Unusual Presentation of De Winter's Sign Due to Bezold-Jarisch Reflex in a Patient With Severe Aortic Valve Stenosis.

The de Winter electrocardiogram (ECG) pattern, marked by upsloping ST depression in leads V2-V6, ST elevation in lead aVR, and tall symmetric T waves, typically indicates left anterior descending artery (LAD) occlusion. Traditionally linked to LAD occlusion, it is rare in severe aortic stenosis and the Bezold-Jarisch reflex (BJR). We report an 83-year-old man with severe aortic stenosis who developed hypotension due to bleeding and exhibited the de Winter ECG pattern. This case highlights how severe aortic stenosis and BJR can lead to significant hemodynamic instability and ischemic ECG changes, resolving after hemodynamic stabilization.

Investigation of von Willebrand factor multimer abnormalities before and after aortic valve replacement using the Hydragel-5 assay.

BACKGROUND: Severe aortic stenosis (sAS) is associated with acquired von Willebrand syndrome (AVWS) by loss of high-molecular-weight multimers (HMWM) of von Willebrand factor (VWF), potentially resulting in perioperative bleeding. Analysis of VWF multimers remains challenging. Recently, the new, rapid Hydragel 5 assay has been developed, using electrophoretic protein separation for dividing VWF-multimers into low (LMWM), intermediate (IMWM), and HMWM, the hemostatically active part of VWF. Here, we evaluated its impact on predicting blood loss in presence of AVWS after surgical aortic valve replacement (SAVR). METHODS: We prospectively examined 52 patients (age: 68 ± 7 years; 54 % male) admitted to SAVR. They were divided in two groups (A: normal VWF, n = 28; B: abnormal VWF, n = 24, defined as VWF-activity/antigen (VWF:Ac/Ag)-ratio < 0.7 and/or HMWM loss). Blood samples and echocardiographic data were collected before, seven days and three months after SAVR. Blood loss and transfusions were recorded. RESULTS: Baseline characteristics and clinical data were similar in both groups. HMWM loss was present in 38.5 % of all patients. HMWM, the VWF:Ac/Ag- and HMWM/(IMWM+LMWM)-ratios were significantly decreased preoperatively in group B but normalized after SAVR. Bleeding, re-thoracotomy and transfusion rates were comparable. HMWM loss was inversely correlated with the peak aortic gradient (Pmax) and positively with the aortic valve area (AVA), while HMWM/(IMWM+LMWM)-ratio negatively correlated with the mean aortic gradient (Pmean). CONCLUSION: HMWM and HMWM/(IMWM+LMWM)-ratio inversely correlate with severity of AS and normalize after SAVR. The Hydragel-5 assay's might be valuable for routine diagnostics to assess bleeding risk and postoperative normalization of AS and VWF abnormalities in SAVR patients.

Antithrombotic Therapy in Patients Undergoing Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) now represents the mainstay of treatment for severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as the cornerstone. Leveraging data from multiple randomized controlled trials, the current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without or with atrial fibrillation, respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

Association between Systolic Blood Pressure Variability and Incident Aortic Stenosis.

Background: This study investigated the potential link between blood pressure variability (BPV) and the incidence of aortic stenosis (AS) using Korean National Health Insurance Service data from 2002 to 2019. Methods: We collected annual systolic blood pressure variability (SBPV) measurements consisting of three consecutive blood pressure readings each year over three years. The obtained SBPV data was divided into five quantiles, with the highest quintile representing a high fluctuation of blood pressure. Results: Analyzing 9,341,629 individuals with a mean age of 40.7 years, the study found 3981 new AS diagnoses during an average 8.66-year follow-up. Independent predictors for AS included higher blood pressure levels and elevated systolic blood pressure variability (SBPV). The hazard ratios (HR) for different SBPV quintiles compared to the reference (1st quintile) were as follows: 2nd quintile HR 1.09 (p = 0.18), 3rd quintile HR 1.13 (p = 0.04), 4th quintile HR 1.13 (p = 0.04), and 5th quintile HR 1.39 (p < 0.001). Conclusion: Our findings suggest that both hypertension and high fluctuations in SBP during consecutive visits are associated with an increased risk of incident AS. These results emphasize the importance of blood pressure management and stability in the prevention of AS.

