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.

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.

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.

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).

Successful treatment of acute heart failure in COVID-19-induced cytokine storm with tocilizumab: a case report.

BACKGROUND: SARS-CoV-2 is known to induce a cytokine storm, a hyperinflammatory state driven by up-regulation of interleukin 6 (IL-6) and immunomodulatory chemokines that may result in acute heart failure. CASE SUMMARY: A 65-year-old woman with confirmed SARS-CoV-2 developed shock with multiorgan system failure, including acute biventricular heart failure, 2 weeks after the initial onset of fever, cough, and shortness of breath. The patient experienced myocardial recovery within 48 h after administration of tocilizumab, a humanized monoclonal anti-IL-6 receptor antibody, and multiple supportive vasoactive medications. DISCUSSION: The differential diagnosis of acute heart failure in critically ill patients with COVID-19 infection is broad, including sepsis-induced cardiomyopathy, Takotsubo syndrome, viral lymphocytic myocarditis, and acute coronary syndrome. Immunomodulatory treatment with tocilizumab may benefit patients who develop cardiogenic shock associated with SARS-CoV-2-induced cytokine storm.

Transcatheter Mitral Valve Repair with MitraClip for Severe Mitral Regurgitation and Cardiogenic Shock During the COVID-19 Pandemic.

Transcatheter mitral valve repair with MitraClip (Abbott) is largely an elective procedure. The ongoing coronavirus disease 2019 (COVID-19) pandemic has posed challenges to health care systems; in many cases elective interventions have been curtailed. Patients with severe mitral regurgitation (MR) and cardiogenic shock are high-risk surgical candidates and at risk of a poor outcome without intervention. The American College of Cardiology (ACC) and the Society of Coronary Angiography and Interventions (SCAI) recently proposed joint guidance on triage of structural heart disease (SHD) interventions during the COVID-19 pandemic. We present two illustrative cases of severe MR and cardiogenic shock that were successfully treated with MitraClip amidst the COVID-19 pandemic with good outcomes at short term follow-up.

Pathophysiology of Acute and Chronic Right Heart Failure.

Right-sided heart failure (RHF) occurs from impaired contractility of the right ventricle caused by pressure, volume overload, or intrinsic myocardial contractile dysfunction. The development of subclinical right ventricle (RV) dysfunction or overt RHF is a negative prognostic indicator. Recent attention has focused on RV-specific inflammatory growth factors and mediators of myocardial fibrosis to elucidate the mechanisms leading to RHF and potentially guide the development of novel therapeutics. This article focuses on the distinct changes in RV structure, mechanics, and function, as well as molecular and inflammatory mediators involved in the pathophysiology of acute and chronic RHF.

Mechanical Mitral Valve Thrombosis in a Patient With Prior Nonbacterial Thrombotic Endocarditis.

A 54-year-old woman with a mechanical mitral valve replacement presented with recurrent admissions for pneumonia and pulmonary edema. Multimodality imaging revealed mobile masses on the prosthesis and discrepant point of care and inpatient international normalized ratio levels owing to antiphospholipid antibody cross-reactivity on the outpatient assay. The prosthetic valve thromboses resolved with therapeutic anticoagulation. (Level of Difficulty: Beginner.).

Immune Checkpoint Inhibitor-Related Adverse Cardiovascular Events in Patients With Lung Cancer.

OBJECTIVES: The purpose of this study was to evaluate whether immune checkpoint inhibitors (ICIs) are associated with an increased risk of major adverse cardiovascular events (MACE) compared with non-ICI therapies in patients with lung cancer. BACKGROUND: ICIs activate the host immune system to target cancer cells. Though uncommon, cardiovascular immune-related adverse events can be life-threatening. METHODS: A retrospective single-institution cohort study of 252 patients with pathologically confirmed lung cancer who received ICI or non-ICI therapy was analyzed. The primary endpoint was MACE, defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure. RESULTS: During a median follow-up of 6 months, MACE occurred in 13.3% of ICI-treated patients, with a median time to event of 51 days, compared with 10.3% and 64 days in non-ICI patients. ICIs were not associated with MACE (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.57 to 2.43; p = 0.66) in a univariable Fine-Gray regression analysis incorporating noncardiovascular death as a competing risk. Multivariable regression analyses determined that patients treated with ICIs with elevated serum troponin I >0.01 ng/ml (HR: 7.27; 95% CI: 2.72 to 19.43; p < 0.001) and B-type natriuretic peptide (BNP) >100 pg/ml (HR: 2.65; 95% CI: 1.01 to 6.92; p = 0.047) had an increased risk of MACE. Patients pre-treated or receiving combined immunotherapy with ICIs and vascular endothelial growth factor inhibitors (VEGFIs) or tyrosine kinase inhibitors (TKIs) had an increased risk of MACE (HR: 2.15; 95% CI: 1.05 to 4.37; p = 0.04). CONCLUSIONS: ICIs were not independently associated with an increased risk of MACE in patients with lung cancer, although power is an important limitation in these analyses. ICI-associated cardiotoxicity was associated with elevations in serum troponin and BNP, and combined immunotherapy with VEGFIs or TKIs. Future studies are needed to further define the role of cardiac biomarkers as a monitoring strategy with ICI therapy.