Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis and Small Aortic Annulus: A Randomized Clinical Trial.

BACKGROUND: The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and clinical outcomes between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with a SAA. METHODS: This prospective multicenter international randomized trial was performed in 15 university hospitals. Participants were 151 patients with severe aortic stenosis and SAA (mean diameter <23 mm) randomized (1:1) to TAVR (n=77) versus SAVR (n=74). The primary outcome was impaired valve hemodynamics (ie, severe prosthesis patient mismatch or moderate-severe aortic regurgitation) at 60 days as evaluated by Doppler echocardiography and analyzed in a central echocardiography core laboratory. Clinical events were secondary outcomes. RESULTS: The mean age of the participants was 75.5±5.1 years, with 140 (93%) women, a median Society of Thoracic Surgeons predicted risk of mortality of 2.50% (interquartile range, 1.67%-3.28%), and a median annulus diameter of 21.1 mm (interquartile range, 20.4-22.0 mm). There were no differences between groups in the rate of severe prosthesis patient mismatch (TAVR, 4 [5.6%]; SAVR, 7 [10.3%]; P=0.30) and moderate-severe aortic regurgitation (none in both groups). No differences were found between groups in mortality rate (TAVR, 1 [1.3%]; SAVR, 1 [1.4%]; P=1.00) and stroke (TAVR, 0; SAVR, 2 [2.7%]; P=0.24) at 30 days. After a median follow-up of 2 (interquartile range, 1-4) years, there were no differences between groups in mortality rate (TAVR, 7 [9.1%]; SAVR, 6 [8.1%]; P=0.89), stroke (TAVR, 3 [3.9%]; SAVR, 3 [4.1%]; P=0.95), and cardiac hospitalization (TAVR, 15 [19.5%]; SAVR, 15 [20.3%]; P=0.80). CONCLUSIONS: In patients with severe aortic stenosis and SAA (women in the majority), there was no evidence of superiority of contemporary TAVR versus SAVR in valve hemodynamic results. After a median follow-up of 2 years, there were no differences in clinical outcomes between groups. These findings suggest that the 2 therapies represent a valid alternative for treating patients with severe aortic stenosis and SAA, and treatment selection should likely be individualized according to baseline characteristics, additional anatomical risk factors, and patient preference. However, the results of this study should be interpreted with caution because of the limited sample size leading to an underpowered study, and need to be confirmed in future larger studies. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03383445.

Aortic Stenosis and Small Aortic Annulus.

The presence of a small aortic annulus poses a considerable challenge in the management of patients with severe aortic stenosis, especially in elderly women, where it is a very frequent finding. The optimal approach for treating these patients remains controversial, and several surgical strategies such as aortic root enlargement, supra-annular stented prosthetic valves, stentless bioprosthesis, and sutureless bioprostheses have been proposed to improve valve hemodynamics and clinical outcomes. More recently, transcatheter aortic valve replacement has emerged as a valid alternative for the treatment of aortic stenosis and excellent valve hemodynamic results have been observed among patients with a small aortic annulus. The purpose of this review is to provide an overview of the current definition, prevalence, and clinical impact of small aortic annulus in patients with aortic stenosis, and evaluate the different therapeutic strategies currently available to improve valve hemodynamics and outcomes in this population.

Drug-eluting balloon angioplasty versus uncoated balloon angioplasty for peripheral arterial disease of the lower limbs.

