Safety and efficacy of everolimus-eluting bioresorbable vascular scaffold for cardiac allograft vasculopathy (CART).

BACKGROUND: Cardiac allograft vasculopathy (CAV) is still the main drawback of heart transplantation (HTx) and percutaneous coronary intervention (PCI) is a palliative measure because of the high incidence of failure. OBJECTIVE: This study aimed to investigate the safety and efficacy of bioresorbable scaffolds (BRSs) as potential novel therapeutic tool for the treatment of coronary stenoses in CAV. METHODS: This is a multicenter, single-arm, prospective, open-label study (CART, NCT02377648), that included patients affected by advanced CAV treated with PCI and second-generation ABSORB BRS (Abbott Vascular). The primary endpoint was the incidence of 12-month angiographic in-segment scaffold restenosis (ISSR). Secondary endpoints were the incidence of major adverse cardiac events (MACEs) at 12- and 36-month follow-up and the incidence of ISSR at 36 months. A paired intracoronary imaging analysis at baseline and follow-up was also performed. RESULTS: Between 2015 and 2017 35 HTx patients were enrolled and treated for 44 coronary lesions with 51 BRSs. The primary endpoint occurred in 13.5% of the lesions (5/37), with a cumulative ISSR rate up to 3 years of 16.2% (6/37). Angiographic lumen loss was 0.40 ± 0.62 mm at 12 months and 0.53 ± 0.57 mm at 36 months. Overall survival rate was 91.4% and 74.3%, and MACEs incidence 14.2% and 31.4% at 12 and 36 months, respectively. At the paired intracoronary imaging analysis, a significant increase of the vessel external elastic membrane area in the treated segment and some progression of CAV proximally to the BRS were detected. CONCLUSIONS: BRS-based PCI for the treatment of CAV is feasible and safe, with an ISSR incidence similar to what reported in retrospective studies with drug-eluting stents.

Angiography-derived index of microvascular resistance in takotsubo syndrome.

Coronary microvascular dysfunction (CMD) has been proposed as a key driver in the etiopathogenesis of Takotsubo syndrome (TTS), likely related to an "adrenergic storm" upon a susceptible microvascular circulation. The aim of our manuscript was to assess CMD in patients with TTS through the computation of the angiography-derived index of microcirculatory resistance (IMR) and its correlation with clinical presentation. Coronary angiograms of 41 consecutive TTS patients were retrospectively analyzed to derive angiography-based indices of CMD. Three indices (NH-IMRangio, AngioIMR and A-IMR) were calculated based on quantitative flow ratio. CMD was defined as an IMRangio value ≥ 25 units. The correlation between CMD and clinical presentation was then assessed. Median age was 76 years, 85.7% were women and mean left ventricular ejection fraction (LVEF) at first echocardiogram was 41.2%. Angiography-derived IMR was higher in left anterior descending artery (LAD) than circumflex and right coronary artery with either NH-IMRangio (53.9 ± 19.8 vs 35.8 ± 15.4 vs 40.8 ± 18.5, p-value < 0.001), AngioIMR (47.2 ± 17.3 vs 31.8 ± 12.2 vs 37.3 ± 13.7, p-value < 0.001) or A-IMR (52.7 ± 19 vs 36.1 ± 14.1 vs 41.8 ± 16.1, p-value < 0.001). All patients presented CMD with angiography-derived IMR ≥ 25 in at least one territory with each formula. Angiography-derived IMR in LAD territory was significantly higher in patients presenting with LVEF impairment (≤ 40%) than in those with preserved ventricular global function (NH-IMRangio: 59.3 ± 18.1 vs 46.3 ± 16.0 p-value = 0.030; AngioIMR: 52.9 ± 17.8 vs 41.4 ± 14.2, p-value = 0.037; A-IMR: 59.2 ± 18.6 vs 46.3 ± 17.0, p-value = 0.035). CMD assessed with angiography-derived IMR is a common finding in TTS and it is inversely correlated with LV function. The available formulas have a substantial superimposable diagnostic performance in assessing coronary microvascular function.