Mitral complex geometric changes aggravate mitral stenosis after transcatheter aortic valve replacement.

Severe aortic valve stenosis (AS) often coexists with mitral valve stenosis (MS). MS aggravation after transcatheter aortic valve replacement (TAVR) is common, and its etiology is multifactorial. We hypothesized that geometric changes in the mitral complex (mitral valvular and annular deformities) are adjunctive factors aggravating MS after TAVR, particularly in older adults with a smaller left ventricle (LV). This study aimed to evaluate the mitral complex geometric changes before and after TAVR and to assess the important predictors of MS aggravation after TAVR. This retrospective study enrolled consecutive adult patients who underwent TAVR and surgical AVR (SAVR) for severe AS. The mitral valve area (MVA), the angle between the anterior mitral valve leaflet (AMVL) and left ventricular outflow tract (LVOT), AMVL length, mitral annular diameter, presence of mitral annular calcification, and LV size were evaluated using transthoracic echocardiography. This study included 258 patients who underwent TAVR and SAVR. MVA index decreased from 2.3 ± 0.6 cm² to 1.9 ± 0.5 cm² in the TAVR group. The angle between the AMVL and LVOT was 56.3 ± 9.7° preoperatively and increased to 67.3 ± 11.5° after TAVR. In multivariate analysis, the most important predictive factors of MS aggravation after TAVR were a smaller mitral annular diameter, restricted AMVL mobility, and implantation depth (odds ratio: 4.5, 5.3,3.0; 95% confidence interval: 1.6-14, 1.9-17, 1.0-8.9; and p = 0.005, p = 0.001, p = 0.042, respectively). The reduction in MVA after TAVR was related to the restriction of AMVL opening, depth of implantation and narrowing of the mitral annulus.

Bicuspid Aortic Valve Function and Aortopathy on Presentation and Progression in Children: Does Sex Difference Have Any Implications?

Bicuspid aortic valve (BAV) is the most common congenital heart defect. It can be accompanied by aortic regurgitation or stenosis with aortopathies. Studies in adults showed a sex difference, but there are limited number of reports in the pediatric population. To evaluate the difference in bicuspid aortic valve morphology and functionality between sexes, and the presence and progression of aortopathies, a retrospective chart review study was performed at a tertiary referral care center in the Midwest. In our study, we analyzed a cohort of 476 pediatric patients diagnosed with BAV who presented between January 2007 and February 2018. During the follow-up period spanning 2 to 10 years, male patients (n = 314, 66%) had larger aortic valve annulus (AVA) and sinus of Valsalva (SOV) at the time of initial presentation with more likelihood for progression. In the subgroup analysis, the larger SOV in males was observed in isolated BAV patients without genetic syndromes or cardiac malformations, and there were no significant differences between both sexes in the ascending aorta dimension, valve functionality, valve morphology, and the need for intervention in any of the studied groups. As such, these findings may alter the follow-up focus and frequency for patients with BAV, particularly before adulthood, and warrant further studies.

Macrophage Migration Inhibitory Factor Promotes Thromboinflammation and Predicts Fast Progression of Aortic Stenosis.

