepting reviews discussing the complexity of the disease and future directions to alleviate the progression of aortic stenosis.

Dr. Rihab Bouchareb
Guest Editor

Manuscript Submission Information

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Keywords

  • lipoproteins
  • PCSK9
  • aortic valve
  • calicification
  • progression of aortic stenosis
  • ECM-lipid retention

Published Papers (15 papers)

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15 pages, 1418 KiB  
Article
Progression of Non-Significant Mitral and Tricuspid Regurgitation after Surgical Aortic Valve Replacement for Aortic Regurgitation
by Shirit Kazum, Mordehay Vaturi, Idit Yedidya, Shmuel Schwartzenberg, Olga Morelli, Keren Skalsky, Hadas Ofek, Ram Sharony, Ran Kornowski, Yaron Shapira and Alon Shechter
J. Clin. Med. 2023, 12(19), 6280; https://doi.org/10.3390/jcm12196280 - 29 Sep 2023
Viewed by 739
Abstract
Little is known about the natural history of non-significant mitral and tricuspid regurgitation (MR and TR) following surgical aortic valve replacement (SAVR) for aortic regurgitation (AR). We retrospectively analyzed 184 patients (median age 64 (IQR, 55–74) years, 76.6% males) who underwent SAVR for [...] Read more.
Little is known about the natural history of non-significant mitral and tricuspid regurgitation (MR and TR) following surgical aortic valve replacement (SAVR) for aortic regurgitation (AR). We retrospectively analyzed 184 patients (median age 64 (IQR, 55–74) years, 76.6% males) who underwent SAVR for AR. Subjects with significant non-aortic valvulopathies, prior/concomitant valvular interventions, or congenital heart disease were excluded. The cohort was evaluated for MR/TR progression and, based on the latter’s occurrence, for echocardiographic and clinical indices of heart failure and mortality. By 5.8 (IQR, 2.8–11.0) years post-intervention, moderate or severe MR occurred in 20 (10.9%) patients, moderate or severe TR in 25 (13.5%), and either of the two in 36 (19.6%). Patients who developed moderate or severe MR/TR displayed greater biventricular disfunction and functional limitation and were less likely to be alive at 7.0 (IQR, 3.4–12.1) years compared to those who did not (47.2 vs. 79.7%, p < 0.001). The emergence of significant MR/TR was associated with preoperative atrial fibrillation/flutter, symptomatic heart failure, and above-mild MR/TR as well as concomitant composite graft use, but not with baseline echocardiographic measures of biventricular function and dimensions, aortic valve morphology, or procedural aspects. In conclusion, among patients undergoing SAVR for AR, significant MR/TR developed in one fifth by six years, correlated with more adverse course, and was anticipated by baseline clinical and echocardiographic variables. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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14 pages, 943 KiB  
Article
Effect of Dapagliflozin on Patients with Rheumatic Heart Disease Mitral Stenosis
by An Aldia Asrial, Reviono Reviono, Soetrisno Soetrisno, Budi Yuli Setianto, Vitri Widyaningsih, Ida Nurwati, Brian Wasita and Anggit Pudjiastuti
J. Clin. Med. 2023, 12(18), 5898; https://doi.org/10.3390/jcm12185898 - 11 Sep 2023
Cited by 1 | Viewed by 960
Abstract
(1) Background: Mitral stenosis is the most common rheumatic heart disease (RHD). Inflammation and fibrosis are the primary pathophysiology, resulting in left atrial stress and dysfunction. Dapagliflozin is a new heart failure treatment with anti-inflammation and anti-fibrosis effects from previous studies. However, the [...] Read more.
