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 before transcatheter aortic valve implantation in patients at risk for coronary obstruction: the ShortCut study.

BACKGROUND AND AIMS: This trial sought to assess the safety and efficacy of ShortCut, the first dedicated leaflet modification device, prior to transcatheter aortic valve implantation (TAVI) in patients at risk for coronary artery obstruction. METHODS: This pivotal prospective study enrolled patients with failed bioprosthetic aortic valves scheduled to undergo TAVI and were at risk for coronary artery obstruction. The primary safety endpoint was procedure-related mortality or stroke at discharge or 7 days, and the primary efficacy endpoint was per-patient leaflet splitting success. Independent angiographic, echocardiographic, and computed tomography core laboratories assessed all images. Safety events were adjudicated by a clinical events committee and data safety monitoring board. RESULTS: Sixty eligible patients were treated (77.0 ± 9.6 years, 70% female, 96.7% failed surgical bioprosthetic valves, 63.3% single splitting and 36.7% dual splitting) at 22 clinical sites. Successful leaflet splitting was achieved in all (100%; 95% confidence interval [CI] 94-100.0%, p<0.001) patients. Procedure time, including imaging confirmation of leaflet splitting, was 30.6 ± 17.9 min. Freedom from the primary safety endpoint was achieved in 59 (98.3%; 95% CI [91.1-100%]) patients, with no mortality and one (1.7%) disabling stroke. At 30 days, freedom from coronary obstruction was 95% (95% CI 86.1-99.0%). Within 90 days, freedom from mortality was 95% (95% CI 86.1-99.0%]), without any cardiovascular deaths. CONCLUSIONS: Modification of failed bioprosthetic aortic valve leaflets using ShortCut was safe, achieved successful leaflet splitting in all patients, and was associated with favorable clinical outcomes in patients at risk for coronary obstruction undergoing TAVI.

Markedly elevated high-sensitivity troponin and in-hospital mortality after cardiac surgery.

BACKGROUND: High-sensitivity troponin (hsTnI) is correlated with cardiac mortality; however, studies on the relationship of markedly elevated hsTnI with in-hospital mortality after cardiac surgery are sparse. Therefore, we aimed to define this relationship in order to help guide in-hospital, acute management of post-surgical patients. METHODS: We retrospectively analyzed all cardiac surgeries completed at our institution between January 2020 and June 2022 in which a peak hsTnI was noted to be >35× upper limit of normal (ULN = 34 ng/L). The primary outcome was in-hospital death. Subgroup analysis was performed to assess differences between coronary artery bypass grafting (CABG) and other cardiac surgeries. RESULTS: A total of 1382 cases met inclusion criteria. The patients' mean age was 64.8 years and 68.2 % were male. Median peak hsTnI after surgery was 4202 ng/L (interquartile ratio: 2427-7654). Univariate analysis of troponin level with mortality found that for every 1000 ng/L increase in hsTnI, odds of in-hospital death increased by 3.8 % (odds ratio [OR]: 1.038; 95 % confidence interval [CI] 1.027-1.050; p < 0.0001). In a multivariate model, troponin (OR 1.02; 95 % CI 1.01-1.04; p = 0.004) maintained a significant association with in-hospital death. CABG was associated with a lower risk of in-hospital death for any given hsTnI level up to 60,000 ng/L compared to other cardiac surgeries. CONCLUSION: Increasing hsTnI level is associated with increasing probability of in-hospital mortality and, therefore, serves as an additional, objective measure of risk to help guide in-hospital clinical management.

Comparing planned versus ad hoc coronary microvascular assessment: Early findings from the Coronary Microvascular Disease Registry.

