Clinical correlates of circulating small dense low-density lipoproteins in acute infective endocarditis.

BACKGROUND AND AIM: Infective endocarditis (IE) is a complex thrombo-inflammatory disorder, the pathogenesis of which involves a multifaceted interplay between vascular damage and bacterial virulence factors. This study aimed to assess the prognostic role of small dense low-density lipoprotein (sdLDL) cholesterol in patients with IE and its correlation with various disease-related features. METHODS: A cohort of 198 patients with definite IE was included in this study. Clinical, laboratory, and echocardiographic parameters were meticulously analyzed, with a specific focus on comorbidities. sdLDL levels were measured using stored plasma samples obtained upon admission during the acute phase of the disease. RESULTS: The median level of sdLDL was 24 mg/dL [with an interquartile range of 17.9-35.2 mg/dL], and this value showed a statistically significant positive correlation with LDL/HDL cholesterol and triglycerides (p < 0.01 for all). Furthermore, a remarkable inverse correlation between C-reactive protein and D-dimer levels was observed (p < 0.0001). Univariate analysis revealed that patients with sdLDL levels ≤ 24 mg/dL had 2.75 times higher odds of in-hospital mortality (95% Confidence Interval:1.08-6.98, p = 0.031). In addition, nonsurvivors had significantly lower median sdLDL levels (19.7 vs. 26.0 mg/dL, p = 0.041). Lower sdLDL levels were also associated with embolic complications, larger vegetation size, and positive blood cultures for Staphylococci (p = 0.019, p = 0.022, and p < 0.001, respectively). CONCLUSIONS: Low circulating sdLDL levels in the acute phase of IE were significantly correlated with unfavorable clinical outcomes. These results suggest that the sdLDL level may serve as an important marker of disease severity in IE and may represent a link between vascular damage, embolic complications, and disease progression.

Insights into the Inherited Basis of Valvular Heart Disease.

PURPOSE OF REVIEW: Increases in the availability of genetic data and advances in the tools and methods for their analyses have enabled well-powered genetic association studies that have significantly enhanced our understanding of the genetic factors underlying both rare and common valve diseases. Valvular heart diseases, such as congenital valve malformations and degenerative valve lesions, increase the risk of heart failure, arrhythmias, and sudden death. In this review, we provide an updated overview of our current understanding of the genetic mechanisms underlying valvular heart diseases. With a focus on discoveries from the past 5 years, we describe recent insights into genetic risk and underlying biological pathways. RECENT FINDINGS: Recently acquired knowledge around valvular heart disease genetics has provided important insights into novel mechanisms related to disease pathogenesis. Newly identified risk loci associated valvular heart disease mainly regulate the composition of the extracellular matrix, accelerate the endothelial-to-mesenchymal transition, contribute to cilia formation processes, and play roles in lipid metabolism. Large-scale genomic analyses have identified numerous risk loci, genes, and biological pathways associated with degenerative valve disease and congenital valve malformations. Shared risk genes suggest common mechanistic pathways for various valve pathologies. More recent studies have combined cardiac magnetic resonance imaging and machine learning to offer a novel approach for exploring genotype-phenotype relationships regarding valve disease. Progress in the field holds promise for targeted prevention, particularly through the application of polygenic risk scores, and innovative therapies based on the biological mechanisms for predominant forms of valvular heart diseases.

Matched comparison of decellularized homografts and bovine jugular vein conduits for pulmonary valve replacement in congenital heart disease.

For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20-22 mm (± 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR.

Antiphospholipid antibodies in patients with calcific aortic valve stenosis.