(1) Background: Mitral stenosis is the most common rheumatic heart disease (RHD). Inflammation and fibrosis are the primary pathophysiology, resulting in left atrial stress and dysfunction. Dapagliflozin is a new heart failure treatment with anti-inflammation and anti-fibrosis effects from previous studies. However, the specific role of dapagliflozin in RHD mitral stenosis is unknown. This study aims to investigate (i) the effect of dapagliflozin on biomarkers of fibrosis, NT-pro BNP levels and left atrial function; (ii) the relationship between the changes in fibrosis biomarkers with left atrial function and NT-pro BNP levels. (2) Methods: An open-label randomized study was conducted on 33 RHD mitral stenosis patients divided into a dapagliflozin group which received 10 mg dapagliflozin and standard therapy, and a control group which only received standard therapy. All patients were examined for levels of PICP, MMP-1/TIMP-1 ratio, TGF-β1, NT-proBNP, mitral valve mean pressure gradient (MPG), and net atrioventricular compliance (Cn) pre- and post-intervention. (3) Results: This study found a significant increase in PICP and TGF-β1 and a reduction in the MMP-1/TIMP-1 ratio in the dapagliflozin group and the control group (p < 0.05). In the dapagliflozin group, the levels of NT-pro BNP decreased significantly (p = 0.000), with a delta of decreased NT-pro BNP levels also significantly greater in the dapagliflozin group compared to the control (p = 0.034). There was a significant increase in Cn values in the dapagliflozin group (p = 0.017), whereas there was a decrease in the control group (p = 0.379). Delta of changes in Cn values between the dapagliflozin and control groups also showed a significant value (p = 0.049). The decreased MPG values of the mitral valve were found in both the dapagliflozin and control groups, with the decrease in MPG significantly greater in the dapagliflozin group (p = 0.031). There was no significant correlation between changes in the value of fibrosis biomarkers with Cn and NT-pro BNP (p > 0.05). (4) Conclusions: This study implies that the addition of dapagliflozin to standard therapy for RHD mitral stenosis patients provides benefits, as evidenced by an increase in net atrioventricular compliance and decreases in the MPG value of the mitral valve and NT-pro BNP levels (p < 0.05). This improvement was not directly related to changes in fibrosis biomarkers, as these biomarkers showed ongoing fibrosis even with dapagliflozin administration. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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12 pages, 2523 KiB  
Article
Targeted Radiation Exposure Induces Accelerated Aortic Valve Remodeling in ApoE−/− Mice
by Guillaume Rucher, Kevin Prigent, Christophe Simard, Anne-Marie Frelin, Maëlle Coquemont-Guyot, Nicolas Elie, Nicolas Delcroix, Nicolas Perzo, Romain Guinamard, Ludovic Berger, Alain Manrique and on behalf of the STOP-AS Investigators
J. Clin. Med. 2023, 12(18), 5854; https://doi.org/10.3390/jcm12185854 - 08 Sep 2023
Viewed by 689
Abstract
Thoracic radiation therapy may result in accelerated atherosclerosis and in late aortic valve stenosis (AS). In this study, we assessed the feasibility of inducing radiation-induced AS using a targeted aortic valve irradiation (10 or 20 Grays) in two groups of C57Bl6/J (WT) and [...] Read more.
Thoracic radiation therapy may result in accelerated atherosclerosis and in late aortic valve stenosis (AS). In this study, we assessed the feasibility of inducing radiation-induced AS using a targeted aortic valve irradiation (10 or 20 Grays) in two groups of C57Bl6/J (WT) and ApoE−/− mice compared to a control (no irradiation). Peak aortic jet velocity was evaluated by echocardiography to characterize AS. T2*-weighted magnetic resonance imaging after injection of MPIO-αVCAM-1 was used to examine aortic inflammation resulting from irradiation. A T2* signal void on valve leaflets and aortic sinus was considered positive. Valve remodeling and mineralization were assessed using von Kossa staining. Finally, the impact of radiation on cell viability and cycle from aortic human valvular interstitial cells (hVICs) was also assessed. The targeted aortic valve irradiation in ApoE−/− mice resulted in an AS characterized by an increase in peak aortic jet velocity associated with valve leaflet and aortic sinus remodeling, including mineralization process, at the 3-month follow-up. There was a linear correlation between histological findings and peak aortic jet velocity (r = 0.57, p < 0.01). In addition, irradiation was associated with aortic root inflammation, evidenced by molecular MR imaging (p < 0.01). No significant effect of radiation exposure was detected on WT animals. Radiation exposure did not affect hVICs viability and cell cycle. We conclude that targeted radiation exposure of the aortic valve in mice results in ApoE−/−, but not in WT, mice in an aortic valve remodeling mimicking the human lesions. This preclinical model could be a useful tool for future assessment of therapeutic interventions. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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14 pages, 2008 KiB  
Article
Predictors of Conduction Disturbances Requiring New Permanent Pacemaker Implantation following Transcatheter Aortic Valve Implantation Using the Evolut Series
by Mahmoud Abdelshafy, Ahmed Elkoumy, Hesham Elzomor, Mohammad Abdelghani, Ruth Campbell, Ciara Kennedy, William Kenny Gibson, Simone Fezzi, Philip Nolan, Max Wagener, Shahram Arsang-Jang, Sameh K. Mohamed, Mansour Mostafa, Islam Shawky, Briain MacNeill, Angela McInerney, Darren Mylotte and Osama Soliman
J. Clin. Med. 2023, 12(14), 4835; https://doi.org/10.3390/jcm12144835 - 22 Jul 2023
Viewed by 1027
Abstract
(1) Background: Conduction disturbance requiring a new permanent pacemaker (PPM) after transcatheter aortic valve implantation (TAVI) has traditionally been a common complication. New implantation techniques with self-expanding platforms have reportedly reduced the incidence of PPM. We sought to investigate the predictors of PPM [...] Read more.
