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BACKGROUND: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials. METHODS: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used. RESULTS: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT (P=0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients (P=0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P=0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P<0.001) and -5.2 mm Hg (-7.1, -3.3; P<0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups. CONCLUSIONS: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.
Subject(s)
Hypertension , Renal Artery , Female , Humans , Male , Antihypertensive Agents/therapeutic use , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Denervation/adverse effects , Denervation/methods , Hypertension/diagnosis , Hypertension/drug therapy , Kidney , Renal Artery/diagnostic imaging , Sympathectomy/methods , Treatment Outcome , Middle AgedABSTRACT
BACKGROUND: Plaque composition and wall shear stress (WSS) magnitude act as well-established players in coronary plaque progression. However, WSS magnitude per se does not completely capture the mechanical stimulus to which the endothelium is subjected, since endothelial cells experience changes in the WSS spatiotemporal configuration on the luminal surface. This study explores WSS profile and lipid content signatures of plaque progression to identify novel biomarkers of coronary atherosclerosis. METHODS: Thirty-seven patients with acute coronary syndrome underwent coronary computed tomography angiography, near-infrared spectroscopy intravascular ultrasound, and optical coherence tomography of at least 1 nonculprit vessel at baseline and 1-year follow-up. Baseline coronary artery geometries were reconstructed from intravascular ultrasound and coronary computed tomography angiography and combined with flow information to perform computational fluid dynamics simulations to assess the time-averaged WSS magnitude (TAWSS) and the variability in the contraction/expansion action exerted by WSS on the endothelium, quantifiable in terms of topological shear variation index (TSVI). Plaque progression was measured as intravascular ultrasound-derived percentage plaque atheroma volume change at 1-year follow-up. Plaque composition information was extracted from near-infrared spectroscopy and optical coherence tomography. RESULTS: Exposure to high TSVI and low TAWSS was associated with higher plaque progression (4.00±0.69% and 3.60±0.62%, respectively). Plaque composition acted synergistically with TSVI or TAWSS, resulting in the highest plaque progression (≥5.90%) at locations where lipid-rich plaque is exposed to high TSVI or low TAWSS. CONCLUSIONS: Luminal exposure to high TSVI, solely or combined with a lipid-rich plaque phenotype, is associated with enhanced plaque progression at 1-year follow-up. Where plaque progression occurred, low TAWSS was also observed. These findings suggest TSVI, in addition to low TAWSS, as a potential biomechanical predictor for plaque progression, showing promise for clinical translation to improve patient prognosis.
Subject(s)
Coronary Artery Disease , Plaque, Atherosclerotic , Humans , Coronary Vessels/diagnostic imaging , Endothelial Cells , Coronary Artery Disease/diagnostic imaging , Computed Tomography Angiography , Lipids , Stress, Mechanical , Coronary AngiographyABSTRACT
BACKGROUND: Transcatheter aortic valve implantation (TAVI) is considered a safe and effective alternative to surgical aortic valve replacement (SAVR) for elderly patients across the operative risk spectrum. In the Netherlands, TAVI is reimbursed only for patients with a high operative risk. Despite this, one fifth of TAVI patients are <â¯75 years of age. We aim to compare patient characteristics and outcomes of TAVI and SAVR patients <â¯75 years. METHODS: This study included all patients <â¯75 years without active endocarditis undergoing TAVI or SAVR for severe aortic stenosis, mixed aortic valve disease or degenerated aortic bioprosthesis between 2015 and 2020 at the Erasmus University Medical Centre. Dutch authority guidelines were used to classify operative risk. RESULTS: TAVI was performed in 292 patients, SAVR in 386 patients. Based on the Dutch risk algorithm, 59.6% of TAVI patients and 19.4% of SAVR patients were at high operative risk. There was no difference in 30-day all-cause mortality between TAVI and SAVR (2.4% vs 0.8%, pâ¯= 0.083). One-year and 5year mortality was higher after TAVI than after SAVR (1-year: 12.5% vs 4.3%, pâ¯< 0.001; 5year: 36.8% vs 12.0%, pâ¯< 0.001). Within risk categories we found no difference between treatment strategies. Independent predictors of mortality were cardiovascular comorbidities (left ventricular ejection fraction <â¯30%, atrial fibrillation, pulmonary hypertension) and the presence of malignancies, liver cirrhosis or immunomodulatory drug use. CONCLUSION: At the Erasmus University Medical Centre, in patients <â¯75 years, TAVI is selected for higher-risk phenotypes and overall has higher long-term mortality than SAVR. We found no evidence for worse outcome within risk categories.
