Bioprosthetic Aortic Valve Thrombosis: Definitions, Clinical Impact, and Management: A State-of-the-Art Review.

Bioprosthetic aortic valve thrombosis is frequently detected after transcatheter and surgical aortic valve replacement due to advances in cardiac computed tomography angiography technology and standardized surveillance protocols in low-surgical-risk transcatheter aortic valve replacement trials. However, evidence is limited concerning whether subclinical leaflet thrombosis leads to clinical adverse events or premature structural valve deterioration. Furthermore, there may be net harm in the form of bleeding from aggressive antithrombotic treatment in patients with subclinical leaflet thrombosis. This review will discuss the incidence, mechanisms, diagnosis, and optimal management of bioprosthetic aortic valve thrombosis after transcatheter aortic valve replacement and bioprosthetic surgical aortic valve replacement.

Overview of the 2023 FDA Circulatory System Devices Advisory Panel meeting on the Recor Paradise Ultrasound-Based Renal Denervation System.

Hypertension continues to be a prominent, avoidable factor contributing to major vascular issues on a global scale. Even with lifestyle adjustments and more aggressive medical treatments, maintaining optimal blood pressure levels remains challenging. This challenge has driven the emergence of device-oriented approaches to address hypertension. To assess the safety and efficacy of the Recor Paradise Ultrasound Renal Denervation System, the Circulatory System Devices Panel was convened by the US Food and Drug Administration (FDA). This manuscript provides a condensed overview of the information put forth by the sponsor and the FDA, along with an account of the considerations and conversations that took place during the meeting.

Overview of 2024 FDA Advisory Panel Meeting on the TriClip Transcatheter Tricuspid Valve Repair System.

Tricuspid regurgitation (TR) is common and associated with significant mortality and morbidity. Because the effectiveness and safety of medical and surgical treatments are limited, there is a significant unmet need for the treatment of this disease. Therefore, there is a growing market for percutaneous devices that offer safer, less invasive, and more effective treatment options in this patient population. On February 13, 2024, the US Food and Drug Administration (FDA) convened a meeting of the Circulatory System Devices Panel to discuss the safety and effectiveness of the TriClip Transcatheter Valve Repair System (Abbott, Santa Clara, CA, USA). Several important points were discussed, including newly published data from the TRILUMINATE Pivotal study, the use of patient-oriented outcomes for device approval, and a discussion about training requirements and rollout plans when approving a breakthrough device. In this manuscript, we summarize the data presented by the sponsor and FDA and describe the deliberations and discussions during the meeting.

Exploring the interplay between coronary microvascular dysfunction and mental health.

BACKGROUND: The intricate relationship between mental health disorders, notably anxiety and depression, and chest pain associated with non-obstructive coronary artery disease has become a focus of investigation. METHODS: This study from the Coronary Microvascular Disease Registry (CMDR) evaluated the association of mental health disorders and coronary microvascular dysfunction (CMD) among patients with angina with no obstructive coronary artery disease (ANOCA) who had undergone comprehensive invasive physiological testing for CMD. Clinical data regarding baseline characteristics, comorbidities, and noninvasive cardiac testing were obtained from chart review. The primary outcome of interest was the potential relationship between mental health diagnoses and the presence of CMD. RESULTS: Of patients included in the CMDR, 27 % (41/152) had at least one documented mental health disorder diagnosis (International Classification of Diseases, Tenth Revision codes) and CMD. There was no difference in mental health diagnosis prevalence between CMD-positive and CMD-negative patients (21.1 % vs. 28.9 %, p = 0.34). The most common mental health diagnoses were depression (15.8 %) and anxiety (15.8 %). Furthermore, 46.3 % (19/41) of patients with mental health disorders were prescribed psychiatric medications, with the most common being benzodiazepines (26.8 %). CONCLUSION: Patients with chest pain not due to CMD did not have an increased prevalence of mental health disorders compared with patients with ANOCA due to CMD, challenging the notion of a psychosomatic component in the pathogenesis of ANOCA.

Coronary microvascular dysfunction and inflammation: Insights from the Coronary Microvascular Disease Registry.

