Arnaldo Poli

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.

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

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.

Integrated analysis of myocardial blush and ST-segment elevation recovery after successful primary angioplasty: Real-time grading of microvascular reperfusion and prediction of early and late recovery of left ventricular function.

Background—ST-segment elevation (&Sgr;STe) recovery and the angiographic myocardial blush (MB) grade are useful markers of microvascular reperfusion after recanalization of the infarct-related artery. We investigated the ability of a combined analysis of MB grade and &Sgr;STe changes to identify different patterns of myocardial reperfusion shortly after primary percutaneous coronary angioplasty (PTCA) and to predict 7-day and 6-month left ventricular (LV) functional recovery. Methods and Results—MB grade and &Sgr;STe recovery were evaluated shortly after successful primary PTCA (restoration of TIMI grade 3 flow) in 114 consecutive patients with &Sgr;STe acute myocardial infarction. LV function was assessed by 2D echocardiograms before PTCA and at 7 days and 6 months thereafter. By combining MB and &Sgr;STe changes, 3 main groups of patients were identified. Group 1 patients (n=60) had both significant MB (grade 2 to 3) and &Sgr;STe recovery (>50% versus basal &Sgr;STe) and a high rate of 7-day (65%) and 6-month (95%) LV functional recovery. In group 2 patients (n=21), who showed MB but persistent &Sgr;STe, the prevalence of early LV functional recovery was low (24%) but increased up to 86% in the late phase. Group 3 patients (n=28), who had neither significant MB nor &Sgr;STe resolution, had poor early (18%) and late (32%) LV functional recovery. Conclusions—After successful primary PTCA, integrated analysis of MB and &Sgr;STe recovery allows a real-time grading of microvascular reperfusion of the infarct area and predicts the time-course and magnitude of LV functional recovery.

Dobutamine stress echocardiography for assessment of myocardial viability and ischemia in acute myocardial infarction treated with thrombolysis

To evaluate the role of dobutamine echocardiography for early assessment of myocardial viability and ischemia in acute myocardial infarction (MI), 59 patients with thrombolyzed acute MI underwent low- (5-10 micrograms/kg/min, 8 patients) and high-dose (20-40 micrograms/kg/min, 51 patients) dobutamine echocardiography at a mean of 8 +/- 4 days after acute MI. Myocardial viability in the infarct zone was documented in 43 of 59 (73%) patients (group 1), in whom mean asynergy score index decreased from 1.6 +/- 0.3 at baseline to 1.3 +/- 0.2 (p < 0.001), after low-dose dobutamine. No viability was present in 16 of 59 (27%) patients (group 2). At follow-up, recovery of regional contractile function was observed in group 1 (asynergy score index decreased from 1.6 +/- 0.3 to 1.4 +/- 0.3; p < 0.001), but not in group 2 patients. Sensitivity, specificity, and negative and positive predictive values of low-dose dobutamine echocardiography in predicting spontaneous recovery of function were 79%, 68%, 50%, and 89%, respectively. Of the 51 patients who underwent high-dose dobutamine, 26 of 36 (72%) group 1 patients showed a deterioration of contractility in the infarct zone indicative of myocardial ischemia compared with only 1 of 15 (7%) group 2 patients. At follow-up, recovery of regional function was greater in patients with no evidence of myocardial ischemia at high doses than in those with an ischemic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombin Activity and Early Outcome in Unstable Angina Pectoris

BACKGROUND The blood coagulation system is frequently activated in the acute phase of unstable angina, but it is unknown whether the augmented function of the hemostatic mechanism may serve as a marker of increased risk for an early unfavorable outcome. METHODS AND RESULTS Plasma concentrations and 24-hour urinary excretion of fibrinopeptide A were prospectively determined in 150 patients with unstable angina. All patients underwent 24-hour Holter monitoring, during which time urine was collected; at the end of this period, a blood sample was taken and coronary arteriography was performed. The patients were followed up for the occurrence of cardiac events (death and myocardial infarction) until they underwent coronary revascularization or until they were discharged from the hospital. Fibrinopeptide A plasma levels and 24-hour urinary excretion were found to be abnormally elevated in 50% and 45% of the study population, respectively. During hospitalization, 11 patients developed myocardial infarction and 2 patients died. Kaplan-Meier analysis demonstrated a significantly higher probability of developing cardiac events in patients with abnormal rather than normal plasma levels of fibrinopeptide A (P<.01), whereas no difference in outcome was observed between patients with normal and those with abnormal 24-hour urinary excretion. Cox regression analysis showed that the only variables independently related to an early unfavorable outcome were the presence of persistent ischemia during 24-hour Holter monitoring (P<.0001), the presence of intracoronary thrombosis at angiography (P=.016), and abnormal fibrinopeptide A plasma levels (P=.038). CONCLUSIONS Patients with unstable angina pectoris and abnormal fibrinopeptide A plasma levels are at increased risk for an early unfavorable outcome.

5-Year Outcomes After Transcatheter Aortic Valve Implantation With CoreValve Prosthesis.

