Left ventricular geometry predicts optimal response to percutaneous mitral repair via MitraClip: Integrated assessment by two- and three-dimensional echocardiography.

OBJECTIVES: To assess impact of left ventricular (LV) chamber remodeling on MitraClip (MClp) response. BACKGROUND: MitraClip is the sole percutaneous therapy approved for mitral regurgitation (MR) but response varies. LV dilation affects mitral coaptation; determinants of MClp response are uncertain. METHODS: LV and mitral geometry were quantified on pre- and post-procedure two-dimensional (2D) transthoracic echocardiography (TTE) and intra-procedural three-dimensional (3D) transesophageal echocardiography (TEE). Optimal MClp response was defined as ≤mild MR at early (1-6 month) follow-up. RESULTS: Sixty-seven degenerative MR patients underwent MClp: Whereas MR decreased ≥1 grade in 94%, 39% of patients had optimal response (≤mild MR). Responders had smaller pre-procedural LV end-diastolic volume (94 ± 24 vs. 109 ± 25 mL/m2 , p = 0.02), paralleling smaller annular diameter (3.1 ± 0.4 vs. 3.5 ± 0.5 cm, p = 0.002), and inter-papillary distance (2.2 ± 0.7 vs. 2.5 ± 0.6 cm, p = 0.04). 3D TEE-derived annular area correlated with 2D TTE (r = 0.59, p < 0.001) and was smaller among optimal responders (12.8 ± 2.1 cm2 vs. 16.8 ± 4.4 cm2 , p = 0.001). Both 2D and 3D mitral annular size yielded good diagnostic performance for optimal MClp response (AUC 0.73-0.84, p < 0.01). In multivariate analysis, sub-optimal MClp response was associated with LV end-diastolic diameter (OR 3.10 per-cm [1.26-7.62], p = 0.01) independent of LA size (1.10 per-cm2 [1.02-1.19], p = 0.01); substitution of mitral annular diameter for LV size yielded an independent association with MClp response (4.06 per-cm2 [1.03-15.96], p = 0.045). CONCLUSIONS: Among degenerative MR patients undergoing MClp, LV and mitral annular dilation augment risk for residual or recurrent MR, supporting the concept that MClp therapeutic response is linked to sub-valvular remodeling.

Transcatheter MitraClip repair alters mitral annular geometry - device induced annular remodeling on three-dimensional echocardiography predicts therapeutic response.

BACKGROUND: Echocardiography (echo) is widely used to guide therapeutic decision-making for patients being considered for MitraClip. Relative utility of two- (2D) and three-dimensional (3D) echo predictors of MitraClip response, and impact of MitraClip on mitral annular geometry, are uncertain. METHODS: The study population comprised patients with advanced (> moderate) MR undergoing MitraClip. Mitral annular geometry was quantified on pre-procedural 2D transthoracic echocardiography (TTE) and intra-procedural 3D transesophageal echocardiography (TEE); 3D TEE was used to measure MitraClip induced changes in annular geometry. Optimal MitraClip response was defined as ≤mild MR on follow-up (mean 2.7 ± 2.5 months) post-procedure TTE. RESULTS: Eighty patients with advanced MR underwent MitraClip; 41% had optimal response (≤mild MR). Responders had smaller pre-procedural global left ventricular (LV) end-diastolic size and mitral annular diameter on 2D TTE (both p ≤ 0.01), paralleling smaller annular area and circumference on 3D TEE (both p = 0.001). Mitral annular size yielded good diagnostic performance for optimal MitraClip response (AUC 0.72, p < 0.01). In multivariate analysis, sub-optimal MitraClip response was independently associated with larger pre-procedural mitral annular area on 3D TEE (OR 1.93 per cm2/m2 [CI 1.19-3.13], p = 0.007) and global LV end-diastolic volume on 2D TTE (OR 1.29 per 10 ml/m2 [CI 1.02-1.63], p = 0.03). Substitution of 2D TTE derived mitral annular diameter for 3D TEE data demonstrated a lesser association between pre-procedural annular size (OR 5.36 per cm/m2 [CI 0.95-30.19], p = 0.06) and sub-optimal MitraClip response. Matched pre- and post-procedural TEE analyses demonstrated MitraClip to acutely decrease mitral annular area and circumference (all p < 0.001) as well as mitral tenting height, area, and volume (all p < 0.05): Magnitude of MitraClip induced reductions in mitral annular circumference on intra-procedural 3D TEE was greater among patients with, compared to those without, sub-optimal MitraClip response (>mild MR) on followup TTE (p = 0.017); greater magnitude of device-induced annular reduction remained associated with sub-optimal MitraClip response even when normalized for pre-procedure annular circumference (p = 0.028). CONCLUSIONS: MitraClip alters mitral annular geometry as quantified by intra-procedural 3D TEE. Pre-procedural mitral annular dilation and magnitude of device-induced reduction in mitral annular size on 3D TEE are each associated with sub-optimal therapeutic response to MitraClip.

