Left Ventricular Remodeling in Patients with Low Flow Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.

Low-flow (LF) aortic stenosis (AS) is common among the elderly and associated with worse outcomes than AS with normal stroke volume. It is unknown whether left ventricular (LV) remodeling identifies patients with LF AS at higher risk of complications. LV remodeling was evaluated in 463 patients with severe LF AS referred for transcatheter aortic valve replacement (TAVR) and classified as adaptive (normal geometry and concentric remodeling) or maladaptive (concentric and eccentric hypertrophy) using American Society of Echocardiography sex-specific criteria. Of these, the 390 who underwent TAVR were followed for the endpoints of heart failure (HF) hospitalization and all-cause mortality. The mean patients age was 79 (74.5-84) years. LV remodeling was adaptive in 57.4% (62 normal geometry, 162 concentric remodeling) and maladaptive in 42.6% (127 concentric hypertrophy, 39 eccentric hypertrophy). During a median follow-up of 3 years, 45 patients (11.5%) were hospitalized for HF and 73 (18.7%) died. After adjustment for widely used echocardiographic parameters, maladaptive remodeling was independently associated with HF hospitalization and death (adjusted HR 1.75, CI 1.03-3.00). There was no significant difference between men and women in the association of maladaptive LV remodeling with the composite outcome (p=0.40 for men and p=0.06 for women). In conclusion, in patients with LF AS, maladaptive LV remodeling prior to TAVR is independently associated with higher incidences of post-procedural HF rehospitalization and death in both men and women. Assessment of LV remodeling has prognostic value over and above LVEF and may improve risk stratification for patients with LF AS.

Severe functional mitral regurgitation and cardiogenic shock after transcatheter aortic valve replacement.

An 83-year-old woman with symptomatic severe aortic stenosis was referred for transcatheter aortic valve replacement. Diagnostic left heart catheterization documented diffuse 3-vessel coronary artery disease.

Do we still need intra-procedural TTE during Transcatheter aortic valve replacement? A high volume, single center experience.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has undergone significant advances in recent years, with the development of improved pre-planning tools and devices. These advances have led to a reduction in the rate of paravalvular leak (PVL), a complication that is associated with poor outcomes even when mild. As some centers around the world are moving to solely fluoroscopy-focused implantation, we aimed to describe the clinical impact of intra-procedural transthoracic echocardiography (TTE) during TAVI in a high volume hospital. METHODS: Observational study during a 3-month period. A limited TTE examination was performed immediately after deployment to assess the existence of PVL and grade its severity. Complete TTE was performed a day after the procedure. In case of ≥mild PVL after valve deployment, a decision was made according to the severity of the PVL, patient anatomy and extent of annular calcification to preform balloon post-dilation. If done, an additional limited TTE was performed to assess possible complication and the degree of PVL post dilatation. RESULTS: 115 patient were included in the study. Intra-procedural TTE identified 16 patients (14 %) with at least mild PVL, three of them with moderate (3 %). Post balloon dilatation was performed in 10 patients (9 % of the cohort) with significant improvement in the degree of PVL. CONCLUSION: Intra-procedural TTE immediately after TAVI deployment can accurately identify PVL, allowing operators to perform post balloon dilatation with improvement in early echocardiographic results. Our findings support the routine use of TTE during procedures, without relying solely on fluoroscopy.

Right coronary artery obstruction following transcatheter aortic valve replacement by aortic valve mass.

A 93-year-old woman with symptomatic severe aortic stenosis and normal biventricular function was referred for transcatheter aortic valve replacement (TAVR) evaluation. Cardiac computed tomography revealed safe coronary heights and multiple large calcified mobile mass-like structures attached to the aortic valve (AV), confirmed also by transesophageal echocardiography, which were thought to be prominent Lambl's excrescences.

Management of Systemic Inflammatory Response Syndrome After Cardiovascular Interventions. Diagnostic, Prognostic, and Therapeutic Implications.