BACKGROUND: Atherosclerotic peripheral arterial disease (PAD) can lead to disabling ischemia and limb loss. Treatment modalities have included risk factor optimization through life-style modifications and medications, or operative approaches using both open and minimally invasive techniques, such as balloon angioplasty. Drug-eluting balloon (DEB) angioplasty has emerged as a promising alternative to uncoated balloon angioplasty for the treatment of this difficult disease process. By ballooning and coating the inside of atherosclerotic vessels with cytotoxic agents, such as paclitaxel, cellular mechanisms responsible for atherosclerosis and neointimal hyperplasia are inhibited and its devastating complications are prevented or postponed. DEBs are considerably more expensive than uncoated balloons, and their efficacy in improving patient outcomes is unclear. OBJECTIVES: To assess the efficacy of drug-eluting balloons (DEBs) compared with uncoated, nonstenting balloon angioplasty in people with symptomatic lower-limb peripheral arterial disease (PAD). SEARCH METHODS: The Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched December 2015) and Cochrane Register of Studies (CRS) (2015, Issue 11). The TSC searched trial databases for details of ongoing and unpublished studies. SELECTION CRITERIA: We included all randomized controlled trials that compared DEBs with uncoated, nonstenting balloon angioplasty for intermittent claudication (IC) or critical limb ischemia (CLI). DATA COLLECTION AND ANALYSIS: Two review authors (AK, TA) independently selected the appropriate trials and performed data extraction, assessment of trial quality, and data analysis. The senior review author (DKR) adjudicated any disagreements. MAIN RESULTS: Eleven trials that randomized 1838 participants met the study inclusion criteria. Seven of the trials included femoropopliteal arterial lesions, three included tibial arterial lesions, and one included both. The trials were carried out in Europe and in the USA and all used the taxane drug paclitaxel in the DEB arm. Nine of the 11 trials were industry-sponsored. Four companies manufactured the DEB devices (Bard, Bavaria Medizin, Biotronik, and Medtronic). The trials examined both anatomic and clinical endpoints. There was heterogeneity in the frequency of stent deployment and the type and duration of antiplatelet therapy between trials. Using GRADE assessment criteria, the quality of the evidence presented was moderate for the outcomes of target lesion revascularization and change in Rutherford category, and high for amputation, primary vessel patency, binary restenosis, death, and change in ankle-brachial index (ABI). Most participants were followed up for 12 months, but one trial reported outcomes at five years.There were better outcomes for DEBs for up to two years in primary vessel patency (odds ratio (OR) 1.47, 95% confidence interval (CI) 0.22 to 9.57 at six months; OR 1.92, 95% CI 1.45 to 2.56 at 12 months; OR 3.51, 95% CI 2.26 to 5.46 at two years) and at six months and two years for late lumen loss (mean difference (MD) -0.64 mm, 95% CI -1.00 to -0.28 at six months; MD -0.80 mm, 95% CI -1.44 to -0.16 at two years). DEB were also superior to uncoated balloon angioplasty for up to five years in target lesion revascularization (OR 0.28, 95% CI 0.17 to 0.47 at six months; OR 0.40, 95% CI 0.31 to 0.51 at 12 months; OR 0.28, 95% CI 0.18 to 0.44 at two years; OR 0.21, 95% CI 0.09 to 0.51 at five years) and binary restenosis rate (OR 0.44, 95% CI 0.29 to 0.67 at six months; OR 0.38, 95% CI 0.15 to 0.98 at 12 months; OR 0.26, 95% CI 0.10 to 0.66 at two years; OR 0.12, 95% CI 0.05 to 0.30 at five years). There was no significant difference between DEB and uncoated angioplasty in amputation, death, change in ABI, change in Rutherford category and quality of life (QoL) scores, or functional walking ability, although none of the trials were powered to detect a significant difference in these clinical endpoints. We carried out two subgroup analyses to examine outcomes in femoropopliteal and tibial interventions as well as in people with CLI (4 or greater Rutherford class), and showed no advantage for DEBs in tibial vessels at six and 12 months compared with uncoated balloon angioplasty. There was also no advantage for DEBs in CLI compared with uncoated balloon angioplasty at 12 months. AUTHORS' CONCLUSIONS: Based on a meta-analysis of 11 trials with 1838 participants, there is evidence of an advantage for DEBs compared with uncoated balloon angioplasty in several anatomic endpoints such as primary vessel patency (high-quality evidence), binary restenosis rate (moderate-quality evidence), and target lesion revascularization (low-quality evidence) for up to 12 months. Conversely, there is no evidence of an advantage for DEBs in clinical endpoints such as amputation, death, or change in ABI, or change in Rutherford category during 12 months' follow-up. Well-designed randomized trials with long-term follow-up are needed to compare DEBs with uncoated balloon angioplasties adequately for both anatomic and clinical study endpoints before the widespread use of this expensive technology can be justified.