OBJECTIVES: The antiphospholipid syndrome is defined by antiphospholipid antibodies (aPL) together with arterial and/or venous thromboembolism and/or obstetric morbidities. aPL are overrepresented in SLE and acute myocardial infarction, but it is unknown whether aPL are associated with calcific aortic valve stenosis (CAVS) in the general population. The prevalence of aPL and other SLE-associated autoantibodies and their impact on aortic valve transcriptomics were therefore determined. METHODS: A total of 233 tricuspid CAVS cases (median age 74, 69% male) and an age- and sex-matched control population were included. aPL were measured as anti-cardiolipin and anti-ß2Glycoprotein-I of IgG/M/A isotypes. Resilient, thickened and calcified aortic valve (AV) tissue derived from five aPL positive and five matched aPL negative CAVS patients undergoing surgical aortic valve replacement were analysed by microarrays. RESULTS: The prevalence of positivity for any aPL (IgG/M/A) in patients with CAVS was 6.4% (95% CI 3.6% - 10.4%: n = 233). aPL IgG was significantly more prevalent in CAVS cases vs controls (4.6% vs 0.6%, P = 0.04). AV tissue from aPL IgG/IgM-positive patients was negatively enriched in pathways related to interferon signalling. One hundred differentially expressed genes could predict local AV CAVS progression with supervised machine learning algorithms. CONCLUSIONS: aPL IgG was more common in CAVS patients compared with matched controls and aPL positivity was associated with altered AV transcriptomics related to local disease progression and interferon pathways. Further studies should aim to establish aPL as a possible risk marker and/or causal factor for CAVS and could offer new precision therapeutic targets.

Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach.

BACKGROUND: Diabetes mellitus (DM) accelerates the progression of aortic stenosis (AS), but how their underlying molecular mechanisms interact is not clear. Moreover, whether DM contributes to clinically relevant sex-differences in AS is unknown. In this work we aim to characterize the sex-specific profile of major pathological mechanisms fundamental to aortic valve (AV) degeneration in AS patients with or without concomitant DM. METHODS: 283 patients with severe AS undergoing surgical valve replacement (27.6% DM, 59.4% men) were recruited. Expression of pathological markers related to AS were thoroughly assessed in AVs and valve interstitial cells (VICs) according to sex and presence of DM. Complementary in vitro experiments in VICs in the presence of high-glucose levels (25 mM) for 24, 48 and 72 h were performed. RESULTS: Oxidative stress and metabolic dysfunction markers were increased in AVs from diabetic AS patients compared to non-diabetic patients in both sexes. However, disbalanced oxidative stress and enhanced inflammation were more predominant in AVs from male AS diabetic patients. Osteogenic markers were exclusively increased in the AVs of diabetic women. Basal characterization of VICs confirmed that oxidative stress, inflammation, calcification, and metabolic alteration profiles were increased in diabetic VICs with sex-specific differences. VICs cultured in hyperglycemic-like conditions triggered inflammatory responses in men, whereas in women rapid and higher production of pro-osteogenic molecules. CONCLUSIONS: DM produces sex-specific pathological phenotypes in AV of AS patients. Importantly, women with diabetes are more prone to develop AV calcification. DM should be considered as a risk factor in AS especially in women.

Clinical and Experimental Study of High Mobility Group Box-2 and Valvular Calcification in Elderly Patients with Degenerative Heart Valve Disease.

INTRODUCTION: The aim of this study was to investigate the relationship between the high mobility group box-2 (HMGB2) and valve calcification in senile degenerative heart valve disease (SDHVD). METHODS: According to the echocardiographic results, patients with calcified heart valves were used as the experimental group and patients without calcified heart valves were used as the control group; blood was drawn for testing, and serum levels of HMGB2 were measured by an enzyme-linked immunosorbent assay. Human heart valve interstitial cells (hVICs) cultured in vitro were randomly divided into two groups. The calcification group was cultured with a medium containing calcification induction solution and cells were induced on days 1, 3, and 5, and the control group was cultured with a standard medium. Expression of bone morphogenetic protein 4 (BMP-4) and HMGB2 in both groups was detected by Western blot. RT-PCR was performed to detect the expression of the HMGB2 gene during calcification. The hVICs were cultured in vitro for 4 days with different concentrations of exogenous HMGB2 (0.01 µg/mL, 0.1 µg/mL, 1 µg/mL, 2 µg/mL), while the control group was cultured with a standard medium and the expression of BMP-4 and NF-κB P65 was detected by Western blot. RESULTS: The serum level of HMGB2 was 7.90 (5.92, 12.39) µg/L, higher than that of 7.06 (5.06, 9.73) µg/L in the valve calcification group in elderly patients with degenerative valve disease (p = 0.005); the differences were statistically significant. In in vitro experiments, the cellular calcification protein BMP-4 and the HMGB2 protein were higher in the calcification group compared to the control group (p < 0.05). Exogenous stimulation of hVICs with HMGB2 was able to upregulate the expression of BMP-4 and NF-κB P65 (p < 0.05). CONCLUSIONS: HMGB2 is correlated with valvular calcification in senile degenerative heart valve disease. The HMGB2 protein may promote the process of SDHVD valve calcification by activating the NF-κB pathway and upregulating the expression of BMP-4.