(1) Background: Conduction disturbance requiring a new permanent pacemaker (PPM) after transcatheter aortic valve implantation (TAVI) has traditionally been a common complication. New implantation techniques with self-expanding platforms have reportedly reduced the incidence of PPM. We sought to investigate the predictors of PPM at 30 days after TAVI using Evolut R/PRO/PRO+; (2) Methods: Consecutive patients who underwent TAVI with the Evolut platform between October 2019 and August 2022 at University Hospital Galway, Ireland, were included. Patients who had a prior PPM (n = 10), valve-in-valve procedures (n = 8) or received >1 valve during the index procedure (n = 3) were excluded. Baseline clinical, electrocardiographic (ECG), echocardiographic and multislice computed tomography (MSCT) parameters were analyzed. Pre-TAVI MSCT analysis included membranous septum (MS) length, a semi-quantitative calcification analysis of the aortic valve leaflets, left ventricular outflow tract, and mitral annulus. Furthermore, the implantation depth (ID) was measured from the final aortography. Multivariate binary logistic analysis and receiver operating characteristic (ROC) curve analysis were used to identify independent predictors and the optimal MS and ID cutoff values to predict new PPM requirements, respectively; (3) Results: A total of 129 TAVI patients were included (age = 81.3 ± 5.3 years; 36% female; median EuroSCORE II 3.2 [2.0, 5.4]). Fifteen patients (11.6%) required PPM after 30 days. The patients requiring new PPM at 30 days were more likely to have a lower European System for Cardiac Operative Risk Evaluation II, increased prevalence of right bundle branch block (RBBB) at baseline ECG, have a higher mitral annular calcification severity and have a shorter MS on preprocedural MSCT analysis, and have a ID, as shown on the final aortogram. From the multivariate analysis, pre-TAVI RBBB, MS length, and ID were shown to be predictors of new PPM. An MS length of <2.85 mm (AUC = 0.85, 95%CI: (0.77, 0.93)) and ID of >3.99 mm (area under the curve (AUC) = 0.79, (95% confidence interval (CI): (0.68, 0.90)) were found to be the optimal cut-offs for predicting new PPM requirements; (4) Conclusions: Membranous septum length and implantation depth were found to be independent predictors of new PPM post-TAVI with the Evolut platform. Patient-specific implantation depth could be used to mitigate the requirement for new PPM. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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10 pages, 404 KiB  
Article
Effects of Atrial Fibrillation Radiofrequency Ablation in Patients Aged > 75 Years Undergoing Mitral Valve Surgery
by Carlo Rostagno, Camilla Tozzetti, Enrico Carone and Pierluigi Stefàno
J. Clin. Med. 2023, 12(5), 1812; https://doi.org/10.3390/jcm12051812 - 24 Feb 2023
Viewed by 1105
Abstract
Background: Few data exist about the efficacy of radiofrequency (RF) maze procedures in elderly patients with atrial fibrillation (AF) undergoing surgery for mitral valve disease. The aim of the present investigation was to evaluate the effects of AF ablation associated with mitral valve [...] Read more.
Background: Few data exist about the efficacy of radiofrequency (RF) maze procedures in elderly patients with atrial fibrillation (AF) undergoing surgery for mitral valve disease. The aim of the present investigation was to evaluate the effects of AF ablation associated with mitral valve surgery on the recovery and long-term maintenance of sinus rhythm in elderly patients aged > 75 years. Moreover, we evaluated the effects on survival. Methods and results: This study included 96 consecutive patients with AF (42 men and 56 women) aged > 75 years (mean age 78 ± 3) who underwent RF ablation associated with mitral valve surgery (group I). This group was compared to 209 younger patients (mean age 65 ± 8 years) treated in the same period (group II). Baseline clinical and echocardiographic characteristics were similar in the two groups. Four patients died during hospitalization, one aged > 75 years. In surviving patients at the end of the follow-up period, sinus rhythm was present respectively in 64% of the elderly and 74% of younger patients (p = 0.778). The rate of persistence of sinus rhythm without AF recurrences (38% vs. 41%, p = 0.705) was similar in the two groups. After surgery, sinus rhythm was frequently never regained in aged patients (27% vs. 20%, p = 0.231). Elderly patients more frequently needed permanent pacing and had more hospitalizations and a higher number of non-AF atrial tachyarrhythmias. At eight-year follow-up, survival was lower in older patients (48% aged > 75 vs. 79% aged < 75 years). Conclusion: Elderly patients had a similar long-term rate of stable sinus rhythm maintenance in comparison to younger patients after AF radiofrequency ablation associated with mitral valve surgery. However, they needed more frequent permanent pacing and had higher rates of hospitalizations and post-procedural atrial tachyarrhythmias. The effects of survival are difficult to evaluate due to the different life expectancies of the two groups. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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9 pages, 1645 KiB  
Article
Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure
by Hind Messaoudi, Thomas Levesque, Nicolas Perzo, Elodie Berg, Guillaume Feugray, Anaïs Dumesnil, Valéry Brunel, Dominique Guerrot, Hélène Eltchaninoff, Vincent Richard, Saïd Kamel, Eric Durand, Youssef Bennis and Jérémy Bellien
J. Clin. Med. 2023, 12(4), 1539; https://doi.org/10.3390/jcm12041539 - 15 Feb 2023
Cited by 1 | Viewed by 1394
Abstract
Introduction. This study addressed the hypothesis that subtotal nephrectomy associated with a high-phosphorus diet (5/6Nx + P) in rats represents a suitable animal model to mimic the cardiovascular consequences of chronic kidney disease (CKD) including calcified aortic valve disease (CAVD). Indeed, the latter [...] Read more.