BACKGROUND: Coronary microvascular dysfunction (CMD) is an etiology for angina with non-obstructive coronary disease. However, the initial adoption of CMD assessment, whether planned or conducted ad hoc, is limited. We characterize planned and ad hoc CMD assessments and highlight evolving trends of a CMD referral center. METHODS: We analyzed outpatient data from the Coronary Microvascular Disease Registry from 2021 to 2023. Patients were categorized into planned or ad hoc CMD assessment groups, and baseline characteristics, hospital stay, medications, and physiological measurements were compared. Secondary analysis evaluated a CMD referral center's evolution. RESULTS: Of 101 included outpatients, 67.3 % underwent ad hoc procedures and 32.7 % planned procedures. Average age was 63.1 ± 10.1 years. The planned procedure group was 87.9 % female, and the ad hoc procedure group was 51.5 % female. There were no significant differences in index of microvascular resistance or coronary flow reserve between groups. Hospital stay duration was <1 day for both groups, and neither reported complications. Ad hoc patients were more frequently prescribed aspirin before (64.7 % vs. 36.4 %, p = 0.007) and after the procedure (66.2 % vs. 39.4 %, p = 0.01). CMD rates were higher for planned procedures (30.3 % vs. 10.3 %, p = 0.01). We observed that CMD referral centers have more planned procedures and a higher rate of positive results over time. CONCLUSION: CMD referral centers' planned procedures, and subsequent positive cases, increased over time. This emphasizes the importance of planned procedures, appropriate patient selection, and increased awareness of CMD among healthcare providers. CLINICAL TRIAL REGISTRATION: Coronary Microvascular Disease (CMD) Registry, NCT05960474, https://clinicaltrials.gov/study/NCT05960474.

Frequency of ventriculography during left heart catheterization for radial vs. femoral access.

BACKGROUND: Radial artery access has been used for left heart catheterization (LHC) and percutaneous coronary intervention (PCI) for over 30 years. This method has gained popularity among operators due to superficial vessel anatomy, allowing for easy accessibility and compressibility, resulting in effective hemostasis. METHODS: We conducted a retrospective analysis of patients who underwent PCI due to ST-elevation myocardial infarction (STEMI), non-ST-elevation acute coronary syndrome (NSTE-ACS), and chest pain (stable angina) from November 2013 to February 2023. RESULTS: We analyzed validated registries and found 7714 PCIs. Of these, 1230 were STEMI patients, 5585 were NSTE-ACS patients, and 899 were stable angina patients, forming the basis of our final analysis. In STEMI patients, there was a trend toward a higher rate of ventriculography with femoral access compared to radial access (53.4 % vs. 47.5 %, p = 0.06), which was also observed in NSTE-ACS patients (34.2 % vs. 31.8 %, p = 0.07). The use of central venous access was more common with femoral access in all three diagnoses, with significantly higher rates seen in STEMI patients (36.2 % vs. 7.6 %, p < 0.001), NSTE-ACS patients (19.3 % vs. 2.8 %, p < 0.001), and chest pain patients (26.4 % vs. 2.7 %, p < 0.001). CONCLUSIONS: The analysis revealed that operators may perform fewer ventriculography and RHC procedures when using radial access as compared to femoral access. While there is discrepancy in performing left ventriculography and RHC when using a radial artery, it is essential to emphasize that routinely performing ventriculography and hemodynamic assessment has not proven to impact outcomes, despite their contributions to proper decision-making and treatment.