A multicenter randomized trial comparing the effectiveness and safety of a novel vascular closure device to manual compression in anticoagulated patients undergoing percutaneous transfemoral procedures: The CELT ACD trial.

OBJECTIVES: This study compared the performance of Celt ACD® , a novel stainless steel based vascular closure device versus manual compression (MC) for femoral arteriotomy site hemostasis in patients undergoing percutaneous coronary procedures. BACKGROUND: Optimal access site management after percutaneous transfemoral procedures remains controversial. METHODS: Patients enrolled in this multicenter, randomized open label trial underwent 6-F diagnostic or interventional procedures and were assigned 2:1 to Celt ACD® versus MC. All patients were on full anticoagulation. The primary efficacy end point was time to hemostasis (TTH) and the primary safety end points were 30-day incidence of major procedural and access site related complications. RESULTS: The trial allocated 207 patients to Celt ACD® (n = 148) versus MC (n = 59) at 5 investigational sites. Baseline characteristics of the two groups were similar. Median TTH was 0 (Interquartile range (IQR): 0, 0.33) in the Celt ACD® compared to 8 min (IQR: 0, 20; P < 0.0001) in the MC group. Procedural success was 99.3% in the Celt ACD® versus 98.1% in the MC group (P = NS). There was a single major adverse event due to device maldeployment and embolization with successful percutaneous retrieval. The 30-day major complication rate was 0.7% in the Celt ACD® and 0% in the MC group (P = NS). CONCLUSIONS: After 6-F percutaneous invasive procedures in fully anticoagulated patients, TTH was significantly reduced in patients assigned to Celt ACD® compared to patients managed with MC. The 30-day rates of vascular complications were similarly low in both groups. (CELT ACD Trial; NCT01600482) © 2017 Wiley Periodicals, Inc.

Impella Versus Intra-Aortic Balloon Pump in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: An Observational Study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for patients with cardiogenic shock. Although Impella or intra-aortic balloon pump (IABP) is frequently used for left ventricular unloading (LVU) during VA-ECMO treatment, there are limited data on comparative outcomes. We compared outcomes of Impella and IABP for LVU during VA-ECMO. METHODS AND RESULTS: Using the Nationwide Readmissions Database between 2016 and 2020, we analyzed outcomes in 3 groups of patients with cardiogenic shock requiring VA-ECMO based on LVU strategies: extracorporeal membrane oxygenation (ECMO) only, ECMO with IABP, and ECMO with Impella. Of 15 980 patients on VA-ECMO, IABP and Impella were used in 19.4% and 16.4%, respectively. The proportion of patients receiving Impella significantly increased from 2016 to 2020 (6.5% versus 25.8%; P-trend<0.001). In-hospital mortality was higher with ECMO with Impella (54.8%) compared with ECMO only (50.4%) and ECMO with IABP (48.4%). After adjustment, ECMO with IABP versus ECMO only was associated with lower in-hospital mortality (adjusted odds ratio [aOR], 0.83; P=0.02). ECMO with Impella versus ECMO only had similar in-hospital mortality (aOR, 1.09; P=0.695) but was associated with more bleeding (aOR, 1.21; P=0.007) and more acute kidney injury requiring hemodialysis (aOR, 1.42; P<0.001). ECMO with Impella versus ECMO with IABP was associated with greater risk of acute kidney injury requiring hemodialysis (aOR, 1.49; P=0.002), higher in-hospital mortality (aOR, 1.32; P=0.001), and higher 40-day mortality (hazard ratio, 1.25; P<0.001). CONCLUSIONS: In patients with cardiogenic shock on VA-ECMO, LVU with Impella, particularly with 2.5/CP, was not associated with improved survival at 40 days but was associated with increased adverse events compared with IABP. More data are needed to assess Impella platform-specific comparative outcomes of LVU.

