2-Year Clinical and Echocardiography Follow-Up of Transcatheter Mitral Valve Replacement With the Transapical Intrepid System.

BACKGROUND: Thirty-day outcomes with the investigational Intrepid transapical (TA) transcatheter mitral valve replacement (TMVR) system have previously demonstrated good technical success, but longer-term outcomes in larger cohorts need to be evaluated. OBJECTIVES: The authors sought to evaluate the 2-year safety and performance of the Intrepid TA-TMVR system in patients with symptomatic, ≥moderate-severe mitral regurgitation (MR) and high surgical risk. METHODS: Patient eligibility was determined by local heart teams and approved by a central screening committee. Clinical events were adjudicated by an independent clinical events committee. Echocardiography was evaluated by an independent core laboratory. RESULTS: The cohort included 252 patients that were enrolled at 58 international sites before February 2021 as part of the global Pilot Study (n = 95) or APOLLO trial (primary cohort noneligible + TA roll-ins, n = 157). Mean age was 74.2 years, mean STS-PROM was 6.3%, 60.3% were male, and 80.6% were in NYHA functional class III/IV. Most presented with secondary MR (70.1%), and nearly all had ≥moderate-severe MR (98.4%). All-cause mortality was 13.1% (30-day), 27.3% (1-year), and 36.2% (2-year). The 30-day ≥major bleeding event rate was 22.3%. Heart failure rehospitalization was 9.6% (30-day) and 36.2% (2-year). At 2 years, >50% of patients were alive with improvement in NYHA functional class (82.1%, class I/II), and all patients with available echocardiograms had ≤mild MR. CONCLUSIONS: This analysis represents the largest reported TA-TMVR experience with the longest follow-up in high-risk ≥moderate-severe MR patients. Early mortality and heart failure rehospitalizations were significant, exacerbated by early TA-related bleeding events; however, meaningful improvements in clinical outcomes and marked reductions in MR severity were observed through 2 years.

The Role of Comorbidities in Predicting Functional Improvement After Transcatheter Aortic Valve Implantation.

BACKGROUND: Patients undergoing transcatheter aortic valve implantation (TAVI) have a high comorbidity burden. We sought to stratify patients into functional outcomes using the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), a patient-reported outcome with benefits over both the New York Heart Association (NYHA) classification and the original 23-item KCCQ, and to evaluate the importance of comorbidities in predicting failure of functional improvement post-TAVI in a contemporary cohort. METHODS: In total, 366 patients with severe aortic stenosis undergoing TAVI with baseline KCCQ-12 were retrospectively analysed and divided into two groups. Failure to improve was defined as a score <60 and a change in score <10 at 1 year in either overall score (KCCQ-OS) or clinical summary score (KCCQ-CSS). RESULTS: Failure to improve was noted in 13% of patients, who were more likely to have lower KCCQ-OS at baseline (47 [35-59] vs 56 [42-74]), chronic obstructive pulmonary disease (COPD) (19% vs 8%), severe chronic kidney disease (CKD) (13% vs 2%), a clinical frailty score (CFS) ≥5 (41% vs 14%), and lower serum albumin (36 g/L [34-38] vs 38 g/L [35-40]). On multivariate analysis, with an area under the curve of 0.71 (0.63-0.78), baseline KCCQ-OS (adjusted odds ratio [aOR] 0.3 [0.1-0.6], p=0.04), COPD (aOR 2.8 [1.2-6.5], p=0.02), and severe CKD (aOR 5.7 [1.7-18.5], p=0.004) remained independent predictors. CFS alone had a similar predictive value as the multivariable model (OR 2.0 [1.3-3.4], area under the curve 0.69 [0.59-0.80], p<0.001). CONCLUSIONS: KCCQ scores were effective in delineating functional outcomes, with most patients in our relatively lower surgical risk cohort showing significant functional improvements post-TAVI. Low baseline KCCQ, moderate or worse COPD, and severe CKD were associated with failure of improvement post-TAVI. Baseline CFS appears to be a good screening tool to predict poor improvement. These factors should be evaluated and weighted accordingly in pre-TAVI assessments and decision-making.

Incidence, Predictors, and Outcomes of Nonhome Discharge Following Transcatheter Aortic Valve Implantation: A Multicenter Australian Experience-The NHD TAVI Study.