Patient preferences for heart valve disease intervention.

BACKGROUND: This study aimed to determine how patients trade-off the benefits and risks of two different types of procedures used to treat heart valve disease (HVD). It also aimed to determine patients' preferences for HVD treatments (predicted uptake) and the relative importance of each treatment attribute. METHODS: A discrete choice experiment (DCE) was conducted in Australia and Japan with patients who required a heart valve procedure. Patients were stratified into three categories: no prior procedure experience, minimally invasive procedure experience and invasive procedure experience. DCE attributes included risk of mortality; risk of stroke; needing dialysis; needing a new pacemaker; valve durability; independence 1 month after surgery; and out-of-pocket expenses. Participants chose between two hypothetical labelled approaches to therapy ('invasive procedure' and 'minimally invasive procedure'), with a separate opt-out included. A mixed multinomial logit model was used to analyse preferences. RESULTS: The DCE was completed by 143 Australian and 206 Japanese patients. Both populations demonstrated an overall preference for the minimally invasive procedure over the invasive procedure. All attributes tested significantly predicted choice and were important to patient decision-making. However, patients' choices were most influenced by the durability of the valve and the likelihood of independence postprocedure, irrespective of their prior procedure experience. Differences in preference were observed between Australian and Japanese patients; valve durability was the most important attribute among Australian patients, while Japanese patients emphasised regaining independence postsurgery. Risk of mortality was less important relative to other key attributes in Japan; however, it remained significant to the model. CONCLUSIONS: HVD patients prefer a minimally invasive procedure over an invasive procedure, irrespective of prior treatment experience. Key attributes contributing to treatment preferences are valve durability and faster recovery. These results can be used to help inform healthcare decision-makers about what features of heart valve procedures patients value most. PATIENT AND PUBLIC CONTRIBUTION: People with lived experience of HVD were included in multiple stages of the design phase of this research. First, patients and doctors were consulted by taking part in qualitative interviews. The qualitative interviews helped inform which treatment attributes to include in the DCE based on what was important to those with lived experience and those who help make treatment decisions on behalf of patients. Qualitative interview participants also assisted with the framing of questions in the online survey to ensure the terminology was patient-friendly and relevant to those with lived experience. Following qualitative interviews, the DCE attribute list was agreed on in expert consultation with a steering committee, which included patient representatives and treating physicians (interventional cardiologists, cardiothoracic surgeons). The survey was also pilot tested with a small sample of patients and minor adjustments were made to the wording to ensure it was appropriate and meaningful to those with lived experience of HVD.

Outcomes Following Triple Cardiac Valve Surgery Over 17-years: A Multicentre Population-Linkage Study.