Nationwide trends of balloon pulmonary angioplasty and pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension (2012-2019).

Chronic thromboembolic pulmonary hypertension (CTEPH) is a sequela of a pulmonary embolus that occurs in approximately 1%-3% of patients. Pulmonary thromboendoarterectomy (PTE) can be a curative procedure, but balloon pulmonary angioplasty (BPA) has emerged as an option for poor surgical candidates. We used the National Inpatient Sample to query patients who underwent PTE or BPA between 2012 and 2019 with CTEPH. The primary outcome was a composite of in-hospital mortality, myocardial infarction, stroke, tracheostomy, and prolonged mechanical ventilation. Outcomes were compared between low- and high-volume centers, defined as 5 and 10 procedures per year for BPA and PTE, respectively. During our study period, 870 BPA and 2395 PTE were performed. There was a 328% relative increase in the number of PTE performed during the study period. Adverse events for BPA were rare. There was an increase in the primary composite outcome for low-volume centers compared to high-volume centers for PTE (24.4% vs. 12.1%, p = 0.003). Patients with hospitalizations for PTE in low-volume centers were more likely to have prolonged mechanical ventilation (20.0%% vs. 7.2%, p < 0.001) and tracheostomy (7.8% vs. 2.6%, p = 0.017). In summary, PTE rates have been rising over the past 10 years, while BPA rates have remained stable. While adverse outcomes are rare for BPA, patients with hospitalizations at low-volume centers for PTE were more likely to have adverse outcomes. For patients undergoing treatment of CTEPH with BPA or PTE, referral to high-volume centers with multidisciplinary teams should be encouraged for optimal outcomes.

Percutaneous closure of giant aneurysmal coronary artery-to-coronary sinus fistulae with guidance from three-dimensional printed models: a case series.

Background: Coronary artery fistulae are abnormal communications of coronary arteries with systemic vasculature, pulmonary vasculature, or cardiac chambers. Use of multimodality imaging can be paramount to understanding anatomical and functional features of these complex vascular lesions, therefore optimizing success of potential curative interventions. Case summary: We present two patients with incidentally discovered giant aneurysmal coronary arteries with distal fistulous connections to the coronary sinus, which were successfully closed percutaneously with Amplatzer Septal Occluders using the assistance of three-dimensional (3D) printed heart models. Conclusion: Computed tomography-guided reconstruction with 3D multiplanar, multicolour printed models can help augment visuospatial understanding of the size, origin, course, and drainage of giant aneurysmal coronary artery-to-coronary sinus fistulae, and with manual bench testing can assist with choosing accurately sized and shaped devices for closure.

Sex-Based Differences in 30-Day Readmissions After Cardiac Arrest: Analysis of the Nationwide Readmissions Database.

Background There are limited data on the sex-based differences in the outcome of readmission after cardiac arrest. Methods and Results Using the Nationwide Readmissions Database, we analyzed patients hospitalized with cardiac arrest between 2010 and 2015. Based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, we identified comorbidities, therapeutic interventions, and outcomes. Multivariable logistic regression was performed to assess the independent association between sex and outcomes. Of 835 894 patients, 44.4% (n=371 455) were women, of whom 80.7% presented with pulseless electrical activity (PEA)/asystole. Women primarily presented with PEA/asystole (80.7% versus 72.4%) and had a greater comorbidity burden than men, as assessed using the Elixhauser Comorbidity Score. Thirty-day readmission rates were higher in women than men in both PEA/asystole (20.8% versus 19.6%) and ventricular tachycardia/ventricular fibrillation arrests (19.4% versus 17.1%). Among ventricular tachycardia/ventricular fibrillation arrest survivors, women were more likely than men to be readmitted because of noncardiac causes, predominantly infectious, respiratory, and gastrointestinal illnesses. Among PEA/asystole survivors, women were at higher risk for all-cause (adjusted odds ratio [aOR], 1.07; [95% CI, 1.03-1.11]), cardiac-cause (aOR, 1.15; [95% CI, 1.06-1.25]), and noncardiac-cause (aOR, 1.13; [95% CI, 1.04-1.22]) readmission. During the index hospitalization, women were less likely than men to receive therapeutic procedures, including coronary angiography and targeted therapeutic management. While the crude case fatality rate was higher in women, in both ventricular tachycardia/ventricular fibrillation (51.8% versus 47.4%) and PEA/asystole (69.3% versus 68.5%) arrests, sex was not independently associated with increased crude case fatality after adjusting for differences in baseline characteristics. Conclusions Women are at increased risk of readmission following cardiac arrest, independent of comorbidities and therapeutic interventions.

