Pickering syndrome in a patient with Takayasu's arteritis.

Takayasu arteritis (TA) is a chronic granulomatous large vessel arteritis. The renal arteries are affected in up to 60% of patients with TA, with renal artery stenosis (RAS) potentially leading to ischemic nephropathy, severe arterial hypertension, and heart failure. Bilateral RAS may rarely present with recurrent flash pulmonary edema, a life-threatening association which has been termed Pickering syndrome. In this report, we describe a 55-year-old woman with severe refractory arterial hypertension admitted for acute pulmonary edema, initially treated unsuccessfully with medical therapy with vasodilators and diuretics. Given the instrumental findings of bilateral RAS and suggestive signs and symptoms, the diagnosis of TA was made, resulting as the first described case of Pickering syndrome being the clinical presentation of TA. Interventional therapy with renal artery angioplasty procedure was performed with stenting of both right and left renal arteries, leading to the resolution of the clinical scenario and the successful discharge of the patient. At the 1 year follow-up visit the patient was asymptomatic and in good clinical conditions; a significant reduction in antihypertensive therapy was achieved while immunosuppressive therapy was continued. This case highlights that secondary causes of TA should always be sought in patients with refractory hypertension who do not respond to standard treatment; also, TA should be suspected in young patients with bilateral RAS, especially when other typical signs of TA are present; lastly, a thorough investigation is essential in complicated cases, as rare diseases like TA may manifest in unusual ways.

[Clinical risk management: a new frontier for Italian Cardiology]. / La gestione del rischio clinico: una nuova frontiera per la Cardiologia italiana.

Patient safety is the moral and ethical responsibility of healthcare professionals, representing a constantly evolving field in industrialized countries whose key factors are sustainability, training and prevention. Clinical risk management is primarily concerned with systems issues, but people are of paramount importance to effective teamwork and leadership. Hospitals have recently been urged to adopt the methods of high-fidelity organizations to identify and change ineffective practice patterns: recognizing that little things that go wrong are early warning signs of trouble, near miss and errors become information about the health of systems and learn from them. Italian Cardiology will have to assume clinical risk as a common practice, through a rigorous examination of the causes of adverse events, staff training, sharing of validated adverse event analysis tools, identification of corrective actions and definition of shared procedures, the systematic control of the adoption of the planned interventions, the evaluation of the results of the measures implemented by applying stringency and scientific method in this area. The text tries to explain, in a pragmatic way, the main problems that hinder the diffusion of the culture of safety in Italian hospitals and in cardiology by proposing solutions.

ANMCO POSITION PAPER: Role of intra-aortic balloon pump in patients with acute advanced heart failure and cardiogenic shock.

The treatment of patients with advanced acute heart failure is still challenging. Intra-aortic balloon pump (IABP) has widely been used in the management of patients with cardiogenic shock. However, according to international guidelines, its routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian Association of Hospital Cardiologists, reviews the available data derived from clinical studies. It also provides practical recommendations for the optimal use of IABP in the treatment of cardiogenic shock and advanced acute heart failure.

[ANMCO Position paper: Current evidence on intra-aortic balloon pump in advanced acute heart failure]. / Position paper ANMCO: Ruolo del contropulsatore aortico nel paziente con insufficienza cardiaca acuta avanzata.

The treatment of patients with advanced acute heart failure is still challenging. Intra-aortic balloon pump (IABP) has widely been used in the management of patients with cardiogenic shock. However, according to international guidelines, its routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian Association of Hospital Cardiologists (ANMCO), reviews the available data derived from clinical studies. It also provides practical recommendations for the optimal use of IABP in the treatment of cardiogenic shock and advanced acute heart failure. Data deriving from a national survey in Italian hospitals about IABP use are also provided.

A single cystatin C determination before coronary angiography can predict short and long-term adverse events.

BACKGROUND: Cystatin C (CyC) role in the detection of contrast induced acute kidney injury (CIAKI) is controversial. This study assessed whether a single CyC determination before coronary angiography (CA)could predict CIAKI and long-term adverse events. METHODS: CyC was assessed before CA in 713 consecutive patients. CIAKI was the primary endpoint, defined as ≥0.3 mg/dl creatinine (sCR) increase at 48 h or ≥50% in 7-days. All-cause death, cardiovascular (CV)death and MACE (acute coronary syndrome, acute pulmonary edema,CV death) were secondary endpoints. Re-hospitalization, in-hospital death and worsening renal function were tertiary endpoints. RESULTS: CIAKI occurred in 47 (6.7%) patients. ROC analysis showed a good accuracy of CyC in the prediction of CIAKI (AUC 0.82,p < 0.01), compared with baseline sCR and sCR-eGFR (AUC 0.70 and 0.75 respectively, both p < 0.01). CyC was associated with 10-year CV-death, all-cause death and MACEs (AUC 0.76,0.74 and 0.64 respectively,all p < 0.01). A CyC cut-off value of 1.4 mg/L was not only accurate in predicting or ruling-out CIAKI following CA (97% negative predictive value, 84% specificity), but also useful as a prognostic marker for 10-year adverse events (50% vs.16% all cause mortality, 29% vs.3% CV death, 39% vs.13% MACE,all p < 0.01), re-hospitalizations (54% vs.35%,p < 0.01) and worsening renal function (34% vs.19%,p < 0.01). The strongest and independent risk factor for 10-year CV death was baseline CyC>1.4 mg/L (HR 17.3, 95% CI 1.94-155.1). CONCLUSIONS: A baseline determination of CyC before CA can accurately rule out CIAKI and predict adverse events in the long term. CIAKI can be ruled out before CA in 97% patients with a CyC value < 1.4 mg/L.