Impact of clopidogrel plus aspirin versus aspirin alone on the progression of native coronary artery disease after bypass surgery: analysis from the Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) randomized trial.

BACKGROUND: The effects of dual antiplatelet therapy with aspirin and clopidogrel on the progression of native coronary artery disease after coronary artery bypass grafting are unknown. METHODS AND RESULTS: In the Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) trial, a total of 113 patients were randomized to receive aspirin plus clopidogrel or aspirin plus placebo for 1 year after coronary artery bypass grafting. In this secondary analysis, the 92 patients who underwent preoperative and 1-year postoperative angiograms at 2 centers had each of their coronary stenoses graded serially by using 6 thresholds (grade 0 [0%-24%], grade 1 [25%-37%], grade 2 [38%-62%], grade 3 [63%-82%], grade 4 [83%-98%], and grade 5 [99%-100%]). We compared the incidence and degree of evolving coronary artery disease between the 2 treatment groups. A total of 543 preoperative stenoses and occlusions were quantified and followed. At 1-year postoperatively, there were 103 evolving (94 worsened, 9 improved) and 22 new lesions. The right coronary artery territory and sites proximal to a graft were more commonly associated with worsening coronary artery disease (P≤0.02). There were no differences in clinical events between treatment groups, and the proportion of patients with evolving or new lesions was also similar (70% versus 74%, aspirin-clopidogrel versus aspirin-placebo, respectively; P=0.8). However, in evolving or new lesions, the mean grade change (1.1±1.0 versus 1.6±1.1, respectively; P=0.01) and the proportion of new occlusions (7% versus 22%; P=0.02) were lower in the aspirin-clopidogrel group. CONCLUSIONS: The addition of clopidogrel to aspirin correlates with less worsening of native coronary artery disease 1 year after coronary artery bypass grafting. These findings may help guide post-coronary artery bypass grafting antiplatelet therapy. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00228423.

Mitral valve interventions in heart failure.

PURPOSE OF REVIEW: This review describes new developments in mitral valve interventions for patients with heart failure. The review also discusses innovative therapies in the treatment of mitral regurgitation in patients with heart failure and describes novel risk factors of recurrent mitral regurgitation following repair in this population. RECENT FINDINGS: Percutaneous strategies are rapidly emerging as an important adjunct to conventional mitral surgery, specially for patients with functional mitral regurgitation and heart failure. Percutaneous therapies are a well-tolerated alternative to surgery in high-risk patients, but their long-term efficacy is not established. Partial ring annuloplasty and preoperative galectin-3 levels may be associated with recurrent mitral regurgitation after repair. Preclinical work has focused on injectable substances, which may ameliorate adverse left ventricular remodeling and recurrent mitral regurgitation after surgery. SUMMARY: Percutaneous therapies will continue to evolve and serve as an alternative to conventional surgery for patients with mitral regurgitation and heart failure. Determining anatomic and biochemical risk factors associated with recurrent mitral regurgitation after repair is crucial in tailoring therapy to individual patients. Preclinical work regarding infarct stabilization may benefit future patients with heart failure.

Hybrid approach for coronary artery revascularization: where do we stand?

