Michele Pighi

Comparison of Serum Creatinine and Cystatin-C for Early Diagnosis of Contrast-Induced Nephropathy after Coronary Angiography and Interventions

BACKGROUND The diagnostic accuracy of serum creatinine and cystatin C (Cys) as early predictors of contrast-induced nephropathy (CIN) has been debated. We investigated the diagnostic sensitivities, diagnostic specificities, and variations from baseline for serum creatinine and Cys in CIN. METHODS We prospectively evaluated 166 patients at risk for CIN at baseline, and at 12, 24, and 48 h after exposure to contrast media. CIN occurred in 30 patients (18%). Changes (Δ) compared to baseline in serum creatinine and Cys were evaluated at the predefined time points. ROC curve analysis was performed for the Δ 12-h basal serum creatinine and Cys. RESULTS The Δ serum creatinine at 12 h from baseline was the earliest predictor of CIN [area under the ROC curve (AUC) = 0.80; P < 0.001]. The Δ serum creatinine 15% variation [0.15 mg/dL (13.2 μmol/L)] yielded 43% diagnostic sensitivity and 93% diagnostic specificity. The ΔCys at 12 h from baseline performed significantly worse than serum creatinine (AUC = 0.48; P = 0.74). CONCLUSIONS Variations from the serum creatinine baseline offer better diagnostic accuracy for predicting CIN at an earlier stage than similar variations in Cys. An additional diagnostic value of Cys over the determination of serum creatinine in the setting of CIN was not observed.

Early Creatinine Shifts Predict Contrast-induced Nephropathy and Persistent Renal Damage after Angiography

PURPOSE The purpose of this study was to evaluate incidence and predictors of contrast-induced nephropathy after coronary angiography and interventions, and to assess renal function at 30 days. The prognostic value of any early shift of serum creatinine compared with baseline was investigated; such measurement, being a delta, is largely independent of creatinine variations. METHODS There were 216 patients at risk for contrast-induced nephropathy prospectively evaluated at baseline and at 12, 24, and 48 hours after exposure to contrast media, and 190 (88%) evaluated 1 month after discharge. RESULTS Contrast-induced nephropathy occurred in 39 patients (18%), and 30-day renal damage was detected in 15 (7%). Contrast media/kg volume predicted contrast-induced nephropathy (P=.002), and percentage change of creatinine 12 hours from baseline was significantly higher in patients with nephropathy (P <.001). At multivariate analysis, percentage change of creatinine 12 hour-basal was the best predictor of nephropathy (P <.001). A 5% increase of its value yielded 75% sensitivity and 72% specificity (area under the curve 0.80; odds ratio 7.37; 95% confidence interval, 3.34-16.23) for early contrast-induced nephropathy detection. Furthermore, it strongly correlated with the development of renal impairment at 30 days (P=.002; sensitivity 87%, specificity 70%; area under the curve 0.85; odds ratio 13.29; 95% confidence interval, 2.91-60.64). CONCLUSION Minimal elevations of serum creatinine at 12 hours are highly predictive of contrast-induced nephropathy and 30-day renal damage after exposure to contrast media.

Randomized Comparison of XiEnce-V and Multi-link VisioN Coronary Stents in the sAme muLtivessel Patient with Chronic kiDnEy diSease (RENAL-DES) Study

