Silvio Klugmann

Incidence and Predictors of Early and Late Mortality After Transcatheter Aortic Valve Implantation in 663 Patients With Severe Aortic Stenosis

Background— There is a lack of information on the incidence and predictors of early mortality at 30 days and late mortality between 30 days and 1 year after transcatheter aortic valve implantation (TAVI) with the self-expanding CoreValve Revalving prosthesis. Methods and Results— A total of 663 consecutive patients (mean age 81.0±7.3 years) underwent TAVI with the third generation 18-Fr CoreValve device in 14 centers. Procedural success and intraprocedural mortality were 98% and 0.9%, respectively. The cumulative incidences of mortality were 5.4% at 30 days, 12.2% at 6 months, and 15.0% at 1 year. The incidence density of mortality was 12.3 per 100 person-year of observation. Clinical and hemodynamic benefits observed acutely after TAVI were sustained at 1 year. Paravalvular leakages were trace to mild in the majority of cases. Conversion to open heart surgery (odds ratio [OR] 38.68), cardiac tamponade (OR 10.97), major access site complications (OR 8.47), left ventricular ejection fraction <40% (OR 3.51), prior balloon valvuloplasty (OR 2.87), and diabetes mellitus (OR 2.66) were independent predictors of mortality at 30 days, whereas prior stroke (hazard ratio [HR] 5.47), postprocedural paravalvular leak ≥2+ (HR 3.79), prior acute pulmonary edema (HR 2.70), and chronic kidney disease (HR 2.53) were independent predictors of mortality between 30 days and 1 year. Conclusions— Benefit of TAVI with the CoreValve Revalving System is maintained over time up to 1 year, with acceptable mortality rates at various time points. Although procedural complications are strongly associated with early mortality at 30 days, comorbidities and postprocedural paravalvular aortic regurgitation ≥2+ mainly impact late outcomes between 30 days and 1 year.

Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II)

BACKGROUND The multicentre, randomised Benestent-II study investigated a strategy of implantation of a heparin-coated Palmar-Schatz stent plus antiplatelet drugs compared with the use of balloon angioplasty in selected patients with stable or stabilised unstable angina, with one or more de-novo lesions, less than 18 mm long, in vessels of diameter 3 mm or more. METHODS 827 patients were randomly assigned stent implantation (414 patients) or standard balloon angioplasty (413 patients). The primary clinical endpoint was event-free survival at 6 months, including death, myocardial infarction, and the need for revascularisation. The secondary endpoints were the restenosis rate at 6 months and the cost-effectiveness at 12 months. There was also one-to-one subrandomisation to either clinical and angiographic follow-up or clinical follow-up alone. Analyses were by intention to treat. FINDINGS Four patients (one stent group, three angioplasty group) were excluded from analysis since no lesion was found. At 6 months, a primary clinical endpoint had occurred in 53 (12.8%) of 413 patients in the stent group and 79 (19.3%) of 410 in the angioplasty group (p=0.013). This significant difference in clinical outcome was maintained at 12 months. In the subgroup assigned angiographic follow-up, the mean minimum lumen diameter was greater in the stent group than in the balloon-angioplasty group, (1.89 [SD 0.65] vs 1.66 [0.57] mm, p=0.0002), which corresponds to restenosis rates (diameter stenosis > or =50%) of 16% and 31% (p=0.0008). In the group assigned clinical follow-up alone, event-free survival rate at 12 months was higher in the stent group than the balloon-angioplasty group (0.89 vs 0.79, p=0.004) at a cost of an additional 2085 Dutch guilders (US

Transcatheter aortic valve implantation: 3-year outcomes of self-expanding CoreValve prosthesis

1020) per patient. INTERPRETATION Over 12-month follow-up, a strategy of elective stenting with heparin-coated stents is more effective but also more costly than balloon angioplasty.