BACKGROUND: Coronary microvascular dysfunction (CMD) is associated with various inflammatory conditions that worsen endothelial dysfunction. This study aimed to investigate the relationship between CMD and inflammation using common inflammatory markers derived from complete blood count (CBC) analysis. METHODS: Information was gathered from the Coronary Microvascular Disease Registry to examine the neutrophil-to-lymphocyte ratio (NLR), eosinophil-to-monocyte ratio (EMR), and monocyte-to-high-density lipoprotein ratio (MHR) in a cohort of patients with angina who showed non-obstructive coronary arteries and underwent invasive physiological assessments for CMD. RESULTS: Of the 171 patients studied, 126 were CMD-negative and 45 were CMD-positive, constituting two groups of interest. The average age of all patients was 61.7 ± 11.1 years, and 63.7 % were female. No significant differences were observed between the two groups in terms of baseline characteristics, cardiovascular risk factors, or potential anti-inflammatory medications. Furthermore, there were no statistically significant differences in NLR (2.54 ± 3.71 vs. 2.52 ± 2.28, p = 0.97), EMR (0.3 ± 0.21 vs. 0.34 ± 0.29, p = 0.31), or MHR (0.02 ± 0.01 vs. 0.01 ± 0.01, p = 0.54) between CMD-positive and CMD-negative patients. CONCLUSION: Our findings did not show a noteworthy connection between CMD and inflammation, as suggested by various simple CBC-based biomarkers.

Coronary microvascular dysfunction and cancer therapy-related cardiovascular toxicity.

BACKGROUND: Coronary microvascular dysfunction (CMD) has been implicated as a potential mechanism in the pathophysiology of different clinical presentations, including ischemia and no obstructive coronary artery disease (INOCA), myocardial infarction and nonobstructive coronary arteries (MINOCA), stress cardiomyopathy, heart failure, and myocarditis. There are limited data about the role of CMD in cancer therapy-related cardiovascular toxicities. CASE PRESENTATIONS: Four women with a diagnosis of active cancer receiving treatment who developed subsequent MINOCA or INOCA presented for cardiac catheterization. Upon coronary angiography showing no obstructive coronary arteries, coronary function testing was performed to evaluate for CMD. METHODS: Coronary physiology was assessed measuring non-hyperemic (resting full-cycle ratio [RFR]) and hyperemic (fractional flow reserve [FFR]) indices using a physiologic pressure wire. The wire also measured coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and RFR using thermodilution technology. CMD was confirmed if the CFR was <2.5 and the IMR was >25. RESULTS: Among 4 patients with diagnosis of active cancer presenting with chest pain, there was no evidence of obstructive coronary artery disease, leading to separate diagnoses of INOCA, MINOCA, stress cardiomyopathy, and myocarditis. We found CMD in 2 patients (1 with INOCA and 1 with immune checkpoint inhibitor-related myocarditis). CONCLUSIONS: CMD may play a role in cardiovascular toxicities. Further coronary physiology studies are needed to understand the mechanisms of cancer therapy-related cardiovascular toxicity and CMD, as well as optimal preventive and treatment options.

From chest pain to coronary functional testing: Clinical and economic impact of coronary microvascular dysfunction.

BACKGROUND: Coronary functional testing to formally diagnose coronary microvascular dysfunction (CMD) reduces cardiovascular events and alleviates angina. This study aims to investigate the extensive and complex journey that patients with CMD undergo, from the onset of chest pain to eventual diagnosis. METHODS: Data from the Coronary Microvascular Disease Registry (CMDR) were analyzed, including information on the date of first documentation of chest pain, number of non-invasive and invasive tests the patient underwent, emergency department visits, and hospitalizations. In addition, we estimated the total cost per patient. A total of 61 patients with CMD diagnosis were included in this analysis. RESULTS: Most patients in our cohort were older than 50 years of age. The median time from initial chest pain symptoms to diagnosis was 0.62 (interquartile range [IQR]: 0.06-2.96) years. During this period, patients visited the emergency department a median of 1.0 (IQR: 0.0-2.0) times. Diagnostic tests included 3.0 (IQR: 2.0-6.0) electrocardiograms, 3.0 (IQR: 0.0-6.0) high-sensitivity troponin tests, and 1.0 (IQR: 1.0-2.0) echocardiograms. Prior to diagnosis of CMD, 13 (21.3 %) patients had left heart catheterization without coronary functional testing. Non-invasive testing for ischemia was conducted in 43 (70.5 %) patients. Alternative non-cardiac diagnoses were given to 11 (18.0 %) patients during the diagnostic process, with referrals made to gastroenterology for 16 (26.2 %) and pulmonology for 10 (16.4 %) patients. The cost was almost $2000/patient. CONCLUSION: Timely identification of CMD offers promising opportunities for prompt symptom alleviation, accompanied by reduced visits to the emergency department, cardiovascular testing, invasive medical procedures, and consequently reduced healthcare expenses.