INTRODUCTION: Studies have reported increasing triple valve surgery (TVS, defined as concomitant aortic, mitral and tricuspid valves surgery) incidence and improved postoperative survival. The epidemiology and outcome of TVS is not known in Australia. METHODS: From the Admission-Patient-Data-Collection registry, all New South Wales residents who underwent cardiac valve surgery between 1 July 2001 and 31 December 2018 were identified, with cause-specific mortality tracked from the death registry. RESULTS: Triple valve surgery comprised 1.2% (347/28,667 cases) of all valvular surgeries. Volumes rose from eight cases-per-annum in 2002 to a peak of 37 in 2012, and between 23 and 30 cases-per-annum since. Mean (±SD) age of study cohort (n=340 persons) was 68.2±15.2 years (50% male); 20.3% had concomitant coronary-artery-bypass-surgery (males vs females: 29.4% vs 11.2%, p<0.001). Main surgery on aortic and mitral valves was replacement (95.9% and 70.6% respectively). Tricuspid valve annuloplasty was performed in 90.6% of patients. Cumulative in-hospital, 180-day, and total mortality (mean follow-up=4.9±4.0 yrs) was 7.4%, 11.8% and 42.6%, respectively. Heart failure (24.0% in-hospital, 22.5% post-discharge) and sepsis (24.0% in-hospital, 20.0% post-discharge) were the main cause-specific deaths. There was no in-hospital stroke-related death. Age (median >72 yrs; hazard ratio [HR]=1.95, 95%CI=1.37-2.79), malignancy (HR=6.35, 95%CI=2.21-18.26), heart failure (HR=1.79, 95%CI=1.25-2.57) and chronic kidney disease (CKD) (HR=2.21, 95%CI=1.39-3.51) (all p<0.005) were independent predictors during intermediate-term follow-up. CONCLUSIONS: Triple valve surgery remains rare in Australia and is associated with high mortality. Multi-centred collaboration and access to comprehensive clinical data are required to identify the drivers of poor outcome.

Single Coronary Artery with Severe Coronary Artery Disease and Aortic Valve Disease.

Coronary artery malformations are rare in the clinic. When with severe atherosclerosis, there is an additional risk. Specific coronary artery malformations, such as single right coronary artery, may be involved in the arteriosclerotic process, especially when accompanied by significant coronary artery tortuosity. It will remarkably challenge the treatment. We report a case of a single right coronary artery with severe stenosis and heart valve disease. She successfully underwent coronary artery bypass grafting and aortic valve replacement.

[Detection method of early heart valve diseases based on heart sound features].

Heart valve disease (HVD) is one of the common cardiovascular diseases. Heart sound is an important physiological signal for diagnosing HVDs. This paper proposed a model based on combination of basic component features and envelope autocorrelation features to detect early HVDs. Initially, heart sound signals lasting 5 minutes were denoised by empirical mode decomposition (EMD) algorithm and segmented. Then the basic component features and envelope autocorrelation features of heart sound segments were extracted to construct heart sound feature set. Then the max-relevance and min-redundancy (MRMR) algorithm was utilized to select the optimal mixed feature subset. Finally, decision tree, support vector machine (SVM) and k-nearest neighbor (KNN) classifiers were trained to detect the early HVDs from the normal heart sounds and obtained the best accuracy of 99.9% in clinical database. Normal valve, abnormal semilunar valve and abnormal atrioventricular valve heart sounds were classified and the best accuracy was 99.8%. Moreover, normal valve, single-valve abnormal and multi-valve abnormal heart sounds were classified and the best accuracy was 98.2%. In public database, this method also obtained the good overall accuracy. The result demonstrated this proposed method had important value for the clinical diagnosis of early HVDs.

Transcatheter Mitral Valve Replacement After Surgical Repair or Replacement: Comprehensive Midterm Evaluation of Valve-in-Valve and Valve-in-Ring Implantation From the VIVID Registry.