Predicting future left anterior descending artery events from non-culprit lesions: insights from the Lipid-Rich Plaque study.

AIMS: The left anterior descending (LAD) artery is the most frequently affected site by coronary artery disease. The prospective Lipid Rich Plaque (LRP) study, which enrolled patients undergoing imaging of non-culprits followed over 2 years, reported the successful identification of coronary segments at risk of future events based on near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) lipid signals. We aimed to characterize the plaque events involving the LAD vs. non-LAD segments. METHODS AND RESULTS: LRP enrolled 1563 patients from 2014 to 2016. All adjudicated plaque events defined by the composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization by coronary bypass or percutaneous coronary intervention, and rehospitalization for angina with >20% stenosis progression and reported as non-culprit lesion-related major adverse cardiac events (NC-MACE) were classified by NIRS-IVUS maxLCBI4 mm (maximum 4-mm Lipid Core Burden Index) ≤400 or >400 and association with high-risk-plaque characteristics, plaque burden ≥70%, and minimum lumen area (MLA) ≤4 mm2. Fifty-seven events were recorded with more lipid-rich plaques in the LAD vs. left circumflex and right coronary artery; 12.5% vs. 10.4% vs. 11.3%, P = 0.097. Unequivocally, a maxLCBI4 mm >400 in the LAD was more predictive of NC-MACE [hazard ratio (HR) 4.32, 95% confidence interval (CI) (1.93-9.69); P = 0.0004] vs. [HR 2.56, 95% CI (1.06-6.17); P = 0.0354] in non-LAD segments. MLA ≤4 mm2 within the maxLCBI4 mm was significantly higher in the LAD (34.1% vs. 25.9% vs. 13.7%, P < 0.001). CONCLUSION: Non-culprit lipid-rich segments in the LAD were more frequently associated with plaque-level events. LAD NIRS-IVUS screening may help identify patients requiring intensive surveillance and medical treatment.

Best Practice Recommendations for Optimizing Care in Structural Heart Programs: Planning Efficient and Resource Leveraging Systems (PEARLS).

The COVID19 pandemic brought unprecedented disruption to healthcare. Staggering morbidity, mortality, and economic losses prompted the review and refinement of care for structural heart disease (SHD). To mitigate negative impacts in the face of crisis or capacity constraints, this paper offers best practice recommendations for Planning Efficient and Resource Leveraging Systems (PEARLS) in structural heart programs. A systematic assessment is recommended for hospital capacity, Heart Team roles and functions, and patient and procedural risks associated with increased resource utilization. Strategies, tactics, and pathways are provided for the delivery of patient-centered, efficient and resource-leveraging care from referral to follow-up. Through the optimal use of capacity and resources, paired with dynamic triage, forecasting, and surveillance, Heart Teams may aspire to plan and implement an optimized system of care for SHD. Abbreviations: AS: aortic stenosis; ASD: atrioseptal defect; COVID19: Coronavirus disease 19; LAAO: left atrial appendage occlusion; MI: myocardial infarction; MR: mitral regurgitation; PFO: patent foramen ovale; PVL: paravalvular leak; SHD: structural heart disease; SAVR: surgical aortic valve replacement; SDM: shared decision-making; TAVR: transcatheter aortic valve replacement; TMVr: transcatheter mitral valve repair; TMVR: transcatheter mitral valve replacement; TEE: transesophageal echocardiography; TTE: transthoracic echocardiography.