BACKGROUND: Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated by circulating inflammatory and valve resident endothelial and interstitial cells. The impact of platelets, platelet-derived mediators, and platelet-monocyte interactions on the acceleration of local valvular inflammation and mineralization is presently unknown. METHODS: We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic valve replacement. Clinical workup included repetitive echocardiography, analysis of platelets, monocytes, chemokine profiling, aortic valve tissue samples for immunohistochemistry, and gene expression analysis. RESULTS: The patients were classified as fast-progressive AS by the median ∆Vmax of 0.45 m/s per year determined by echocardiography. Immunohistological aortic valve analysis revealed enhanced cellularity in fast-progressive AS (slow- versus fast-progressive AS; median [interquartile range], 247 [142.3-504] versus 717.5 [360.5-1234]; P<0.001) with less calcification (calcification area, mm2: 33.74 [27.82-41.86] versus 20.54 [13.52-33.41]; P<0.001). MIF (macrophage migration inhibitory factor)-associated gene expression was significantly enhanced in fast-progressive AS accompanied by significantly elevated MIF plasma levels (mean±SEM; 6877±379.1 versus 9959±749.1; P<0.001), increased platelet activation, and decreased intracellular MIF expression indicating enhanced MIF release upon platelet activation (CD62P, %: median [interquartile range], 16.8 [11.58-23.8] versus 20.55 [12.48-32.28], P=0.005; MIF, %: 4.85 [1.48-9.75] versus 2.3 [0.78-5.9], P<0.001). Regression analysis confirmed that MIF-associated biomarkers are strongly associated with an accelerated course of AS. CONCLUSIONS: Our findings suggest a key role for platelet-derived MIF and its interplay with circulating and valve resident monocytes/macrophages in local and systemic thromboinflammation during accelerated AS. MIF-based biomarkers predict an accelerated course of AS and represent a novel pharmacological target to attenuate progression of AS.

Sex-specific aspects on prognosis after aortic valve replacement for aortic stenosis: a SWEDEHEART registry study.

OBJECTIVE: To compare long-term cardiovascular (CV) outcomes between men and women with aortic stenosis (AS) undergoing aortic valve replacement (AVR) by the type of valve implant. METHODS: The study population consisted of 14 123 non-selected patients with AS undergoing first-time AVR and included in the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry during 2008-2016. Comparisons were made between men and women and type of valve implant (ie, surgical implantation with a mechanical (mSAVR) (n=1 966) or biological valve (bioSAVR) (n=9 801)) or by a transcatheter approach (TAVR) (n=2 356). Outcomes included all-cause mortality, ischaemic stroke, major bleeding, thromboembolic events, heart failure and myocardial infarction, continuously adjusted for significant comorbidities and medical treatment. RESULTS: In the mSAVR cohort, there were no significant sex differences in any CV events. In the bioSAVR cohort, a higher risk of death (HR: 1.14; 95% CI: 1.04 to 1.26, p=0.007) and major bleeding (HR: 1.41; 95% CI: 1.18 to 1.69, p<0.001) was observed in men. In the TAVR cohort, men suffered a higher risk of death (HR: 1.24; 95% CI: 1.07 to 1.45, p=0.005), major bleeding (HR: 1.35; 95% CI: 1.00 to 1.82, p=0.022) and thromboembolism (HR: 1.35, 95% CI: 1.00 to 1.82, p=0.047). CONCLUSION: No significant long-term difference in CV events was noted between men and women undergoing AVR with a mechanical aortic valve. In both the bioSAVR and TAVR cohort, mortality was higher in men who also had an increased incidence of several other CV events.

Outcomes of Transcatheter Aortic Valve Implantation in Patients with and without Diabetes Mellitus.

INTRODUCTION: Diabetes mellitus (DM) in patients undergoing cardiac transcatheter or surgical interventions usually is correlated with poor outcomes. Transcatheter aortic valve implantation (TAVI) has been developed as a therapy choice for inoperable, high-, or intermediate-risk surgical patients with severe aortic stenosis (AS). OBJECTIVE: To evaluate the impact of DM and hemoglobin A1c (HbA1c) on outcomes and survival after TAVI. METHODS: Five hundred and fifty-two symptomatic severe AS patients who underwent TAVI, of whom 164 (29.7%) had DM, were included in this retrospective study. Follow-up was performed after 30 days, six months, and annually. RESULTS: The device success and risks of procedural-related complications were similar between patients with and without DM, except for acute kidney injury, which was more frequent in the DM group (2.4% vs. 0%, P=0.021). In-hospital and first-year mortality were similar between the groups (4.9% vs. 3.6%, P=0.490 and 15.0% vs. 11.2%, P=0.282, respectively). There was a statistical difference between HbA1c ≥ 6.5 and HbA1c ≤ 6.49 groups in total mortality (34.4% vs. 15.8%, P<0.001, respectively). The only independent predictors were Society of Thoracic Surgeons score (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.09-1.51; P=0.003) and HbA1c level ≥ 6.5 (HR 10.78, 95% CI 2.58-21.50; P=0.003) in multivariable logistic regression analysis. CONCLUSION: In this study, we conclude that DM was not correlated with an increased mortality risk or complication rates after TAVI. Also, it was shown that mortality was higher in patients with HbA1c ≥ 6.5, and it was an independent predictor for long-term mortality.