BACKGROUND: Mitral valve-in-valve (ViV) and valve-in-ring (ViR) are alternatives to surgical reoperation in patients with recurrent mitral valve failure after previous surgical valve repair or replacement. Our aim was to perform a large-scale analysis examining midterm outcomes after mitral ViV and ViR. METHODS: Patients undergoing mitral ViV and ViR were enrolled in the Valve-in-Valve International Data Registry. Cases were performed between March 2006 and March 2020. Clinical endpoints are reported according to the Mitral Valve Academic Research Consortium (MVARC) definitions. Significant residual mitral stenosis (MS) was defined as mean gradient ≥10 mm Hg and significant residual mitral regurgitation (MR) as ≥ moderate. RESULTS: A total of 1079 patients (857 ViV, 222 ViR; mean age 73.5±12.5 years; 40.8% male) from 90 centers were included. Median STS-PROM score 8.6%; median clinical follow-up 492 days (interquartile range, 76-996); median echocardiographic follow-up for patients that survived 1 year was 772.5 days (interquartile range, 510-1211.75). Four-year Kaplan-Meier survival rate was 62.5% in ViV versus 49.5% for ViR (P<0.001). Mean gradient across the mitral valve postprocedure was 5.7±2.8 mm Hg (≥5 mm Hg; 61.4% of patients). Significant residual MS occurred in 8.2% of the ViV and 12.0% of the ViR patients (P=0.09). Significant residual MR was more common in ViR patients (16.6% versus 3.1%; P<0.001) and was associated with lower survival at 4 years (35.1% versus 61.6%; P=0.02). The rates of Mitral Valve Academic Research Consortium-defined device success were low for both procedures (39.4% total; 32.0% ViR versus 41.3% ViV; P=0.01), mostly related to having postprocedural mean gradient ≥5 mm Hg. Correlates for residual MS were smaller true internal diameter, younger age, and larger body mass index. The only correlate for residual MR was ViR. Significant residual MS (subhazard ratio, 4.67; 95% CI, 1.74-12.56; P=0.002) and significant residual MR (subhazard ratio, 7.88; 95% CI, 2.88-21.53; P<0.001) were both independently associated with repeat mitral valve replacement. CONCLUSIONS: Significant residual MS and/or MR were not infrequent after mitral ViV and ViR procedures and were both associated with a need for repeat valve replacement. Strategies to improve postprocedural hemodynamics in mitral ViV and ViR should be further explored.

Targeted Screening for Chronic Q Fever, the Netherlands.

Early detection of and treatment for chronic Q fever might prevent potentially life-threatening complications. We performed a chronic Q fever screening program in general practitioner practices in the Netherlands 10 years after a large Q fever outbreak. Thirteen general practitioner practices located in outbreak areas selected 3,419 patients who had specific underlying medical conditions, of whom 1,642 (48%) participated. Immunofluorescence assay of serum showed that 289 (18%) of 1,642 participants had a previous Coxiella burnetii infection (IgG II titer >1:64), and 9 patients were suspected of having chronic Q fever (IgG I y titer >1:512). After medical evaluation, 4 of those patients received a chronic Q fever diagnosis. The cost of screening was higher than estimated earlier, but the program was still cost-effective in certain high risk groups. Years after a large Q fever outbreak, targeted screening still detected patients with chronic Q fever and is estimated to be cost-effective.

Clinically Optimal Neuropsychological Tests for Postoperative Cognitive Dysfunction in Heart Valve Surgeries.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is widely recognized and reported, but the lack of a uniform definition makes it difficult to evaluate its clinical impact. The aim of this study is to establish the optimal neuropsychological tests and definition of POCD relevant to clinical outcomes in heart valve surgeries.Methods and Results: Between June 2015 and December 2019, 315 patients undergoing elective heart valve surgeries (age ≥65 years) were enrolled. The Mini-Mental Status Examination, Montreal Cognitive Assessment (MoCA), and the Trail Making Test A and B were performed to evaluate cognitive function. Clinical endpoints were defined as readmission and death. The postoperative readmission and death rate were 17% and 3% (54/315 and 8/315; follow-up 266-1,889 days). By multivariable Cox hazard analysis, Short Physical Performance Battery (adjusted hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.49-0.98, P=0.001), MoCA change rate (adjusted HR: 0.64, 95% CI: 0.01-1.22, P=0.024), and intensive care unit stay (adjusted HR: 0.55%, 95% CI: 0.99-1.12, P=0.054) were detected as independent risk factors for combined events. The cutoff value was -12% in the change rate of MoCA. CONCLUSIONS: MoCA was the only neuropsychological test that predicted the clinical impact on complex events and has the potential to define POCD.