Safety and Efficacy of the Subclavian Approach for Transcatheter Aortic Valve Implantation With the CoreValve Revalving System

AIMS The paucity of evidences about the long-term durability of currently available transcatheter prostheses is one of the main issues of transcatheter aortic valve implantation (TAVI). We sought to assess 3-year clinical and echocardiographic outcomes of patients undergoing TAVI with the third generation CoreValve prosthesis (Medtronic Incorporation, MN, USA). METHODS AND RESULTS From the Italian CoreValve registry, 181 who underwent TAVI from June 2007 to August 2008 and eligible for 3-year follow-up were analysed. All outcomes were defined according to the Valve Academic Research Consortium. All-cause mortality at 1, 2, and 3 years was 23.6, 30.3, and 34.8%, respectively. Cardiovascular death at 1, 2, and 3 years was 11.2, 12.1, and 13.5%, respectively. The actuarial survival free from a composite of death, major stroke, myocardial infarction, and life-threatening bleeding was 69.6% at 1 year, 63.5% at 2 years, and 59.7% at 3 years. Patients with renal insufficiency had a higher mortality at 3-year follow-up (49.0 vs. 29.2%, P = 0.007); moreover, patients experiencing post-procedural major or life-threatening bleeding had a higher rate of mortality already seen at 30 days (21.6 vs. 2.8%; P < 0.001) and this result was sustained at 3-year follow-up (62.2 vs. 27.7%; P < 0.001). Mean pressure gradients decreased from 52.2 ± 18.1 mmHg (pre-TAVI) to 10.3 ± 3.1 mmHg (1-year post-TAVI) (P < 0.001); aortic valve area increased from 0.6 ± 0.2 cm(2) (pre-TAVI) to 1.8 ± 0.4 cm(2) (1-year post-TAVI); these results remained stable over the 3 years of follow-up. Paravalvular leak was observed in the majority of patients. There were no cases of progression to moderate or severe regurgitation. No cases of structural valve deterioration were observed. CONCLUSION This multicentre study demonstrates that TAVI with the 18-Fr CoreValve ReValving System is associated with sustained clinical and functional cardiovascular benefits in high-risk patients with symptomatic aortic stenosis up to 3-year follow-up. Non-cardiac causes accounted for the majority of deaths at follow-up.

Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol

Background—Transcatheter aortic valve implantation (TAVI) is a new option for patients with severe aortic stenosis at high surgical risk. The standard retrograde approach through the femoral artery is contraindicated in case of unfavorable iliofemoral anatomy or extensive disease. In these patients, a trans-subclavian approach may be feasible. Methods and Results—Between June 2007 and July 2009, TAVI with the CoreValve bioprosthesis (Medtronic, Minneapolis, Minn) was performed in 514 consecutive patients at 13 Italian hospitals, using the subclavian approach in 54 cases. The median logistic EuroSCORE was significantly higher in the subclavian (19.4; interquartile range, 12.5 to 29.8) versus femoral group (25.3; interquartile range, 15.1 to 36.6) (P=0.03), as well as the rate of comorbidities. Procedural success was obtained in 100% versus 98.4% of the subclavian versus femoral groups, respectively (P=0.62), with intraprocedural mortality of 0% versus 0.9% (P=1.00). The most common in-hospital complications were a new left bundle-branch block (22.4%) and the need for pacemaker (16.3%). No specific complications for the subclavian access (vessel rupture, vertebral or internal mammary ischemia) were reported. The learning curve for the subclavian approach led to a wider use of local anesthesia. Thirty-day mortality was 0% versus 6.1% in the subclavian versus femoral groups, respectively (P=0.13). Six-month mortality rate was 9.4% versus 15.8% (P=0.44), whereas valve-related adverse events were 13.6% versus 13.9% (P=0.79). Conclusions—TAVI through the subclavian approach appeared feasible and safe, with excellent procedural success and low in-hospital complication rates. This new technique allows patients with contraindications to the femoral approach to be treated with TAVI.

Emergency percutaneous coronary intervention in patients with ST-elevation myocardial infarction complicated by out-of-hospital cardiac arrest: Early and medium-term outcome