Human Genetics of Semilunar Valve and Aortic Arch Anomalies.

Lesions of the semilunar valve and the aortic arch can occur either in isolation or as part of well-described clinical syndromes. The polygenic cause of calcific aortic valve disease will be discussed including the key role of NOTCH1 mutations. In addition, the complex trait of bicuspid aortic valve disease will be outlined, both in sporadic/familial cases and in the context of associated syndromes, such as Alagille, Williams, and Kabuki syndromes. Aortic arch abnormalities particularly coarctation of the aorta and interrupted aortic arch, including their association with syndromes such as Turner and 22q11 deletion, respectively, are also discussed. Finally, the genetic basis of congenital pulmonary valve stenosis is summarized, with particular note to Ras-/mitogen-activated protein kinase (Ras/MAPK) pathway syndromes and other less common associations, such as Holt-Oram syndrome.

Heart failure hospitalization following surgical or transcatheter aortic valve implantation in low-risk aortic stenosis.

AIMS: In low-risk patients with severe aortic stenosis (AS), sutureless surgical aortic valve replacement (SU-SAVR) may be an alternative to transcatheter aortic valve implantation (TAVI). The risk of heart failure hospitalization (HFH) after aortic valve replacement (AVR) in this population is incompletely characterized. This study aims to investigate the incidence, predictors, and outcomes of HFH in patients undergoing SU-SAVR versus TAVI. METHODS AND RESULTS: Patients referred for AVR between 2013 and 2020 at two centres were consecutively included. The decision for SU-SAVR or TAVI was determined by a multidisciplinary Heart Team. Cox regression and competing risk analysis were conducted to assess adverse events. Of 594 patients (mean age 77.5 ± 6.4, 59.8% male), 424 underwent SU-SAVR, while 170 underwent TAVI. Following a mean follow-up of 34.1 ± 23.1 months, HFH occurred in 112 (27.8%) SU-SAVR patients and in 8 (4.8%) TAVI patients (P < 0.001). The SU-SAVR cohort exhibited higher all-cause mortality (138 [32.5%] patients compared with 30 [17.6%] in the TAVI cohort [P < 0.001]). These differences remained significant after sensitivity analyses with 1:1 propensity score matching for baseline variables. SU-SAVR with HFH was associated with increased all-cause mortality (61.6% vs. 23.1%, P < 0.001). Independent associates of HFH in SU-SAVR patients included diabetes, atrial fibrillation, chronic obstructive pulmonary disease, lower glomerular filtration rate and lower left ventricular ejection fraction. SU-SAVR patients with HFH had a 12-month LVEF of 59.4 ± 12.7. CONCLUSIONS: In low-risk AS, SU-SAVR is associated with a higher risk of HFH and all-cause mortality compared to TAVI. In patients with severe AS candidate to SU-SAVR or TAVI, TAVI may be the preferred intervention.

Diagnostic Efficacy and Safety of Low-Contrast-Dose Dual-Energy CT in Patients With Renal Impairment Undergoing Transcatheter Aortic Valve Replacement.