A substantial number of patients may experience systemic inflammatory response syndrome (SIRS) and related adverse events after transcatheter aortic valve implantation and endovascular aortic aneurysm repair. Although a clear etiology has not been established, endothelial disruption and tissue-ischemic response secondary to the foreign material may represent the trigger events. A latency period (0 to 48 hours) may occur between the initial injury and onset of symptoms mirroring an initial local response followed by a systemic response. Clinical presentation can be mild or severe depending on external triggers and characteristics of the patient. Diagnosis is challenging because it simulates an infection, but lack of response to antibiotics, negative cultures are supportive of SIRS. Increased in-hospital stay, readmissions, major cardiovascular events, and reduced durability of the device used are the main complications. Treatment includes non-steroidal anti-inflammatory drugs or corticosteroids. In conclusion, further studies are warranted to fully explore pathophysiologic mechanisms underpinning SIRS and the possibility of enhancing device material immune compatibility to reduce the inflammatory reaction of the host tissue.

Transcatheter aortic valve replacement outcomes in patients with low-flow very low-gradient aortic stenosis.

AIMS: In patients with severe aortic stenosis (AS), low-flow low-gradient (LG) is a known predictor of worse outcomes. However, very LG may represent a distinct population with further cardiac dysfunction. It is unknown whether this population benefits from transcatheter aortic valve replacement (TAVR). We aimed to describe the patient characteristics and clinical outcomes of low-flow very LG severe AS. METHODS AND RESULTS: This single-centre study included all patients with low-flow severe AS between 2019 and 2021. Patients were divided into groups with very LG [mean pressure gradient (MPG) ≤ 20 mmHg], LG (20 < MPG < 40 mmHg), and high-gradient (HG) (MPG ≥ 40 mmHg). Composite endpoint of all-cause mortality and heart failure rehospitalization was compared. A total of 662 patients [very LG 130 (20%); LG 339 (51%); HG 193 (29%)] were included. Median follow-up was 12 months. Very LG cohort had a higher prevalence of comorbid conditions with lower left ventricular ejection fraction (45% vs. 57% vs. 60%; P < 0.001). There was a graded increase in the risk of composite endpoint in the lower MPG strata (P < 0.001). Among those who underwent TAVR, very LG was an independent predictor of the composite endpoint (adjusted HR 2.42 [1.29-4.55]). While LG and HG cohorts had decreased risk of composite endpoint after TAVR compared with conservative management, very LG was not associated with risk reduction (adjusted HR 0.69 [0.35-1.34]). CONCLUSION: Low-flow very LG severe AS represents a distinct population with significant comorbidities and worse outcomes. Further studies are needed to evaluate the short- and long-term benefits of TAVR in this population.

Echo HALT: do we really need a cardiac CT?

Leaflet thrombosis is usually an incidental finding and Cardiac CT is the gold standard for its diagnosis, but the classic features of hypoattenuation leaflet thickening (HALT) and hypoattenuation affecting motion (HAM) can also be seen on echocardiography and more specifically on trans-esophageal echocardiography. We describe a case of transcatheter aortic valve thrombosis where both the diagnosis and treatment were based exclusively on the echocardiographic evaluation, without the need of cardiac CT, with good outcome for the patient.

Beyond the Cardiovascular Effects of Glucagon-like Peptide-1 Receptor Agonists: Body Slimming and Plaque Stabilization. Are New Statins Born?

Atherosclerosis is a chronic inflammatory disease characterized by lipid and inflammatory cell deposits in the inner layer of large- and medium-sized elastic and muscular arteries. Diabetes mellitus (DM) significantly increases the risk of cardiovascular diseases and the overall and cardiovascular mortality, and it is a pro-atherogenic factor that induces atherosclerosis development and/or accelerates its progression through a multifactorial process. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of drugs, belonging to the armamentarium to fight type 2 DM, that have shown robust reductions in atherosclerotic events and all-cause mortality in all studies. Preclinical studies have shown that GLP-1RAs play a role in the immunomodulation of atherosclerosis, affecting multiple pathways involved in plaque development and progression. In this review, we wanted to explore the translational power of such preclinical studies by analyzing the most recent clinical trials investigating the atheroprotective effect of GLP-1RAs.

Prognostic Implication of Pulmonary Hypertension in Low-Flow Low-Gradient Aortic Stenosis After Transcatheter Aortic Valve Replacement.