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The clinical implications of hypertension in addition to a high prevalence of both uncontrolled blood pressure and medication nonadherence promote interest in developing device-based approaches to hypertension treatment. The expansion of device-based therapies and ongoing clinical trials underscores the need for consistency in trial design, conduct, and definitions of clinical study elements to permit trial comparability and data poolability. Standardizing methods of blood pressure assessment, effectiveness measures beyond blood pressure alone, and safety outcomes are paramount. The Hypertension Academic Research Consortium (HARC) document represents an integration of evolving evidence and consensus opinion among leading experts in cardiovascular medicine and hypertension research with regulatory perspectives on clinical trial design and methodology. The HARC document integrates the collective information among device-based therapies for hypertension to better address existing challenges and identify unmet needs for technologies proposed to treat the world's leading cause of death and disability. Consistent with the Academic Research Consortium charter, this document proposes pragmatic consensus clinical design principles and outcomes definitions for studies aimed at evaluating device-based hypertension therapies.
Subject(s)
Hypertension , Clinical Trials as Topic , Consensus , Humans , Hypertension/diagnosis , Hypertension/therapyABSTRACT
BACKGROUND: Physiological assessment of intermediate coronary lesions to guide coronary revascularization is currently recommended by international guidelines. Vessel fractional flow reserve (vFFR) has emerged as a new approach to derive fractional flow reserve (FFR) from 3D-quantitative coronary angiography (3D-QCA) without the need for hyperemic agents or pressure wires. STUDY DESIGN AND OBJECTIVES: The FAST III is an investigator-initiated, open label, multicenter randomized trial comparing vFFR guided versus FFR guided coronary revascularization in approximately 2228 patients with intermediate coronary lesions (defined as 30%-80% stenosis by visual assessment or QCA). Intermediate lesions are physiologically assessed using on-line vFFR or FFR and treated if vFFR or FFR ≤0.80. The primary end point is a composite of all-cause death, any myocardial infarction, or any revascularization at 1-year post-randomization. Secondary end points include the individual components of the primary end point and cost-effectiveness will be investigated. CONCLUSIONS: FAST III is the first randomized trial to explore whether a vFFR guided revascularization strategy is non-inferior to an FFR guided strategy in terms of clinical outcomes at 1-year follow-up in patients with intermediate coronary artery lesions.
Subject(s)
Coronary Artery Disease , Coronary Stenosis , Fractional Flow Reserve, Myocardial , Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Coronary Angiography , Fractional Flow Reserve, Myocardial/physiology , Prospective Studies , Follow-Up Studies , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/surgery , Treatment Outcome , Coronary Artery Disease/diagnosis , Coronary Artery Disease/surgeryABSTRACT
