Nevio Taglieri

Acute kidney injury following transcatheter aortic valve implantation: incidence, predictors and clinical outcome

BACKGROUND Limited data exist on renal complications of transcatheter aortic valve implantation (TAVI) within a comprehensive program using different valves with transfemoral, transapical, and trans-subclavian approach. METHODS Prospective single-center registry of 102 consecutive patients undergoing TAVI using both approved bioprostheses and different access routes. The main objective was to assess the incidence, predictors and the clinical impact of acute kidney injury (AKI). AKI was defined according to the valve academic research consortium (VARC) indications. RESULTS Mean age was 83.7 ± 5.3 years, logistic EuroSCORE 22.6 ± 12.4%, and STS score 8.2 ± 4.1%. Chronic kidney disease at baseline was present in 87.3%. Periprocedural AKI developed in 42 patients (41.7%): 32.4% stage 1, 4.9% stage 2 and 3.9% stage 3. The incidence of AKI was 66.7% in transapical, 30.3% in transfemoral, and 50% in trans-subclavian procedures. The only independent predictor of AKI was transapical access, with a hazard ratio (HR) between 4.57 and 5.18 based on the model used. Cumulative 1-year survival was 88.2%. At Cox regression analysis, the only independent predictor of 30-day mortality was diabetes mellitus (HR 7.05, 95% CI 1.07-46.32; p=0.042), whilst the independent predictors of 1-year death were baseline glomerular filtration rate<30 mL/min (HR 5.74, 95% CI 1.42-23.26; p=0.014) and post-procedural AKI 3 (HR 8.59, 95% CI 1.61-45.86, p=0.012). CONCLUSIONS TAVI is associated with a high incidence of AKI. Although in the majority of the cases AKI is of mild entity and reversible, AKI 3 holds a strong negative impact on 1-year survival. The incidence of AKI is higher with transapical access.

The role of percutaneous balloon aortic valvuloplasty as a bridge for transcatheter aortic valve implantation.

AIMS Many inoperable patients with severe aortic stenosis (AS) are not immediately eligible for transcatheter aortic valve implantation (TAVI). We evaluated the role of percutaneous balloon aortic valvuloplasty (BAV) in this setting. METHODS AND RESULTS Among 210 consecutive patients referred to our institution for BAV, we identified three groups: immediately eligible for TAVI (n=65, 31%), excluded from TAVI (n=67, 32%), BAV as a bridge to TAVI (n=78, 37%). This last group comprised patients with low left ventricular ejection fraction, frailty or enfeebled status, symptoms of uncertain origin, critical conditions, moderate-to-severe mitral valve regurgitation, need of major non-cardiac surgery. Outpatient clinic visit and echocardiography were performed around one month after BAV to decide the final therapeutic strategy. Mean age was 81±8 years and the vast majority of patients had comorbidities and high-risk features. The incidence of periprocedural adverse events was 6.4%: 5.1% death (four patients: one procedural complication, three, natural disease progression), 1.3% minor stroke. After BAV, 46% of these patients were deemed eligible for TAVI, and 28% for cardiac surgery. Patients who underwent TAVI after bridge BAV showed 94% 30-day survival. CONCLUSIONS BAV is a safe and effective tool to bridge selected patients to TAVI when indications are not obvious.

Long-term effectiveness of early administration of glycoprotein IIb/IIIa agents to real-world patients undergoing primary percutaneous interventions: results of a registry study in an ST-elevation myocardial infarction network

AIMS To evaluate the clinical impact of early administration of glycoprotein IIb/IIIa agents (IIb/IIIa agents) in the context of a dedicated hub and spoke network allowing very prompt pharmacological/mechanical interventions. METHODS AND RESULTS Using a prospective database, we conducted a cohort study of ST-elevation myocardial infarction (STEMI) patients (n = 1124) undergoing primary percutaneous coronary interventions (PPCIs) and IIb/IIIa agents administration (period, 2003-2006). Comparisons were planned between patients receiving early IIb/IIIa agents administration (in hub/spoke centre emergency departments or during ambulance transfer; early group, n = 380) or delayed administration (in the catheterization laboratory; late group, n = 744). The primary outcome measure was long-term overall mortality/re-infarction. Baseline characteristics of the two groups were largely comparable. Angiographically, early group patients more often achieved pre-PPCI TIMI Grade 2-3 and TIMI Grade 3 flow. Clinically, the early administration group experienced lower 2-year risk of unadjusted mortality/re-infarction (17 vs. 23%; P = 0.01). After adjustment for potential confounders, early administration was associated with favourable outcome in the overall population (HR = 0.71, P = 0.03) and in high-risk subgroups (TIMI risk index >25, HR = 0.64, P = 0.02; Killip class >1, HR = 0.54, P = 0.01). CONCLUSION In patients treated by PPCI within a STEMI network setting, early administration of IIb/IIIa agents may provide long-term clinical benefits. Notably, these results appeared magnified in high-risk patients.