Predictors and Prognostic Impact of Left Ventricular Ejection Fraction Recovery after Impella-Supported Percutaneous Coronary Interventions in Acute Myocardial Infarction.

Aim: The aim of our study is to assess the predictors and the prognostic role of left ventricle ejection fraction (LVEF) recovery after Impella-supported percutaneous coronary intervention (PCI) in patients presenting with acute myocardial infarction (AMI). Methods: This retrospective, observational study included patients admitted for AMI who underwent Impella-supported PCI in two Italian high-volume cardiac catheterization laboratories. Only patients who underwent an echocardiographic assessment of left ventricle ejection fraction (LVEF) before the procedure (acute LVEF) and during follow-up (follow-up LVEF) were included in the present analysis. Patients with a baseline LVEF ≥40% were excluded from the present analysis. LVEF recovery was calculated as the difference between follow-up LVEF and acute LVEF. A delta ≥5% was considered significant and was used to define the responder group. Results: From April 2007 to December 2020, 64 consecutive patients were included in our study. A total of 55 patients (86%) received hemodynamic support with Impella 2.5, and 9 patients (14%) with Impella CP. Median LVEF at follow-up was significantly higher compared to baseline (36% (30−42) vs. 30% (24−33), p < 0.001). Based on LVEF recovery, 37 patients (57.8%) were deemed responders. According to multivariate analysis, complete functional revascularization was an independent predictor of a significant EF recovery (OR: 0.159; 95% CI: 0.038−0.668; p = 0.012). At three-year follow-up, lack of LVEF recovery was the only predictor of mortality (HR: 5.315; 95% CI: 1.100−25.676; p = 0.038). Conclusions: Functional complete revascularization is an independent predictor of the recovery of LVEF in patients presenting with AMI who underwent Impella-supported PCI. The recovery of LV function is associated with improved prognosis and could be used to stratify the risk of future events at long-term follow-up.

The Treatment of Aortic Valve Stenosis in Intermediate and Low-Risk Patients-When, How and Where.

Until now, treatment of severe aortic stenosis (AS) is recommended after the disease becomes symptomatic or causes "silent" damages such as myocardial dysfunction [...].

Prognostic impact of antiplatelet therapy in Takotsubo syndrome: a systematic review and meta-analysis of the literature.

While the most recent evidence suggests a lack of benefit, antithrombotic therapy is still extensively prescribed in patients with Takotsubo syndrome (TTS). The objective of this study was to determine whether patients with TTS benefit from anti-aggregation, in terms of either short-term or long-term outcomes. A systematic review and meta-analysis was conducted. A comprehensive search of the literature included MEDLINE, Cochrane Library, Clinicaltrials.gov, EU Clinical Trial Register, References, and contact with the authors. Methodological quality assessment and data extraction were systematically performed. The review adhered to the PRISMA framework guidelines. A total of 86 citations were identified, six being eligible for inclusion, for a total of 1997 patients. One of them considered both short-term and long-term outcomes. One reported outcomes during the index event, while the remaining four focused on potential long-term benefits. They were all retrospective cohort studies.Based on our data, the long-term use of antiplatelet therapy (AT) led to a significantly higher incidence of the composite outcome (OR: 1.54; 95% CI 1.09-2.17; p = 0.014) and overall mortality (OR 1.72; 95% CI 1.07-2.77; p = 0.027). The analysis did not show a statistically significant difference in TTS recurrences, stroke/TIA, and MI or CAD worsening with AT compared with no anti-aggregation. The AT in this settings did not show any clear benefit in improving the long-term outcomes, and it may be even detrimental and it may be detrimental. These results warrant further future research and the design of adequately powered randomized controlled trials focusing on the impact of aspirin on the outcomes in patients presenting with TTS.

Contrast-Induced Nephropathy in Patients Undergoing Staged Versus Concomitant Transcatheter Aortic Valve Implantation and Coronary Procedures.