OBJECTIVES: To evaluate the stent expansion of the durable-polymer Zotarolimus-eluting stent (dp-ZES), the durable-polymer Everolimus-eluting stent (dp-EES), and the bioabsorbable-polymer Sirolimus-eluting stent (bp-SES) in calcified coronary chronic total occlusions (CTO). BACKGROUND: The newer generation stents with ultrathin struts might raise concerns regarding reduced radial strength and higher stent recoil (SR) when implanted in calcified CTOs. METHODS: Between January 2017 and June 2021 consecutive patients with CTO undergoing percutaneous coronary intervention with dp-ZES, dp-EES, or bp-SES were evaluated. The analysis was performed in calcific and in noncalcific CTOs. Quantitative coronary angiography analysis was used to assess diameter stenosis (DS), absolute and relative SR, absolute and relative focal SR, absolute and relative balloon deficit (BD), and absolute and relative focal BD. The primary endpoint was DS. RESULTS: A total of 213 CTOs were evaluated, 115 calcific CTOs (dp-ZES:25, dp-EES:29, bp-SES:61) and 98 non-calcific CTOs (dp-ZES:41, dp-EES:11, bp-SES:46). In calcific CTOs, residual DS was lower in dp-ZES than in dp-EES and bp-SES (-1.00% [-6.50-6.50] vs. 13.00% [7.0-19.00] vs. 15.00% [5.00-20.00]; p < 0.001). Dp-ZES was also an independent predictor of residual DS ≤ 10% (OR 11.34, 95% CI 2.6-49.43, p = 0.001). Absolute and relative focal SR and absolute and relative SR were similar between dp-ZES, dp-EES, and bp-SES (p = 0.913, p = 0.890, p = 0.518, p = 0.426, respectively). In noncalcified CTOs, the residual DS was similar in the three groups (p = 0.340). High relative focal SR was less frequent in dp-ZES than in dp-EES and in bp-SES (19.5% vs. 54.5% vs. 37.0%; p < 0.048). CONCLUSIONS: The three stent platforms demonstrated an overall low residual DS when implanted in CTOs. However, dp-ZES was associated with the lowest residual DS and identified as independent predictor of residual DS ≤ 10% in patients with calcific CTOs. Dp-ZES was associated with a lower incidence of high relative focal stent recoil, in noncalcific CTOs. Balloon deficit might be considerate as a surrogate for stent expansion in calcified CTOs.
Subject(s)
Coronary Artery Disease , Coronary Occlusion , Drug-Eluting Stents , Percutaneous Coronary Intervention , Humans , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/therapy , Treatment Outcome , Percutaneous Coronary Intervention/adverse effects , Everolimus/adverse effects , Stents , Polymers , Absorbable Implants , Prosthesis Design , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapyABSTRACT
BACKGROUND: Severe coronary artery calcification is associated with stent underexpansion and subsequent stent failure. AIMS: We aimed to identify optical coherence tomography (OCT)-derived predictors of absolute (minimal stent area [MSA]) and relative stent expansion in calcified lesions. METHODS: This retrospective cohort study included patients who underwent percutaneous coronary intervention (PCI) with OCT assessment before and after stent implantation between May 2008 and April 2022. Pre-PCI OCT was used to assess calcium burden and post-PCI OCT was used to assess absolute and relative stent expansion. RESULTS: A total of 361 lesions in 336 patients were analyzed. Target lesion calcification (defined as OCT-detected maximum calcium angle ≥ 30°) was present in 242 (67.0%) lesions. Following PCI, median MSA was 5.37 mm2 in calcified lesions and 6.24 mm2 in noncalcified lesions (p < 0.001). Median stent expansion was 78% in calcified lesions and 83% in noncalcified lesions (p = 0.325). In the subset of calcified lesions, average stent diameter, preprocedural minimal lumen area, and total calcium length were independent predictors of MSA in multivariable analysis (mean difference 2.69 mm2 /mm2 , 0.52 mm2 /mm, and -0.28 mm2 /5 mm, respectively, all p < 0.001). Total stent length was the only independent predictor of relative stent expansion (mean difference -0.465% per mm, p < 0.001). Calcium angle, thickness, and the presence of nodular calcification were not significantly associated with MSA or stent expansion in multivariable analyses. CONCLUSION: Calcium length appeared to be the most important OCT-derived predictor of MSA, whereas stent expansion was mainly determined by total stent length.
Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , Vascular Calcification , Humans , Percutaneous Coronary Intervention/adverse effects , Tomography, Optical Coherence/methods , Retrospective Studies , Calcium , Treatment Outcome , Vascular Calcification/diagnostic imaging , Vascular Calcification/therapy , Vascular Calcification/pathology , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Predictive Value of Tests , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Coronary Artery Disease/pathology , Stents , Coronary Angiography/methodsABSTRACT
BACKGROUND: Dedicated prospective studies investigating high-definition intravascular ultrasound (HD-IVUS)-guided primary percutaneous coronary intervention (PCI) are lacking. The aim of this study was to qualify and quantify culprit lesion plaque characteristics and thrombus using HD-IVUS in patients presenting with ST-segment elevation myocardial infarction (STEMI). METHODS: The SPECTRUM study is a prospective, single-center, observational cohort study investigating the impact of HD-IVUS-guided primary PCI in 200 STEMI patients (NCT05007535). The first 100 study patients with a de novo culprit lesion and a per-protocol mandated preintervention pullback directly after vessel wiring were subject to a predefined imaging analysis. Culprit lesion plaque characteristics and different thrombus types were assessed. An IVUS-derived thrombus score, including a 1-point adjudication for a long total thrombus length, long occlusive thrombus length, and large maximum thrombus angle, was developed to differentiate between low (0-1 points) and high (2-3 points) thrombus burden. Optimal cut-off values were obtained using receiver operating characteristic curves. RESULTS: The mean age was 63.5 (±12.1) years and 69 (69.0%) patients were male. The median culprit lesion length was 33.5 (22.8-38.9) mm. Plaque rupture and convex calcium were appreciated in 48 (48.0%) and 10 (10.0%) patients, respectively. Thrombus was observed in 91 (91.0%) patients (acute thrombus 3.3%; subacute thrombus 100.0%; organized thrombus 22.0%). High IVUS-derived thrombus burden was present in 37/91 (40.7%) patients and was associated with higher rates of impaired final thrombolysis in myocardial infarction flow (grade 0-2) (27.0% vs. 1.9%, p < 0.001). CONCLUSIONS: HD-IVUS in patients presenting with STEMI allows detailed culprit lesion plaque characterization and thrombus grading that may guide tailored PCI.
Subject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , Plaque, Atherosclerotic , ST Elevation Myocardial Infarction , Thrombosis , Humans , Male , Middle Aged , Female , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , Prospective Studies , Percutaneous Coronary Intervention/adverse effects , Coronary Angiography , Treatment Outcome , Ultrasonography, Interventional/methods , Myocardial Infarction/pathologyABSTRACT
Importance: Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. Objective: To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. Design, Setting, and Participants: Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. Interventions: Ultrasound renal denervation vs a sham procedure. Main Outcomes and Measures: The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. Results: Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, -7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, -1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, -6.3 mm Hg [95% CI, -9.3 to -3.2 mm Hg], P < .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group. Conclusions and Relevance: In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT03614260.
Subject(s)
Denervation , Hypertension , Ultrasonography, Interventional , Female , Humans , Male , Middle Aged , Antihypertensive Agents/therapeutic use , Denervation/methods , Endovascular Procedures , Hypertension/surgery , Kidney/diagnostic imaging , Kidney/innervation , Ultrasonography, Interventional/methods , Vascular Surgical Procedures , Single-Blind MethodABSTRACT
BACKGROUND: In January 2021, the Diamondback 360 orbital atherectomy (OA) system received CE mark approval and became available in Europe. The first procedure in Europe was performed at the Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands. AIMS: To report the procedural safety and efficacy of the initial experience with OA in a tertiary care institution in the Netherlands. METHODS: Patients with de novo severely calcified coronary artery disease who were treated with intended invasive imaging-guided OA were included in a prospective single-centre registry. Device success, defined as less than 50% stenosis after OA, and procedural success, defined as successful stent implantation with less than 50% residual stenosis, were evaluated. Calcium debulking effects were assessed by invasive imaging. Safety was assessed up to 30 days after the index procedure. RESULTS: Between February 2021 and June 2021, 29 patients with a total of 39 coronary arteries underwent OA. Target lesions were heavily calcified with a mean length of 32â¯mm and a calcium arc of 320 degrees. Invasive imaging was applied in all but one patient and 36 vessels. Superficial sanding was observed in almost all vessels (90%) and fracturing of deeper medial calcium in more than half of the vessels (63%), with a device success of 66% and procedural success of 94%. The mean stent symmetry index was 0.84, indicating good circular stent expansion. No primary safety events occurred during 30 days of follow-up. CONCLUSION: Our initial experience with OA for heavily calcified coronary lesions demonstrated favourable debulking effects and plaque modification, with high procedural success and clinical safety.
