Characteristics and Outcomes of Patients with Inflammatory Cardiomyopathies Receiving Mechanical Circulatory Support: An STS-INTERMACS Registry Analysis.

BACKGROUND: Durable mechanical circulatory support (MCS) therapy improves survival in patients with advanced heart failure. Knowledge regarding the outcomes experienced by patients with inflammatory cardiomyopathy (CM) who receive durable MCS therapy is limited. METHODS AND RESULTS: We compared patients with inflammatory CM with patients with idiopathic dilated CM enrolled in the STS-INTERMACS registry. Among 19,012 patients, 329 (1.7%) had inflammatory CM and 5978 had idiopathic dilated CM (31.4%). The patients with inflammatory CM were younger, more likely to be White, and women. These patients experienced more preoperative arrhythmias and higher use of temporary MCS. Patients with inflammatory CM had a higher rate of early adverse events (<3 months after device implant), including bleeding, arrhythmias, non-device-related infections, neurologic dysfunction, and respiratory failure. The rate of late adverse events (≥3 months) was similar in the 2 groups. Patients with inflammatory CM had a similar 1-year (80% vs 84%) and 2-year (72% vs 76%, P = .15) survival. Myocardial recovery resulting in device explant was more common among patients with inflammatory CM (5.5% vs 2.3%, P < .001). CONCLUSIONS: Patients with inflammatory CM who received durable MCS appear to have a similar survival compared with patients with idiopathic dilated CM despite a higher early adverse event burden. Our findings support the use of durable MCS in an inflammatory CM population.

Balloon-Expandable Valve Geometry After Transcatheter Aortic Valve Replacement in Low-Risk Patients With Bicuspid Versus Tricuspid Aortic Stenosis.

BACKGROUND: Prospective bicuspid low-risk transcatheter aortic valve replacement (TAVR) registries' data demonstrated encouraging short-term results. Detailed data on transcatheter heart valve (THV) geometry after deployment using contemporary devices are lacking. This study sought to examine valve geometry after TAVR in patients with bicuspid aortic stenosis (AS). METHODS: The study population was patients from the LRT (Low Risk TAVR) trial who underwent TAVR using the SAPIEN 3 THV for bicuspid and tricuspid AS. THV geometry measured on 30-day computed tomography (CT) included valve height, angle, depth, and eccentricity. Additionally, THV hemodynamics and outcomes post-TAVR were compared among patients with bicuspid and tricuspid AS. RESULTS: A total of 107 patients from the LRT trial using the SAPIEN 3 THV were included in our analysis. On 30-day CT, the valve height ratio (1.07 vs. 1.07; p = 0.348), depths (right [5.6 mm vs. 6.2 mm; p = 0.223], left [5.3 mm vs. 4.4 mm; p = 0.082] and non [4.8 mm vs. 4.5 mm; p = 0.589] coronary cusps), eccentricities (1.08 vs. 1.07; p = 0.9550), and angles (except the right [3.9 degrees vs. 6.3 degrees; p = 0.003] and left [3.6 degrees vs. 6.0 degrees; p = 0.007]) were similar between bicuspid and tricuspid patients. Hemodynamics, stroke, and mortality were similar at 1 year. CONCLUSION: Despite challenging bicuspid anatomy of the aortic valve, our comprehensive CT analysis supports similar THV geometry between patients with bicuspid and tricuspid AS undergoing TAVR using the SAPIEN 3 THV in low-risk patients. This translated to excellent short-term clinical outcomes and THV hemodynamics in both aortic valve morphologies. TRIAL REGISTRY: NCT02628899, https://clinicaltrials.gov/ct2/show/NCT02628899.

A Patient-Level, Pooled Analysis of Mortality Rates With the Passeo-18 Lux Paclitaxel Drug-Coated Balloon in Peripheral Arterial Disease.