Optimisation of therapeutic strategies for ST-segment elevation acute myocardial infarction: the impact of a territorial network on reperfusion therapy and mortality

Objective: To assess the clinical impact of a regional network for the treatment of ST-segment elevation myocardial infarction (STEMI). Methods: All patients with STEMI (n = 1823) admitted to any of the hospitals of an area with one million inhabitants during the year 2002 (n = 858)—that is, before the network was implemented, and in 2004 (n = 965), the year of full implementation of the network, were enrolled in this study. The primary evaluation was in-hospital mortality. Secondary outcomes included the incidence of major adverse cardiac and cerebrovascular events (MACCE), defined as death, myocardial infarction, stroke and coronary revascularisation procedures over 1-year follow-up. Results: Between 2002 and 2004, there was a major change in reperfusion strategy: primary angioplasty increased from 20.2% to 65.6% (p<0.001), fibrinolytic therapy decreased from 38.2% to 10.7% (p<0.001) and the rate of patients not undergoing reperfusion was reduced from 41.6% to 23.7% (p<0.001). In-hospital mortality decreased from 17.0% to 12.3% (p = 0.005), and this reduction was sustained at 1-year follow-up (23.9% in 2002 and 18.8% in 2004, p = 0.009). Similarly, the 1-year incidence of all MACCE was reduced from 39.5% in 2002 to 34.3% in 2004 (p = 0.01). Conclusions: Organisation of a territorial network for STEMI is associated with increased rates of reperfusion therapy and reduction of in-hospital and 1-year mortality.

Randomized comparison between tirofiban and abciximab to promote complete ST-resolution in primary angioplasty: results of the facilitated angioplasty with tirofiban or abciximab (FATA) in ST-elevation myocardial infarction trial

AIMS To test the equivalence of high-dose bolus (HDB) tirofiban vs. abciximab during primary percutaneous coronary intervention (PPCI) in terms of ST-segment resolution (STR). METHODS AND RESULTS The FATA trial (Facilitated Angioplasty with Tirofiban or Abciximab) was a prospective, multicentre, open-label trial that enrolled 692 patients with ST-segment elevation myocardial infarction (STEMI) undergoing PPCI. Patients were randomized 1:1 to receive abciximab (n = 341) or HDB tirofiban (n = 351). Primary endpoint was the rate of complete (> or =70%) STR 90 min after first balloon inflation. Thirty-day incidence of major bleedings, death, re-infarction and new revascularizations was also evaluated. Baseline characteristics of the two groups were well-balanced, with the exception of previous MI rates (tirofiban 6% vs. abciximab 2.6%, P = 0.03). The procedure was successful in 96.7% of the abciximab and in 96.6% of the tirofiban cohort (P = 0.94). Complete STR was obtained in 67.05% of the tirofiban and 70.45% of the abciximab group (Delta -3.4%, 95% confidence interval -10.35 to +3.56), which falls beyond the predefined Delta +/- 10% equivalence boundaries. Rates of secondary endpoints were similar between the two groups. CONCLUSION This study failed to show the equivalence of HBD of tirofiban and abciximab as adjunctive therapy to PPCI.

Emerging indications, in-hospital and long-term outcome of balloon aortic valvuloplasty in the transcatheter aortic valve implantation era.