OBJECTIVES The purpose of this study was to analyze whether long-term treatment with the nonselective beta-adrenergic blocking agent carvedilol may have beneficial effects in patients with dilated cardiomyopathy (DCM), who are poor responders in terms of left ventricular (LV) function and exercise tolerance to chronic treatment with the selective beta-blocker metoprolol. BACKGROUND Although metoprolol has been proven to be beneficial in the majority of patients with heart failure, a subset of the remaining patients shows long-term survival without satisfactory clinical improvement. METHODS Thirty consecutive DCM patients with persistent LV dysfunction (ejection fraction #40%) and reduced exercise tolerance (peak oxygen consumption ,25 ml/kg/min) despite chronic (.1 year) tailored treatment with metoprolol and angiotensin-converting enzyme inhibitors were enrolled in a 12-month, open-label, parallel trial and were randomized either to continue on metoprolol (n 5 16, mean dosage 142 6 44 mg/day) or to cross over to maximum tolerated dosage of carvedilol (n 5 14, mean dosage 74 6 23 mg/day). RESULTS At 12 months, patients on carvedilol, compared with those continuing on metoprolol, showed a decrease in LV dimensions (end-diastolic volume 28 6 7 vs. 17 6 6 ml/m 2 ,p 5 0.053; end-systolic volume 27 6 5 vs. 16 6 4 ml/m 2 ,p 5 0.047), an improvement in LV ejection fraction (17 6 3% vs. 21 6 2%, p 5 0.045), a reduction in ventricular ectopic beats (212 6 9 vs. 162 6 50 n/h, p 5 0.05) and couplets (20.5 6 0.4 vs. 11.5 6 0.6 n/h, p 5 0.048), no significant benefit on symptoms and quality of life and a negative effect on peak oxygen consumption (20.6 6 0.6 vs. 11.3 6 0.5 ml/kg/min, p 5 0.03). CONCLUSIONS In DCM patients who were poor responders to chronic metoprolol, carvedilol treatment was associated with favorable effects on LV systolic function and remodeling as well as on ventricular arrhythmias, whereas it had a negative effect on peak oxygen consumption. (J Am Coll Cardiol 1999;33:1926 ‐34)

Adjunctive thrombus aspiration and mechanical protection from distal embolization in primary percutaneous intervention for acute myocardial infarction

BACKGROUND The role of emergency reperfusion therapy in patients with ST-elevation myocardial infarction (STEMI) resuscitated after an out-of-hospital cardiac arrest (OHCA) has not been clearly established yet. The aim of this study was to evaluate the in-hospital and postdischarge outcomes of STEMI patients surviving OHCA and undergoing emergency angioplasty (percutaneous coronary intervention [PCI]) within an established regional network. METHODS We prospectively collected data on 2,617 consecutive patients with STEMI treated with emergency PCI in 2005; in-hospital and 6-month outcomes of 99 patients who had experienced OHCA were compared with those of 2,518 patients without OHCA. The OHCA patients also underwent a cerebral performance evaluation after 12 months. RESULTS OHCA patients were at higher clinical risk at presentation (cardiogenic shock 26% vs 5%, P < .0001). Percutaneous coronary intervention was successful in 80% of the OHCA and 89% of the non-OHCA patients (P = NS). In-hospital mortality rates were 22% and 3%, respectively (P < .0001). Independent predictors of in-hospital mortality among OHCA patients were longer delay between the call to the emergency medical system and the start of cardiopulmonary resuscitation (odds ratio [OR] 3.5, P = .03), nonshockable initial rhythms (OR 10.5, P = .002), cardiogenic shock (OR 3.05, P = .035), and a Glasgow Coma Scale score of 3 on admission (OR 2.9, P = .032). The 6-month composite rate of death, myocardial infarction, and revascularization among OHCA patients surviving the acute phase was comparable to that of non-OHCA patients (16% vs 13.9%, P = NS), and 87% of them showed a favorable neurologic recovery after 1 year. CONCLUSIONS Resuscitated OHCA patients undergoing emergency PCI for STEMI have worse clinical presentation and higher in-hospital mortality compared to those without OHCA. However, subsequent cardiac events are similar, and neurologic recovery is more favorable than reported in most previous series.

The Valve-in-Valve Technique for Treatment of Aortic Bioprosthesis Malposition: An Analysis of Incidence and 1-Year Clinical Outcomes From the Italian CoreValve Registry

Primary percutaneous intervention for acute occlusion of a native coronary artery may be complicated by distal embolization of plaque or thrombotic debris, with infarct extension. We tested the clinical application of a new therapeutic strategy combining maximal antiplatelet therapy, with glycoprotein IIb/IIIa inhibition, and adjunctive mechanical protection from distal embolization and direct aspiration of thrombus with a new balloon and catheter system (PercuSurge™). Successful aspiration of thrombus could be obtained in 7 out of 8 attempted procedures, with inability to negotiate the angulated take‐off of the circumflex coronary artery in one patient. The current mechanical characteristics of the device, primarily developed for use in larger saphenous vein grafts, and certain caveats and limitations are discussed. New dedicated systems should be available in the near future for the native coronary circulation. Excellent immediate angiographic results were obtained in all treated patients, without evidence of loss of distal branches and no intraprocedural complications. Cathet. Cardiovasc. Intervent. 50:362–370, 2000.