Background The impact of staged versus concomitant coronary procedures on renal function in patients with aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) remains unclear. Methods and Results Three-hundred thirty-nine patients undergoing coronary procedures and TAVI as a staged strategy (160, 47.2%) or concomitant strategy (179, 52.8%) were retrospectively analyzed. Contrast-induced acute kidney injury (CI-AKI) occurred in 49 patients in the staged strategy group (30.6%) and in 18 patients (10.1%) in the concomitant strategy group (P<0.001). Among the staged strategy group, 25 (15.6%) patients developed CI-AKI after coronary angiography or percutaneous coronary intervention, 17 (10.6%) after TAVI, and 7 (4.3%) after both the procedures. Staged strategy was associated with a higher risk of CI-AKI (odds ratio, 3.948; P<0.001) after adjustment for multiple confounders and regardless of the baseline renal function (P for interaction=0.4) when compared with the concomitant strategy. At a median follow-up of 24.0 months (3.0-35.3), CI-AKI was not associated with sustained renal injury (P=0.794), irrespective of the adopted strategy. The concomitant strategy did not impact the overall early safety at 30 days follow-up after TAVI compared to the staged strategy (P=0.609). Conclusions Performing coronary procedures with a staged strategy before TAVI was associated with a higher risk of CI-AKI compared with a concomitant strategy. Moreover, a concomitant strategy did not increase the risk of procedure-related complications.

Refractory vasospastic angina in a patient with fibromuscular dysplasia: A case report.

A 49-year-old woman affected by fibromuscular dysplasia (FMD) of the carotid artery with recurrent coronary vasospasm, refractory to medical therapy was admitted for anginal pain. Coronary involvement related to FMD is uncommon and its diagnosis "in vivo" still represents a challenge. Although a clear association between FMD and spontaneous coronary artery dissections is described, the presentation as severe coronary vasospasm is rare and it is associated with unfavorable outcome, especially when treated by means of percutaneous coronary intervention. The use of intravascular ultrasound played a key role in choosing the appropriate strategy for the management of the patient. .

Insights on safety and efficacy of renal artery denervation for uncontrolled-resistant hypertension in a high risk population with chronic kidney disease: first Italian real-world experience.

AIMS: To evaluate the safety and efficacy of catheter-based radiofrequency renal sympathetic denervation (RSD) in a daily practice population of patients with uncontrolled resistant hypertension, on top of medical therapy. METHODS: Consecutive unselected patients with uncontrolled resistant hypertension undergoing RSD were enrolled. Office and ambulatory blood pressure (BP) measurements were collected at baseline and 3, 6 and 12 months after RSD. Efficacy was assessed even in patients with an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2. Patients were defined as responders if systolic BP decreased by at least 5 mmHg at ambulatory BP or by 10 mmHg at office BP at their last follow-up visit. RESULTS: Forty patients with multiple comorbidities underwent RSD from 2012 to 2019. Baseline office and ambulatory BP was 159.0/84.9 ± 26.2/14.9 mmHg and 155.2/86.5 ± 20.9/14.0 mmHg, respectively. At 12-month follow up a significant reduction in office and ambulatory systolic BP, respectively by - 19.7 ± 27.1 mmHg and by - 13.9 ± 23.6 mmHg, was observed. BP reduction at 12-month follow-up among patients with eGFR < 45 mL/min was similar to that obtained in patients with higher eGFR. Twenty-nine patients (74.4%) were responders. Combined hypertension, higher ambulatory systolic BP and lower E/E' at baseline emerged as predictors of successful RSD at univariate analysis. No major complications were observed and renal function (was stable up to 12 months), even in patients with the lowest eGFR values at baseline. CONCLUSION: RSD is safe and feasible in patients with uncontrolled resistant hypertension on top of medical therapy, even in a high-risk CKD population with multiple comorbidities, with a significant reduction in systolic BP and a trend towards a reduction in diastolic BP lasting up to 12 months.

Extravalvular Cardiac Damage and Renal Function Following Transcatheter Aortic Valve Implantation for Severe Aortic Stenosis.