Introduction. This study addressed the hypothesis that subtotal nephrectomy associated with a high-phosphorus diet (5/6Nx + P) in rats represents a suitable animal model to mimic the cardiovascular consequences of chronic kidney disease (CKD) including calcified aortic valve disease (CAVD). Indeed, the latter contributes to the high morbidity and mortality of CKD patients and sorely lacks preclinical models for pathophysiological and pharmacological studies. Methods. Renal and cardiovascular function and structure were compared between sham-operated and 5/6 Nx rats + P 10 to 12 weeks after surgery. Results. As expected, 11 weeks after surgery, 5/6Nx + P rats developed CKD as demonstrated by their increase in plasma creatinine and urea nitrogen and decrease in glomerular filtration rate, estimated by using fluorescein-isothiocyanate-labelled sinistrin, anemia, polyuria, and polydipsia compared to sham-operated animals on a normal-phosphorus diet. At the vascular level, 5/6Nx + P rats had an increase in the calcium content of the aorta; a decrease in mesenteric artery dilatation in response to a stepwise increase in flow, illustrating the vascular dysfunction; and an increase in blood pressure. Moreover, immunohistology showed a marked deposition of hydroxyapatite crystals in the aortic valve of 5/6Nx + P rats. Echocardiography demonstrated that this was associated with a decrease in aortic valve cusp separation and an increase in aortic valve mean pressure gradient and in peak aortic valve velocity. Left-ventricular diastolic and systolic dysfunction as well as fibrosis were also present in 5/6Nx + P rats. Conclusion. This study demonstrates that 5/6Nx + P recapitulates the cardiovascular consequences observed in humans with CKD. In particular, the initiation of CAVD was shown, highlighting the interest of this animal model to study the mechanisms involved in the development of aortic stenosis and test new therapeutic strategies at an early stage of the disease. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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9 pages, 645 KiB  
Article
In-Hospital Mortality and Risk Prediction in Minimally Invasive Sutureless versus Conventional Aortic Valve Replacement
by Giuseppe Santarpino, Roberto Lorusso, Armin Darius Peivandi, Francesco Atzeni, Maria Avolio, Angelo Maria Dell’Aquila and Giuseppe Speziale
J. Clin. Med. 2022, 11(24), 7273; https://doi.org/10.3390/jcm11247273 - 07 Dec 2022
Cited by 2 | Viewed by 951
Abstract
Objective. Available evidence suggests that a minimally invasive approach with the use of sutureless bioprostheses has a favorable impact on the outcome of patients undergoing aortic valve replacement (AVR). Methods. From 2010 to 2019, 2732 patients underwent conventional AVR through median sternotomy with [...] Read more.
