Carlo Zivelonghi

Functional Assessment of Coronary Artery Disease in Patients Undergoing Transcatheter Aortic Valve Implantation: Influence of Pressure Overload on the Evaluation of Lesions Severity

Background—Aortic valve stenosis may influence fractional flow reserve (FFR) of concomitant coronary artery disease by causing hypertrophy and reducing the vasodilatory reserve of the coronary circulation. We sought to investigate whether FFR values might change after valve replacement. Methods and Results—The functional relevance of 133 coronary lesions was assessed by FFR in 54 patients with severe aortic valve stenosis before and after transcatheter aortic valve implantation (TAVI) during the same procedure. A linear mixed model was used to verify the interaction of TAVI effect with the FFR values. No significant overall change in FFR values was found before and after the aortic valve stenosis removal (0.89±0.10 versus 0.89±0.13; P=0.73). A different trend in FFR groups (positive if ⩽0.8; negative if >0.8) was found after TAVI (P for interaction <0.001). Positive FFR values worsened after TAVI (0.71±0.11 versus 0.66±0.14). Conversely, negative FFR values improved after TAVI (0.92±0.06 versus 0.93±0.07). Similarly, FFR values in coronary arteries with lesions presenting percent diameter stenosis >50 worsened after TAVI (0.84±0.12 versus 0.82±0.16; P=0.02), whereas FFR values in arteries with mild lesions (percent diameter stenosis <50) tended toward improvement after TAVI (0.90±0.07 versus 0.91±0.09; P=0.69). Functional FFR variations after TAVI changed the indication to treat the coronary stenosis in 8 of 133 (6%) lesions. Conclusions—Coronary hemodynamics are influenced by aortic valve stenosis removal. Nevertheless, FFR variations after TAVI are minor and crossed the diagnostic cutoff of 0.8 in a small number of patients after valve replacement. Borderline coronary lesions might become functionally significant after valve replacement, although FFR-guided interventions were infrequent even in patients with angiographically significant lesions.

Long-term clinical follow-up of the multicentre, randomized study to test immunosuppressive therapy with oral prednisone for the prevention of restenosis after percutaneous coronary interventions: Cortisone plus BMS or DES veRsus BMS alone to EliminAte Restenosis (CEREA-DES)

AIMS To analyse the clinical outcome at 4 years in patients with coronary artery disease treated with bare metal stents (BMS) vs. BMS and oral prednisone, or drug-eluting stents (DES), all assuming similar adjunctive medical treatment. METHODS AND RESULTS Five Italian hospitals enrolled 375 non-diabetic, ischaemic patients without contraindications to dual anti-platelet treatment or corticosteroid therapy in a randomized controlled study. The primary endpoint was the event-free survival of cardiovascular death, myocardial infarction, and recurrence of ischaemia needing repeated target vessel revascularization at 1 year, and this was significantly lower in the BMS group (80.8%) compared with the prednisone (88.0%) and DES group (88.8%, P = 0.04 and 0.006, respectively). The long-term analysis of the primary endpoint was a pre-specified aim of the trial, and was performed at 1447 days (median, IQ range = 1210-1641). Patients receiving BMS alone had significantly lower event-free survival (75.3%) compared with 84.1% in the prednisone group (HR: 0.447; 95% CI: 0.25-0.80, P = 0.007) and 80.6% in DES patients (HR: 0.519; 95% CI: 0.29-0.93, P = 0.03). Prednisone-treated patients did not develop new treatment-related clinical problems. Drug-eluting stents patients suffered more very late stent thrombosis as a cause of spontaneous myocardial infarction. The need for target vessel revascularization remained lower in the prednisone and DES groups (13.6 and 15.2%, respectively), compared with BMS (23.2%). CONCLUSIONS The clinical benefits of prednisone compared with BMS only persisted almost unchanged at 4 years. Drug-eluting stents performed better than BMS at long-term, although the advantages observed at 1 year were in part attenuated because of the occurrence of very late stent thrombosis and late revascularizations. Clinical Trial NCT 00369356.