An Adapted Neural-Fuzzy Inference System Model Using Preprocessed Balance Data to Improve the Predictive Accuracy of Warfarin Maintenance Dosing in Patients After Heart Valve Replacement.

BACKGROUND: Tailoring warfarin use poses a challenge for physicians and pharmacists due to its narrow therapeutic window and substantial inter-individual variability. This study aimed to create an adapted neural-fuzzy inference system (ANFIS) model using preprocessed balance data to improve the predictive accuracy of warfarin maintenance dosing in Chinese patients undergoing heart valve replacement (HVR). METHODS: This retrospective study enrolled patients who underwent HVR between June 1, 2012, and June 1, 2016, from 35 centers in China. The primary outcomes were the mean difference between predicted warfarin dose by ANFIS models and actual dose and the models' predictive accuracy, including the ideal predicted percentage, the mean absolute error (MAE), and the mean squared error (MSE). The eligible cases were divided into training, internal validation, and external validation groups. We explored input variables by univariate analysis of a general linear model and created two ANFIS models using imbalanced and balanced training sets. We finally compared the primary outcomes between the imbalanced and balanced ANFIS models in both internal and external validation sets. Stratified analyses were conducted across warfarin doses (low, medium, and high doses). RESULTS: A total of 15,108 patients were included and grouped as follows: 12,086 in the imbalanced training set; 2820 in the balanced training set; 1511 in the internal validation set; and 1511 in the external validation set. Eight variables were explored as predictors related to warfarin maintenance doses, and imbalanced and balanced ANFIS models with multi-fuzzy rules were developed. The results showed a low mean difference between predicted and actual doses (< 0.3 mg/d for each model) and an accurate prediction property in both the imbalanced model (ideal prediction percentage, 74.39-78.16%; MAE, 0.37 mg/daily; MSE, 0.39 mg/daily) and the balanced model (ideal prediction percentage, 73.46-75.31%; MAE, 0.42 mg/daily; MSE, 0.43 mg/daily). Compared to the imbalanced model, the balanced model had a significantly higher prediction accuracy in the low-dose (14.46% vs. 3.01%; P < 0.001) and the high-dose warfarin groups (34.71% vs. 23.14%; P = 0.047). The results from the external validation cohort confirmed this finding. CONCLUSIONS: The ANFIS model can accurately predict the warfarin maintenance dose in patients after HVR. Through data preprocessing, the balanced model contributed to improved prediction ability in the low- and high-dose warfarin groups.

The role of the extracellular matrix in the development of heart valve disease: Underestimation or undercomprehension?

The function of metalloproteinases of the extracellular matrix and their inhibitors has emerged with a crucial role in valve diseases. Both the expression of matrix metalloproteinases and their inhibitors are susceptible to modification in patients with severe mitral insufficiency. This process is due to substantial changes in the collagen structure during mechanical stress on the mitral valve leaflets. Several studies have measured the level of deformation of the mitral leaflets with the use of the finite element analysis method by establishing the stiffness of the cellular and extracellular elements of the mitral valve leaflets. Evidence suggested the possible underestimation of the stiffness of the leaflets. This implies greater stress on the components of the extracellular matrix in the circumferential and radial strains that involve the mitral leaflets during chronic regurgitation. The remodeling process during mechanical stress phenomena involves both the cellular compartment and the extracellular matrix and can be adaptive or maladaptive as showed in patients who receive a pulmonary autograft to replace the diseased aortic valve. However, adaptive remodeling can be driven using resorbable polymers that interfere with the extracellular matrix. Further investigation is required for the understanding of the mechanisms that determine the structural changes of the extracellular matrix and to prevent them.