PURPOSE OF REVIEW: Recently, hybrid coronary artery revascularization (HCAR), combining the benefits of both percutaneous coronary intervention and coronary artery bypass graft surgery (CABG) while minimizing their respective shortcomings, has been developed. This review is aimed to explore and discuss recent clinical outcomes and patient selection, and comment on surgical approaches for HCAR. RECENT FINDINGS: Current forms of HCAR include off-pump mini-sternotomy or on-pump full sternotomy CABG [left internal mammary artery (LIMA)-to-left anterior descending artery(LAD) CABG followed by drug-eluting stents (DES) to non-LAD territories], robotic-assisted off-pump HCAR (robotic LIMA-to-LAD CABG and DES to non-LAD territories), and off-pump mini-thoracotomy single-vessel small thoracotomy (LIMA-to-LAD CABG), all of which have reported acceptable early to mid-term patency rates and freedom from major cardiac and cerebrovascular adverse events. As long-term effectiveness compared with conventional CABG remains to be demonstrated, especially in patients with diabetes and patients with higher SYNTAX scores, appropriate discussion between the 'Heart Team' and patient is needed prior to HCAR. SUMMARY: HCAR presents an attractive alternative option for treating patients with multivessel coronary artery disease because it maximizes the clear survival benefits of LIMA-LAD grafting, improves quality assurance with completion angiography, and allows quicker patient recovery; furthermore, patients avoid the negative systemic inflammatory effects of cardiopulmonary bypass and delayed healing after sternotomy.

An update on mechanical circulatory support for heart failure therapy.

PURPOSE OF REVIEW: This article aims to review contemporary studies that utilized mechanical circulatory support (MCS) in the treatment of heart failure and to elaborate on prospective mechanical alternatives. RECENT FINDINGS: There is a growing need for a well-tolerated, durable and effective MCS option in patients with refractory heart failure. In previous years, the primary indication for MCS therapy supported bridge to transplantation. These early left ventricular assist devices (LVADs) suffered significant adverse events, thereby limiting their prolonged use. With the introduction of newer continuous flow LVADs, with lower morbidity, neurological events, pump failure and the expanded indication use (i.e. destination therapy), the overall number of implanted patients has grown. SUMMARY: There has been a dramatic advancement of durability found in the second and third-generation, continuous flow LVADs, along with improved survival rates in patients receiving these devices for destination therapy. MCS may soon become the treatment option of choice in refractory heart failure patients, especially with further evolution of less invasive approaches, smaller designs, and energy sources.

Endovascular treatment for cerebral septic embolic stroke.

This case demonstrates an alternative approach to cerebral revascularization by performing both intravascular mechanical thrombectomy and local injection of thrombolytics that may reduce mortality, bleeding, and the diminished quality of life experienced by patients following an acute septic embolic stroke.

Hemiarch versus extended arch repair for acute type A dissection: Results from a multicenter national registry.

OBJECTIVE: We compared perioperative outcomes of patients with acute type A aortic dissection undergoing hemiarch (HA) versus extended arch (EA) repair with or without descending aortic intervention. METHODS: Nine hundred twenty-nine patients underwent acute type A aortic dissection repair (2002-2021, 9 centers) including open distal repair (HA) with or without additional EA repair. EA with intervention on the descending aorta (EAD) included elephant trunk, antegrade thoracic endovascular aortic replacement, or uncovered dissection stent. EA with no descending intervention (EAND), included unstented suture-only methods. Primary outcomes were in-hospital mortality, permanent neurologic deficit, computed tomography malperfusion resolution, and a composite. Multivariable logistic regression was also performed. RESULTS: Mean age was 66 ± 18 years, 30% (278 out of 929) were women, and HA was performed more frequently (75% [n = 695]) than EA (25% [n = 234]). EAD techniques included: dissection stent (39 out of 234 [17%]), thoracic endovascular aortic replacement (18 out of 234 [7.7%]), and elephant trunk (87 out of 234 [37%]). In-hospital mortality (EA: n = 49 [21%] and HA: n = 129 [19%]; P = .42), and neurological deficit (EA: n = 43 [18%] and HA: n = 121 [17%]; P = .74) were similar. EA was not independently associated with death (EA vs HA odds ratio, 1.09; 95% CI, 0.77-1.54; P = .63) or neurologic deficit (EA vs HA odds ratio, 0.85; 95% CI, 0.47-1.55; P = .59). Composite adverse events differed significantly (EA vs HA odds ratio, 1.47; 95% CI, 1.16-1.87; P = .001). Malperfusion resolved more frequently after EAD (EAD: n = 32 [80%], EAND: n = 18 [56%], HA: n = 71 [50%]; P = .004), although multivariable analysis was not significant (EAD vs HA odds ratio, 2.17; 95% CI, 0.83-5.66; P = .10). CONCLUSIONS: Extended arch interventions pose similar perioperative mortality and neurologic risks as Hemiarch. Descending aortic reinforcement may promote malperfusion restoration. Extended techniques should be approached with caution in acute dissection due to increased risk of adverse events.