OBJECTIVES The purpose of this analysis was to assess 5-year outcomes of transcatheter aortic valve implantation (TAVI) using the current technology of the self-expanding CoreValve prosthesis (Medtronic Inc., Minneapolis, Minnesota). BACKGROUND There is a paucity of evidence on long-term durability of currently available transcatheter heart valves. METHODS Starting in June 2007, all consecutive patients with severe aortic stenosis undergoing TAVI with the third-generation 18-F CoreValve device in 8 Italian centers were prospectively included in the ClinicalService Project. For the purposes of this study, we included only consecutive patients with 5-year follow-up data available (n = 353) treated from June 2007 to August 2009. All outcomes were reported according to VARC (Valve Academic Research Consortium)-1 criteria. RESULTS All-cause mortality rates at 1, 2, 3, 4, and 5 years were 21%, 29%, 38%, 48%, and 55.0%, respectively. Cardiovascular mortality rates at 1, 2, 3, 4, and 5 years were 10%, 14%, 19%, 23%, and 28.0%, respectively. The overall neurological event rate at 5 years was 7.5%, of which more than two-thirds occurred early after the procedure. During follow-up, there were 241 rehospitalizations for cardiovascular reasons in 164 (46%) patients. Among all rehospitalizations, acute heart failure was the most frequently reported (42.7%), followed by requirement of permanent pacemaker implantation (17.4%). On echocardiography, mean transaortic gradients decreased from 55.6 ± 16.8 mm Hg (pre-TAVI) to 12.8 ± 10.9 mm Hg (5-year post-TAVI) (p < 0.001). Late prosthesis failure occurred in 5 cases (1.4%); among these, redo TAVI was successfully carried out in 2 patients (0.6%) presenting with symptomatic prosthesis restenosis. The remaining 3 cases of prosthesis failure did not undergo further invasive interventions. Ten patients (2.8%) showed late mild stenosis with a mean transaortic gradient ranging from 20 to 40 mm Hg. No other cases of structural or nonstructural valvular deterioration were observed. Valve thrombosis or late valve embolization were not reported. CONCLUSIONS TAVI with the currently adopted CoreValve generation was associated with sustained clinical outcomes up to 5-year follow-up, with a low rate (1.4%) of significant prosthetic valve degeneration. The procedure appears to be an adequate and lasting resolution of aortic stenosis in selected high-risk patients.

Clinical impact of persistent left bundle-branch block after transcatheter aortic valve implantation with CoreValve revalving system

Background— Conduction disturbances are relatively common after transcatheter aortic valve implantation. Previous data demonstrated an adverse impact of persistent left bundle-branch block (LBBB) after surgical aortic valve replacement. It is unclear whether new-onset LBBB may also impact the prognosis of patients after transcatheter aortic valve implantation. Methods and Results— Among 1060 patients treated with a CoreValve Revalving System transcatheter aortic valve implantation between October 2007 and April 2011 in high-volume centers in Italy, we analyzed those without LBBB or pacemaker at admission (879 patients [82.9%]). We further excluded those who underwent permanent pacemaker implantation within 48 hours after the procedure (61 patients [7%]), for a final study population of 818 patients. Among them, 224 patients (group A; 27.4%) developed a persistent LBBB and the remaining 594 (group B; 72.6%) did not. Clinical characteristics were similar between groups. A low implantation was significantly more frequent in group A (15% versus 9.8%, P=0.02). No patients were censored before 1 year (median follow-up period 438 days, interquartile range 174–798 days). Survival analyses and inherent log-rank tests showed that LBBB was not associated with higher all-cause mortality, cardiac mortality, or hospitalization for heart failure at 30 days or 1 year. At 30 days, but not at 1 year, group A had a significantly higher rate of pacemaker implantation. Conclusions— In this registry of high-volume centers, persistent LBBB after CoreValve Revalving System transcatheter aortic valve implantation showed no effect on hard end points. On the other hand, LBBB was associated with a higher short-term rate of pacemaker implantation.

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

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.

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

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.

Interplay Between Mitral Regurgitation and Transcatheter Aortic Valve Replacement With the CoreValve Revalving System A Multicenter Registry

Background— Little is known of the prognostic significance of mitral regurgitation (MR) on transcatheter aortic valve replacement (TAVR), the impact of TAVR on MR severity, and the variables associated with possible post-TAVR improvement in MR. We evaluated these issues in a multicenter registry of patients undergoing CoreValve Revalving System–TAVR. Methods and Results— Among 1007 consecutive patients, 670 (66.5%), 243 (24.1%), and 94 (9.3%) presented with no/mild, moderate, and severe MR, respectively. At 1 month after TAVR, patients with severe or moderate MR showed comparable mortality rates (odds ratio, 1.1; 95% confidence interval [95% CI], 0.7–1.55; P=0.2), but both were significantly higher compared with patients with mild/no MR (odds ratio, 2.2; 95% CI, 1.78–3.28; P<0.001; and odds ratio, 1.9; 95% CI, 1.1–3.3; P=0.02, respectively). One-year mortality was also similar between patients with severe and those with moderate MR (hazard ratio, 1.4; 95% CI, 0.94–2.4; P=0.06) and still significantly higher compared with patients with mild/no MR (hazard ratio, 1.7; 95% CI, 1.2–3.41; P<0.001; and hazard ratio, 1.4; 95% CI, 1.2–2.2; P=0.03, respectively). Severe pulmonary hypertension, atrial fibrillation, and MR more than mild, but not an improvement of ≥1 grade in MR severity, were independent predictors of mortality at 1 year. At 1 year, an improved MR was observed in 47% and 35% of patients with severe and moderate MR, respectively. The rate of low implantation was consistent across groups with improved, unchanged, or worsened MR. A functional type of MR and the absence of severe pulmonary hypertension and atrial fibrillation independently predicted the improvement in MR severity. Conclusions— Baseline MR greater than mild is associated with higher mortality after CoreValve Revalving System–TAVR. A significant improvement in MR was more likely in patients with functional MR and without severe pulmonary hypertension or atrial fibrillation. The improvement in MR did not independently predict mortality.