Endocarditis-TR: Diagnosis, treatment, and prognosis of the infective endocarditis patients admitting tertiary centres of Turkey.

BACKGROUND: Infective endocarditis (IE) is still a significant cause of morbidity and mortality among cardiovascular diseases. ENDOCARDITIS-TR study aims to evaluate the compliance of the diagnostic and therapeutic methods being used in Turkey with current guidelines. METHODS: The ENDOCARDITIS-TR trial is a multicentre, prospective, observational study consisting of patients admitted to tertiary centres with a definite diagnose of IE. In addition to the demographic, clinical, microbiological, and echocardiographic findings of the patients, adverse events, indications for surgery, and in-hospital mortality were recorded during a 2-year time interval. RESULTS: A total of 208 IE patients from 7 tertiary centres in Turkey were enrolled in the study. The study population included 125 (60.1%) native valve IE (NVE), 65 (31.3%) prosthetic IE (PVIE), and 18 (8.7%) intracardiac device-related IE (CDRIE). One hundred thirty-five patients (64.9%) were culture positive, and the most frequent pathogenic agent was methicillin-susceptible Staphylococcus aureus (MSSA) (18.3%). Among 155 (74.5%) patients with an indication for surgery, only 87 (56.1%) patients underwent surgery. The all-cause mortality rate was 29.3% in-hospital follow-up. Multivariable Cox regression analysis revealed that absence of surgery when indicated (HR: 3.29 95% CI: 0.93-11.64 p = 0.05), albumin level at admission (HR: 0.46 95% CI: 0.29-0.73 P < 0.01), abscess formation (HR: 2.11 95% CI: 1.01-4.38 p = 0.04) and systemic embolism (HR: 1.78 95% CI: 1.05-3.02 p = 0.03) were ascertained independent predictors of in-hospital all-cause mortality. DISCUSSION: The short-term results of the ENDOCARDITIS-TR trial showed the high frequency of staphylococcal IE, relatively high in-hospital mortality rates, shortage of surgical treatment despite guideline-based surgical indications and low usage of novel imaging techniques. The results of this study will provide a better insight to physicians in respect to their adherence to clinical practice guidelines.

Balloon-Expandable Versus Self-Expanding Transcatheter Aortic Valve Replacement: A Propensity-Matched Comparison From the FRANCE-TAVI Registry.

BACKGROUND: No randomized study powered to compare balloon expandable (BE) with self expanding (SE) transcatheter heart valves (THVs) on individual end points after transcatheter aortic valve replacement has been conducted to date. METHODS: From January 2013 to December 2015, the FRANCE-TAVI nationwide registry (Registry of Aortic Valve Bioprostheses Established by Catheter) included 12 141 patients undergoing BE-THV (Edwards, n=8038) or SE-THV (Medtronic, n=4103) for treatment of native aortic stenosis. Long term mortality status was available in all patients (median 20 months; interquartile range, 14 to 30). Patients treated with BE-THV (n=3910) were successfully matched 1:1 with 3910 patients treated with SE-THV by using propensity score (25 clinical, anatomical, and procedural variables) and by date of the procedure (within 3 months). The first coprimary outcome was ≥ moderate occurrence of paravalvular regurgitation or in-hospital mortality, or both. The second coprimary outcome was 2-year all-cause mortality. RESULTS: In propensity-matched analyses, the incidence of the first coprimary outcome was higher with SE-THV (19.8%) compared with BE-THV (11.9%; relative risk, 1.68 [95% CI, 1.46-1.91]; P<0.0001). Each component of the outcome was also higher in patients receiving SE-THV: ≥ moderate paravalvular regurgitation (15.5% versus 8.3%; relative risk, 1.90 [95% CI, 1.63-2.22]; P<0.0001) and in hospital mortality (5.6% versus 4.2%; relative risk, 1.34 [95% CI, 1.07-1.66]; P=0.01). During follow up, all cause mortality occurred in 899 patients treated with SE-THV (2-year mortality, 29.8%) and in 801 patients treated with BE-THV (2-year mortality, 26.6%; hazard ratio, 1.17 [95% CI, 1.06-1.29]; P=0.003). Similar results were found using inverse probability of treatment weighting using propensity score analysis. CONCLUSION: The present study suggests that use of SE-THV was associated with a higher risk of paravalvular regurgitation and higher in-hospital and 2-year mortality compared with use of BE-THV. These data strongly support the need for a randomized trial sufficiently powered to compare the latest generation of SE-THV and BE-THV. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT01777828.