Objective. Available evidence suggests that a minimally invasive approach with the use of sutureless bioprostheses has a favorable impact on the outcome of patients undergoing aortic valve replacement (AVR). Methods. From 2010 to 2019, 2732 patients underwent conventional AVR through median sternotomy with a stented bioprosthesis (n = 2048) or minimally invasive AVR with a sutureless bioprosthesis (n = 684). Results. Using the propensity score, 206 patients in each group were matched, and the matched groups were well balanced regarding preoperative risk factors. Both unmatched and matched patients of the sutureless + minimally invasive group showed significantly shorter cross-clamp times and longer ICU stay. In-hospital mortality was the only outcome measure that was confirmed in both analyses, and was higher in the stented + conventional group (2.54% and 2.43% in unmatched and matched patients, respectively) compared with the sutureless + minimally invasive group (0.88% and 0.97% in unmatched and matched patients, respectively) (p = 0.0047 and p < 0.0001, respectively). No differences in postoperative pacemaker implantation were recorded in matched patients of both groups (n = 2 [1%] in the stented + conventional group vs. n = 4 [2%] in the sutureless + minimally invasive group; p = 0.41). The discrimination power of EuroSCORE II was not confirmed in the sutureless + minimally invasive group, yielding an area under the ROC curve of 0.568. Conclusions. Minimally invasive sutureless AVR has a favorable impact on the immediate outcome and is associated with significantly lower in-hospital mortality rates compared with conventional AVR, resulting in the absence of the discrimination power of EuroSCORE II for predicting AVR outcomes. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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8 pages, 247 KiB  
Article
Looking Back to Look Forward: What to Expect in a Redo Surgery for a Bioprosthesis Replacement
by Ilaria Giambuzzi, Giorgia Bonalumi, Giulia Ballan, Pietro Messi, Alice Bonomi, Analia Maggiore, Giampiero Esposito, Michele Di Mauro, Francesco Alamanni and Marco Zanobini
J. Clin. Med. 2022, 11(23), 7104; https://doi.org/10.3390/jcm11237104 - 30 Nov 2022
Viewed by 909
Abstract
Redo surgeries are becoming more common because of an increased rate of bioprosthesis implantation. We performed a retrospective study on patients who underwent redo replacement of an aortic and/or mitral bioprosthesis between 2005 and 2018 to evaluate intra-hospital mortality and morbidity. Univariate analysis [...] Read more.
Redo surgeries are becoming more common because of an increased rate of bioprosthesis implantation. We performed a retrospective study on patients who underwent redo replacement of an aortic and/or mitral bioprosthesis between 2005 and 2018 to evaluate intra-hospital mortality and morbidity. Univariate analysis was performed on the propensity score variables to determine predictors of mortality. A total of 180 patients were enrolled in the study: Group A (replacement of aortic bioprosthesis) with 136 patients (75.56%) and group B (replacement of mitral bioprosthesis ± aortic bioprosthesis) with 44 patients (24.44%). NYHA class ≥ 3 and female sex were significantly more common in group B. Cardiopulmonary-bypass time and aortic cross-clamping time in group A and group B were, respectively, 154.95 ± 74.35 and 190.25 ± 77.44 (p = 0.0005) and 115.99 ± 53.54 and 144.91 ± 52.53 (p = 0.0004). Overall mortality was 8.89%. After propensity score adjustment, Group B was confirmed to have an increased risk of death (OR 3.32 CI 95% 1.02–10.88 p < 0.0001), gastrointestinal complications (OR 7.784 CI 95% 1.005–60.282 p < 0.0002) and pulmonary complications (OR 2.381 CI 95% 1.038–5.46 p < 0.0001). At the univariate analysis, endocarditis, cardiopulmonary-bypass and aortic cross clamping time, NYHA class ≥ 3 and urgency setting were significantly associated to death. Intra-hospital outcomes were acceptable regarding mortality and complications. Patients who need redo surgery on mitral bioprosthesis have an increased risk of post-operative pulmonary and gastrointestinal complications and mortality. Therefore the choice of mitral bioprosthesis at time of first surgery should be carefully evaluated. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
13 pages, 1820 KiB  
Article
Global Burden and Improvement Gap of Non-Rheumatic Calcific Aortic Valve Disease: 1990–2019 Findings from Global Burden of Disease Study 2019
by Chengzhi Yang, Haobo Xu, Ruofei Jia, Zening Jin, Changlin Zhang and Jiansong Yuan
J. Clin. Med. 2022, 11(22), 6733; https://doi.org/10.3390/jcm11226733 - 14 Nov 2022
Cited by 5 | Viewed by 1565
Abstract
The aim of this study was to explore the most updated changing trends of non-rheumatic calcific aortic valve disease (nrCAVD) and reveal possible improvements. We analyzed the age-standardized rates (ASRs) of prevalence, incidence, disability-adjusted life-years (DALYs), and mortality trends of nrCAVD from 1990 [...] Read more.