Cerebral microembolization after bioprosthetic aortic valve replacement: comparison of warfarin plus aspirin versus aspirin only.

BACKGROUND: No human physiological data exists on whether aspirin only is as effective as warfarin plus aspirin in preventing cerebral microembolization in the early postoperative period after bioprosthetic aortic valve replacement (bAVR). METHODS AND RESULTS: We prospectively enrolled 56 patients who had no other indication for oral anticoagulation, who underwent bAVR and received, in an open-label fashion, either daily warfarin (for INR 2.0-3.0) plus 81 mg of aspirin (n=28) or 325 mg of aspirin only (n=28). Cerebral microembolization was quantified at 4 hours (baseline) and at 1 month postoperatively, by recording 1-hour bilateral middle cerebral artery (MCA) microembolic signals (MES). Platelet-function analysis (PFA) of closure times (CT) on collagen was also used as a marker of platelet-dependent activation. Follow-up to 1 year was complete. Preoperative demographics and baseline platelet function were equivalent in both groups. There was no mortality, stroke, or transient ischemic attack at 1 year in either group. No significant differences were found in the proportion of patients with MES among those receiving warfarin plus aspirin versus aspirin only, at baseline (68% versus 82%, respectively; P=0.4) and at 1 month (46% versus 43%; P=1.0) after bAVR. The total MES and PFA were also equivalent between groups, at baseline and follow-up. CONCLUSIONS: Early after bAVR, the effects of these 2 antithrombotic regimens on cerebral microembolization and platelet function are equivalent. These data bring new mechanistic support to the premise that aspirin only may safely be used early after bAVR in patients who have no other indication for oral anticoagulation.

Late Outcome of a Left-Atrial-to-Coronary-Sinus Shunt.

Frail patients with severe calcific mitral stenosis have few treatment options. We present a novel case successfully treated with a left-atrial-to-coronary-sinus shunt. However, the patient's symptoms returned, and, at surgery, the shunt was found to be occluded and associated with left atrial and ventricular fibrosis and calcification. (Level of Difficulty: Intermediate.).

Utility of a smartphone application in assessing palmar circulation prior to radial artery harvesting for coronary artery bypass grafting: rationale and design of the randomised CAPITAL iRADIAL-CABG trial.

INTRODUCTION: There is emerging evidence supporting the use of the radial artery (RA) as a preferred secondary conduit for coronary artery bypass grafting (CABG) as it is associated with higher rates of graft patency at 5 years when compared with saphenous vein grafts (SVG). The modified Allen's test (MAT) is traditionally regarded as the standard of care in the assessment of ulnar artery (UA) patency prior to RA harvesting. Unfortunately, due to high false-positive rates, a substantial number of pre-CABG patients are found to have an abnormal MAT despite normal UA patency, resulting in inappropriate exclusion from RA harvesting. The SVG is generally used in its place when this occurs, resulting in potentially lower rates of long-term graft patency. METHODS AND ANALYSIS: The CAPITAL iRADIAL-CABG trial is currently enrolling participants 18 years of age or older undergoing CABG for whom the treating physician is considering the use of an RA conduit. Eligible patients will be randomised in a 1:1 fashion to MAT or smartphone-based photoplethysmography application assessment to assess collateral palmar circulation prior to RA harvesting. The primary outcome of the trial is the use of the RA as a conduit during CABG. The primary safety outcome is postoperative palmar ischaemia as determined by clinical assessment or requirement of vascular intervention. Secondary outcomes include vascular complications, early graft failure, need for rescue percutaneous coronary intervention during the index hospitalisation and a composite cardiovascular outcome of myocardial infarction, stroke and cardiovascular death prior to discharge from hospital. A total of 236 participants are planned to be recruited. ETHICS AND DISSEMINATION: The study was approved by the Ottawa Heart Science Network Research Ethics Board (approval number 20180865-01H). The study results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03810729.