Clinical outcomes of transcatheter aortic valve implantation: from learning curve to proficiency

Objective The use of transcatheter aortic valve implantation (TAVI) is growing rapidly in countries with a predominantly elderly population, posing a huge challenge to healthcare systems worldwide. The increment of human and economic resource consumption imposes a careful monitoring of clinical outcomes and cost-benefit balance, and this article is aimed at analysing clinical outcomes related to the TAVI learning curve. Methods Outcomes of 177 consecutive transfemoral TAVI procedures performed in 5 years by a single team were analysed by the Cumulative Sum of failures method (CUSUM) according to the clinical events comprised in the Valve Academic Research Consortium (VARC-2) safety end point and the VARC-2 definition of device success. Margins for events acceptance were extrapolated from landmark trials that tested both balloon or self-expandable percutaneous valves. Results 30-day and 1-year survival rates were 97.2% and 89.9%, respectively. Achievement of the primary end point (number of cases needed to provide the acceptable margin of the composite end point of any death, stroke, myocardial infarction, life-threatening bleeding, major vascular complications, stage 2–3 acute kidney injury and valve-related dysfunction requiring a repeat procedure) required the performance of 54 cases, while the learning curve to achieve ‘device success’ identified 32 cases to reach the expected proficiency. In this experience, the baseline clinical risk as assessed by the Society of Thoracic Surgeons (STS) score determined the long-term survival rather than the adverse events related to the learning curve. Conclusions A relatively large number of cases are required to achieve clinical outcomes comparable to those reported in high-volume centres and controlled trials. According to our national workload standards, this represents more than 2 years of continuous activity.

Coronary Catheterization and Percutaneous Interventions After Transcatheter Aortic Valve Implantation

Coronary artery disease (CAD) is often present in patients with severe aortic valve stenosis candidates to transcatheter aortic valve implantation (TAVI). Mild CAD may also worsen and need treatment years after TAVI. The implantation of a transcatheter valve may interfere with the capability of reengaging the coronary arteries. We prospectively assessed the feasibility of performing coronary angiography (CA), fractional flow reserve, and, where indicated, percutaneous coronary intervention after valve implantation in a consecutive series of patients with CAD undergoing TAVI. Valve type and size were decided according to accurate computed tomography scan and angiographic measurement of the aortic root structures. We analyzed 66 consecutive patients undergoing TAVI, 41 with balloon-expandable, and 25 with self-expandable transcatheter valves. Right and left coronary catheterization (132 vessels) was successful in all cases except in 1 left coronary artery after a high implantation of a self-expandable valve (unsuccess rate, 1 in 50 vessels). In 6 of 132 vessels (4%), CA was initially nonselective, but after positioning the 0.014″ intracoronary guidewire, selective injections were obtained in all these cases. Percutaneous coronary intervention was performed successfully in 19 coronary vessels (17 patients) as indicated by fractional flow reserve measurements. In conclusion, catheterization of the coronary ostia after transfemoral TAVI with balloon or self-expandable valves is safe and feasible in almost all cases. Accurate imaging of the aortic root and procedural planning may help to avoid too high implantation of supra-annular self-expandable valves to obviate difficulties in accessing coronary ostia. Use of intracoronary guidewires facilitates selective CA in cases with difficult access.

Repeat revascularization: Percutaneous coronary intervention after coronary artery bypass graft surgery

Repeat myocardial revascularization procedures are markedly different from de novo interventions, with increased procedural risk and technical-demanding complexity. However the number of patients previously treated with coronary artery bypass graft (CABG) that need a repeat revascularization due to graft failure is increasing consistently. Late graft failure, usually caused by saphenous vein grafts (SVG) attrition, is certainly not uncommon. However PCI on degenerated SVG presents higher complication rate and worse clinical outcome compared with native arteries interventions. In acute graft failure setting, PCI represents a valuable option to treat postoperative myocardial infarction.

iFR-FFR comparison in daily practice: a single-center, prospective, online assessment.

Aims To compare the performance of instantaneous wave-free ratio (iFR) with fractional flow reserve (FFR) in a real-life, prospective, single-center, and independent study. Methods and results Fifty-four patients were included and 89 angiographic intermediate lesions underwent functional evaluation with both iFR and FFR. FFR was used as the gold standard, and the patients having FFR values 0.80 or less only underwent percutaneous coronary intervention. Linear regression demonstrated close agreement between the two techniques (R = 0.83, P < 0.0001). Receiver operator characteristic analysis confirmed the strong correlation, with an area under the curve approximately equal to unity. iFR detected ischemia with a sensitivity and specificity of 100 and 87%, respectively, thus revealing a positive predictive value of 78% and a negative predictive value of 100%. In addition, according to FFR assessment, percutaneous coronary intervention was performed on 39 lesions (43.8%) in 27 patients (50%), whereas positive iFR values were found in 52 lesions (+14.6% compared with FFR). At clinical follow-up (ranging from 6 to 16 months), all patients remained asymptomatic and none of them experienced major adverse cardiovascular events. Conclusions In this independent, online, comparison of iFR-FFR values in patients with angiographic intermediate lesions, results are consistent with those derived from previous offline controlled trials, and support the correlation between iFR and FFR in daily clinical practice.