Prognostic implications of pulmonary hypertension (PH) in low-flow low-gradient (LG) aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR) remains unexplored. We aimed to investigate the impact of baseline and changes in PH after TAVR. In this single-center retrospective study, we included patients who underwent TAVR for low-flow LG AS. Patients were categorized into 2 groups: baseline pulmonary artery systolic pressure (PASP) <46 mm Hg (no-to-mild PH) and PASP ≥46 mm Hg (moderate-to-severe PH). On the basis of changes in PASP after TAVR, patients were stratified into increased (ΔPASP ≥ + 5 mm Hg), no change (-4 to +4 mm Hg), and decreased (≤ -5 mm Hg) groups. Primary end point was a composite of all-cause mortality and heart failure rehospitalization. In total, 210 patients were included, 148 in the no-to-mild PH group and 62 in the moderate-to-severe PH group. Median follow-up was 13.2 months. The moderate-to-severe PH group was at an increased risk of composite end point (adjusted hazard ratio [HR] 3.5, 95% confidence interval [CI] 1.8 to 6.9), all-cause mortality (HR 2.4, 95% CI 1.1 to 5.6), and heart failure rehospitalization (HR 8.3, 95% CI 2.9 to 23.7). There were no differences in clinical outcomes among those with increased (32%), no change (28%), and decreased (39%) PASP after TAVR. In conclusion, moderate-to-severe PH at baseline is an independent predictor of worse clinical outcomes in patients with low-flow LG AS who undergo TAVR, and this cohort of patients do not seem to derive the benefits of postoperative reduction of PASP.

Gut Microbiota Composition and Cardiovascular Disease: A Potential New Therapeutic Target?

A great deal of evidence has revealed an important link between gut microbiota and the heart. In particular, the gut microbiota plays a key role in the onset of cardiovascular (CV) disease, including heart failure (HF). In HF, splanchnic hypoperfusion causes intestinal ischemia resulting in the translocation of bacteria and their metabolites into the blood circulation. Among these metabolites, the most important is Trimethylamine N-Oxide (TMAO), which is responsible, through various mechanisms, for pathological processes in different organs and tissues. In this review, we summarise the complex interaction between gut microbiota and CV disease, particularly with respect to HF, and the possible strategies for influencing its composition and function. Finally, we highlight the potential role of TMAO as a novel prognostic marker and a new therapeutic target for HF.

Effect of acute CORticosteroids on conduction defects after Transcatheter Aortic Valve Implantation: the CORTAVI study.

AIMS: Conduction abnormalities, requiring a permanent pacemaker (PPM), are the most common electrical complications after transcatheter aortic valve implantation (TAVI). The exact mechanism for conduction system defects is not yet clear. The local inflammatory process and edema are thought to play a role in the development of electrical disorders. Corticosteroids are effective anti-inflammatory and antiedematous agents. We aim to investigate the potential protective effect of corticosteroids on conduction defects after TAVI. METHODS: This is a retrospective study of a single center. We analyzed 96 patients treated with TAVI. Thirty-two patients received oral prednisone 50 mg for 5 days after the procedure. This population was compared with the control group. All patients were followed up after 2 years. RESULTS: Of the 96 patients included, 32 (34%) were exposed to glucocorticoids after TAVI. No differences in age, preexisting right bundle branch block or left bundle branch block, or valve type were seen among patients exposed to glucocorticoids versus those who were unexposed. We observed no significant differences between the two groups in the overall frequency of new PPM implantations during hospitalization (12% vs. 17%, P  = 0.76). The incidence of atrioventricular block (AVB) (STx 9% vs. non-STx 9%, P  = 0.89), right bundle branch block (STx 6% vs. non-STx 11%, P  = 0.71), and left bundle branch block (STx 34% vs. non-STx 31%, P  = 0.9) was not significantly different between the STx and non-STx groups. At 2 years after TAVI, none of the patients had implanted PPM or had severe arrhythmias documented by 24-h Holter ECG or cardiac examination. CONCLUSION: Oral prednisone treatment does not appear to significantly reduce the incidence of AVB requiring acute PPM implantation after TAVI.