Patients who undergo transcatheter aortic valve implantation (TAVI) commonly experience nonhome discharge (NHD), a phenomenon associated with increased health care expenditure and possibly poorer outcomes. Despite its clinical relevance in TAVI, the incidence and predictors of NHD and its impact on the quality of life remain poorly characterized. Also unknown is the proportion of patients who undergo TAVI that require long-term residential care after initial NHD. Therefore, we aimed to address these questions using a large, multicenter Australian cohort. A total of 2,229 patients who underwent TAVI from 2010 to 2023 included in the Alfred-Cabrini-Epworth TAVI Registry were analyzed. The median age was 82 (interquartile range 78 to 86) years and 41% were women. A total of 257 patients (12%) were not discharged home after TAVI, with the incidence falling over time (R2 = 0.636, p <0.001). A multivariable logistic regression model for NHD prediction was developed with excellent calibration and discrimination (C-statistic = 0.835). The independent predictors of NHD were postprocedural stroke (adjusted odds ratio [aOR] 11.05), procedure at a private hospital (aOR 3.01), living alone (aOR 2.35), vascular access site complications (aOR 2.09), frailty (aOR 1.89), age >80 years (aOR 1.82), hypoalbuminemia (aOR 1.76), New York Heart Association III to IV (aOR 1.74), and hospital length of stay (aOR 1.13) (all p <0.05). NHD was not associated with mortality at 30 days and <1% of all patients required longer-term residential care. In conclusion, although common after TAVI, NHD does not predict short-term mortality, most patients successfully return home within 30 days, and when used appropriately, NHD may serve as a brief and effective method of optimizing functional status without compromising long-term independence.

Long-Term Blood Pressure Reductions Following Catheter-Based Renal Denervation: A Systematic Review and Meta-Analysis.

BACKGROUND: Renal denervation is a recognized adjunct therapy for hypertension with clinically significant blood pressure (BP)-lowering effects. Long-term follow-up data are critical to ascertain durability of the effect and safety. Aside from the 36-month follow-up data available from randomized control trials, recent cohort analyses extended follow-up out to 10 years. We sought to analyze study-level data and quantify the ambulatory BP reduction of renal denervation across contemporary randomized sham-controlled trials and available long-term follow-up data up to 10 years from observational studies. METHODS: A systematic review was performed with data from 4 observational studies with follow-up out to 10 years and 2 randomized controlled trials meeting search and inclusion criteria with follow-up data out to 36 months. Study-level data were extracted and compared statistically. RESULTS: In 2 contemporary randomized controlled trials with 36-month follow-up, an average sham-adjusted ambulatory systolic BP reduction of -12.7±4.5 mm Hg from baseline was observed (P=0.05). Likewise, a -14.8±3.4 mm Hg ambulatory systolic BP reduction was found across observational studies with a mean long-term follow-up of 7.7±2.8 years (range, 3.5-9.4 years; P=0.0051). The observed reduction in eGFR across the long-term follow-up was in line with the predicted age-related decline. Antihypertensive drug burden was similar at baseline and follow-up. CONCLUSIONS: Renal denervation is associated with a significant and clinically meaningful reduction in ambulatory systolic BP in both contemporary randomized sham-controlled trials up to 36 months and observational cohort studies up to 10 years without adverse consequences on renal function.

Impact of Antihypertensive Medication Changes After Renal Denervation Among Different Patient Groups: SPYRAL HTN-ON MED.

BACKGROUND: The SPYRAL HTN-ON MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications)trial showed significant office and nighttime systolic blood pressure (BP) reductions in patients with hypertension following renal denervation (RDN) compared with sham-control patients, despite similar 24-hour BP reductions. We compared antihypertensive medication and BP changes among prespecified subpopulations. METHODS: The multicenter, randomized, sham-controlled, blinded SPYRAL HTN-ON MED trial (n=337) evaluated BP changes after RDN compared with a sham procedure in patients with hypertension prescribed 1 to 3 antihypertensive drugs. Most patients (n=187; 54%) were enrolled outside the United States, while 156 (46%) US patients were enrolled, including 60 (18%) Black Americans. RESULTS: Changes in detected antihypertensive drugs were similar between RDN and sham group patients in the outside US cohort, while drug increases were significantly more common in the US sham group compared with the RDN group. Patients from outside the United States showed significant reductions in office and 24-hour mean systolic BP at 6 months compared with the sham group, whereas BP changes were similar between RDN and sham in the US cohort. Within the US patient cohort, Black Americans in the sham control group had significant increases in medication burden from baseline through 6 months (P=0.003) but not in the RDN group (P=0.44). CONCLUSIONS: Patients enrolled outside the United States had minimal antihypertensive medication changes between treatment groups and had significant office and 24-hour BP reductions compared with the sham group. Increased antihypertensive drug burden in the US sham cohort, especially among Black Americans, may have diluted the treatment effect in the combined trial population. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02439775.