Coronary Microvascular Disease Registry (CMDR): Study design and rationale.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a prevalent condition among patients with cardiovascular risk factors, leading to a reduced quality of life and an increased risk of major adverse cardiovascular events. Novel invasive techniques have emerged to more accurately diagnose CMD. However, CMD's natural history remains poorly understood due to limited data. To address this knowledge gap, the Coronary Microvascular Disease Registry (CMDR) was established with the primary aim of standardizing comprehensive coronary functional testing and understanding of CMD. DESIGN: CMDR is a prospective, multicenter registry enrolling an unlimited number of consecutive subjects who undergo comprehensive invasive hemodynamic assessment of the entire coronary arterial vasculature. Patients undergoing acetylcholine provocation test for coronary vasospasm will also be included. Follow-up assessments will be conducted at 30 days and annually for up to 5 years. The primary endpoint is Canadian Cardiovascular Society angina grade over time. Secondary endpoints, including all-cause mortality, cardiovascular death, acute myocardial infarction, stroke, hospitalizations, medication changes, and subsequent coronary interventions, will be analyzed to establish long-term safety and clinical outcomes in patients undergoing invasive CMD assessment. SUMMARY: CMDR aims to characterize the clinical and physiologic profile of patients undergoing comprehensive invasive coronary functional testing, simultaneously providing crucial longitudinal information on the natural history and outcomes of these patients. This will shed light on CMD's course and clinical implications, which, in turn, holds the potential to significantly improve diagnostic and treatment strategies for CMD patients, ultimately leading to the enhancement of their overall prognosis and quality of life. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, NCT05960474.

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.

A novel approach to saline/contrast delivery in excimer laser coronary atherectomy (ELCA) to enhance efficacy: MAXCon ELCA technique.

The advent of excimer laser coronary atherectomy (ELCA) nearly four decades ago heralded a novel way to treat complex lesions, both coronary and peripheral, which were previously untraversable and thus untreatable. These complex lesions include heavily calcified lesions, ostial lesions, bifurcation lesions, chronic total occlusions, in-stent restenosis (including stent underexpansion), and degenerative saphenous vein grafts. We discuss the technology of ELCA, its indications, applications, and complications, and suggest the "MAXCon ELCA" technique for better outcomes without increased risk. Lastly, we present a case of MAXCon ELCA effectively treating a complex lesion.

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.

Coronary microvascular dysfunction assessment: A comparative analysis of procedural aspects.

BACKGROUND: Full adoption of coronary microvascular dysfunction (CMD) assessment faces challenges due to its invasive nature and concerns about prolonged procedure time and increased contrast and/or radiation exposure. We compared procedural aspects of CMD invasive assessment to diagnostic left heart catheterization (DLHC) in patients with chest pain who were not found to have obstructive coronary artery disease. METHODS: A total of 227 patients in the Coronary Microvascular Disease Registry were compared to 1592 patients who underwent DLHC from August 2021 to November 2023. The two cohorts were compared using propensity-score matching; primary outcomes were fluoroscopy time and total contrast use. RESULTS: The participants' mean age was 64.1 ± 12.6 years. CMD-assessed patients were more likely to be female (66.5% vs. 45.2%, p < 0.001) and have hypertension (80.2% vs. 44.5%, p < 0.001), history of stroke (11.9% vs. 6.3%, p = 0.002), and history of myocardial infarction (20.3% vs. 7.7%, p < 0.001). CMD assessment was safe, without any reported adverse outcomes. A propensity-matched analysis showed that patients who underwent CMD assessment had slightly higher median contrast exposure (50 vs. 40 mL, p < 0.001), and slightly longer fluoroscopy time (6.9 vs. 4.7 min, p < 0.001). However, there was no difference in radiation dose (209.3 vs. 219 mGy, p = 0.58) and overall procedure time (31 vs. 29 min, p = 0.37). CONCLUSION: Compared to DLHC, CMD assessment is safe and requires only slightly additional contrast use (10 mL) and slightly longer fluoroscopy time (2 min) without clinical implications. These findings emphasize the favorable safety and feasibility of invasive CMD assessment.

Reasons for repeat urgent cardiac procedures within the same day.