Moderate to Severe Acute Kidney Injury Leads to Worse Outcomes in Complex Thoracic Aortic Surgery.

BACKGROUND: The impact of acute kidney injury (AKI) in thoracic aortic surgery is not well defined. This study aimed to examine the impact of varying severity of AKI on in-hospital and long-term outcome in these patients. METHODS: From 2004 to 2018, 1142 patients underwent thoracic aortic surgery at a single institution (University of Ottawa Heart Institute, Ottawa, Canada) and were stratified into 4 groups on the basis of the severity of postoperative AKI: no AKI (n = 705), Acute Kidney Injury Network (AKIN) stage 1 (n = 261), AKIN stage 2 (n = 72), and AKIN stage 3 (n = 104). Outcomes include in-hospital mortality, morbidity, and long-term survival. Multivariable logistic regression was used to identify independent predictors of AKI. Propensity score matching was performed to identify pairs of patients without postoperative AKI or with AKIN stage 1 AKI, as well as pairs of patients without postoperative AKI and those with AKIN stage 2 or higher AKI. Kaplan-Meier curves were plotted for late survival. RESULTS: In the propensity-matched cohort, patients with postoperative AKIN stage I AKI had worse in-hospital mortality but comparable long-term survival when compared with patients without postoperative AKI. Patients with AKIN stage 2 or higher AKI experienced significantly higher in-hospital mortality compared with patients without postoperative AKI (15.9% vs 4.6%; P < .01) and worse 8-year survival (65.9% ± 34.1% vs 80.1% ± 20.0%; P < .01). CONCLUSIONS: Moderate to severe AKI is a serious complication and is associated with significantly worse short- and long-term outcomes; targeting mild AKI with therapeutic intervention is an important step in improving patient outcomes.

Perioperative and Long-Term Morbidity and Mortality for Elderly Patients Undergoing Thoracic Aortic Surgery.

The impact of age on outcome in elective thoracic aortic surgery is not well characterized. We aim to evaluate age-related differences in short- and long-term outcomes in elderly patients undergoing elective thoracic aortic surgery. From 2004 to 2018, 786 patients underwent elective thoracic aortic surgery at a single center and were divided into 2 groups; <75 years old (n = 651) and ≥75 years old (n = 135). Outcomes include in-hospital mortality, morbidity, and long-term survival. Median follow-up was 4.8 years. Multivariable logistic regression was used to identify independent predictors of mortality and morbidity; Kaplan-Meier curves were plotted for late survival. Similar analysis was performed to the propensity-matched cohort. The elderly cohort had higher in-hospital mortality (8.2% vs 1.7%; P < 0.01), stroke (11.9 vs 2.8%; P< 0.01) and prolonged ventilation (17.3% vs 8.3%; P < 0.01), and intensive care unit stay (5.6 ± 10.9 vs 2.9 ± 6.0 days; P < 0.01). After adjusting for baseline differences and surgical complexity, age ≥75 years remained a significant predictor of hospital mortality (odds ratio [95% confidence interval]: 3.7 [1.3-10.3]). Eight-year survival was 75.4 ± 7.7% in the older group compared to 93.3 ± 1.9% in the younger group (hazard ratio [95% confidence interval]: 4.2 [1.7-11.0]). Propensity score-matched analysis also confirmed worse early- and long-term outcomes in the elderly group. Elderly patients experience higher in-hospital mortality and morbidity following elective thoracic aortic surgery compared to their younger counterparts and have a higher burden of mortality over long-term follow-up.