The aim of this study was to explore the most updated changing trends of non-rheumatic calcific aortic valve disease (nrCAVD) and reveal possible improvements. We analyzed the age-standardized rates (ASRs) of prevalence, incidence, disability-adjusted life-years (DALYs), and mortality trends of nrCAVD from 1990 to 2019 using data from the Global Burden of Disease (GBD) study 2019. The relations between ASRs and socio-demographic index (SDI) were analyzed with Pearson’s correlation coefficients. Decomposition and frontier analysis were employed to reveal the contribution proportion of influence factors and regions where improvement can be achieved. In 2019, there were 9.40 million (95% uncertainty interval (UI): 8.07 to 10.89 million) individuals with nrCAVD globally. From 1990 to 2019, the prevalence rate of nrCAVD increased by 155.47% (95% IU: 141.66% to 171.7%), with the largest increase observed in the middle SDI region (821.11%, 95% UI: 709.87% to 944.23%). Globally, there were no significant changes in the mortality rate of nrCAVD (0.37%, 95% UI: −8.85% to 7.99%). The global DALYs decreased by 10.97% (95% UI: −17.94% to −3.46%). The population attributable fraction (PAF) of high systolic blood pressure increased in the population aged 15–49 years, while it declined slightly in population aged 50+ years. Population growth was the main contributing factor to the increased DALYs across the globe (74.73%), while aging was the driving force in the high-SDI region (80.27%). The Netherlands, Finland, Luxembourg, Germany, and Norway could reduce DALY rates of nrCAVD using their socio-demographic resources. According to these results, we revealed that the burden of nrCAVD increased markedly from 1990 to 2019 in high-SDI and high-middle-SDI regions. There was a downward trend in the mortality due to nrCAVD since 2013, which is possibly owing to profound advances in transcatheter aortic valve replacement. Some countries may reduce burdens of nrCAVD using their socio-demographic resources. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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12 pages, 884 KiB  
Article
Core Lab Adjudication of the ACURATE neo2 Hemodynamic Performance Using Computed-Tomography-Corrected Left Ventricular Outflow Tract Area
by Ahmed Elkoumy, Andreas Rück, Won-Keun Kim, Mohamed Abdel-Wahab, Mahmoud Abdelshafy, Ole De Backer, Hesham Elzomor, Christian Hengstenberg, Sameh K. Mohamed, Nawzad Saleh, Shahram Arsang-Jang, Henrik Bjursten, Andrew Simpkin, Christopher U. Meduri and Osama Soliman
J. Clin. Med. 2022, 11(20), 6103; https://doi.org/10.3390/jcm11206103 - 17 Oct 2022
Cited by 2 | Viewed by 1494
Abstract
(1) Background: Hemodynamic assessment of prosthetic heart valves using conventional 2D transthoracic Echocardiography-Doppler (2D-TTE) has limitations. Of those, left ventricular outflow tract (LVOT) area measurement is one of the major limitations of the continuity equation, which assumes a circular LVOT. (2) Methods: This [...] Read more.
(1) Background: Hemodynamic assessment of prosthetic heart valves using conventional 2D transthoracic Echocardiography-Doppler (2D-TTE) has limitations. Of those, left ventricular outflow tract (LVOT) area measurement is one of the major limitations of the continuity equation, which assumes a circular LVOT. (2) Methods: This study comprised 258 patients with severe aortic stenosis (AS), who were treated with the ACURATE neo2. The LVOT area and its dependent Doppler-derived parameters, including effective orifice area (EOA) and stroke volume (SV), in addition to their indexed values, were calculated from post-TAVI 2D-TTE. In addition, the 3D-LVOT area from pre-procedural MDCT scans was obtained and used to calculate corrected Doppler-derived parameters. The incidence rates of prosthesis patient mismatch (PPM) were compared between the 2D-TTE and MDCT-based methods (3) Results: The main results show that the 2D-TTE measured LVOT is significantly smaller than 3D-MDCT (350.4 ± 62.04 mm2 vs. 405.22 ± 81.32 mm2) (95% Credible interval (CrI) of differences: −55.15, −36.09), which resulted in smaller EOA (2.25 ± 0.59 vs. 2.58 ± 0.63 cm2) (Beta = −0.642 (95%CrI of differences: −0.85, −0.43), and lower SV (73.88 ± 21.41 vs. 84.47 ± 22.66 mL), (Beta = −7.29 (95% CrI: −14.45, −0.14)), respectively. PPM incidence appears more frequent with 2D-TTE- than 3D-MDCT-corrected measurements (based on the EOAi) 8.52% vs. 2.32%, respectively. In addition, significant differences regarding the EOA among the three valve sizes (S, M and L) were seen only with the MDCT, but not on 2D-TTE. (4) Conclusions: The corrected continuity equation by combining the 3D-LVOT area from MDCT with the TTE Doppler parameters might provide a more accurate assessment of hemodynamic parameters and PPM diagnosis in patients treated with TAVI. The ACURATE neo2 THV has a large EOA and low incidence of PPM using the 3D-corrected LVOT area than on 2D-TTE. These findings need further confirmation on long-term follow-up and in other studies. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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7 pages, 496 KiB  
Article
N-Terminal of the Prohormone Brain Natriuretic Peptide Predicts Postoperative Cardiogenic Shock Requiring Extracorporeal Membrane Oxygenation
by Piotr Duchnowski
J. Clin. Med. 2022, 11(19), 5493; https://doi.org/10.3390/jcm11195493 - 20 Sep 2022
Cited by 6 | Viewed by 1104
Abstract
Aims: Heart valve surgery is associated with a risk of serious postoperative complications including postoperative cardiogenic shock (described as postcardiotomy shock (PCS)). The indication for extracorporeal membrane oxygenation (ECMO) is cardiogenic shock, which is resistant to optimal causal and pharmacological treatment, including the [...] Read more.