Potential impact of dynamic automated CT aortic annular measurements on outcomes for transcatheter aortic valve replacement sizing.

To determine the potential impact of automated computed tomography (CT) software used for aortic annular sizing for transcatheter aortic valve replacement (TAVR) on paravalvular leak (PVL) and major adverse cardiovascular events (MACE) as compared to standard CT manual measurement. In 60 TAVR patients (84 ± 7 years, 60% male), we evaluated the preprocedural CT scans. For the standard manual measurement, we measured the perimeter and area from a single cardiac phase deemed to be of maximum systolic opening. Valve type and size were determined by a multidisciplinary TAVR team per clinical routine. From the dynamic automated software, we determined the aortic annular perimeter and area as the maximum value from an entire cardiac cycle. Valve size was readjudicated by a blinded interventional cardiologist who was provided with valve type and automated values. Clinical endpoints were adjudicated for presence of at least mild PVL and MACE at 30 days. There were 16 (28%) patients with PVL and 4 (7%) with 30-day MACE. When reclassifying valve size using dynamic automated values, 12 (20%) patients were undersized and 3 (5%) patients were oversized. Undersized patients were more likely to have mild-to-moderate PVL at 30 days (27% vs 4%, p = 0.04) than those not undersized. Of the 5 (45%) undersized patients with at least mild PVL, all were balloon-expandable valves. Automated dynamic CT annular measurements have the potential to reclassify patients with PVL with larger TAVR valve size, particularly balloon-expandable valves.

Tricuspid Stenosis in Pregnancy: A Valve-in-Valve Conundrum.

Redo tricuspid valve replacement has high surgical operative mortality. Transcatheter valve-in-valve provides a viable option for valve replacement. We discuss the decision-making process involved in performing transcatheter tricuspid valve-in-valve replacement in a 23-week pregnant woman with multiple comorbidities and symptomatic severe bioprosthetic stenosis. (Level of Difficulty: Intermediate.).

Subclinical Leaflet Thrombosis in Transcatheter and Surgical Bioprosthetic Valves: PARTNER 3 Cardiac Computed Tomography Substudy.

BACKGROUND: Subclinical leaflet thrombosis, characterized by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion observed on 4-dimensional computed tomography (CT), may represent a form of bioprosthetic valve dysfunction. OBJECTIVES: The U.S. Food and Drug Administration mandated CT studies to understand the natural history of this finding, differences between transcatheter and surgical valves, and its association with valve hemodynamics and clinical outcomes. METHODS: The PARTNER 3 (The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low-Risk Patients With Aortic Stenosis) CT substudy randomized 435 patients with low-surgical-risk aortic stenosis to undergo transcatheter aortic valve replacement (n = 221) or surgery (n = 214). Serial 4-dimensional CTs were performed at 30 days and 1 year and were analyzed independently by a core laboratory. RESULTS: The incidence of HALT increased from 10% at 30 days to 24% at 1 year. Spontaneous resolution of 30-day HALT occurred in 54% of patients at 1 year, whereas new HALT appeared in 21% of patients at 1 year. HALT was more frequent in transcatheter versus surgical valves at 30 days (13% vs. 5%; p = 0.03), but not at 1 year (28% vs. 20%; p = 0.19). The presence of HALT did not significantly affect aortic valve mean gradients at 30 days or 1 year. Patients with HALT at both 30 days and 1 year, compared with those with no HALT at 30 days and 1 year, had significantly increased aortic valve gradients at 1 year (17.8 ± 2.2 mm Hg vs. 12.7. ± 0.3 mm Hg; p = 0.04). CONCLUSIONS: Subclinical leaflet thrombosis was more frequent in transcatheter compared with surgical valves at 30 days, but not at 1 year. The impact of HALT on thromboembolic complications and structural valve degeneration needs further assessment.

Transcatheter Aortic Valve Replacement as a Bridge to Left Ventricular Assist Device Implantation.

We describe a case of the pre-emptive use of transcatheter aortic valve replacement in a patient with end-stage ischemic cardiomyopathy and native aortic stenosis/aortic insufficiency as a bridge to left ventricular assist device implantation. The use of this strategy can not only medically optimize patients before left ventricular assist device implantation but also provide a minimally invasive bridge to left ventricular assist device support, avoiding concomitant surgical aortic valve replacement or closure.