Leaflet modification with the ShortCut™ device to prevent coronary artery obstruction during TAVR.

Transcatheter heart valve (THV) procedures require careful planning and consideration to prevent coronary artery obstruction (CAO), which poses a significant and potentially life-threatening condition, especially in patients undergoing valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR). Despite identifying predictors of CAO and utilization of computed tomography and inputting THV features, a significant uncertainty remains in predicting CAO. The ShortCut™ device (Pi-Cardia, Rehovot, Israel) was purposefully designed to modify the leaflets in patients undergoing TAVR, especially prior to ViV procedures, to overcome the risk for CAO. This review aims to detail the device's objectives, structure, procedural steps, the available clinical data, and future directions for its intended utilization in the structural arena for the prevention of CAO.

Overview of the 2023 FDA Circulatory System Devices Advisory Panel Meeting on the Symplicity Spyral Renal Denervation System.

Hypertension remains a leading preventable cause of myocardial infarction, stroke, kidney disease, and cardiovascular death worldwide. Despite lifestyle modifications and intensification of medical therapy, suboptimal blood pressure control is common, spurring the development of device-based therapies for hypertension. The US Food and Drug Administration (FDA) assembled the Circulatory System Devices Panel on August 22-23, 2023, to discuss the safety and effectiveness of renal denervation devices manufactured by Recor Medical and Medtronic. After reviewing the ultrasound-based Recor Paradise renal denervation system the day prior, the panel reconvened to discuss the radiofrequency-based Medtronic Symplicity Spyral Renal Denervation System. In this manuscript, we summarize the data presented by the sponsor and FDA and detail the deliberation and discussion during the meeting.

Implementation of Robotic-Assisted Percutaneous Coronary Intervention Into a High-Risk PCI Program.

BACKGROUND: How to implement robotic-assisted PCI safely and when to escalate to more complex cases has not been previously described. We sought to evaluate clinical outcomes in patients undergoing robotic-assisted PCI in the first year of a newly established robotic-assisted PCI program. METHODS: All patients who underwent robotic-assisted PCI in the first 12 months at a single academic center were included in the study. Lesion complexity was characterized as "PRECISE-like", "CORA-PCI-like", or "CORA-PCI excluded" based on established criteria. The primary outcome was clinical success, defined as <30% residual stenosis after stenting with a final TIMI flow grade 2-3 and no procedural complications. Secondary outcomes included robotic success, defined as clinical success with robotic completion, unintentional manual conversion rate, procedure time, and procedural complications. RESULTS: Of the 57 consecutive lesions treated, 12 (22.6%) had a PRECISE-like lesion complexity while 32 (56.1%) had a CORA- PCI-like, and 13 (22.8%) a CORA-PCI excluded lesion complexity. There was no significant difference in clinical success (100.0% vs. 96.7% vs. 100.0%, p = 1.00) among the groups but robotic success was numerically lower as complexity increased (100.0% vs. 80.0% vs. 72.7%, p = 0.15), with an increased frequency of manual conversion. There was no significant difference in procedural complication rates among the groups. The robotic completion rate improved during the study period. CONCLUSION: Robotic-assisted PCI, can be safely implemented in a moderate-sized academic center, with a rapid escalation in patient and lesion complexity.

Clinical Impact of Tricuspid Regurgitation on Transcatheter Edge-to-Edge Mitral Valve Repair for Mitral Regurgitation.

OBJECTIVES: This study aimed to evaluate whether baseline tricuspid regurgitation (TR) impacted clinical outcomes after mitral valve transcatheter edge-to-edge repair (M-TEER) for severe secondary mitral regurgitation (MR). BACKGROUND: Baseline TR is common among patients undergoing M-TEER for secondary MR, although its impact on clinical outcomes is unclear. METHODS: The Cochrane Library, PubMed/MEDLINE, and Google Scholar were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines from January 1, 2011 through January 31, 2021. Randomized controlled trials and nonrandomized prospective studies that evaluated baseline TR by echocardiography before M-TEER for MR were included. The primary outcome was a composite of mortality and heart failure hospitalization (HFH) at 1-year. RESULTS: A total of 5 studies (n = 1395 patients) were included in the primary analysis. Concurrent moderate/severe TR was associated with a worse 1 year composite of all-cause mortality and HFH (OR: 2.13; 95% CI: 1.12-4.05; p = 0.02) after M-TEER for severe MR. In studies that reported TR grade pre- and post-M-TEER for severe MR, 32% of patients with moderate-to-severe baseline TR had a reduction in TR severity after the intervention. CONCLUSIONS: Baseline moderate-to-severe TR was associated with increased 1-year mortality and heart failure hospitalizations among patients undergoing M-TEER. Further randomized studies are needed to assess the interaction of TR among patients undergoing M-TEER.