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INTRODUCTION: Delays in the diagnosis and referral of aortic stenosis (AS) during the coronavirus disease 2019 (COVID-19) pandemic may have affected the haemodynamic status of AS patients. We aimed to compare clinical and haemodynamic characteristics of severe AS patients referred for transcatheter aortic valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) before the pandemic versus two subsequent periods. METHODS: This study compared three 1year historical cohorts: a pre-COVID-19 group (PCOV), a 1st-year COVID-19 group (COV-Y1) and a 2nd-year COVID-19 group (COV-Y2). The main parameters were baseline New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP). Demographics, procedural characteristics and 30-day clinical outcomes were assessed. The transition time between heart team decision and TAVI was examined. Pairwise group comparisons were performed (PCOV vs COV-1Y and COV-1Y vs COV-2Y). RESULTS: A total of 720 patients were included with 266, 249 and 205 patients in the PCOV, COV-Y1 and COV-Y2 groups, respectively. BAV was performed in 28 patients (4%). NYHA class did not differ across the cohorts. Compared to PCOV, LVEF was slightly lower in COV-Y1 (58% (49-60%) vs 57% (45-60%), pâ¯= 0.03); no difference was observed when comparing COV-Y1 and COV-Y2. LVEDP was higher in COV-Y1 than in PCOV (20â¯mmâ¯Hg (16-26â¯mmâ¯Hg) vs 17â¯mmâ¯Hg (13-24â¯mmâ¯Hg), pâ¯= 0.01). No difference was found when comparing LVEDP between COV-Y1 and COV-Y2. Thirty-day mortality did not differ between groups. Transition time was reduced in the COVID era. Duration of hospital stay declined over the study period. CONCLUSIONS: Patients undergoing TAVI during the COVID-19 pandemic had more advanced AS illustrated by lower LVEF and higher LVEDP, but there were no differences in clinical outcome. The TAVI pathway became more efficient.
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BACKGROUND: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. METHODS: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426. FINDINGS: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. INTERPRETATION: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. FUNDING: ReCor Medical.
Subject(s)
Denervation/methods , Endovascular Procedures/methods , Hypertension/therapy , Renal Artery/innervation , Renal Artery/surgery , Ultrasonic Surgical Procedures/methods , Angiotensin Receptor Antagonists/therapeutic use , Blood Pressure Monitoring, Ambulatory , Calcium Channel Blockers/therapeutic use , Drug Resistance , Female , Humans , Kidney/blood supply , Male , Middle Aged , Single-Blind Method , Sodium Chloride Symporter Inhibitors/therapeutic useABSTRACT
OBJECTIVES: To validate a simplified core laboratory intravascular ultrasound (IVUS) analysis method based on frames with visually determined minimal lumen areas (MLAs) as compared with a comprehensive (per frame) analysis method. BACKGROUND: IVUS-guided percutaneous coronary intervention has proven to be superior to angiography-guided stenting. In clinical practice, cross-sections with visually determined MLA are measured to determine lesion severity or minimal stent area (MSA), however, its accuracy has not been compared with a comprehensive per frame analysis method. METHODS: A total of 50 stented coronary segments of anonymized core lab datasets were analyzed using a comprehensive analysis method and reanalyzed by two core lab analysts using the simplified method including a maximum of seven frames to be analyzed (the visually determined MSA, the first and last frame, and the MLA of each reference segment). The main parameters of interest were MSA, MLA in the reference segments, and plaque burden. RESULTS: The simplified method showed moderate agreement for measurement of the proximal MLA (7.51 ± 2.52 vs. 6.32 ± 1.88 mm2 , intraclass correlation coefficient [ICC] = 0.73), good agreement for the distal MLA (5.41 ± 1.85 vs. 5.11 ± 1.38 mm2 , ICC = 0.84) and plaque burden proximal (0.49 ± 0.12 vs. 0.50 ± 0.11, ICC = 0.88), and excellent agreement for the MSA (5.35 ± 1.05 vs. 5.32 ± 0.99 mm2 , ICC = 0.94) and plaque burden distal (0.47 ± 0.14 vs. 0.47 ± 0.12, ICC = 0.92), when compared with the comprehensive analysis method. Inter- and intraobserver analysis revealed good-to-excellent agreement for all parameters. CONCLUSIONS: Measuring poststenting IVUS cross-sections with visually determined MLAs by experienced core lab analysts is an accurate and reproducible method to identify MLAs.