Predictors of Persistent Tricuspid Regurgitation After Transcatheter Aortic Valve Replacement in Patients With Baseline Tricuspid Regurgitation.

OBJECTIVE: This study sought to analyze outcomes in patients with moderate-severe tricuspid regurgitation (TR) undergoing transcatheter aortic valve replacement (TAVR). The consequences of uncorrected significant TR in patients undergoing TAVR remain undefined. METHODS: Between 2009 and 2014, 369 patients underwent TAVR at our institution, and 58 of these had baseline moderate-severe TR. Preoperative, 30-day, and 1-year transthoracic echocardiograms were analyzed. Predictors of persistent TR at 30 days and survival were assessed. RESULTS: Fifty-eight patients with baseline moderate-severe TR underwent TAVR. Transcatheter aortic valve replacement resulted in significant reductions in pulmonary artery pressures and TR severity (100% vs 64%; P < 0.001) at 30 days. This was sustained at 1 year and was associated with significant improvements in stroke volume index and New York Heart Association functional class. No changes in right ventricular function or size were noted. The only independent predictor of persistent moderate-severe TR at 30 days was preoperative atrial fibrillation [AF; odds ratio (OR), 4.56; 95% confidence interval, 1.1-18.3; P = 0.033]. Independent predictors of overall long-term survival included AF (OR, 0.41; P = 0.001) and chronic lung disease (OR, 0.47; P = 0.011), but not baseline moderate-severe TR. In patients with baseline moderate-severe TR, persistent moderate-severe TR at 30 days was associated with worsened overall survival (log-rank P = 0.02). CONCLUSIONS: Baseline moderate-severe TR is not uncommon in patients undergoing TAVR, and frequently improves. However, the presence of AF suggests that that TR is likely to persist after TAVR and is also indicative of a poor long-term outcome. Whether redirecting such patients to surgery for concomitant tricuspid valve repair will further improve outcomes requires further study.

Absence of electrocardiographic left ventricular hypertrophy is associated with increased mortality after transcatheter aortic valve replacement.

BACKGROUND: Electrocardiographic (ECG) left ventricular hypertrophy (LVH) has been associated with increased mortality in patients with asymptomatic aortic stenosis (AS) and hypertension. However, patients with symptomatic AS undergoing transcatheter aortic valve replacement (TAVR) have higher percentages of myocardial fibrosis or amyloidosis that have been associated with decreased ECG voltage and worse outcomes. HYPOTHESIS: We tested the hypothesis that baseline ECG LVH is independently associated with increased all-cause mortality after TAVR. METHODS: A total of 231 patients (96 men; mean age 84.7 ± 7.8 years) that underwent TAVR at our institution were included. Cornell voltage, defined as SV3 + RaVL, was used to assess for presence of ECG LVH using gender-specific cut-off values. We used the Kaplan-Meier estimator to derive survival curves. Multivariate Cox regression analysis was used to compare mortality between patients without vs with ECG LVH and adjust for echocardiographic LVH and predictors of mortality in this cohort. RESULTS: Over a follow-up time of 16.3 ± 10.4 months, the absence of ECG LVH was significantly associated with increased mortality (40.4% vs 23.6% at 2-years, log rank P = 0.003). After adjusting for echocardiographic LVH and predictors of mortality in our cohort, the absence of ECG LVH remained a predictor of increased mortality (HR = 1.79, CI 95% 1.02-3.14, P = 0.042). CONCLUSIONS: The absence of ECG LVH was independently associated with increased mortality in patients undergoing TAVR. Baseline ECG may have an important prognostic role in these patients and could lead to further testing to evaluate for myocardial fibrosis or amyloidosis.

Vascular tenascin-C regulates cardiac endothelial phenotype and neovascularization.