Cardiovascular Risks with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors and Monoclonal Antibody Therapy.

PURPOSE OF REVIEW: Tyrosine kinase inhibitors (TKI) and monoclonal antibodies (mAbs) that target the epidermal growth factor receptor (EGFR) have changed the therapeutic landscape across a range of solid malignancies. However, there is little data regarding the cardiovascular (CV) impact of these agents. The purpose of this review is to discuss reported CV effects, pathophysiology, pre-treatment screening, diagnostic workup, and treatment recommendations in this patient population. RECENT FINDINGS: It is apparent that CV events are not class dependent, and while infrequently reported in clinical trials, unique CV toxicity may occur with EGFR inhibitors, including structural, electrical, and vascular events. There remains an unmet need to fully elucidate the spectrum of CV events associated with EGFR inhibitors. Early CV screening, close clinical monitoring, coupled with a multidisciplinary approach between medical and cardio-oncology is needed to minimize the potentially detrimental impact of cardiotoxicity in this patient population.

Loperamide Toxicity Revealing Apical Hypertrophic Cardiomyopathy.

Loperamide, a µ-opioid receptor agonist, can cause cardiotoxicity by inhibiting the potassium ion channel and slowing cardiomyocyte repolarization. This, in turn, can lead to frequent early afterdepolarizations, the most common mechanism of drug-induced long QT syndrome and torsades de pointes. Apical hypertrophic cardiomyopathy (AHCM) is a nonobstructive hypertrophic cardiomyopathy rarely associated with malignant arrhythmias. We present a case of loperamide-induced malignant ventricular arrhythmia revealing underlying AHCM in a 25-year-old woman with a history of sudden cardiac arrest (SCA) and opioid use. It is important to evaluate for structural heart disease in all patients presenting with SCA, regardless of presumed etiology such as drug-induced cardiotoxicity, to prevent missed opportunities for adequate treatment. Furthermore, the diagnosis of AHCM in SCA warrants further genetic evaluation for variances with a predilection for malignant arrhythmias.

Baseline global longitudinal strain predictive of anthracycline-induced cardiotoxicity.

BACKGROUND: Cancer therapy-related cardiac dysfunction (CTRD) is a major source of morbidity and mortality in long-term cancer survivors. Decreased GLS predicts decreased left ventricular ejection fraction (LVEF) in patients receiving anthracyclines, but knowledge regarding the clinical utility of baseline GLS in patients at low-risk of (CTRD) is limited. OBJECTIVES: The purpose of this study was to investigate whether baseline echocardiographic assessment of global longitudinal strain (GLS) before treatment with anthracyclines is predictive of (CTRD) in a broad cohort of patients with normal baseline LVEF. METHODS: Study participants comprised 188 patients at a single institution who underwent baseline 2-dimensional (2D) speckle-tracking echocardiography before treatment with anthracyclines and at least one follow-up echocardiogram 3 months after chemotherapy initiation. Patients with a baseline LVEF <55% were excluded from the analysis. The primary endpoint, (CTRD), was defined as an absolute decline in LVEF > 10% from baseline and an overall reduced LVEF <50%. Potential and known risk factors were evaluated using univariable and multivariable Cox proportional hazards regression analysis. RESULTS: Twenty-three patients (12.23%) developed (CTRD). Among patients with (CTRD), the mean GLS was -17.51% ± 2.77%. The optimal cutoff point for (CTRD) was -18.05%. The sensitivity was 0.70 and specificity was 0.70. The area under ROC curve was 0.70. After adjustment for cardiovascular and cancer therapy related risk factors, GLS or decreased baseline GLS ≥-18% was predictive of (CTRD) (adjusted hazards ratio 1.17, 95% confidence interval 1.00, 1.36; p = 0.044 for GLS, or hazards ratio 3.54; 95% confidence interval 1.34, 9.35; p = 0.011 for decreased GLS), along with history of tobacco use, pre-chemotherapy systolic blood pressure, and cumulative anthracycline dose. CONCLUSIONS: Baseline GLS or decreased baseline GLS was predictive of (CTRD) before anthracycline treatment in a cohort of cancer patients with a normal baseline LVEF. This data supports the implementation of strain-protocol echocardiography in cardio-oncology practice for identifying and monitoring patients who are at elevated risk of (CTRD).