Acute Kidney Injury Following Transcatheter Aortic Valve Implantation-A Contemporary Perspective of Incidence, Predictors, and Outcomes.

BACKGROUND: Acute kidney injury (AKI) is a known complication following transcatheter aortic valve implantation (TAVI), associated with increased morbidity and mortality. Most of this data relates to higher-risk patients with early-generation TAVI valves. With TAVI now established as a safe and cost-effective procedure for low-risk patients, there is a distinct need for updated analysis. We aimed to assess the incidence, predictors, and outcomes of AKI in a contemporary cohort of TAVI patients, concurrently examining the role of temporal evolution on AKI. METHOD: A total of 2,564 patients undergoing TAVI from 2008-2023 included in the Alfred-Cabrini-Epworth (ACE) TAVI Registry were analysed. Patients were divided into AKI and no AKI groups. Outcomes were reported according to the Valve Academic Research Consortium-3 (VARC-3) criteria. RESULTS: Of 2,564 patients, median age 83 (78-87) years, 57.4% men and a median Society of Thoracic Surgeons score of 3.6 (2.4-5.5), 163 (6.4%) patients developed AKI with incidence falling from 9.7% between 2008-2014 to 6% between 2015-2023 (p=0.022). On multivariable analysis, independent predictors of AKI were male sex (adjusted odds ratio [aOR] 1.89, p=0.005), congestive cardiac failure (aOR 1.52, p=0.048), estimated glomerular filtration rate 30-59 (aOR: 2.79, p<0.001), estimated glomerular filtration rate <30 (aOR 8.65, p<0.001), non-femoral access (aOR 5.35, p<0.001), contrast volume (aOR 1.01, p<0.001), self-expanding valve (aOR 1.60, p=0.045), and bleeding (aOR 2.88, p=0.005). Acute kidney injury was an independent predictor of 30-day (aOR: 6.07, p<0.001) and 12-month (aOR: 3.01, p=0.002) mortality, an association that remained consistent when excluding TAVIs performed prior to 2015. CONCLUSIONS: Acute kidney injury remains a relatively common complication of TAVI, associated with significant morbidity and mortality even in less comorbid, contemporary practice patients.

Salt sensitivity risk derived from nocturnal dipping and 24-h heart rate predicts long-term blood pressure reduction following renal denervation.

BACKGROUND: Renal denervation (RDN) has been consistently shown in recent sham-controlled clinical trials to reduce blood pressure (BP). Salt sensitivity is a critical factor in hypertension pathogenesis, but cumbersome to assess by gold-standard methodology. Twenty-four-hour average heart rate (HR) and mean arterial pressure (MAP) dipping, taken by ambulatory blood pressure monitoring (ABPM), stratifies patients into high, moderate, and low salt sensitivity index (SSI) risk categories. OBJECTIVES: We aimed to assess whether ABPM-derived SSI risk could predict the systolic blood pressure reduction at long-term follow-up in a real-world RDN patient cohort. METHODS: Sixty participants had repeat ABPM as part of a renal denervation long-term follow-up. Average time since RDN was 8.9 ±â€Š1.2 years. Based on baseline ABPM, participants were stratified into low (HR < 70 bpm and MAP dipping > 10%), moderate (HR ≥70 bpm or MAP dipping ≤ 10%), and high (HR ≥ 70 bpm and MAP dipping ≤ 10%) SSI risk groups, respectively. RESULTS: One-way ANOVA indicated a significant treatment effect ( P  = 0.03) between low ( n  = 15), moderate ( n  = 35), and high ( n  = 10) SSI risk with systolic BP reduction of 9.6 ±â€Š3.7 mmHg, 8.4 ±â€Š3.5 mmHg, and 28.2 ±â€Š9.6 mmHg, respectively. Baseline BP was not significantly different between SSI Risk groups ( P  = 0.18). High SSI risk independently correlated with systolic BP reduction ( P  = 0.02). CONCLUSIONS: Our investigation indicates that SSI risk may be a simple and accessible measure for predicting the BP response to RDN. However, the influence of pharmacological therapy on these participants is an important extraneous variable requiring testing in prospective or drug naive RDN cohorts.