Subject(s)
Coronary Artery Disease , Coronary Vessels , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Coronary Vessels/diagnostic imaging , Humans , Treatment Outcome , Ultrasonography, Interventional/methodsABSTRACT
OBJECTIVES: To compare stent recoil (SR) of the thin-strut durable-polymer Zotarolimus-eluting stent (dp-ZES) and the ultrathin-strut bioabsorbable-polymer Sirolimus-eluting stent (bp-SES) in chronic total occlusions (CTOs) and to investigate the predictors of high SR in CTOs. BACKGROUND: Newer ultrathin drug eluting stent might be associated with lower radial force and higher elastic recoil due to the thinner strut design, possibly impacting on the rate of in-stent restenosis and thrombosis. METHODS: Between January 2017 and November 2019, consecutive patients with CTOs undergoing percutaneous coronary intervention were evaluated. Only patients treated with dp-ZES or bp-SES were included and stratified accordingly. Quantitative coronary angiography analysis was used to assess absolute SR, relative SR, absolute focal SR, relative focal SR, high absolute, and high relative focal SR. RESULTS: A total of 128 lesions (67 treated with dp-ZES and 61 with bp-SES) in 123 patients were analyzed. Between bp-SES and dp-ZES no differences were found in absolute SR (p = .188), relative SR (p = .138), absolute focal SR (p = .069), and relative focal SR (p = .064). High absolute and high relative focal SR occurred more frequently in bp-SES than in dp-ZES (p = .004 and p = .015). Bp-SES was a predictor of high absolute focal SR (Odds ratio [OR] 3.29, 95% confidence interval [CI] 1.50-7.22, p = .003]. High-pressure postdilation and bp-SES were predictors of high relative focal SR (OR 2.22, 95% CI 1.01-4.86, p = .047; OR 2.74, 95% CI 1.24-6.02, p = .012, respectively). CONCLUSIONS: Both stents showed an overall low SR. However, ultra-thin strut bp-SES was a predictor of high absolute and high relative focal SR.
Subject(s)
Cardiovascular Agents , Coronary Artery Disease , Drug-Eluting Stents , Percutaneous Coronary Intervention , Absorbable Implants , Cardiovascular Agents/adverse effects , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/surgery , Everolimus , Humans , Percutaneous Coronary Intervention/adverse effects , Polymers , Prosthesis Design , Sirolimus/analogs & derivatives , Treatment OutcomeABSTRACT
OBJECTIVES: To study the safety and feasibility of a restrictive temporary-RV-pacemaker use and to evaluate the need for temporary pacemaker insertion for failed left ventricular (LV) pacing ability (no ventricular capture) or occurrence of high-degree AV-blocks mandating continuous pacing. BACKGROUND: Ventricular pacing remains an essential part of contemporary transcatheter aortic valve implantation (TAVI). A temporary-right-ventricle (RV)-pacemaker lead is the standard approach for transient pacing during TAVI but requires central venous access. METHODS: An observational registry including 672 patients who underwent TAVI between June 2018 and December 2020. Patients received pacing on the wire when necessary, unless there was a high-anticipated risk for conduction disturbances post-TAVI, based on the baseline-ECG. The follow-up period was 30 days. RESULTS: A temporary-RV-pacemaker lead (RVP-cohort) was inserted in 45 patients, pacing on the wire (LVP-cohort) in 488 patients, and no pacing (NoP-cohort) in 139 patients. A bailout temporary pacemaker was implanted in 14 patients (10.1%) in the NoP-cohort and in 24 patients (4.9%) in the LVP-cohort. One patient in the LVP-cohort needed an RV-pacemaker for incomplete ventricular capture. Procedure time was significantly longer in the RVP-cohort (68 min [IQR 52-88.] vs. 55 min [IQR 44-72] in NoP-cohort and 55 min [IQR 43-71] in the LVP-cohort [p < 0.005]). Procedural high-degree AV-block occurred most often in the RVP-cohort (45% vs. 14% in the LVP and 16% in the NoP-cohort [p ≤ 0.001]). Need for new PPI occurred in 47% in the RVP-cohort, versus 20% in the NoP-cohort and 11% in the LVP-cohort (p ≤ 0.001). CONCLUSION: A restricted RV-pacemaker strategy is safe and shortens procedure time. The majority of TAVI-procedures do not require a temporary-RV-pacemaker.