AIMS The introduction of transcatheter aortic valve implantation (TAVI) has generated a renewed interest in the treatment of high-risk patients with severe aortic stenosis. This study describes the indications and long-term outcome of balloon aortic valvuloplasty (BAV) in recent years. METHODS AND RESULTS Between 2000 and 2010, 415 consecutive patients at our institution underwent BAV. The number of BAV per year increased sharply after the introduction of TAVI. Patients were 77.5±10.9 years old and showed important comorbidities (average logistic EuroSCORE=23.9±15.3%). We identified four cohorts according to the indications: 1) bridge for TAVI (B-TAVI; n=162); 2) bridge for aortic valve replacement (B-AVR, n=97); 3) cardiogenic shock (n=23); 4) palliation (n=133). Baseline characteristics were significantly different among groups. In-hospital mortality was 5.1%, and occurred predominantly in patients who underwent BAV in the setting of cardiogenic shock (56.5% vs. around 2% in the other subgroups). Other major events were stroke (0.5%), major vascular complications (2.2%), and life-threatening bleedings (1.5%). The cumulative one-year and two-year mortality rates were 33.2% and 57.4%, respectively, with the highest incidence in the shock group (70.7% and 80.4%) and the lowest in the B-AVR group (21.7% and 38.4%). Rehospitalisation for heart failure was 26.3% at one-year and 47.2% at two-year follow-up. CONCLUSIONS The number of BAV is increasing, mainly due to increased referral of high-risk patients and to the emerging indication of bridge for TAVI. In this complex population, BAV is relatively safe but two-year survival remains poor, and more effective and definitive treatments should be pursued in a timely fashion.

Short- and Long-Term Prognostic Significance of ST-Segment Elevation in Lead aVR in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome

We sought to evaluate the prognostic significance of ST-segment elevation (STE) in lead aVR in unselected patients with non-STE acute coronary syndrome (NSTE-ACS). We enrolled 1,042 consecutive patients with NSTE-ACS. Patients were divided into 5 groups according to the following electrocardiographic (ECG) patterns on admission: (1) normal electrocardiogram or no significant ST-T changes, (2) inverted T waves, (3) isolated ST deviation (ST depression [STD] without STE in lead aVR or transient STE), (4) STD plus STE in lead aVR, and (5) ECG confounders (pacing, right or left bundle branch block). The main angiographic end point was left main coronary artery (LM) disease as the culprit artery. Clinical end points were in-hospital and 1-year cardiovascular death defined as the composite of cardiac death, fatal stroke, and fatal bleeding. Prevalence of STD plus STE in lead aVR was 13.4%. Rates of culprit LM disease and in-hospital cardiovascular death were 8.1% and 3.8%, respectively. On multivariable analysis, patients with STD plus STE in lead aVR (group 4) showed an increased risk of culprit LM disease (odds ratio 4.72, 95% confidence interval [CI] 2.31 to 9.64, p <0.001) and in-hospital cardiovascular mortality (odds ratio 5.58, 95% CI 2.35 to 13.24, p <0.001) compared to patients without any ST deviation (pooled groups 1, 2, and 5), whereas patients with isolated ST deviation (group 3) did not. At 1-year follow-up 127 patients (12.2%) died from cardiovascular causes. On multivariable analysis, STD plus STE in lead aVR was a stronger independent predictor of cardiovascular death (hazard ratio 2.29, 95% CI 1.44 to 3.64, p <0.001) than isolated ST deviation (hazard ratio 1.52, 95% CI 0.98 to 2.36, p = 0.06). In conclusion, STD plus STE in lead aVR is associated with high-risk coronary lesions and predicts in-hospital and 1-year cardiovascular deaths in patients with NSTE-ACS. Therefore, this promptly available ECG pattern could be useful to improve risk stratification and management of patients with NSTE-ACS.