Background— Percutaneous coronary interventions in patients with chronic kidney disease have shown suboptimal results. Drug-eluting stents (DES) might reduce the rate of target vessel revascularization in comparison with bare-metal stents (BMS) in patients with chronic kidney disease. However, given the multiple concomitant individual variables present in such patients, the comparison of neointimal growth after percutaneous coronary intervention is complex and difficult to assess. Methods and Results— Randomized Comparison of Xience V and Multi-Link Vision Coronary Stents in the Same Multivessel Patient with Chronic Kidney Disease (RENAL-DES) was a prospective, randomized, multicenter study to directly compare the efficacy in the prevention of clinical restenosis of everolimus-eluting stent (Xience V) and BMS with an identical design (Multi-Link Vision), both implanted in the same patient with multivessel coronary artery disease and chronic kidney disease (estimated glomerular filtration rate <60 mL/min). The primary end point of the study was the ischemia-driven target vessel revascularization as detected with myocardial scintigraphy at 12 months. In 215 patients, 512 coronary vessels were successfully treated with the randomly assigned DES (n=257) or BMS (n=255). At 1 year, the rate of ischemia-driven target vessel revascularization for DES and BMS groups was 2.7% (95% confidence interval, 1.1%–5.6%) and 11.4% (95% confidence interval, 7.8% to 16%), respectively, P<0.001. For the multivariate analysis, independent predictors of the ischemia-driven target vessel revascularization were BMS implantation (odds ratio, 4.95; 95% confidence interval, 2.1–11.6; P<0.001) and vessel size (odds ratio, 0.32; 95% confidence interval, 0.1–0.7; P=0.006). Conclusions— This is the first randomized trial showing a reduction of clinical restenosis with a new-generation DES in comparison with a BMS of equal design, in patients who have chronic kidney disease with multivessel coronary artery disease. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00818792.

Pooled Estimates of Immediate and Late Outcome of Mitral Valve Surgery in Octogenarians: A Meta-analysis and Meta-regression

OBJECTIVE The authors evaluated the outcome of patients≥80 years undergoing mitral valve (MV) surgery. DESIGN Systematic review of the literature and meta-analysis. SETTING None. PARTICIPANTS None. INTERVENTIONS None. MAIN RESULTS Twenty-four studies reporting on 5,572 patients ≥80 years of age who underwent MV surgery were included in this analysis. Pooled proportion of operative mortality was 15.0% (95% confidence interval [CI] 11.9-18.1), stroke was 3.9% (95% CI 2.6-5.2), and dialysis was 2.7% (95% CI 0.5-4.9). Early date of study (p = 0.014), increased age (p = 0.006), MV replacement (p = 0.008), procedure other than isolated MV surgery (p = 0.010), MV surgery associated with coronary artery surgery (p = 0.029), aortic cross-clamping time (p<0.001), and cardiopulmonary bypass time (p<0.001) were associated significantly with increased operative mortality. MV repair had lower operative mortality compared with MV replacement (7.3% v 14.2%, relative risk 0.573, 95% CI 0.342-0.962). Random-effects metaregression showed that prolonged aortic cross-clamping time (p = 0.005) was the only determinant of increased operative mortality, even when adjusted (p<0.001) for date of study (p = 0.004). Operative mortality was significantly higher in studies reporting a mean cross-clamp time >90 minutes (17.0% v 7.4%, p<0.001). Survival rates at 1, 3, and 5 years were 76.1%, 67.7%, and 56.5%, respectively. CONCLUSIONS MV surgery in patients ≥80 years of age is associated with operative mortality, which has decreased significantly during recent years. Prolonged aortic cross-clamp time is a major determinant of operative mortality. MV repair may achieve better results than MV replacement in the very elderly. Five-year survival of these patients is good and justifies surgical treatment of MV diseases in octogenarians.

Outcome after percutaneous edge-to-edge mitral repair for functional and degenerative mitral regurgitation: a systematic review and meta-analysis