BACKGROUND: In this study we sought to determine the differences in incidence of acute kidney injury (AKI) and acute kidney recovery (AKR) among patients undergoing transcatheter aortic valve implantation (TAVI), according to the degree of extravalvular cardiac damage (EVCD). METHODS: From the Verona Valvular Heart Disease Registry, 674 symptomatic severe aortic stenosis (AS) patients were selected and retrospectively analysed. Using echocardiographic data, patients were classified based on the degree of EVCD. RESULTS: After dichotomized analysis, patients in EVCD stage 3 or 4 reported a significantly higher rate of AKI (29.5% vs 11.2%; P < 0.001). Using a multivariate analysis model, higher EVCD stage, lower glomerular filtrate rate (GFR) at admission, and amount of contrast used were found to be independent predictors of AKI, whereas stage of cardiac damage and GFR were found to be independent predictors of AKR. For the overall population after multivariate analysis AKI was associated with a higher incidence of 12-month all-cause mortality (hazard ratio, 2.142; 95% confidence interval, 1.082-4.239; P = 0.029) with a significant impact in the advanced cardiac damage stages, but not in the early stages (P for interaction = 0.006). AKR did not reduce adverse clinical outcomes but was associated with improved renal function at 12 months. CONCLUSIONS: Increase in EVCD stage was associated with a higher rate of AKI after TAVI. AKI had a negative impact on long-term clinical outcomes but only in patients with advanced cardiac damage. AKR did not reduce adverse clinical outcomes but was associated with improved renal function at 12 months.

Contrast-Induced Acute Kidney Injury in Patients Undergoing TAVI Compared With Coronary Interventions.

Background Differences in the impact of contrast medium on the development of contrast-induced acute kidney injury (CI-AKI) in patients undergoing transcatheter aortic valve implantation (TAVI) or a coronary angiography/percutaneous coronary intervention (CA/PCI) have not been previously investigated. Methods and Results Patients treated with TAVI or elective CA/PCI were retrospectively analyzed in terms of baseline and procedural characteristics, including preprocedural and postprocedural kidney function. CI-AKI was defined as a relative increase in serum creatinine concentration of at least 0.3 mg/dL within 72 hours of contrast-medium administration compared with baseline. The incidence of CI-AKI in the TAVI versus CA/PCI group was compared. After the exclusion of patients in dialysis and emergency procedures, 977 patients were analyzed; there were 489 patients who had undergone TAVI (50.1%) and 488 patients who had undergone CA/PCI (49.9%). Patients treated by TAVI were older, presenting a higher rate of anemia and chronic kidney disease (P<0.001 for all comparisons). Consistently, they also had a significantly lower glomerular filtration rate and higher serum creatinine concentration (P<0.001 for all). However, the occurrence of CI-AKI was significantly lower in these patients compared with patients treated by a CA/PCI (6.7% versus 14.5%, P<0.001). At multivariate analysis, the TAVI procedure had an independent protective effect on CI-AKI incidence among total population (odds ratio, 0.334; 95% CI, 0.193-0.579; P<0.001). This observation was confirmed after propensity score matching among 360 patients (180 by TAVI and 180 by CA/PCI; P=0.002). Conclusions CI-AKI occurred less frequently in patients undergoing TAVI than in patients undergoing a CA/PCI, despite a worse-risk profile. The impact of contrast administration on kidney function in patients who had undergone TAVI may be better tolerated because of the hemodynamic changes following aortic valve replacement.

Short-and-Long-Term Outcomes after Coronary Rotational Atherectomy in Patients Treated with Trans-Catheter Aortic Valve Implantation.