BACKGROUND: Recent meta-analyses have raised concerns about mortality with paclitaxel drug-coated balloons (DCB). This pooled, patient-level analysis of the BIOLUX P-I, P-II, and P-III studies was performed to evaluate the safety and efficacy of Passeo-18 Lux DCB. MATERIALS AND METHODS: Individual patient-level demographic, clinical, diagnostic, and procedural data from the BIOLUX P-I, BIOLUX P-II, and BIOLUX P-III studies were pooled in a common database. Clinical safety (all-cause mortality and cardiovascular mortality) and efficacy (any amputation, target lesion/vessel revascularization) were extracted. Cox proportional modeling was used to assess the effect of critical limb ischemia at the time of enrollment and the occurrence of new amputation as a time-dependent variable on mortality. RESULTS: A total of 1009 patients were included in the analysis. Sixty-six patients were treated with percutaneous transluminal angioplasty (PTA) and 943 underwent DCB angioplasty. The cumulative incidence of all-cause mortality did not differ between the groups (PTA 6.7%, DCB 6.7%, p = 0.65). The composite efficacy endpoint of freedom from any amputation and target lesion/vessel revascularization was superior in the DCB arm compared to PTA [PTA 28.8%, DCB 16.7%, p = 0.02]. Both in unadjusted and adjusted Cox proportional models (adjusted for critical limb ischemia and amputation), the use of DCB was not associated with any mortality at 1 year. CONCLUSIONS: Our patient-level analysis shows that overall, the use of the Passeo-18 Lux paclitaxel DCB in infrainguinal arteries was not associated with increased mortality at 1 year and reinforces the efficacy of DCB angioplasty in preventing amputation or the need for reintervention.

Transcatheter Aortic Valve Replacement in Low-Risk Patients With Symptomatic Severe Bicuspid Aortic Valve Stenosis.

OBJECTIVES: The aim of this study was to evaluate clinical outcomes and transcatheter heart valve hemodynamic parameters after transcatheter aortic valve replacement (TAVR) in low-risk patients with bicuspid aortic stenosis (AS). BACKGROUND: TAVR is approved for low-risk patients in the United States. However, patients with bicuspid AS were excluded from the randomized cohorts of the pivotal low-risk trials. METHODS: The LRT (Low Risk TAVR) trial was an investigator-initiated, prospective, multicenter study and was the first and only U.S. Food and Drug Administration-approved investigational device exemption trial to evaluate the feasibility of TAVR with either balloon-expandable or self-expanding valves in low-risk patients with bicuspid AS. The primary endpoint was all-cause mortality at 30 days. Baseline and follow-up echocardiography and computed tomography to detect leaflet thickening were analyzed in an independent core laboratory. RESULTS: Sixty-one low-risk patients with symptomatic, severe AS and bicuspid aortic valves (78.3% Sievers type 1 morphology) underwent TAVR at 6 centers from 2016 to 2019. The mean age was 68.6 years, and 42.6% were men. At 30 days, there was zero mortality and no disabling strokes. The rate of new permanent pacemaker implantation was 13.1%; just 1 patient had a moderate paravalvular leak at 30 days. Hypoattenuated leaflet thickening was observed in 10% of patients at 30 days. CONCLUSIONS: TAVR appears to be safe in patients with bicuspid AS, with short length of hospital stay, zero mortality, and no disabling strokes at 30 days. Subclinical leaflet thrombosis was observed in a minority of patients at 30 days but did not appear to be associated with clinical events.

Coronary Artery Disease Assessed by Computed Tomography-Based Leaman Score in Patients With Low-Risk Transcatheter Aortic Valve Implantation.

We aimed to evaluate the burden of coronary artery disease (CAD) using the computed tomography (CT) Leaman score in low-risk transcatheter aortic valve implantation (TAVI) patients. The extent of CAD in low-risk patients with aortic stenosis who are candidates for TAVI has not been accurately quantified. The CT Leaman score was developed to quantify coronary CT angiography (CCTA) atherosclerotic burden and has been validated to evaluate the extent of CAD. CT Leaman score >5 has been associated with an increase in major adverse cardiac events over long-term follow-up. The study population included patients enrolled in the Low Risk TAVI trial who underwent CCTA before the procedure. For the CT Leaman score, we used 3 sets of weighting factors: (1) location of coronary plaques, (2) type of plaque, and (3) degree of stenosis. A total of 200 patients were enrolled in the Low Risk TAVI trial. Excluded were 31 patients who had no analyzable CCTA imaging. For the remaining 169 patients, the mean CT Leaman score was 6.27 ± 0.27, of whom 102 (60.4%) had CT Leaman score >5. Nearly all analyzed patients (97%) had coronary plaques. Furthermore, 33 patients (19.5%) had potentially obstructive coronary plaques (>50% stenosis by CCTA) in proximal segments. Most low-risk TAVI patients have significant CAD burden by CCTA. It should be a priority for future TAVI devices to guarantee unimpeded access to the coronary arteries for selective angiography and interventions.