Objectives Differences in terms of safety and efficacy of percutaneous edge-to-edge mitral repair between patients with functional and degenerative mitral regurgitation (MR) are not well established. We performed a systematic review and meta-analysis to clarify these differences. Methods PubMed, EMBASE, Google scholar database and international meeting abstracts were searched for all studies about MitraClip. Studies with <25 patients or where 1-year results were not delineated between MR aetiology were excluded. This study is registered with PROSPERO. Results A total of nine studies investigating the mid-term outcome of percutaneous edge-to-edge repair in patients with functional versus degenerative MR were included in the meta-analysis (n=2615). At 1 year, there were not significant differences among groups in terms of patients with MR grade≤2 (719/1304 vs 295/504; 58% vs 54%; risk ratio (RR) 1.12; 95% CI: 0.86 to 1.47; p=0.40), while there was a significantly lower rate of mitral valve re-intervention in patients with functional MR compared with those with degenerative MR (77/1770 vs 80/818; 4% vs 10%; RR 0.60; 95% CI: 0.38 to 0.97; p=0.04). One-year mortality rate was 16% (408/2498) and similar among groups (RR 1.26; 95% CI: 0.90 to 1.77; p=0.18). Functional MR group showed significantly higher percentage of patients in New York Heart Association class III/IV (234/1480 vs 49/583; 16% vs 8%; p<0.01) and re-hospitalisation for heart failure (137/605 vs 31/220; 23% vs 14%; p=0.03). No differences were found in terms of single leaflet device attachment (25/969 vs 20/464; 3% vs 4%; p=0.81) and device embolisation (no events reported in both groups) at 1 year. Conclusions This meta-analysis suggests that percutaneous edge-to-edge repair is likely to be an efficacious and safe option in patients with both functional and degenerative MR. Large, randomised studies are ongoing and awaited to fully assess the clinical impact of the procedure in these two different MR aetiologies.

The 2011-2012 pilot European Society of Cardiology Sentinel Registry of Transcatheter Aortic Valve Implantation: 12-month clinical outcomes

AIMS Our aim was to assess one-year outcomes of patients enrolled in the pilot European Sentinel Registry of Transcatheter Aortic Valve Implantation (TAVI). METHODS AND RESULTS One-year outcomes of 4,571 patients (81.4±7.2 years, 2,291 [50.1%] male) receiving TAVI with the SAPIEN XT (57.3%) or CoreValve prosthesis at 137 European centres were analysed using Kaplan-Meier and Cox proportional hazards regression techniques. At one year, 3,341 patients were alive, 821 had died, and 409 were lost to follow-up. Of 2,125 patients who underwent functional assessment, 1,916 (90%) were in New York Heart Association (NYHA) Class I/II at one year, with functional improvement from baseline noted in 1,682 patients (88%). One-year survival based on 4,564 patients was estimated at 79.1%. Independent baseline predictors of mortality were increasing age and logistic EuroSCORE, the presence of NYHA III/IV, chronic obstructive pulmonary disease, and atrial fibrillation. Female gender was associated with a 4% survival benefit at one year. Vascular access routes other than transfemoral were associated with poorer survival. Procedural failure and major periprocedural complications had an adverse impact on survival. CONCLUSIONS Contemporary European experience attests to the effectiveness of routine TAVI in unselected elderly patients.

Effect of advanced chronic kidney disease in clinical and echocardiographic outcomes of patients treated with MitraClip system.

BACKGROUND Data regarding the influence of different levels of renal dysfunction on clinical and echocardiographic results of MitraClip therapy are scarce. We aimed to evaluate the impact of baseline advance renal failure in the outcomes of a cohort of patients treated with MitraClip. METHODS AND RESULTS We analyzed data from a multicenter registry of 173 patients treated with MitraClip between 2009 and 2012. Patients were classified as advanced chronic kidney disease (CKD, creatinine clearance [CrCl] <30 ml/min, group 1, n=20), moderate CKD (CrCl 30-60 ml/min, group 2, n=78) and normal renal function (CrCl >60 ml/min, group 3, n=75). Twenty patients (11.5%) presented advanced CKD. Procedural success was equal in the 3 groups (95.0% group 1, 100% in group 2 and 96.0% in group 3, p=0.180). Post-procedural MR and NYHA class at 1 month (MR ≥ 3+5.0% vs. 0% vs. 4.0% p=0.190 and NYHA>II 40.0% vs. 21.0% vs. 18.3%, p=0.101) and 6 months (MR ≥ 3+0% vs. 13.0% vs. 2.7%, p=0.330; and NYHA class>II 54.5% vs. 26.9% vs. 25.6%, p=0.298) did not differ between groups. However, patients in group 1 experienced higher frequency of the composite end-point of mortality or readmission at 16.2 ± 11.1 months of follow-up (HR 4.8, CI 95% 1.1-21.3). CONCLUSION Advanced CKD is linked to an excess of cardiac adverse events. This should be judiciously taken into account when selecting patients for MitraClip.