Microenvironmental cues mediate postnatal neovascularization via modulation of endothelial cell and bone marrow-derived endothelial progenitor cell (EPC) activity. Numerous signals regulate the activity of both of these cell types in response to vascular injury, which suggests that parallel mechanisms regulate angiogenesis in the vascular beds of both the heart and bone marrow. To identify mediators of such shared pathways, in vivo bone marrow/cardiac phage display biopanning was performed and led to the identification of tenascin-C as a candidate protein. Functionally, tenascin-C inhibits cardiac endothelial cell spreading and enhances migration in response to angiogenic growth factors. Analysis of human coronary thrombi revealed tenascin-C protein expression colocalized with the endothelial cell/EPC marker Tie-2 in intrathrombi vascular channels. Immunostains in the rodent heart demonstrated that tenascin-C also colocalizes with EPCs homing to sites of cardiac angiogenic induction. To determine the importance of tenascin-C in cardiac neovascularization, we used an established cardiac transplantation model and showed that unlike wild-type mice, tenascin-C-/- mice fail to vascularize cardiac allografts. This demonstrates for the first time that tenascin-C is essential for postnatal cardiac angiogenic function. Together, our data highlight the role of tenascin-C as a microenvironmental regulator of cardiac endothelial/EPC activity.

The role and clinical implications of diastolic dysfunction in aortic stenosis.

Diastolic dysfunction in aortic stenosis results primarily from left ventricular hypertrophy and myocardial fibrosis due to chronically elevated left ventricular systolic pressure. Currently, diastolic dysfunction does not have an explicit clinical role in management of patients with aortic stenosis. Studies have shown that improvement in diastolic dysfunction follows left ventricular remodelling after aortic valve replacement and that it occurs gradually or incompletely. Retrospective studies suggest that advanced grades of diastolic dysfunction at baseline are associated with increased mortality and adverse events even after aortic valve replacement. Recent studies have also associated myocardial fibrosis, a hallmark of diastolic dysfunction, with worse outcomes. In addition, these results were independent of the degree of aortic stenosis or valve replacement. Indirect evidence of the role of diastolic dysfunction in aortic stenosis also comes from paradoxical low-flow, low-gradient aortic stenosis, where disproportionate left ventricular hypertrophy leads to underfilling of the left ventricle, low-flow state and is associated with worse prognosis. Lastly, a limited number of studies suggest that worse diastolic dysfunction at baseline is detrimental in patients who develop aortic regurgitation after transcatheteraortic valve replacement, due to superimposition of volume overload on a stiff left ventricle. Current major limitations in our understanding of the prognostic role of diastolic dysfunction are the lack of universally accepted classification schemes, its dependence on dynamic loading conditions and the lack of larger prospective studies.

Comparison of percutaneous coronary intervention and coronary artery bypass grafting after acute myocardial infarction complicated by cardiogenic shock: results from the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial.

BACKGROUND: The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial demonstrated the survival advantage of emergency revascularization versus initial medical stabilization in patients developing cardiogenic shock after acute myocardial infarction. The relative merits of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with shock have not been defined. The objective of this analysis was to compare the effects of PCI and CABG on 30-day and 1-year survival in the SHOCK trial. METHODS AND RESULTS: Of the 302 trial patients, 128 with predominant left ventricular failure had emergency revascularization. The selection of revascularization procedures was individualized. Eighty-one patients (63.3%) had PCI, and 47 (36.7%) had CABG. The median time from randomization to intervention was 0.9 hours (interquartile range [IQR], 0.3 to 2.2 hours) for PCI and 2.7 hours (IQR, 1.3 to 5.5 hours) for CABG. Baseline demographics and hemodynamics were similar, except that there were more diabetics (48.9% versus 26.9%; P=0.02), 3-vessel disease (80.4% versus 60.3%; P=0.03), and left main coronary disease (41.3% versus 13.0%; P=0.001) in the CABG group. In the PCI group, 12.3% had 2-vessel and 2.5% had 3-vessel interventions. In the CABG group, 84.8% received > or =2 grafts, 52.2% received > or =3 grafts, and 87.2% were deemed completely revascularized. The survival rates were 55.6% in the PCI group compared with 57.4% in the CABG group at 30 days (P=0.86) and 51.9% compared with 46.8%, respectively, at 1 year (P=0.71). CONCLUSIONS: Among SHOCK trial patients randomized to emergency revascularization, those treated with CABG had a greater prevalence of diabetes and worse coronary disease than those treated with PCI. However, survival rates were similar. Emergency CABG is an important component of an optimal treatment strategy in patients with cardiogenic shock, and should be considered a complementary treatment option in patients with extensive coronary disease.