Variability in Contemporary Heparin Prescription and Activated Clotting Time Monitoring During Percutaneous Coronary Intervention: Call for Up-To-Date Evidence-Based Guidelines.

BACKGROUND: Unfractionated heparin (UFH) is the preferred anticoagulant agent in percutaneous coronary intervention (PCI) procedures for minimising the risk of thrombotic complications. Because of the narrow therapeutic range of UFH, some society guidelines have advocated the use of the activated clotting time (ACT) test to monitor anticoagulation intensity during PCI to reduce thrombotic and bleeding complications. We aimed to assess the current practice of UFH prescription and its monitoring in Australia and New Zealand (ANZ). METHOD: We conducted an anonymous voluntary cross-sectional survey of interventional cardiologists (ICs) who were members of the Cardiac Society of Australia and New Zealand in 2022. The survey included 10 questions pertaining to the current practice of anticoagulation during PCI. RESULTS: Of 430 ICs surveyed, 148 responded (response rate, 34.4%). Most ICs (84.4%) prescribed 70-100 IU/kg of UFH for PCI. Over half of ICs (58.7%) routinely measured ACT during PCI, whereas only 22.2% routinely measured ACT after PCI to guide additional UFH prescription. Among ICs who prescribed additional UFH, approximately half (48%) aimed for ACT ≥250 seconds. Factors that influenced post-PCI UFH prescription included vascular access site and concomitant antiplatelet or anticoagulant therapy. CONCLUSIONS: The contemporary practice of UFH prescription during PCI and ACT monitoring in ANZ is variable and based on outdated evidence preceding current drug-eluting stents, antiplatelet therapies, and radial-first practice. Current society guideline recommendations lack clarity and agreement, reflecting the quality of the available evidence. Up-to-date clinical trials evaluating UFH prescription and ACT monitoring are needed to optimise clinical outcomes in contemporary PCI procedures.

Stroke reduction by cerebral embolic protection devices in transcatheter aortic valve implantation: a systematic review and Bayesian meta-analysis.

OBJECTIVES: The use of cerebral embolic protection (CEP) during transcatheter aortic valve implantation (TAVI) has been studied in several randomised trials. We aimed to perform a systematic review and Bayesian meta-analysis of randomised CEP trials, focusing on a clinically relevant reduction in disabling stroke. METHODS: A systematic search was applied to three electronic databases, including trials that randomised TAVI patients to CEP versus standard treatment. The primary outcome was the risk of disabling stroke. Outcomes were presented as relative risk (RR), absolute risk differences (ARDs), numbers needed to treat (NNTs) and the 95% credible intervals (CrIs). The minimal clinically important difference was determined at 1.1% ARD, per expert consensus (NNT 91). The principal Bayesian meta-analysis was performed under a vague prior, and secondary analyses were performed under two informed literature-based priors. RESULTS: Seven randomised studies were included for meta-analysis (n=3996: CEP n=2126, control n=1870). Under a vague prior, the estimated median RR of CEP use for disabling stroke was 0.56 (95% CrI 0.28 to 1.19, derived ARD 0.56% and NNT 179, I2=0%). Although the estimated posterior probability of any benefit was 94.4%, the probability of a clinically relevant effect was 0-0.1% under the vague and informed literature-based priors. Results were robust across multiple sensitivity analyses. CONCLUSION: There is a high probability of a beneficial CEP treatment effect, but this is unlikely to be clinically relevant. These findings suggest that future trials should focus on identifying TAVI patients with an increased baseline risk of stroke, and on the development of new generation devices. PROSPERO REGISTRATION NUMBER: CRD42023407006.

Safety and Performance of the Aortix Device in Acute Decompensated Heart Failure and Cardiorenal Syndrome.