Effects of prednisone on biomarkers of tubular damage induced by radiocontrast in interventional cardiology

BACKGROUND Contrast-induced nephropathy (CI-AKI) is a complication of diagnostic/therapeutic hemodynamic procedures in cardiology, which may also cause renal cholesterolinic atheroembolism. Despite the 
severe clinical impact of these complications, there is no optimal therapy for preventing and treating them. We suggest a short course of high-dose steroids as an effective preventive measure. METHODS Patients at risk of CI-AKI (n = 38) undergoing cardiovascular procedures were assigned 1:1 to 1 of 2 experimental arms (prednisone+hydration vs. hydration alone). Oral prednisone 1 mg/kg was administered 12 hours before, at 6 am on the same day, and 24 hours following the procedure. Serum creatinine was tested immediately before and again 24-48 hours after the procedure; neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), protein and albumin were assayed in spot urine before and 6 hours after the procedure.
 RESULTS NGAL and KIM-1 tended to rise after the procedure, but to a lesser degree in the prednisone group (delta NGAL: hydration = +128%, prednisone = +46%; 
p = 0.26; delta KIM-1: hydration = +99%, prednisone = +11%; p = 0.02). Proteinuria and albuminuria decreased significantly in the prednisone group. In 5 patients developing CI-AKI, their delta NGAL and delta KIM-1 did not differ from the values seen in patients without 
CI-AKI. Hypertension, peripheral arteriopathy and use of low-dose aspirin or diuretics were positive predictors of baseline NGAL, while treatment with calcium channel blockers and statins were negative predictors. Statins were negative predictors of baseline KIM-1. CONCLUSIONS A short course of prednisone reduces the procedure-induced changes in biomarkers of renal tubular damage. This study suggests that steroids had a tubule-protecting effect.

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.

Thrombus Aspiration in Primary Angioplasty for ST-segment Elevation Myocardial Infarction

Mechanical reperfusion with primary percutaneous coronary intervention in acute ST-segment-elevation myocardial infarction is superior to fibrinolysis in terms of short-term and long-term outcome, provided that it can be delivered on time and by an experienced team. Balloon angioplasty and stent implantation of an occluded epicardial vessel during ST-segment-elevation myocardial infarction can cause disruption of the frail thrombus containing lesions associated with suboptimal myocardial reperfusion and microcirculatory obstruction. Distal embolization of atherothrombotic material can be prevented by thrombus aspiration during primary angioplasty. Mechanical aspiration via end-hole large-lumen thrombectomy catheters has been shown to improve Thrombolysis in Myocardial Infarction (TIMI) flow and result in a more consistent early resolution of ST-segment elevation in multiple registries. More recently, a more sophisticated quantification of the myocardial damage has been applied using myocardial scintigraphy and magnetic resonance, with no difference between patients treated with thrombectomy and patients treated with conventional therapy. The expectations in terms of lasting mortality benefit raised by the first Dutch single-center randomized trial of thrombectomy versus predilation with plain old balloon angioplasty (Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction, TAPAS) were not confirmed by a much larger Swedish trial (Thrombus Aspiration ST-Segment Elevation Myocardial Infarction, TASTE) showing no outcome changes. Although we are waiting for new trials to clarify these controversial results, thrombectomy is still used in selected patients with high thrombus load or with persistent occlusion of the infarct-related artery after wire passage. Here we review the various systems available and discuss their relative merits and the reported results.