Differential Effect of Everolimus on Progression of Early and Late Cardiac Allograft Vasculopathy in Current Clinical Practice

Randomized trials showed that mTOR inhibitors prevent early development of cardiac allograft vasculopathy (CAV). However, the action of these drugs on CAV late after transplant is controversial, and their effectiveness for CAV prevention in clinical practice is poorly explored. In this observational study we included 143 consecutive heart transplant recipients who underwent serial intravascular ultrasound (IVUS), receiving either everolimus or mycophenolate as adjunctive therapy to cyclosporine. Ninety‐one recipients comprised the early cohort, receiving IVUS at weeks 3–6 and year 1 after transplant, and 52 the late cohort, receiving IVUS at years 1 and 5 after transplant. Everolimus independently reduced the odds for early CAV (0.14 [0.01–0.77]; p = 0.02) but it did not appear to influence late CAV progression. High‐dose statins were found to be associated with reduced CAV progression both early and late after transplant (p ≤ 0.05). Metabolic abnormalities, such as high triglycerides, were associated with late, but not with early CAV progression. By highlighting a differential effect of everolimus and metabolic abnormalities on early and late changes of graft coronary morphology, this observational study supports the hypothesis that everolimus may be effective for CAV prevention but not for CAV treatment, and that risk factors intervene in a time‐dependent sequence during CAV development.

Relation Between Angiographic Lesion Severity, Vulnerable Plaque Morphology and Future Adverse Cardiac Events (from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree Study)

Previous angiographic studies have suggested that the future risk for major adverse cardiovascular events (MACEs) is related to coronary stenosis severity. The aim of this study was to use the grayscale and virtual histology (VH)-intravascular ultrasound (IVUS) data from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study to identify underlying lesion morphologic characteristics that might explain these findings. In PROSPECT, patients presenting with acute coronary syndromes in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and VH-IVUS and were followed for a median of 3.4 years for the incidence of MACEs. Overall, 3,115 nonculprit lesions detected by IVUS were divided into quartiles according to baseline angiographic diameter stenosis. From the first to fourth quartiles, there were increases in the prevalence of lesions with IVUS minimum luminal areas ≤ 4 mm(2), IVUS plaque burden ≥ 70%, and VH-IVUS thin-cap fibroatheroma (13.4%, 22.0%, 24.2%, and 30.3%, respectively, p <0.001), along with an increased frequency of plaque ruptures and greater necrotic core volumes. The incidence of lesions with plaque burden ≥ 70%, minimum luminal area ≤ 4 mm(2), and VH thin-cap fibroatheroma was highest in the fourth quartile (0%, 0.4%, 0.4%, and 2.8% in the first through fourth quartiles, respectively, p <0.001). Three-year MACE rates were also highest in the fourth quartile (0.3%, 0.7%, 1.3%, and 5.1%, respectively, p <0.001). In conclusion, increasing angiographic diameter stenosis was associated with an increased frequency of grayscale and VH-IVUS lesion morphologic features that have been associated with adverse events and that may, in part, explain why future MACEs were related to baseline lesion severity.

Randomized comparative trial of a thin‐strut bare metal cobalt‐chromium stent versus a sirolimus‐eluting stent for coronary revascularization

OBJECTIVES: To see whether use of a sirolimus‐eluting stent (SES) is superior to a third‐generation thin‐strut, cobalt‐chromium stent (CCS) in terms of in‐segment late loss at 9 months in patients with symptomatic coronary artery disease. BACKGROUND: Stent‐strut thickness has been shown to be strictly related with risk of in‐stent restenosis, but available demonstrations of the angiographic efficacy of SES have been based on comparisons with thick‐strut bare metal control stents. METHODS: The primary outcome measure of this single‐center, single‐blind randomized comparative trial was 9‐month in‐segment late loss. Eligibility criteria were symptomatic coronary artery disease and target vessel diameter appropriate for implantation a 3‐mm stent. Based on a power calculation, 104 patients were randomly assigned to receive a SES (Cypher™) or a CCS (Vision™). RESULTS: In‐segment late loss was significantly lower in the SES group (0.18 ± 0.40 mm vs 0.58 ± 0.51 mm, P < 0.001). Regarding subsidiary outcome measures, in‐segment restenosis (at 9 months) was recorded in 10% (5/50) patients treated with SES and 23% (11/48) receiving CCS (P = 0.14). No clinical difference between the two groups was apparent at 12 months. Freedom from target vessel failure at 12 months was 72% for SES patients and 68% for CCS patients (P = 0.65). CONCLUSIONS: In patients with de‐novo coronary lesions at medium risk of restenosis the anti‐proliferative effect of SES is greater than that of a thin‐strut CCS. Nevertheless, the angiographic results of the CCS were rather good. It remains to be seen whether the angiographic superiority of SES can translate into clinical superiority.