Update in carcinoid heart disease - the heart of the matter.

Carcinoid heart disease (CHD) is a paraneoplastic cardiac manifestation occurring in patients with carcinoid syndrome (CS) and advanced neuroendocrine malignancy. In about 20-40% of patients with CS, chronic exposure to tumor-released circulating vasoactive peptides typically results in right-sided valvular fibrosis leading to valve dysfunction and right heart failure. CHD remains a significant cause of morbidity and mortality. The management of patients with CHD is complex, as both the systemic malignant disease and the heart involvement have to be addressed. Early diagnosis and timely surgical intervention in selected patients are of utmost importance and offer a survival benefit. In patients with advanced carcinoid heart disease, valve replacement surgery is the most effective option to alleviate cardiac symptoms and contribute to survival outcomes. A collaboration of a multidisciplinary team in centers with experience is required to provide optimal patient management. Here, we review the current literature regarding CHD presentation, pathophysiology, diagnostic tools, and available treatment strategies.

Temporal outcomes of transcatheter mitral valve replacement in native mitral valve disease with annular calcification.

BACKGROUND: Surgical intervention in patients with native mitral disease due to severe mitral annular calcification (MAC) carries significant risk. Transcatheter mitral valve replacement (TMVR) using balloon-expandable aortic transcatheter heart valve (THV) in MAC had emerged as alternative treatment. OBJECTIVES: We aim to study the temporal change in clinical outcomes of the procedure at a single center. METHODS: We retrospectively studied 23 patients who underwent TMVR in MAC at Mayo Clinic from January, 14, 2014 to March, 15, 2019. Cases were divided into early (n = 11) and late (n = 12) experience. The primary end point was 30-day all-cause mortality. The secondary end points were immediate technical success, 30-day procedural success, and 1-year all-cause mortality. RESULTS: Mean age of patients was 75.2 ± 8.9 years and 17 (74.0%) were female. Median STS score for 30-day mortality was 8 (Interquartile range 4.3-13.4) for the entire population. Immediate technical success was achieved in 21 out of 23 patients (two failures in the early experience were related to tamponade and procedural death). Thirty-day procedural success was higher in the late experience (10 out of 12 patients) compared to early experience (5 out of 11 patients, p = .06). Four deaths in the first 30-days were observed in the early experience while all patients survived to hospital discharge in the late experience (p = .01). CONCLUSIONS: Procedural success and 30-day survival of transcatheter mitral valve replacement in severe mitral annular calcification procedure using balloon-expandable aortic prosthesis had improved over the years. This is likely attributed to significant advancement in procedural planning, valve design, and techniques.

Aortic Valve Stenosis: From Basic Mechanisms to Novel Therapeutic Targets.

Aortic valve stenosis is the most prevalent heart valve disease worldwide. Although interventional treatment options have rapidly improved in recent years, symptomatic aortic valve stenosis is still associated with high morbidity and mortality. Calcific aortic valve stenosis is characterized by a progressive fibro-calcific remodeling and thickening of the aortic valve cusps, which subsequently leads to valve obstruction. The underlying pathophysiology is complex and involves endothelial dysfunction, immune cell infiltration, myofibroblastic and osteoblastic differentiation, and, subsequently, calcification. To date, no pharmacotherapy has been established to prevent aortic valve calcification. However, novel promising therapeutic targets have been recently identified. This review summarizes the current knowledge of pathomechanisms involved in aortic valve calcification and points out novel treatment strategies.