Subject(s)
Aortic Valve Stenosis , Atrioventricular Block , Pacemaker, Artificial , Transcatheter Aortic Valve Replacement , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Atrioventricular Block/therapy , Cardiac Pacing, Artificial , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Treatment OutcomeABSTRACT
BACKGROUND: Angiography-based vessel fractional flow reserve (vFFR) demonstrated a strong correlation with invasive fractional flow reserve (FFR) in both a pre- and post-percutaneous coronary intervention (PCI) setting. However, the role of vFFR and its correlation with post-PCI FFR in chronic coronary occlusions (CTO) has not been evaluated yet. We sought to investigate the diagnostic performance of post-PCI vFFR with post-PCI FFR as a reference in patients undergoing successful CTO PCI. METHODS: Between March 2016 and April 2020, a total of 80 patients from the FFR-SEARCH (prospective registry) and FFR REACT (randomized controlled trial) studies underwent successful CTO recanalization with post-PCI FFR measurements. RESULTS: A total of 50 patients (median age 66 (interquartile range [IQR]: 56-74) years, 76% were male) were eligible for the analysis. Median post-PCI FFR was 0.89 (IQR: 0.84-0.94), while median post-PCI vFFR was 0.91 (IQR: 0.85-0.94) (p 0.10). Suboptimal physiological results, defined as FFR and vFFR <0.90, were identified in 26 (52%) and in 21 (42%) patients, respectively. A strong correlation (r = 0.82) was found between vFFR and FFR with a mean bias of 0.013 ± 0.051. Receiver-operating characteristics curve analysis revealed an excellent accuracy of vFFR in predicting FFR <0.90 (area under the curve: 0.97; 95% confidence interval: 0.93-1.00). CONCLUSION: Post-PCI vFFR shows a good correlation with post-PCI FFR and a high diagnostic accuracy for post-PCI FFR ≤0.90 in patients undergoing successful PCI of a CTO lesion.
Subject(s)
Coronary Artery Disease , Fractional Flow Reserve, Myocardial , Percutaneous Coronary Intervention , Humans , Male , Middle Aged , Aged , Female , Fractional Flow Reserve, Myocardial/physiology , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Coronary Angiography/methods , Predictive Value of Tests , Treatment Outcome , Coronary Artery Disease/diagnosisABSTRACT
Large thrombus burden (LTB) during ST-segment elevation myocardial infarction (STEMI) could translate into worse clinical outcomes. The impact of a LTB in terms of long-term clinical outcomes on different myocardial infarct territories has not yet been fully evaluated. From April 2002 to December 2004, consecutive patients with STEMI undergoing percutaneous coronary intervention with drug eluting stent were evaluated. The study sample was stratified in two groups: anterior STEMI and non-anterior STEMI. LTB was considered as a thrombus larger than or equal to 2-vessel diameters, and small thrombus burden less than 2-vessel diameters. Major adverse cardiac events (MACE) were evaluated at 10-year and survival data were collected up to 15-year. A total of 812 patients were evaluated, 6 patients were excluded due to inadequate angiographic images, 410 (50.9%) had an anterior STEMI and 396 (49.1%) a non-anterior STEMI. Patients with LTB had higher rates of 10-year mortality (aHR 2.27, 95%CI 1.42-3.63; p = 0.001) and 10-year MACE (aHR 1.46, 95%CI 1.03-2.08; p = 0.033) in anterior STEMI, but not in non-anterior STEMI (aHR 0.78, 95%CI 0.49-1.24; p = 0.298; aHR 0.71, 95%CI 0.50-1.02; p = 0.062). LTB was associated with increased 30-day mortality (aHR 5.60, 95%CI 2.49-12.61; p < 0.001) and 30-day MACE (aHR 2.72, 95%CI 1.45-5.08; p = 0.002) in anterior STEMI, but not in non-anterior STEMI (aHR 0.39, 95%CI 0.15-1.06; p = 0.066; aHR 0.67, 95%CI 0.31-1.46; p = 0.316). Beyond 30-day, LTB had no impact on mortality and MACE in both groups. In anterior STEMI, LTB is associated with worse long-term clinical outcomes, this effect was driven by early events.