BACKGROUND: Cardiorenal syndrome (CRS) complicates 33% of acute decompensated heart failure (ADHF) admissions, and patients with persistent congestion at discharge have high 30-day event rates. OBJECTIVES: The purpose of this study was to evaluate a novel catheter-deployed intra-aortic entrainment pump (IAEP) in patients with ADHF with CRS and persistent congestion. METHODS: A multicenter (n = 14), nonrandomized, single-arm, safety and feasibility study of IAEP therapy was conducted. Within patient changes (post-pre IAEP therapy) in fluid loss, hemodynamics, patient-reported dyspnea, and serum biomarkers were assessed using Wilcoxon signed-rank testing. RESULTS: Of 21 enrolled patients, 18 received Aortix therapy. Mean ± SD patient age was 60.3 ± 7.9 years. The median left ventricular ejection fraction was 22.5% (25th-75th percentile: 10.0%-53.5%); 27.8% had a left ventricular ejection fraction ≥50%. Pre-therapy, patients received 8.7 ± 4.1 days of loop diuretic agents and 44% were on inotropes. Pump therapy averaged 4.6 ± 1.6 days, yielding net fluid losses of 10.7 ± 6.5 L (P < 0.001) and significant (P < 0.01) reductions in central venous pressure (change from baseline: -8.5 mm Hg [25th-75th percentile: -3.5 to -10.0 mm Hg]), pulmonary capillary wedge pressure (-11.0 mm Hg [25th-75th percentile: -5.0 to -14.0 mm Hg]), and serum creatinine (-0.2 mg/dL [25th-75th percentile: -0.1 to -0.5 mg/dL]) with improved estimated glomerular filtration rate (+5.0 mL/min/1.73 m2 [25th-75th percentile: 2.0-9.0 mL/min/1.73 m2]) and patient-reported dyspnea score (+16 [25th-75th percentile: 3-37]). Dyspnea scores, natriuretic peptides, and renal function improvements persisted through 30 days. CONCLUSIONS: This pilot study of patients with ADHF, persistent congestion, and worsening renal function due to CRS supports the potential for safely achieving decongestion using IAEP therapy. These initial promising results provide the basis for future randomized clinical trials of this novel pump. (An Evaluation of the Safety and Performance of the Aortix System for Intra-Aortic Mechanical Circulatory Support in Patients with Cardiorenal Syndrome [The Aortix CRS Pilot Study]; NCT04145635).

Coronary Artery Disease Risk Prediction in Patients With Severe Aortic Stenosis: Development and Validation of the Aortic Stenosis-Coronary Artery Disease (AS-CAD) Score.

Patients at a low risk of coronary artery disease (CAD) could be triaged to noninvasive coronary computed tomography angiogram instead of invasive coronary angiography, reducing health care costs and patient morbidity. Therefore, we aimed to develop a CAD risk prediction score to identify those who underwent transcatheter aortic valve implantation (TAVI) at a low risk of CAD. We enrolled 1,782 patients who underwent TAVI and randomized the patients to the derivation or validation cohort 2:1. The aortic stenosis-CAD (AS-CAD) score was developed using logistic regression, followed by separation into low- (score 0 to 5), intermediate- (6 to 10), or high-risk (>11) categories. The AS-CAD was validated initially through the k-fold cross-validation, followed by a separately held validation cohort. The average age of the cohort was 82 ± 7 years, and 41% (730 of 1,782) were female; 35% (630) had CAD. The male sex, previous percutaneous coronary intervention, stroke, peripheral arterial disease, diabetes, smoking status, left ventricular ejection fraction <50%, and right ventricular systolic pressure >35 mm Hg were all associated with an increased risk of CAD and were included in the final AS-CAD model (all p <0.03). Within the validation cohort, the AS-CAD score stratified those into low, intermediate, and high risk of CAD (p <0.001). Discrimination was good within the internal validation cohort, with a c-statistic of 0.79 (95% confidence interval 0.74 to 0.84), with similar power obtained using k-fold cross-validation (c-statistic 0.74 [95% confidence interval 0.70 to 0.77]). In conclusion, The AS-CAD score robustly identified those at a low risk of CAD in patients with severe AS. The use of AS-CAD in practice could avoid potential complications of invasive coronary angiogram by triaging low-risk patients to noninvasive coronary assessment using existing computed tomography data.

Patients hospitalized with acute heart failure, worsening renal function, and persistent congestion are at high risk for adverse outcomes despite current medical therapy.