BACKGROUND: With advances in technology and technique, the expectations are that patients undergoing procedures in the cardiac catheterization laboratory will not need to return for a repeat procedure within the same day. OBJECTIVES: Report why subjects undergoing cardiac procedures return urgently to the catheterization laboratory for a repeat procedure during the same day. METHODS: We retrospectively reviewed patients who were brought back to the cardiac catheterization laboratory within the same day for a repeat procedure. The reasons for index and repeat procedure were identified. Patients who were transferred from an outside center after an initial procedure at other centers were excluded. RESULTS: Between November 2013 and January 2022, 55,942 catheterization procedures were performed at our institution, of which 140 entries were included in our analysis. Common reasons for the index procedure were diagnostic angiography (35.0%), percutaneous coronary intervention (PCI, 29.2%), and transcatheter aortic valve replacement (15.0%). The most common reason for bringing these patients back to the cardiac catheterization laboratory within the same day was vascular complications (24.2%), followed by repeat PCI (20.7%), need for hemodynamic support (15.0%), heart team discussion and PCI (10%), and pacemaker implantation (10%). Acute limb ischemia was the most commonly identified vascular complication (7.1%), followed by pseudoaneurysm (5%). CONCLUSION: Our study demonstrates that a very small number of patients underwent repeat procedures within the same day. Special attention should be paid to vascular access and closure and assessment of recurrent chest pain postprocedure, as these are the main reasons for same-day repeat procedures.

Impact of preprocedural left ventricular systolic function on the safety and durability of percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is considered less safe in patients with reduced ejection fraction (EF), an impression based on older data. Whether the safety and durability of contemporary PCI are different in patients with reduced EF compared with normal EF patients is unknown. METHODS: Patients from the BIOFLOW II, IV and V clinical trials were grouped as normal EF (≥50%) and reduced EF (30%-50%). Using multivariable logistic regression and cox proportional hazards regression, we determined relations of EF category with procedural safety (a composite of cardiac death, myocardial infarction, stroke and urgent coronary artery bypass grafting within 30 days of PCI) and target lesion failure (TLF; comprising cardiac death, target vessel myocardial infarction, target vessel revascularization within 1 year of PCI) respectively. In sensitivity analyses, we regrouped patients into EF < 45% and ≥55% and repeated the aforementioned analyses. RESULTS: In 1685 patients with normal EF (mean age 65 years; 27% women; mean EF 61%) and 259 with low EF (mean age 64 years; 17% women; mean EF 41%), 101 safety and 148 TLF events occurred. Compared with patients in the normal EF group, those with reduced EF had neither a statistically significant higher proportion of safety events, nor a higher multivariable-adjusted risk for such events. Similarly, patients with reduced EF and normal EF did not differ in terms of TLF event proportions or multivariable-adjusted risk for TLF. The results were similar in sensitivity analyses with EF groups redefined to create a 10% between-group EF separation. CONCLUSION: PCI safety and durability outcomes are similar in patients with mild-moderately reduced EF and normal EF.

Angiographic characteristics of patients with STEMI and COVID-19: Insights from NACMI registry.

BACKGROUND: To date, there has been no independent core lab angiographic analysis of patients with COVID-19 and STEMI. The study characterized the angiographic parameters of patients with COVID-19 and STEMI. METHODS: Angiograms of patients with COVID-19 and STEMI from the North American COVID-19 Myocardial Infarction (NACMI) Registry were sent to a Core Laboratory in Vancouver, Canada. Culprit lesion(s), Thrombolysis In Myocardial Infarction (TIMI) flow, Thrombus Grade Burden (TGB), and percutaneous coronary intervention (PCI) outcome were assessed. RESULTS: From 234 patients, 74% had one culprit lesion, 14% had multiple culprits and 12% had no culprit identified. Multivessel thrombotic disease and multivessel CAD were found in 27% and 53% of patients, respectively. Stent thrombosis accounted for 12% of the presentations and occurred in 55% of patients with previous coronary stents. Of the 182 who underwent PCI, 60 (33%) had unsuccessful PCI due to post-PCI TIMI flow <3 (43/60), residual high thrombus burden (41/60) and/or thrombus related complications (27/60). In-hospital mortality for successful, partially successful, and unsuccessful PCI was 14%, 13%, and 27%, respectively. Unsuccessful PCI was associated with increased risk of in-hospital mortality (risk ratio [RR] 1.96; 95% CI: 1.05-3.66, P = .03); in the adjusted model this estimate was attenuated (RR: 1.24; 95% CI: 0.65-2.34, P = .51). CONCLUSION: In patients with COVID-19 and STEMI, thrombus burden was pervasive with notable rates of multivessel thrombotic disease and stent thrombosis. Post-PCI, persistent thrombus and sub-optimal TIMI 3 flow rates led to one-third of the PCI's being unsuccessful, which decreased over time but remained an important predictor of in-hospital mortality.