BACKGROUND: Coronary artery disease (CAD) is a common finding among patients undergoing trans-catheter aortic valve implantation (TAVI), who often present severely calcified coronary lesions. Evidence is scarce about the use of rotational atherectomy (RA) in this setting, in particular regarding long-term outcome. METHODS: RA was performed on severely calcified coronary lesions concomitant with TAVI in a consecutive series of patients treated between 2010 and 2020. Immediate and long-term clinical outcomes are reported. RESULTS: A concomitant CAD (coronary stenosis visually > 50%) was observed in 402/845 (47.6%) consecutive patients undergoing TAVI at the University Hospital of Verona. Angioplasty was performed in 104 patients (12.3%). Among these, 19 patients (18.3%, 20 coronary arteries), were treated with RA after TAVI: 10 after implantation of a balloon-expandable trans-catheter valve and 9 after a self-expandable valve. All procedures were successful. Hypotension occurred in 3 patients (15.8%), with rapid recovery after the procedure; CI-AKI (contrast-induced acute kidney injury) in 3 patients (15.8%), of which two recovered within discharge. At a median follow-up of 21.5 months (Q1-3: 6-36) event free survival was 83.3%. Only one patient suffered a target vessel failure >2 years after RA. Neither stroke nor peri-procedural infarctions were detected. CONCLUSIONS: RA concomitant with TAVI was feasible and safe in patients treated with implantation of either self-expandable, or balloon-expandable trans-catheter aortic valves. Long-term clinical events related to the coronary procedure were extremely infrequent and the survival rate at median follow-up of 21.5 months was 83.3%.

Early Small Creatinine Shift Predicts Contrast-Induced Acute Kidney Injury and Persistent Renal Damage after Percutaneous Coronary Procedures.

PURPOSE: Little is known on the impact of contrast-induced acute kidney injury (CI-AKI) on mid- and long-term renal function after percutaneous coronary procedure. The aim of the study was to investigate the incidence of persistent renal damage (PRD) after CI-AKI in a cohort of patients undergoing coronary angiography and/or intervention. Moreover, we sought to assess the predictive value of small creatinine change at 12-24 h (SCrΔ%12-24 h) from contrast exposure in predicting CI-AKI and PRD. METHODS: Complete clinical and biochemical data of 731 patients were retrospectively analyzed at sequential time intervals at baseline, 12-24 h and 48-72 h from the procedure. Data at 30 ±â€¯10 days and 12-24 months were available in 59% and 49% of the cases respectively. Logistic regression was used to assess variables associated with CI-AKI and PRD. ROC analysis was used to test the diagnostic accuracy of SCrΔ%12-24 h in predicting CI-AKI and PRD. RESULTS: CI-AKI occurred in 130/731 patients (17.8%). At 30 ±â€¯10 days PRD occurred in 54.8% patients who developed CI-AKI. A SCrΔ%12-24 h >5% demonstrated independent predictive value (OR = 1.05, CI = 1.04-1.06, p < 0.001) and fair accuracy (AUC = 0.80, CI = 0.77-0.84) for CI-AKI. CONCLUSION: CI-AKI was associated with PRD in >50% of the cases in this single centre cohort. A small and early SCrΔ%12-24 h demonstrated high predictive value for CI-AKI and may be used as a useful tool to unmask a group of patients at risk for PRD after percutaneous coronary procedures.

Physiological Versus Angiographic Guidance for Myocardial Revascularization in Patients Undergoing Transcatheter Aortic Valve Implantation.

Background Management of coronary artery disease in patients undergoing transcatheter aortic valve implantation is uncertain. Fractional flow reserve (FFR) has never been clinically validated in aortic stenosis. The study aim was to analyze the clinical outcome of FFR-guided revascularization in patients undergoing transcatheter aortic valve implantation. Methods and Results Patients with severe aortic stenosis and coronary artery disease at coronary angiography were included in this retrospective analysis and divided in 2 groups: angiography guided (122/216; 56.5%) versus FFR-guided revascularization (94/216; 43.5%). Patients were clinically followed up and evaluated for the occurrence of major adverse cardiac and cerebrovascular events at 2-year follow-up. Most lesions in the FFR group resulted negative according to the conventional 0.80 cutoff value (111/142; 78.2%) and were deferred. The FFR-guided group showed a better major adverse cardiac and cerebrovascular event-free survival compared with the angio-guided group (92.6% versus 82.0%; hazard ratio, 0.4; 95% CI, 0.2-1.0; P=0.035). Patients with deferred lesions based on FFR presented better outcome compared with patients who underwent angio-guided percutaneous coronary intervention (91.4% versus 68.1%; hazard ratio, 0.3; 95% CI, 0.1-0.6; P=0.001). Conclusions FFR guidance was associated with favorable outcome in this observational study in patients undergoing transcatheter aortic valve implantation. Randomized trials are needed to investigate the long-term effects of FFR-guided revascularization against angiographic guidance alone in patients with aortic stenosis.