OBJECTIVE: This study aimed to evaluate the diagnostic efficacy and safety of low-contrast-dose, dual-source dual-energy CT before transcatheter aortic valve replacement (TAVR) in patients with compromised renal function. MATERIALS AND METHODS: A total of 54 consecutive patients (female:male, 26:38; 81.9 ± 7.3 years) with reduced renal function underwent pre-TAVR dual-energy CT with a 30-mL contrast agent between June 2022 and March 2023. Monochromatic (40- and 50-keV) and conventional (120-kVp) images were reconstructed and analyzed. The subjective quality score, vascular attenuation, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were compared among the imaging techniques using the Friedman test and post-hoc analysis. Interobserver reliability for aortic annular measurement was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. The procedural outcomes and incidence of post-contrast acute kidney injury (AKI) were assessed. RESULTS: Monochromatic images achieved diagnostic quality in all patients. The 50-keV images achieved superior vascular attenuation and CNR (P < 0.001 in all) while maintaining a similar SNR compared to conventional CT. For aortic annular measurement, the 50-keV images showed higher interobserver reliability compared to conventional CT: ICC, 0.98 vs. 0.90 for area and 0.97 vs. 0.95 for perimeter; 95% limits of agreement width, 0.63 cm² vs. 0.92 cm² for area and 5.78 mm vs. 8.50 mm for perimeter. The size of the implanted device matched CT-measured values in all patients, achieving a procedural success rate of 92.6%. No patient experienced a serum creatinine increase of ≥ 1.5 times baseline in the 48-72 hours following CT. However, one patient had a procedural delay due to gradual renal function deterioration. CONCLUSION: Low-contrast-dose imaging with 50-keV reconstruction enables precise pre-TAVR evaluation with improved image quality and minimal risk of post-contrast AKI. This approach may be an effective and safe option for pre-TAVR evaluation in patients with compromised renal function.

Unraveling the Enigma of Moderate Aortic Stenosis: Challenges and Future Prospects.

According to current guidelines, only clinical surveillance is recommended for patients with moderate aortic valve stenosis (AS), while aortic valve replacement may be considered in patients undergoing surgery for other indications. Recent studies have shown that moderate AS is associated with a high risk of adverse cardiovascular events, including death, especially in patients with left ventricular dysfunction. In this context, multimodality imaging can help to improve the accuracy of moderate AS diagnosis and to assess left ventricular remodeling response. This review discusses the natural history of this valve disease and the role of multimodality imaging in the diagnostic process, summarizes current evidence on the medical and non-medical management, and highlights ongoing trials on valve replacement.

Impact of Stress Echocardiography on Aortic Valve Stenosis Management.

Rest and stress echocardiography (SE) play a fundamental role in the evaluation of aortic valve stenosis (AS). According to the current guidelines for the echocardiographic evaluation of patients with aortic stenosis, four broad categories can be defined: high-gradient AS (mean gradient ≥ 40 mmHg, peak velocity ≥ 4 m/s, aortic valve area (AVA) ≤ 1 cm2 or indexed AVA ≤ 0.6 cm2/m2); low-flow, low-gradient AS with reduced ejection fraction (mean gradient < 40 mmHg, AVA ≤ 1 cm2, left ventricle ejection fraction (LVEF) < 50%, stroke volume index (Svi) ≤ 35 mL/m2); low-flow, low-gradient AS with preserved ejection fraction (mean gradient < 40 mmHg, AVA ≤ 1 cm2, LVEF ≥ 50%, SVi ≤ 35 mL/m2); and normal-flow, low-gradient AS with preserved ejection fraction (mean gradient < 40 mmHg, AVA ≤ 1 cm2, indexed AVA ≤ 0.6 cm2/m2, LVEF ≥ 50%, SVi > 35 mL/m2). Aortic valve replacement (AVR) is indicated with the onset of symptoms development or LVEF reduction. However, there is often mismatch between resting transthoracic echocardiography findings and patient's symptoms. In these discordant cases, SE and CT calcium scoring are among the indicated methods to guide the management decision making. Additionally, due to the increasing evidence that in asymptomatic severe aortic stenosis an early AVR instead of conservative treatment is associated with better outcomes, SE can help identify those that would benefit from an early AVR by revealing markers of poor prognosis. Low-flow, low-gradient AS represents a challenge both in diagnosis and in therapeutic management. Low-dose dobutamine SE is the recommended method to distinguish true-severe from pseudo-severe stenosis and assess the existence of flow (contractile) reserve to appropriately guide the need for intervention in these patients.