Impact of transcatheter heart valve type on outcomes of surgical explantation after failed transcatheter aortic valve replacement: the EXPLANT-TAVR international registry.

BACKGROUND: There are limited data on the impact of transcatheter heart valve (THV) type on the outcomes of surgical explantation after THV failure. AIMS: We sought to determine the outcomes of transcatheter aortic valve replacement (TAVR) explantation for failed balloon-expandable valves (BEV) versus self-expanding valves (SEV). METHODS: From November 2009 to February 2022, 401 patients across 42 centres in the EXPLANT-TAVR registry underwent TAVR explantation during a separate admission from the initial TAVR. Mechanically expandable valves (N=10, 2.5%) were excluded. The outcomes of TAVR explantation were compared for 202 (51.7%) failed BEV and 189 (48.3%) failed SEV. RESULTS: Among 391 patients analysed (mean age: 73.0±9.8 years; 33.8% female), the median time from index TAVR to TAVR explantation was 13.3 months (interquartile range 5.1-34.8), with no differences between groups. Indications for TAVR explantation included endocarditis (36.0% failed SEV vs 55.4% failed BEV; p<0.001), paravalvular leak (21.2% vs 11.9%; p=0.014), structural valve deterioration (30.2% vs 21.8%; p=0.065) and prosthesis-patient mismatch (8.5% vs 10.4%; p=0.61). The SEV group trended fewer urgent/emergency surgeries (52.0% vs 62.3%; p=0.057) and more root replacement (15.3% vs 7.4%; p=0.016). Concomitant cardiac procedures were performed in 57.8% of patients, including coronary artery bypass graft (24.8%), and mitral (38.9%) and tricuspid (14.6%) valve surgery, with no differences between groups. In-hospital, 30-day, and 1-year mortality and stroke rates were similar between groups (allp>0.05), with no differences in cumulative mortality at 3 years (log-rank p=0.95). On multivariable analysis, concomitant mitral surgery was an independent predictor of 1-year mortality after BEV explant (hazard ratio [HR] 2.00, 95% confidence interval [CI]: 1.07-3.72) and SEV explant (HR 2.00, 95% CI: 1.08-3.69). CONCLUSIONS: In the EXPLANT-TAVR global registry, BEV and SEV groups had different indications for surgical explantation, with more root replacements in SEV failure, but no differences in midterm mortality and morbidities. Further refinement of TAVR explantation techniques are important to improving outcomes.

Targeting inflammation in atherosclerosis: overview, strategy and directions.

Atherosclerosis is a chronic condition characterised by the build-up of plaque in the inner lining of the blood vessels and it is the main underlying cause of cardiovascular disease. The development of atherosclerosis is associated with the accumulation of cholesterol and inflammation. Although effective therapies exist to lower low-density lipoprotein cholesterol (LDL-C) levels, some patients still experience cardiovascular events due to persistent inflammation, known as residual inflammatory risk (RIR). Researchers have conducted laboratory and animal studies to investigate the measurement and targeting of the inflammatory cascade associated with atherosclerosis, which have yielded promising results. In addition to guideline-directed lifestyle modifications and optimal medical therapy focusing on reducing LDL-C levels, pharmacological interventions targeting inflammation may provide further assistance in preventing future cardiac events. This review aims to explain the mechanisms of inflammation in atherosclerosis, identifies potential biomarkers, discusses available therapeutic options and their strengths and limitations, highlights future advancements, and summarises notable clinical studies. Finally, an evaluation and management algorithm for addressing RIR is presented.