INTRODUCTION: Approximately 1/3 of patients with acute decompensated heart failure (ADHF) are discharged with persistent congestion. Worsening renal function (WRF) occurs in approximately 50% of patients hospitalized for ADHF and the combination of WRF and persistent congestion are associated with higher risk of mortality and HF readmissions. METHODS: We designed a multicenter, prospective registry to describe current treatments and outcomes for patients hospitalized with ADHF complicated by WRF (defined as a creatinine increase ≥0.3 mg/dL) and persistent congestion at 96 h. Study participants were followed during the hospitalization and through 90-day post-discharge. Hospitalization costs were analyzed in an economic substudy. RESULTS: We enrolled 237 patients hospitalized with ADHF, who also had WRF and persistent congestion. Among these, the average age was 66 ± 13 years and 61% had a left ventricular ejection fraction (LVEF) ≤ 40%. Mean baseline creatinine was 1.7 ± 0.7 mg/dL. Patients with persistent congestion had a high burden of clinical events during the index hospitalization (7.6% intensive care unit transfer, 2.1% intubation, 1.7% left ventricular assist device implantation, and 0.8% dialysis). At 90-day follow-up, 33% of patients were readmitted for ADHF or died. Outcomes and costs were similar between patients with reduced and preserved LVEF. CONCLUSIONS: Many patients admitted with ADHF have WRF and persistent congestion despite diuresis and are at high risk for adverse events during hospitalization and early follow-up. Novel treatment strategies are urgently needed for this high-risk population.

Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). OBJECTIVES: This study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. METHODS: Study investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. RESULTS: Among 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. CONCLUSIONS: In HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden. (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure [REDUCE LAP-HF II]; NCT03088033).

Thirty-day and one-year outcomes of the Navitor transcatheter heart valve in patients with aortic stenosis: the prospective, multicentre, global PORTICO NG Study.

BACKGROUND: The Navitor transcatheter heart valve (THV) is a self-expanding valve, with an intra-annular leaflet position and an outer cuff intended to reduce paravalvular leak (PVL). AIMS: The aim of the PORTICO NG Study is to assess the safety and performance of the Navitor THV in patients with symptomatic, severe aortic stenosis who are at high or extreme surgical risk. METHODS: PORTICO NG is a prospective, multicentre, global, single-arm, investigational study with follow-up at 30 days, 1 year, and annually up to 5 years. The primary endpoints are all-cause mortality and moderate or greater PVL at 30 days. Valve Academic Research Consortium-2 events and valve performance are assessed by an independent clinical events committee and echocardiographic core laboratory. RESULTS: A total of 120 high- or extreme-risk subjects (age 83.5±5.4 years; 58.3% female; Society of Thoracic Surgeons score 4.0±2.0%) were enrolled in the European conformity (CE) mark cohort. Procedural success was high at 97.5%. At 30 days, the rate of all-cause mortality was 0%, and no subjects had moderate or greater PVL. The rate of disabling stroke was 0.8%, life-threatening bleeding was 2.5%, stage 3 acute kidney injury 0%, major vascular complications 0.8%, and new pacemaker implantation 15.0%. At 1 year, the rates of all-cause mortality and disabling stroke were 4.2% and 0.8%, respectively. The rate of moderate PVL was 1.0% at 1 year. Haemodynamic performance with a mean gradient of 7.5±3.2 mmHg and effective orifice area of 1.9±0.4 cm2 was sustained up to 1 year. CONCLUSIONS: The PORTICO NG Study demonstrates low rates of adverse events and PVL up to 1 year in patients at high or extreme surgical risk, confirming the safety and efficacy of the Navitor THV system.

30-Day Clinical Outcomes of a Self-Expanding Transcatheter Aortic Valve: The International PORTICO NG Study.