Aims: Heart valve surgery is associated with a risk of serious postoperative complications including postoperative cardiogenic shock (described as postcardiotomy shock (PCS)). The indication for extracorporeal membrane oxygenation (ECMO) is cardiogenic shock, which is resistant to optimal causal and pharmacological treatment, including the supply of catecholamines and/or an intra-aortic balloon pump (IABP). The aim of this study was to assess the usefulness of the selected preoperative biomarkers in the prediction of postoperative cardiogenic shock requiring ECMO in patients undergoing heart valve surgery. Methods: A prospective study was conducted on a group of consecutive patients with significant valvular heart disease that underwent elective valve surgery. The primary endpoint at the intra-hospital follow-up was postoperative cardiogenic shock requiring ECMO. Univariate analysis, followed by multivariate regression analysis, were performed. Results: The study included 610 patients. The primary endpoint occurred in 15 patients. At multivariate analysis, the preoperative N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level (OR 1.022; 95% CI 1.011–1.034; p = 0.001) remained an independent predictor of the primary endpoint. Conclusions: An elevated NT-proBNP level was associated with a higher risk of postoperative cardiogenic shock requiring the use of ECMO. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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Review

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12 pages, 766 KiB  
Review
Aortic Valve Stenosis and Cancer: Problems of Management
by Gloria Santangelo, Silvia Moscardelli, Lucia Barbieri, Andrea Faggiano, Stefano Carugo and Pompilio Faggiano
J. Clin. Med. 2023, 12(18), 5804; https://doi.org/10.3390/jcm12185804 - 06 Sep 2023
Viewed by 989
Abstract
Aortic valve stenosis and malignancy frequently coexist and share the same risk factors as atherosclerotic disease. Data reporting the prognosis of patients with severe aortic stenosis and cancer are limited. Tailoring the correct and optimal care for cancer patients with severe aortic stenosis [...] Read more.
Aortic valve stenosis and malignancy frequently coexist and share the same risk factors as atherosclerotic disease. Data reporting the prognosis of patients with severe aortic stenosis and cancer are limited. Tailoring the correct and optimal care for cancer patients with severe aortic stenosis is complex. Cancer patients may be further disadvantaged by aortic stenosis if it interferes with their treatment by increasing the risk associated with oncologic surgery and compounding the risks associated with cardiotoxicity and heart failure (HF). Surgical valve replacement, transcatheter valve implantation, balloon valvuloplasty, and medical therapy are possible treatments for aortic valve stenosis, but when malignancy is present, the choice between these options must take into account the stage of cancer and associated treatment, expected outcome, and comorbidities. Physical examination and Doppler echocardiography are critical in the diagnosis and evaluation of aortic stenosis. The current review considers the available data on the association between aortic stenosis and cancer and the therapeutic options. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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16 pages, 1385 KiB  
Review
Effects of Probiotics on Intermediate Cardiovascular Outcomes in Patients with Overweight or Obesity: A Systematic Review and Meta-Analysis
by Frank Mayta-Tovalino, Carlos Diaz-Arocutipa, Alejandro Piscoya and Adrian V. Hernandez
J. Clin. Med. 2023, 12(7), 2554; https://doi.org/10.3390/jcm12072554 - 28 Mar 2023
Cited by 2 | Viewed by 1539
Abstract
Background: Clinical trials evaluating the effect of probiotics on cardiovascular intermediate outcomes have been scarce in recent years. We systematically evaluated the efficacy of probiotics on intermediate cardiovascular outcomes in patients with overweight or obesity. Methods: We searched for randomized controlled trials (RCTs) [...] Read more.