Impact of Intravascular Ultrasound on Outcomes Following PErcutaneous Coronary InterventioN in Complex Lesions (iOPEN Complex).

BACKGROUND: Clinical data support the use of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) as being associated with improved outcomes. Nonetheless, global utilization of IVUS remains low. We hypothesize that, in the revascularization of complex lesions, IVUS use is associated with improved outcomes. METHODS: All patients with complex lesions treated with PCI at a single center from 2003 to 2016 were stratified by use of IVUS. Complex lesions were defined as follows: American College of Cardiology/American Heart Association type C lesions, in-stent restenosis, long lesions, bifurcations, severe calcification, left main lesions, and chronic total occlusions. The primary end point was the rate of major adverse cardiac events (MACE) at 1-year follow-up, defined as the composite of all-cause mortality, Q-wave myocardial infarction, and target vessel revascularization. Inverse probability weighting was used in the adjusted analysis. RESULTS: A total of 6,855 patients were included in the final analysis, of whom 67.3% had IVUS and 32.7% had angiography alone. The primary end point occurred in 13.4% of patients treated with IVUS and 18.3% of patients treated with angiography alone (P < .001). Inverse probability weighting-adjusted 1-year MACE rates demonstrated significant reduction with IVUS for each complex lesion type. CONCLUSIONS: Among patients with complex lesions, the use of IVUS was associated with lower MACE 1 year after PCI than angiography alone was. Because of the increased procedural risk in complex lesions, routine utilization of IVUS-guided PCI should be considered in this subset of patients.

Hemodynamics and Subclinical Leaflet Thrombosis in Low-Risk Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: This analysis evaluated echocardiographic predictors of hypoattenuated leaflet thickening (HALT) in low-risk patients undergoing transcatheter aortic valve replacement and assessed 1-year clinical and hemodynamic consequences. HALT by computed tomography may be associated with early valve degeneration and increased neurological events. METHODS: Echocardiograms were performed at baseline, discharge, 30 days, and 1 year post-procedure. Four-dimensional contrast-enhanced computed tomography assessed HALT at 30 days. Independent core laboratories analyzed images. Doppler hemodynamic parameters were tested in a univariable regression model to identify HALT predictors. One-year clinical and hemodynamic outcomes were compared between HALT (+) and (-) patients. RESULTS: Analysis included 170 patients with Sapien 3 valves and diagnostic 30-day computed tomographies, of whom 27 (16%) had HALT. Baseline characteristics were similar between groups. After transcatheter aortic valve replacement, aortic flow was nonsignificantly reduced in patients who developed HALT. Regression analysis did not show significant association between baseline or discharge valve hemodynamics and development of HALT at 30 days. Patients with HALT had smaller aortic valve areas (1.4±0.4 versus 1.7±0.5 cm2; P=0.018) and Doppler velocity index (0.4±0.1 versus 0.5±0.1; P=0.003) than those without HALT at 30 days but not at 1 year. There was no difference in aortic mean gradient at 30 days. There was no difference between the groups in New York Heart Association class, 6-minute walk distance, and mortality at 1 year. CONCLUSIONS: There were no early hemodynamic predictors of HALT. At 30 days, patients with HALT had worse valve hemodynamics than those without HALT, but hemodynamic and clinical outcomes at 1 year were similar. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02628899.

Identification of patients and plaques vulnerable to future coronary events with near-infrared spectroscopy intravascular ultrasound imaging: a prospective, cohort study.