Effectiveness and Safety of Transcatheter Aortic Valve Implantation in Patients With Pure Aortic Regurgitation and Advanced Heart Failure.

Results of transcatheter aortic valve implantation (TAVI) for treatment of severe noncalcific isolated aortic regurgitation (AR) complicated by advanced heart failure or cardiogenic shock has been previously reported only in isolated case reports. Current self-expanding transcatheter aortic valves are designed to treat aortic valve stenosis, and have also been implanted in cases of severe AR due to degenerated bioprosthesis and in very few cases of native aortic valves. We report 13 consecutive inoperable patients with noncalcific, pure AR, and advanced heart failure treated with emergency percutaneous transfemoral implantation with self-expandable CoreValves at our institution between July 2012 and September 2017. The immediate and long-term clinical outcome was prospectively assessed according to the Valve Academic Research Consortium-2 criteria for device success and safety. All but 3 patients had previous surgery of the aortic root, including 2 implants of Heart Mate-II left ventricle assist device; none had surgical aortic bioprosthesis at the time of the TAVI. Valve implantation was successful in 12 of 13 patients (92%) and 1 patient required a second unplanned valve procedure within 18 hours. Oversizing the prosthesis by approximately 15% yielded better results with 1 valve. Two patients with left ventricle assist device died within 30 days of TAVI. All patients who survived to hospital discharge had none or just mild residual AR, improved their cardiac function, and survived at long-term without recurrence of clinical events. In conclusion, implanting self-expandable transcatheter valves in patients pure AR in this small study was safe and effective, and represented an important option for inoperable patients with noncalcific severe AR.

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.

Observations from a real-time, iFR-FFR "hybrid approach" in patients with severe aortic stenosis and coronary artery disease undergoing TAVI.

BACKGROUND: The complexity of coronary physiology in presence of severe aortic stenosis (AS) raises concerns about the reliability of pressure-derived indexes in this clinical setting. Furthermore, neither fractional flow reserve (FFR) nor instantaneous wave-free period (iFR) has been validated in AS. Combining iFR and FFR in a tailored decision-making strategy may help to increase simplicity, accuracy and safety of physiology-guided revascularization in AS. METHODS: In this prospective observational study iFR and FFR were measured before and after TAVI during the same procedure in patients with severe AS and concomitant coronary artery disease (CAD). All decisions about revascularization were based on post-TAVI FFR assessment. The best iFR "defer" and "treatment" values were identified according to their baseline negative (NPV) and positive predictive values (PPV) respectively. A post-hoc analysis was then performed to compare the hybrid iFR-FFR approach with the FFR-only strategy. RESULTS: Sixty-two patients underwent pre- and post-TAVI pressure-wire assessment and were included in the analysis. A "defer iFR value" >0.93 yielded a NPV of 98.4% (91.7%-99.9%) to exclude FFR non-significant stenosis (>0.80), and a "treatment iFR value" <0.83 had a PPV of 91.3% (72%-98.9%) to identify FFR-significant stenosis (≤0.80). A hybrid decision-making strategy based on iFR and FFR spared 63% of patients from adenosine, while maintaining 97% overall agreement with FFR lesions classification. CONCLUSION: A hybrid iFR-FFR diagnostic strategy is feasible and safe in patients with severe AS undergoing TAVI and allows to spare the majority of patients from adenosine, while maintaining a high agreement with FFR classification of coronary lesions.