Background: Clinical trials evaluating the effect of probiotics on cardiovascular intermediate outcomes have been scarce in recent years. We systematically evaluated the efficacy of probiotics on intermediate cardiovascular outcomes in patients with overweight or obesity. Methods: We searched for randomized controlled trials (RCTs) in four databases (until August 2021) that evaluated the effects of probiotics versus controls on intermediate cardiovascular outcomes. The outcomes were body mass index (BMI), weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. Inverse variance random effects meta-analyses were used. The effects were reported as mean difference (MD), with their 95% confidence intervals (95% CI). The quality of evidence (QoE) was assessed with GRADE (grading of recommendations, assessment, development and evaluations) methodology. Results: A total of 25 RCTs were included (n = 2170), with a range of follow-up from two to six months. Probiotics likely reduced BMI (MD −0.27 kg/m2, 95%CI: −0.35 to −0.19; 17 RCTs; I2 = 26%, QoE: moderate), as well as likely reduced weight (MD −0.61 kg, 95%CI: −0.89 to −0.34; 15 RCTs; I2 = 0%, QoE: moderate), and may have slightly reduce LDL (MD −4.08 mg/dL; 95%CI: −6.99 to −1.17; 9 RCTs; I2 = 87%, QoE: low) in comparison to the controls. However, probiotics had no effect on SBP (MD −0.40 mmHg; 95%CI: −5.04 to 4.25; 7 RCTs; I2 = 100%, QoE: very low), DBP (MD −1.73 mmHg; 95%CI: −5.29 to 1.82; 5 RCTs; I2 = 98%, QoE: very low), glucose (MD −0.07 mg/dL; 95%CI −0.89 to 0.75; I2 = 96%, QoE: very low), HDL (MD −1.83 mg/dL; 95%CI: −4.14 to 2.47; 14 RCTs; I2 = 98%, QoE: very low), or triglycerides (MD −3.29 mg/dL, 95%CI −17.03 to 10.45; 14 RCTs, I2 = 95%, QoE: very low) compared to control arms, and the evidence was very uncertain. Conclusions: In obese or overweight patients, BMI, weight, and LDL were lower in patients who received probiotics compared to those who received controls. Other lipids, glucose, and blood pressure were not affected by the probiotics. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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13 pages, 2500 KiB  
Review
Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?
by Mohamed J. Nsaibia, Anichavezhi Devendran, Eshak Goubaa, Jamal Bouitbir, Romain Capoulade and Rihab Bouchareb
J. Clin. Med. 2022, 11(12), 3331; https://doi.org/10.3390/jcm11123331 - 10 Jun 2022
Cited by 4 | Viewed by 2248
Abstract
Calcific Aortic Valve Disease (CAVD) is a fibrocalcific disease. Lipoproteins and oxidized phospholipids play a substantial role in CAVD; the level of Lp(a) has been shown to accelerate the progression of valve calcification. Indeed, oxidized phospholipids carried by Lp(a) into the aortic valve [...] Read more.
Calcific Aortic Valve Disease (CAVD) is a fibrocalcific disease. Lipoproteins and oxidized phospholipids play a substantial role in CAVD; the level of Lp(a) has been shown to accelerate the progression of valve calcification. Indeed, oxidized phospholipids carried by Lp(a) into the aortic valve stimulate endothelial dysfunction and promote inflammation. Inflammation and growth factors actively promote the synthesis of the extracellular matrix (ECM) and trigger an osteogenic program. The accumulation of ECM proteins promotes lipid adhesion to valve tissue, which could initiate the osteogenic program in interstitial valve cells. Statin treatment has been shown to have the ability to diminish the death rate in subjects with atherosclerotic impediments by decreasing the serum LDL cholesterol levels. However, the use of HMG-CoA inhibitors (statins) as cholesterol-lowering therapy did not significantly reduce the progression or the severity of aortic valve calcification. However, new clinical trials targeting Lp(a) or PCSK9 are showing promising results in reducing the severity of aortic stenosis. In this review, we discuss the implication of lipids in aortic valve calcification and the current findings on the effect of lipid-lowering therapy in aortic stenosis. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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Other

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10 pages, 1078 KiB  
Brief Report
The Effect of Celecoxib on the Progression of Calcific Aortic Valve Disease—Protective or Pathogenic?
by Zachary Vinton, Kevin Wolfe, Jensen Fisher and Amanda Brooks
J. Clin. Med. 2023, 12(7), 2717; https://doi.org/10.3390/jcm12072717 - 05 Apr 2023
Viewed by 1232
Abstract
Calcific aortic valve disease (CAVD) is a debilitating condition for which there are limited therapeutic options aside from valve replacement. As such, it is crucial to explore alternative management strategies for CAVD. Non-steroidal anti-inflammatory drugs (NSAIDs), particularly celecoxib, have been the subject of [...] Read more.
Calcific aortic valve disease (CAVD) is a debilitating condition for which there are limited therapeutic options aside from valve replacement. As such, it is crucial to explore alternative management strategies for CAVD. Non-steroidal anti-inflammatory drugs (NSAIDs), particularly celecoxib, have been the subject of debate in the literature regarding their potential impact on CAVD. We conducted an in-depth analysis of five studies exploring the effect of celecoxib on CAVD and found discrepancies in both methods and results. Our findings suggest that celecoxib may impact the development of this disease via multiple mechanisms, each of which may have different effects on its pathogenesis. We also discovered limited clinical research examining the connection between celecoxib use and CAVD in medical patients. As such, further studies are needed to clarify the role of celecoxib and other NSAIDs in CAVD progression in order to inform future treatment options and clarify their impact on the disease. Full article
(This article belongs to the Special Issue Valvular Heart Disease: From Basic to Clinical Advances)
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