Coronary Obstruction during Valve-in-Valve Transcatheter Aortic Valve Replacement: Pre-Procedural Risk Evaluation, Intra-Procedural Monitoring, and Follow-Up.

Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) is emerging as an effective treatment for patients with symptomatically failing bioprosthetic valves and a high prohibitive surgical risk; a longer life expectancy has led to a higher demand for these valve reinterventions due to the increased possibilities of outliving the bioprosthetic valve's durability. Coronary obstruction is the most feared complication of valve-in-valve (ViV) TAVR; it is a rare but life-threatening complication and occurs most frequently at the left coronary artery ostium. Accurate pre-procedural planning, mainly based on cardiac computed tomography, is crucial to determining the feasibility of a ViV TAVR and to assessing the anticipated risk of a coronary obstruction and the eventual need for coronary protection measures. Intraprocedurally, the aortic root and a selective coronary angiography are useful for evaluating the anatomic relationship between the aortic valve and coronary ostia; transesophageal echocardiographic real-time monitoring of the coronary flow with a color Doppler and pulsed-wave Doppler is a valuable tool that allows for a determination of real-time coronary patency and the detection of asymptomatic coronary obstructions. Because of the risk of developing a delayed coronary obstruction, the close postprocedural monitoring of patients at a high risk of developing coronary obstructions is advisable. CT simulations of ViV TAVR, 3D printing models, and fusion imaging represent the future directions that may help provide a personalized lifetime strategy and tailored approach for each patient, potentially minimizing complications and improving outcomes.

Advances in Imaging for Tricuspid Transcatheter Edge-to-Edge Repair: Lessons Learned and Future Perspectives.

Severe tricuspid valve (TV) regurgitation (TR) has been associated with adverse long-term outcomes in several natural history studies, but isolated TV surgery presents high mortality and morbidity rates. Transcatheter tricuspid valve interventions (TTVI) therefore represent a promising field and may currently be considered in patients with severe secondary TR that have a prohibitive surgical risk. Tricuspid transcatheter edge-to-edge repair (T-TEER) represents one of the most frequently used TTVI options. Accurate imaging of the tricuspid valve (TV) apparatus is crucial for T-TEER preprocedural planning, in order to select the right candidates, and is also fundamental for intraprocedural guidance and post-procedural follow-up. Although transesophageal echocardiography represents the main imaging modality, we describe the utility and additional value of other imaging modalities such as cardiac CT and MRI, intracardiac echocardiography, fluoroscopy, and fusion imaging to assist T-TEER. Developments in the field of 3D printing, computational models, and artificial intelligence hold great promise in improving the assessment and management of patients with valvular heart disease.

Novel 3D Echocardiographic Technique for Mitral Calcium Mapping.

Mitral annular calcification (MAC) is a common chronic degenerative process of the mitral valve fibrous support ring. MAC increases the risk of mitral valve dysfunction, all-cause and cardiovascular mortality, and worse outcomes in cardiac interventions. Echocardiography represents the first imaging modality for MAC assessment, but it has low specificity compared to cardiac CT in terms of distinguishing between calcium and dense collagen. Novel three-dimensional transesophageal maximal intensity projection (MIP) mapping allows for the real-time MAC distribution and depth visualization of the cardiac anatomy and represents a useful and promising tool for pre-procedural assessment and intra-procedural guidance of cardiac interventions.

Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease.