BACKGROUND: Near-infrared spectroscopy (NIRS) intravascular ultrasound imaging can detect lipid-rich plaques (LRPs). LRPs are associated with acute coronary syndromes or myocardial infarction, which can result in revascularisation or cardiac death. In this study, we aimed to establish the relationship between LRPs detected by NIRS-intravascular ultrasound imaging at unstented sites and subsequent coronary events from new culprit lesions. METHODS: In this prospective, cohort study (LRP), patients from 44 medical centres were enrolled in Italy, Latvia, Netherlands, Slovakia, UK, and the USA. Patients with suspected coronary artery disease who underwent cardiac catheterisation with possible ad hoc percutaneous coronary intervention were eligible to be enrolled. Enrolled patients underwent scanning of non-culprit segments using NIRS-intravascular ultrasound imaging. The study had two hierarchal primary hypotheses, patient and plaque, each testing the association between maximum 4 mm Lipid Core Burden Index (maxLCBI4mm) and non-culprit major adverse cardiovascular events (NC-MACE). Enrolled patients with large LRPs (≥250 maxLCBI4mm) and a randomly selected half of patients with small LRPs (<250 maxLCBI4mm) were followed up for 24 months. This study is registered with ClinicalTrials.gov, NCT02033694. FINDINGS: Between Feb 21, 2014, and March 30, 2016, 1563 patients were enrolled. NIRS-intravascular ultrasound device-related events were seen in six (0·4%) patients. 1271 patients (mean age 64 years, SD 10, 883 [69%] men, 388 [31%]women) with analysable maxLCBI4mm were allocated to follow-up. The 2-year cumulative incidence of NC-MACE was 9% (n=103). Both hierarchical primary hypotheses were met. On a patient level, the unadjusted hazard ratio (HR) for NC-MACE was 1·21 (95% CI 1·09-1·35; p=0·0004) for each 100-unit increase maxLCBI4mm) and adjusted HR 1·18 (1·05-1·32; p=0·0043). In patients with a maxLCBI4mm more than 400, the unadjusted HR for NC-MACE was 2·18 (1·48-3·22; p<0·0001) and adjusted HR was 1·89 (1·26-2·83; p=0·0021). At the plaque level, the unadjusted HR was 1·45 (1·30-1·60; p<0·0001) for each 100-unit increase in maxLCBI4mm. For segments with a maxLCBI4mm more than 400, the unadjusted HR for NC-MACE was 4·22 (2·39-7·45; p<0·0001) and adjusted HR was 3·39 (1·85-6·20; p<0·0001). INTERPRETATION: NIRS imaging of non-obstructive territories in patients undergoing cardiac catheterisation and possible percutaneous coronary intervention was safe and can aid in identifying patients and segments at higher risk for subsequent NC-MACE. NIRS-intravascular ultrasound imaging adds to the armamentarium as the first diagnostic tool able to detect vulnerable patients and plaques in clinical practice. FUNDING: Infraredx.

TAVR in Low-Risk Patients: 1-Year Results From the LRT Trial.

OBJECTIVES: This study sought to evaluate clinical outcomes and transcatheter heart valve hemodynamics at 1 year after transcatheter aortic valve replacement (TAVR) in low-risk patients. BACKGROUND: Early results from the LRT (Low Risk TAVR) trial demonstrated that TAVR is safe in patients with symptomatic severe aortic stenosis who are at low risk for surgical valve replacement. METHODS: The LRT trial was an investigator-initiated, prospective, multicenter study and was the first Food and Drug Administration-approved Investigational Device Exemption trial to evaluate feasibility of TAVR in low-risk patients. The primary endpoint was all-cause mortality at 30 days. Secondary endpoints included clinical outcomes and valve hemodynamics at 1 year. RESULTS: The LRT trial enrolled 200 low-risk patients with symptomatic severe AS to undergo TAVR at 11 centers. Mean age was 73.6 years and 61.5% were men. At 30 days, there was zero mortality, zero disabling stroke, and low permanent pacemaker implantation rate (5.0%). At 1-year follow-up, mortality was 3.0%, stroke rate was 2.1%, and permanent pacemaker implantation rate was 7.3%. Two (1.0%) subjects underwent surgical reintervention for endocarditis. Of the 14% of TAVR subjects who had evidence of hypoattenuated leaflet thickening at 30 days, there was no impact on valve hemodynamics at 1 year, but the stroke rate was numerically higher (3.8% vs. 1.9%; p = 0.53). CONCLUSIONS: TAVR in low-risk patients with symptomatic severe aortic stenosis appears to be safe at 1 year. Hypoattenuated leaflet thickening, observed in a minority of TAVR patients at 30 days, did not have an impact on valve hemodynamics in the longer term.