Comparison of the efficacy of direct coronary stenting with sirolimus-eluting stents versus stenting with predilation by intravascular ultrasound imaging (from the DIRECT trial).

A direct coronary stenting technique using drug-eluting stents may decrease drug-eluting stent efficacy due to possible damage to the surface coating of the stent. The DIRECT is a multicenter, prospective, nonrandomized trial designed to evaluate the direct stenting strategy for the sirolimus-eluting Bx-Velocity stent compared with the historical control (SIRIUS trial, stenting with predilation). Volumetric and cross-sectional intravascular ultrasound analyses at 8-month follow-up were performed in 115 patients (DIRECT n= 64, control n = 51). Patient and lesion characteristics were comparable between groups. The DIRECT group achieved an equivalent uniform expansion index, defined as minimum stent area/maximum stent area x 100, compared with the control group (65.9 +/- 11.7 vs 63.1 +/- 12.7, p = NS). At 8-month follow-up, vessel, stent, lumen, and neointimal volume index (volume in cubic millimeters/length in millimeters) and percent neointimal volume were similar between the DIRECT and control groups (vessel volume index 13.9 +/- 4.40 vs 15.0 +/- 3.83; stent volume index 6.83 +/- 2.02 vs 6.94 +/- 2.04; lumen volume index 6.71 +/- 2.04 vs 6.81 +/- 2.07; neointimal volume index 0.14 +/- 0.24 vs 0.16 +/- 0.23; percent neointimal volume 3.73 +/- 6.97 vs 3.14 +/- 5.32, p = NS for all). In addition, in-stent neointimal hyperplasia distribution was significantly smaller near the distal stent edge (0.22 vs 0.098 mm(3)/mm, p = 0.01 for an average neointimal volume index within 3 mm from the distal stent edge). In conclusion, direct coronary stenting with the sirolimus-eluting Bx-Velocity stent is equally effective in terms of uniform stent expansion and long-term quantitative intravascular ultrasound results compared with conventional stenting using predilation. This strategy appears to be associated with less neointimal hyperplasia near the distal stent edge.

Safety of single versus multi-vessel angioplasty for patients with acute myocardial infarction and multi-vessel coronary artery disease: report from the New York State Angioplasty Registry.

BACKGROUND: The conventional strategy for primary angioplasty during acute myocardial infarction is angioplasty of the infarct-related vessel, even in patients with multi-vessel disease. Patients, however, often have significant lesions in multiple coronary arteries and a strategy for multi-vessel angioplasty during acute myocardial infarction has not been explored. The purpose of this study was to examine whether multi-vessel angioplasty is as safe as infarct-related vessel angioplasty in patients with multi-vessel coronary artery disease during acute myocardial infarction. METHODS: Using the 2000-2001 New York State Angioplasty Registry database, we compared the in-hospital clinical outcomes of patients with multi-vessel disease (>70% stenosis in at least two major coronary arteries), who underwent either multi-vessel angioplasty (n=632) or infarct-related vessel angioplasty (n=1350) within 24 h of acute myocardial infarction. Patients with previous myocardial infarction, angioplasty, bypass surgery, or cardiogenic shock were excluded. RESULTS: Patients in the multi-vessel angioplasty group were less likely to be female, to have peripheral vascular disease or diabetes. They had more complex lesions and were more likely to receive stents. In-hospital mortality was three-fold lower (0.8 versus 2.3%, P=0.018) in the multi-vessel angioplasty group. No differences were observed in other ischemic complications, renal failure, or length of stay. After multivariate analysis, multi-vessel angioplasty remained a significant predictor of lower in-hospital death (odds ratio=0.27, 95% confidence interval=0.08-0.90, P=0.03). CONCLUSIONS: Despite the added complexity of multi-vessel angioplasty, patients in this group had significantly lower in-hospital mortality. Therefore, a strategy of multi-vessel angioplasty during acute myocardial infarction may be safe compared with infarct-related angioplasty in selected patients.