Unraveling the Mechanisms of Valvular Heart Disease to Identify Medical Therapy Targets: A Scientific Statement From the American Heart Association.

Valvular heart disease is a common cause of morbidity and mortality worldwide and has no effective medical therapy. Severe disease is managed with valve replacement procedures, which entail high health care-related costs and postprocedural morbidity and mortality. Robust ongoing research programs have elucidated many important molecular pathways contributing to primary valvular heart disease. However, there remain several key challenges inherent in translating research on valvular heart disease to viable molecular targets that can progress through the clinical trials pathway and effectively prevent or modify the course of these common conditions. In this scientific statement, we review the basic cellular structures of the human heart valves and discuss how these structures change in primary valvular heart disease. We focus on the most common primary valvular heart diseases, including calcific aortic stenosis, bicuspid aortic valves, mitral valve prolapse, and rheumatic heart disease, and outline the fundamental molecular discoveries contributing to each. We further outline potential therapeutic molecular targets for primary valvular heart disease and discuss key knowledge gaps that might serve as future research priorities.

Early structural valve deterioration of balloon expandable transcatheter aortic valve leaflets due to intrinsic and extrinsic nodular calcifications in a haemodialysis patient: a case report.

Background: Several reports have shown that transcatheter aortic valves are comparable in durability to surgical aortic valves. However, early structural valve deterioration (SVD) is rarely reported to occur, especially in haemodialysis patients. Case summary: We present a case of rapidly progressive bioprosthetic aortic valve stenosis in a patient with end-stage renal disease secondary to diabetic nephropathy in an 83-year-old female admitted due to progressive dyspnoea and orthopnoea. A 23 mm sized SAPIEN3 bioprosthetic aortic valve showed normal function for the first year after transcatheter aortic valve implantation (TAVI), but then rapidly developed stenosis and required acute hospitalization for heart failure a year and a half after surgery. Emergent surgical aortic valve replacement with a 19 mm On-X valve (CryoLife, Kennesaw, GA, USA) was performed. Pathological examination of the explanted SAPIEN 3 valve demonstrated severely degenerated bioprosthetic pericardial leaflets with severe intrinsic and extrinsic nodular calcifications, which could limit the leaflet motion. Discussion: There is a lack of reports on the long-term procedural outcomes of TAVI in haemodialysis patients. The development of SVD in patients undergoing dialysis is multifactorial and has yet to be fully elucidated. In the presented case, the removed TAVI valve had severe extrinsic calcified nodules alongside a fibrin thrombus. Considering these pathological findings, antithrombotic therapy to prevent fibrin thrombus from adhering to the TAVI valve may be important to avoid early SVD.

Insights into calcific aortic valve stenosis: a comprehensive overview of the disease and advancing treatment strategies.

Aortic valve stenosis is a disease characterized by thickening and narrowing of the aortic valve (AV), most commonly due to calcification, which leads to left ventricular outflow obstruction called calcific aortic valve disease (CAVD). CAVD presents as a progressive clinical syndrome with cardiorespiratory symptoms, often with rapid deterioration. The modern-day pathophysiology of CAVD involves a complex interplay of genetic factors, chronic inflammation, lipid deposition, and valve calcification, with early CAVD stages resembling atherosclerosis. Various imaging modalities have been used to evaluate CAVD, with a recent trend of using advanced imaging to measure numerous AV parameters, such as peak jet velocity. Significant improvements in mortality have been achieved with transcatheter AV repair, but numerous therapeutics and modalities are being researched to delay the progression of CAVD. This article aims to provide a comprehensive review of CAVD, explore recent developments, and provide insights into future treatments with various novel modalities.