BACKGROUND: The self-expanding, intra-annular Navitor (Abbott Structural Heart) valve includes an outer cuff to reduce paravalvular leak (PVL) and large stent cells for future coronary access. OBJECTIVES: The purpose of the PORTICO NG (Evaluation of the Portico NG [Next Generation] Transcatheter Aortic Valve in High and Extreme Risk Patients With Symptomatic Severe Aortic Stenosis) study is to evaluate the safety and effectiveness of the Navitor valve in patients with symptomatic, severe aortic stenosis who are at high or extreme surgical risk. METHODS: PORTICO NG is a prospective, multicenter, global study with follow-up at 30 days, 1 year, and annually through 5 years. The primary endpoints are all-cause mortality and moderate or greater PVL at 30 days. Valve Academic Research Consortium-2 events and valve performance are assessed by an independent clinical events committee and echocardiographic core laboratory. RESULTS: A total of 260 subjects were treated at 26 clinical sites across Europe, Australia, and the United States between September 2019 and August 2022. The mean age was 83.4 ± 5.4 years, 57.3% were female, and the average Society of Thoracic Surgeons score was 3.9% ± 2.1%. At 30 days, the rate of all-cause mortality was 1.9%, and no subjects had moderate or greater PVL. The rate of disabling stroke was 1.9%, life-threatening bleeding was 3.8%, stage 3 acute kidney injury was 0.8%, major vascular complications were 4.2%, and new permanent pacemaker implantation was 19.0%. Hemodynamic performance included a mean gradient of 7.4 ± 3.5 mm Hg and an effective orifice area of 2.00 ± 0.47 cm2. CONCLUSIONS: The Navitor valve is safe and effective for the treatment of subjects with severe aortic stenosis who are at high or greater risk for surgery, which is supported by low rates of adverse events and PVL. (Evaluation of the Portico NG [Next Generation] Transcatheter Aortic Valve in High and Extreme Risk Patients With Symptomatic Severe Aortic Stenosis [PORTICO NG]; NCT04011722).

Catheter-Based Renal Denervation: 9-Year Follow-Up Data on Safety and Blood Pressure Reduction in Patients With Resistant Hypertension.

BACKGROUND: Recent sham-controlled randomized clinical trials have confirmed the safety and efficacy of catheter-based renal denervation (RDN). Long-term safety and efficacy data beyond 3 years are scarce. Here, we report on outcomes after RDN in a cohort of patients with resistant hypertension with an average of ≈9-year follow-up (FU). METHODS: We recruited patients with resistant hypertension who were previously enrolled in various RDN trials applying radiofrequency energy for blood pressure (BP) lowering. All participants had baseline assessments before RDN and repeat assessment at long-term FU including medical history, automated office and ambulatory BP measurement, and routine blood and urine tests. We analyzed changes between baseline and long-term FU. RESULTS: A total of 66 participants (mean±SD, 70.0±10.3 years; 76.3% men) completed long-term FU investigations with a mean of 8.8±1.2 years post-procedure. Compared with baseline, ambulatory systolic BP was reduced by -12.1±21.6 (from 145.2 to 133.1) mm Hg (P<0.0001) and diastolic BP by -8.8±12.8 (from 81.2 to 72.7) mm Hg (P<0.0001). Mean heart rate remained unchanged. At long-term FU, participants were on one less antihypertensive medication compared with baseline (P=0.0052). Renal function assessed by estimated glomerular filtration rate fell within the expected age-associated rate of decline from 71.1 to 61.2 mL/min per 1.73 m2. Time above target was reduced significantly from 75.0±25.9% at baseline to 47.3±30.3% at long-term FU (P<0.0001). CONCLUSIONS: RDN results in a significant and robust reduction in both office and ambulatory systolic and diastolic BP at ≈9-year FU after catheter-based RDN on less medication and without evidence of adverse consequences on renal function.

Impact of Concomitant Mitral Regurgitation on the Hemodynamic Indicators of Aortic Stenosis.

Background In patients with aortic stenosis (AS), the presence of mitral regurgitation (MR) can lead to underestimation of AS severity and worse clinical outcomes. The objective of this study was to characterize the magnitude of the effects of concomitant MR on hemodynamic indicators of AS severity using clinical data and a computational cardiovascular simulation. Methods and Results Echocardiographic data from 1427 patients with severe AS were used to inform a computational cardiovascular system model, and varying degrees of MR and AS were simulated. Hemodynamic data, including left ventricular and aortic pressure waveforms, were generated for all simulations. Simulated reduction in mean transaortic pressure gradient (MPG) associated with MR was then used to calculate the adjusted MPG in the clinical cohort. MR was present in 861 (60%) patients. Compared with patients without MR, patients with MR had a lower aortic-valve area (0.83±0.2 cm2 versus 0.75±0.2; P<0.001) and were more likely to have a low-gradient pattern (MPG <40 mm Hg) (45% versus 54%; P<0.001). Simulations showed that the presence of concomitant mild, moderate, and severe MR with AS was accompanied by a mean reduction in MPG of 10%, 29%, and 40%, respectively. For patients with MR, their calculated adjusted MPG was on average 24% higher than their MPG (52±22 versus 42±16 mm Hg). Of the 467 patients with low-gradient AS and MR, 240 (51%) would reclassify as high gradient based on their adjusted MPG. Conclusions Concomitant MR results in lower MPG and reduced forward flow compared with isolated AS. Careful quantitation of MR should be factored into the assessment of AS severity to mitigate for potential underestimation.