2-year results of CoreValve implantation through the subclavian access: a propensity-matched comparison with the femoral access.

OBJECTIVES We appraised the incidence and clinical outcomes of patients who were treated with the valve-in-valve (ViV) technique for hemodynamically destabilizing paraprosthetic leak (PPL). BACKGROUND Device malpositioning causing severe PPL after transcatheter aortic valve implantation is not an uncommon finding. It occurs after release of the prosthesis, leading to hemodynamic compromise. It can be managed successfully in selected cases with implantation of a second device inside the malpositioned primary prosthesis (ViV technique). METHODS Consecutive patients (n = 663) who underwent transcatheter aortic valve implantation with the 18-F CoreValve ReValving System (Medtronic, Inc., Minneapolis, Minnesota) at 14 centers across Italy were included in this prospective web-based registry. We identified patients treated with the ViV technique for severe PPL and analyzed their clinical and echocardiographic outcomes. Primary end points were major adverse cerebrovascular and cardiac events and prosthesis performance at the 30-day and midterm follow-up. RESULTS Overall procedural success was obtained in 650 patients (98.0%). The ViV technique was used in 24 (3.6%) of 663 patients. The 30-day major adverse cerebrovascular and cardiac event rates were 7.0% and 0% in patients undergoing the standard procedure and ViV technique, respectively (p = 0.185); the mortality rates were 5.6% versus 0% in patients undergoing the standard procedure and ViV technique, respectively (p = 0.238). There was an improvement in the mean transaortic gradient in all patients without significant difference between the 2 groups (from 52.1 ± 17.1 mm Hg and 45.4 ± 14.8 mm Hg [p = 0.060] to 10.1 ± 4.2 mm Hg and 10.5 ± 5.2 mm Hg, respectively [p = 0.838]). At 12 months, the major adverse cerebrovascular and cardiac event rates in the standard procedure and ViV technique groups were 4.5% and 14.1%, respectively (p = 0.158), and the mortality rates were 4.5% versus 13.7%, respectively (p = 0.230). CONCLUSIONS This large, multicenter registry provides important information about the feasibility, safety, and efficacy of the ViV technique with the third-generation CoreValve ReValving System. The clinical and echocardiographic end points compare favorably with those of patients undergoing the standard procedure. The ViV technique offers a viable therapeutic option in patients with acute significant PPL without recourse to emergent surgery.

Safety of a conservative strategy of permanent pacemaker implantation after transcatheter aortic CoreValve implantation

OBJECTIVES The goal of this study was to assess the procedural and 2-year results of the subclavian approach for transcatheter aortic valve implantation (TAVI) compared with those of the femoral approach by using propensity-matched analysis. BACKGROUND The subclavian approach with the CoreValve prosthesis (Medtronic, Inc., Minneapolis, Minnesota) represents an interesting opportunity when the femoral access is unfeasible. METHODS All consecutive patients enrolled in the Italian CoreValve Registry who underwent TAVI with the subclavian approach were included. Propensity score analysis was used to identify a matching group of patients undergoing femoral TAVI. RESULTS Subclavian approach was used in 141 patients (61% men; median age 83 years; median logistic European System for Cardiac Operative Risk Evaluation score 23.7%). The femoral group of 141 patients was matched for baseline clinical characteristics, except for peripheral artery disease. The 2 groups showed similar procedural success (97.9% vs. 96.5%; p = 0.47), major vascular complications (5.0% vs. 7.8%; p = 0.33), life-threatening bleeding events (7.8% vs. 5.7%; p = 0.48), and combined safety endpoint (19.9% vs. 25.5%; p = 0.26). The subclavian group showed lower rates of acute kidney injury/stage 3 (4.3% vs. 9.9%; p = 0.02), of minor vascular complications at the 18-F sheath insertion site (2.1% vs. 11.3%; p = 0.003), and of all types of bleeding events related to vascular complications. Survival at 2 years was 74.0 ± 4.0% in the subclavian group compared with 73.7 ± 3.9% in the femoral group (p = 0.78). The 2-year freedom from cardiovascular death was 87.2 ± 3.1% versus 88.7 ± 2.8% in the subclavian versus femoral group, respectively (p = 0.84). CONCLUSIONS The subclavian approach for TAVI is safe and feasible, with procedural and medium-term results similar to the femoral approach. Subclavian access should be considered a valid option not only when the femoral approach is impossible but also when it is difficult, albeit feasible.