Late and very late coronary stent thrombosis: Intravascular ultrasound findings and associations with antiplatelet therapy

Late and very‐late stent occlusion remains a serious complication of coronary stenting. Despite their high anti‐restenotic efficacy, drug‐eluting stents (DES) have been associated to more late‐thrombosis as compared to bare‐metal stents (BMS). The aim of this study is to analyze the clinical presentation, angiographic, and intravascular ultrasound (IVUS) findings in patients with late or very late stent thrombosis and the relationship with the antiplatelet regimen.

Physiologic evaluation of coronary lesions using instantaneous wave-free ratio (iFR) in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation

AIMS We sought to assess eventual changes in iFR measurements in patients with aortic stenosis (AS) before and after TAVI in coronary lesions with different degrees of angiographic severity. METHODS AND RESULTS The functional relevance of 145 coronary lesions was assessed by online iFR and FFR measurement in 66 patients with severe AS before and after TAVI, during the same procedure. The iFR-FFR classification agreement was calculated for pre-TAVI and post-TAVI measurements. Mean iFR values remained identical before and after TAVI, irrespective of the angiographic severity of the coronary stenosis (0.89±0.12 vs. 0.89±0.12, p=0.66). However, individual iFR values varied widely after TAVI and the 0.89 iFR threshold was crossed by 15% of the investigated coronary lesions. Higher iFR variation was related to a higher transaortic gradient drop after valve intervention. The diagnostic accuracy of iFR in predicting an FFR ≤0.8 was poor (65%) in lesions with severe obstructions, and tended to increase post TAVI. CONCLUSIONS Although overall values did not change after TAVI, iFR presented significant and mostly erratic individual variations after valve replacement. Delta iFR was influenced by the extent of the transaortic gradient drop induced by TAVI. Therefore, caution is advisable in the interpretation of iFR in the presence of AS.

Optical coherence tomography characteristics of in-stent restenosis are different between first and second generation drug eluting stents

Aims Characterization of neointimal tissue is essential to understand the pathophysiology of in-stent restenosis (ISR) after drug eluting stent (DES) implantation. Using optical coherence tomography (OCT), we compared the morphologic characteristics of ISR between first and second generation DES. Methods and Results OCT was performed in 66 DES-ISR, defined as > 50% angiographic diameter stenosis within the stented segment. Patients with ISR of first generation sirolimus-eluting stents (SES), paclitaxel eluting stents (PES) and second generation zotarolimus-eluting stents (ZES), everolimus-eluting stents (EES) and biolimus-eluting stents (BES) were enrolled. Quantitative and qualitative ISR tissue analysis was performed at 1-mm intervals along the entire stent, and categorised as homogeneous, heterogeneous and neo-atherosclerosis. The presence of microvessels and peri-strut low intensity area (PSLIA) was determined in all ISR. Neoatherosclerosis was identified by lipid, calcium and thin-cap fibro-atheroma (TCFA) like lesions. We compared the two DES generations at both early (< 1 year) and late (> 1 year) follow-ups. In second generation DES a heterogeneous pattern was prevalent both before and after 1 year (57.1% and 58.6% respectively). Neo-atherosclerosis was more common in the early period in first generation DES (19.4% vs 11.7%, p < 0.01), but after one year was more prevalent in second generation DES (7.0% vs 19.3%, p < 0.01). Similar prevalence of TCFAs was observed in both groups in all comparisons. Conclusions When ISR restenosis occurs in second generation DES, the current data suggest a different time course and different morphological characteristics from first generation. Future prospective studies should evaluate the relationship between ISR morphology, time course and clinical events.

Percutaneous coronary interventions during ST-segment elevation myocardial infarction: current status and future perspectives

The present article focuses on recent innovations and possible future perspectives in the reperfusion treatment of ST-segment elevation myocardial infarction (STEMI). Among these, the shift from the femoral to the radial vascular access, the recent availability of bioresorbable coronary scaffolds, other innovative forms of stent specifically designed for STEMI patients, the use of cardioprotective strategies, as well as the possibility of including autologous bone marrow stem cell transplantation as part of the treatment of patients with STEMI are described and commented on as a glance into the future.