UpStreAm doxycycline in ST-eLeVation myocArdial infarction: targetinG infarct hEaling and ModulatIon (SALVAGE-MI trial).

AIMS: Experimental studies demonstrate protective effects of doxycycline on myocardial ischaemia-reperfusion injury. The trial investigated whether doxycycline administered prior to reperfusion in patients presenting with ST-elevation myocardial infarction (STEMI) reduces infarct size (IS) and ameliorates adverse left ventricular (LV) remodelling. METHODS AND RESULTS: In this randomized, double-blind, placebo-controlled trial, patients presenting with STEMI undergoing primary percutaneous coronary intervention (PPCI) were randomized to either intravenous doxycycline or placebo prior to reperfusion followed by 7 days of oral doxycycline or placebo. The primary outcome was final IS adjusted for area-at-risk (fIS/AAR) measured on two cardiac magnetic resonance scans ∼6 months apart. Of 103 participants, 50 were randomized to doxycycline and 53 to placebo and were matched for age (59 ± 12 vs. 60 ± 10 years), male sex (92% vs. 79%), diabetes mellitus (26% vs. 11%) and left anterior descending artery occlusion (50% vs. 49%), all P > 0.05. Patients treated with doxycycline had a trend for larger fIS/AAR [0.79 (0.5-0.9) vs. 0.61 (0.47-0.76), P = 0.06], larger fIS at 6 months [18.8% (12-26) vs. 13.6% (11-21), P = 0.08], but similar acute IS [21.7% (17-34) vs. 19.4% (14-27), P = 0.19] and AAR [26% (20-36) vs. 24.7% (16-31), P = 0.22] compared with placebo. Doxycycline did not ameliorate adverse LV remodelling [%Δend-diastolic volume index, 1.1% (-3.8-8.4) vs. -1.34% (-6.1-5.8), P = 0.42] and was independently associated with larger fIS (regression coefficient = 0.175, P = 0.03). CONCLUSION: Doxycycline prior to PPCI neither reduced IS acutely or at six months nor attenuated adverse LV remodelling. These data raise safety concerns regarding doxycycline use in STEMI for infarct modulation and healing.

Waiting times of women vs. men undergoing transcatheter aortic valve implantation.

AIMS: Increasing transcatheter aortic valve implantation (TAVI) rates have resulted in prolonged waiting times. These have been associated with heart failure hospitalizations (HFH) and mortality yet sex differences have not yet been reported. METHODS AND RESULTS: All patients who underwent TAVI for severe aortic stenosis at a tertiary referral hospital in Australia were prospectively included. Total waiting time was divided into 'work-up' waiting time (period from referral date until heart team approval) and, 'procedural' waiting time (period from heart team approval until procedure date). Patients were analysed according to sex. Cohorts were matched to correct for differences in baseline and procedural variables. The primary endpoints were waiting times. Secondary outcomes included a composite of 30-day mortality and HFH, quality of life, and mobility. A total of 407 patients (42% women) were included. After matching of the two cohorts (345 patients), women had significantly longer total waiting times than men: median 156 [interquartile range (IQR) 114-220] days in women vs. 147 [IQR 92-204] days in men (P = 0.037) including longer work-up (83 [IQR 50-128] vs. 71 [IQR 36-119], P = 0.15) and procedural waiting times (65 [IQR 44-100] vs. 58 [IQR 30-93], P = 0.042). Increasing waiting times were associated with higher 30-day mortality and HFH (P = 0.01 for work-up waiting time, P = 0.02 for procedural waiting time) and decreased 30-day mobility (P = 0.044 for procedural waiting time) in women, but not in men. CONCLUSION: TAVI waiting times are significantly longer in women compared to men and are associated with increased mortality and HFH and reduced mobility at 30-days.