Transcatheter Aortic Valve Replacement in Low-Risk Patients With Symptomatic Severe Aortic Stenosis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is now the standard of care for patients with symptomatic severe aortic stenosis who are extreme, high, or intermediate risk for surgical aortic valve replacement (SAVR). OBJECTIVES: The authors sought to evaluate TAVR in a prospective multicenter trial involving low-risk patients. METHODS: The Low Risk TAVR (Feasibility of Transcatheter Aortic Valve Replacement in Low-Risk Patients With Symptomatic, Severe Aortic Stenosis) trial was the first U.S. Food and Drug Administration-approved Investigational Device Exemption trial to enroll in the United States. This investigator-led trial was a prospective, multicenter, unblinded, comparison to historical controls from the Society of Thoracic Surgeons (STS) database. The primary endpoint was all-cause mortality at 30 days. RESULTS: The authors enrolled 200 low-risk patients with symptomatic severe aortic stenosis at 11 centers to undergo TAVR. The authors compared outcomes with an inverse probability weighting-adjusted control cohort of 719 patients who underwent SAVR at the same institutions using the STS database. At 30 days, there was zero all-cause mortality in the TAVR group versus 1.7% mortality in the SAVR group. There was zero in-hospital stroke rate in the TAVR group versus 0.6% stroke in the SAVR group. Permanent pacemaker implantation rates were similar between TAVR and SAVR (5.0% vs. 4.5%). The rates of new-onset atrial fibrillation (3.0%) and length of stay (2.0 ± 1.1 days) were low in the TAVR group. One patient (0.5%) in the TAVR group had >mild paravalvular leak at 30 days. Fourteen percent of TAVR patients had evidence of subclinical leaflet thrombosis at 30 days. CONCLUSIONS: TAVR is safe in low-risk patients with symptomatic severe aortic stenosis, with low procedural complication rates, short hospital length of stay, zero mortality, and zero disabling stroke at 30 days. Subclinical leaflet thrombosis was observed in a minority of TAVR patients at 30 days. (Feasibility of Transcatheter Aortic Valve Replacement in Low-Risk Patients With Symptomatic, Severe Aortic Stenosis [Low Risk TAVR; NCT02628899).

Aberrant synaptic integration in adult lamina I projection neurons following neonatal tissue damage.

Mounting evidence suggests that neonatal tissue damage evokes alterations in spinal pain reflexes which persist into adulthood. However, less is known about potential concomitant effects on the transmission of nociceptive information to the brain, as the degree to which early injury modulates synaptic integration and membrane excitability in mature spinal projection neurons remains unclear. Here we demonstrate that neonatal surgical injury leads to a significant shift in the balance between synaptic excitation and inhibition onto identified lamina I projection neurons of the adult mouse spinal cord. The strength of direct primary afferent input to mature spino-parabrachial neurons was enhanced following neonatal tissue damage, whereas the efficacy of both GABAergic and glycinergic inhibition onto the same population was compromised. This was accompanied by reorganization in the pattern of sensory input to adult projection neurons, which included a greater prevalence of monosynaptic input from low-threshold A-fibers when preceded by early tissue damage. In addition, neonatal incision resulted in greater primary afferent-evoked action potential discharge in mature projection neurons. Overall, these results demonstrate that tissue damage during early life causes a long-term increase in the gain of spinal nociceptive circuits, and suggest that the prolonged consequences of neonatal trauma may not be restricted to the spinal cord but rather include excessive ascending signaling to supraspinal pain centers.