Coronary heart disease (CHD), one of the leading causes of disability and death worldwide, is a multifactorial disease whose early diagnosis is demanding. Thus, biomarkers predicting the occurrence of this pathology are of great importance from a clinical and therapeutic standpoint. By means of a pilot study on peripheral blood cells (PBMCs) of subjects with no coronary lesions (CTR; n = 2) and patients with stable CAD (CAD; n = 2), we revealed 61 differentially methylated regions (DMRs) (18 promoter regions, 24 genes and 19 CpG islands) and 14.997 differentially methylated single CpG sites (DMCs) in CAD patients. MiRNA-seq results displayed a peculiar miRNAs profile in CAD patients with 18 upregulated and 32 downregulated miRNAs (FC ≥ ±1.5, p ≤ 0.05). An integrated analysis of genome-wide DNA methylation and miRNA-seq results indicated a significant downregulation of hsa-miR-200c-3p (FCCAD = −2.97, p ≤ 0.05) associated to the hypermethylation of two sites (genomic coordinates: chr12:7073122-7073122 and chr12:7072599-7072599) located intragenic to the miR-200c/141 genomic locus (encoding hsa-miR-200c-3p) (p-value = 0.009) in CAD patients. We extended the hsa-miR-200c-3p expression study in a larger cohort (CAD = 72, CTR = 24), confirming its reduced expression level in CAD patients (FCCAD = −2; p = 0.02). However, when we analyzed the methylation status of the two CpG sites in the same cohort, we failed to identify significant differences. A ROC curve analysis showed good performance of hsa-miR-200c-3p expression level (AUC = 0.65; p = 0.02) in distinguishing CAD from CTR. Moreover, we found a significant positive correlation between hsa-miR-200c-3p expression and creatinine clearance (R2 = 0.212, p < 0.005, Pearson r = 0.461) in CAD patients. Finally, a phenotypic correlation performed in the CAD group revealed lower hsa-miR-200c-3p expression levels in CAD patients affected by dyslipidemia (+DLP, n = 58) (p < 0.01). These results indicate hsa-miR-200c-3p as potential epi-biomarker for the diagnosis and clinical progression of CAD and highlight the importance of deeper studies on the expression of this miRNA to understand its functional role in coronary artery disease development.

Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: molecular abnormalities and phenotypical variants.

Diabetic cardiomyopathy (DCM) is a diabetes mellitus-induced pathophysiological condition characterized by cardiac structural, functional, and metabolic changes that can result in heart failure (HF), in the absence of coronary artery disease, hypertension, and valvular heart disease. Metabolic alterations such as hyperglycemia, insulin resistance, hyperinsulinemia, and increased metabolism of free fatty acids result in oxidative stress, inflammation, advanced glycation end products formation, abnormalities in calcium homeostasis, and apoptosis that are responsible for structural remodeling. Cardiac stiffness, hypertrophy, and fibrosis eventually lead to dysfunction and HF with preserved ejection fraction and/or HF with reduced ejection fraction. In this review, we analyzed in detail the cellular and molecular mechanisms and the metabolic pathways involved in the pathophysiology of DCM. Different phenotypes are observed in DCM, and it is not clear yet if the restrictive and the dilated phenotypes are distinct or represent an evolution of the same disease. Phenotypic differences can be observed between T1DM and T2DM DCM, possibly explained by the different myocardial insulin action. Further studies are needed in order to better understand the underlying mechanisms of DCM and to identify appropriate therapeutic targets and novel strategies to prevent and reverse the progression toward heart failure in diabetic patients.

Prognostic value of left ventricular global longitudinal strain in mitral regurgitation: a systematic review.

Conventional echocardiographic assessment may overestimate the left ventricular (LV) function in mitral regurgitation (MR). LV global longitudinal strain (GLS) is more sensitive marker to detect subclinical LV dysfunction. Multiple studies have investigated the prognostic value of LV-GLS in MR to examine its potential to determine the timing and indication of intervention. This systematic review aimed to assess the prognostic value of LV-GLS in patients with mitral regurgitation (MR) to define its clinical applicability. PUBMED and EMBASE were queried through July 2021 to identify studies investigating the prognostic value of LV-GLS in MR. A total of 24 observational studies with 5267 patients were identified. Sixteen studies investigated for primary MR, 7 studies for secondary MR, and 1 study for both. Most studies included patients who underwent intervention. There was significant heterogeneity in patient population, intervention status, follow-up period, LV-GLS cutoff value, outcomes, and statistical methods among the studies. Meta-analysis was not performed considering the significant variability. With exception to 1 study, all studies demonstrated significant association between impaired LV-GLS and worse clinical and echocardiographic outcomes in primary MR. Prognostic value of LV-GLS in secondary MR was less certain due to inconsistent findings and limited reporting. LV-GLS is a promising parameter of prognostication in primary MR and can be considered as alternative to determine the timing of intervention. However, the optimal cutoff value remains unclear. The prognostic value of LV-GLS in secondary MR is less clear. Further large-scale prospective study is warranted before its routine clinical application.