Subject(s)
Coronary Thrombosis , Drug-Eluting Stents , Myocardial Infarction , Non-ST Elevated Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Coronary Angiography , Coronary Thrombosis/complications , Humans , Myocardial Infarction/etiology , Percutaneous Coronary Intervention/adverse effects , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/surgery , Treatment OutcomeABSTRACT
PURPOSE OF REVIEW: Three-dimensional quantitative coronary angiography-based methods of fractional flow reserve (FFR) derivation have emerged as an appealing alternative to conventional pressure-wire-based physiological lesion assessment and have the potential to further extend the use of physiology in general. Here, we summarize the current evidence related to angiography-based FFR and perspectives on future developments. RECENT FINDINGS: Growing evidence suggests good diagnostic performance of angiography-based FFR measurements, both in chronic and acute coronary syndromes, as well as in specific lesion subsets, such as long and calcified lesions, left main coronary stenosis, and bifurcations. More recently, promising results on the superiority of angiography-based FFR as compared to angiography-guided PCI have been published. Currently available angiography -FFR indices proved to be an excellent alternative to invasive pressure wire-based FFR. Dedicated prospective outcome data comparing these indices to routine guideline recommended PCI including the use of FFR are eagerly awaited.
Subject(s)
Coronary Artery Disease , Coronary Stenosis , Fractional Flow Reserve, Myocardial , Percutaneous Coronary Intervention , Coronary Angiography/methods , Coronary Stenosis/diagnostic imaging , Coronary Vessels/diagnostic imaging , Fractional Flow Reserve, Myocardial/physiology , Humans , Predictive Value of Tests , Prospective Studies , Severity of Illness IndexABSTRACT
Importance: Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown. Objective: To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction. Design, Setting, and Participants: The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrollment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals. Interventions: Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 hours after urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg). Main Outcomes and Measures: Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 non-infarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary end points were changes in near-infrared spectroscopy-derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography-derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52. Results: Among 300 randomized patients (mean [SD] age, 58.5 [9.7] years; 56 [18.7%] women; mean [SD] low-density lipoprotein cholesterol level, 152.4 [33.8] mg/dL), 265 (88.3%) underwent serial IVUS imaging in 537 arteries. At 52 weeks, mean change in percent atheroma volume was -2.13% with alirocumab vs -0.92% with placebo (difference, -1.21% [95% CI, -1.78% to -0.65%], P < .001). Mean change in maximum lipid core burden index within 4 mm was -79.42 with alirocumab vs -37.60 with placebo (difference, -41.24 [95% CI, -70.71 to -11.77]; P = .006). Mean change in minimal fibrous cap thickness was 62.67 µm with alirocumab vs 33.19 µm with placebo (difference, 29.65 µm [95% CI, 11.75-47.55]; P = .001). Adverse events occurred in 70.7% of patients treated with alirocumab vs 72.8% of patients receiving placebo. Conclusions and Relevance: Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy resulted in significantly greater coronary plaque regression in non-infarct-related arteries after 52 weeks. Further research is needed to understand whether alirocumab improves clinical outcomes in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT03067844.
Subject(s)
Coronary Artery Disease , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Myocardial Infarction , PCSK9 Inhibitors , Plaque, Atherosclerotic , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Cholesterol, LDL , Coronary Artery Disease/complications , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/drug therapy , Double-Blind Method , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/drug therapy , PCSK9 Inhibitors/therapeutic use , Plaque, Atherosclerotic/complications , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/drug therapy , Treatment OutcomeABSTRACT
BACKGROUND: The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown. AIMS: To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI4 mm) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI. METHODS: In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI4 mm, and OCT-derived minimal FCT, will be assessed 52 weeks post randomization. SUMMARY: The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI. CLINICAL TRIAL REGISTRATION: NCT03067844.