Risk factors for primary ventricular fibrillation during a first myocardial infarction: Clinical findings from PREDESTINATION (PRimary vEntricular fibrillation and suDden dEath during firST myocardIal iNfArcTION).

BACKGROUND: Few studies prospectively assessed risk factors for ventricular fibrillation (VF) during a first myocardial infarction (MI). We designed a nation-wide study aiming to identify clinical and genetic characteristics associated with primary VF; and report here about clinical features. METHODS: PREDESTINATION (PRimary vEntricular fibrillation and suDden dEath during a firST myocardIal iNfArcTION) is an Italian case-control, prospective multicentre study. Cases are patients aged 18-80 years with a first MI and at least one VF episodes occurring within 24 h of symptoms onset, before reperfusion. Cases and controls are paired 1: 2 by gender and age (±5 years). RESULTS: Among 1026 patients enrolled between 2007 and 2017, 970 entered the primary analysis: 375 cases and 595 controls (mean age 59 years, 85% males). Multivariable analysis identified 5 independent predictors of primary VF: systolic blood pressure (OR 0.982, 95% CI: 0.98-0.99 for each mm Hg) and K+ levels <3.5 mEq/L at presentation (OR 2.28, 95% CI: 1.6-3.3), family history of sudden death (OR 1.80, 95% CI: 1.1-3.0), physical inactivity (OR 1.73, 95% CI: 1.1-2.8) and anterior MI (OR 1.52, 95% CI: 1.1-2.1). Excluding K+ levels obtained after VF, the OR associated with K+ levels <3.5 mEq/L was1.99 (95 CI 1.22-3.21). CONCLUSIONS: The present study identified 5 independent predictors of primary VF: familiarity, anterior MI, low systolic blood pressure, physical inactivity and hypokalaemia. Importantly, the last two risk factors are modifiable and, especially in the presence of a family history of sudden death, they should be avoided as much as possible.

Efficacy and Safety of Clopidogrel, Prasugrel and Ticagrelor in ACS Patients Treated with PCI: A Propensity Score Analysis of the RENAMI and BleeMACS Registries.

INTRODUCTION: Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks. METHODS: A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents. RESULTS: A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3-5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3-5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3-5 events. CONCLUSION: In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events.

Meta-Analysis Comparing Complete or Culprit Only Revascularization in Patients With Multivessel Disease Presenting With Cardiogenic Shock.

The optimal strategy for patients with an acute myocardial infarction (MI) and multivessel (MV) coronary artery disease complicated by cardiogenic shock (CS) remains unknown. We conducted a meta-analysis of all randomized controlled trials and observational studies that reported adjusted effect measures to evaluate the association of MV-PCI (percutaneous coronary intervention), compared with culprit only (C)-PCI, with cardiovascular events in patients admitted for CS and MV disease. We identified 12 studies (n = 1 randomized controlled trials, n = 11 observational) that included 7,417 patients (n = 1,809 treated with MV-PCI and n = 5,608 with C-PCI). When compared with C-PCI, MV-PCI was not associated with an increased risk of short-term death (odds ratio [OR] 1.14, 95% confidence interval [CI] 0.87 to 1.48, p = 0.35 and adjusted OR [ORadj] 1.00, 95% CI 0.70 to 1.43, p = 1.00). In-hospital and/or short-term mortality tended to be higher with MV-PCI, when compared with C-PCI, for CS patients needing dialysis (ß 0.12, 95% CI from 0.049 to 0.198; p= 0.001), whereas MV-PCI was associated with lower in-hospital and/or short-term mortality in patients with an anterior MI (ß -0.022, 95% CI -0.03 to -0.01; p <0.001). MV-PCI strategy was associated with a more frequent need for dialysis or contrast-induced nephropathy after revascularization (OR 1.36, 95% CI 1.06 to 1.75, p = 0.02). In conclusion, MV-PCI seems not to increase risk of death during short- or long-term follow-up when compared with C-PCI in patients admitted for MV coronary artery disease and MI complicated by CS. Furthermore, it appears a more favorable strategy in patients with anterior MI, whereas the increased risk for AKI and its negative prognostic impact should be considered in decision-making process. Further studies are needed to confirm our hypothesis on in these subpopulations of CS patients.

Contrast-induced kidney injury: how does it affect long-term cardiac mortality?

AIMS: Contrast-induced acute kidney injury (CIAKI) is a common complication after coronary angiography or percutaneous revascularization (PCI). This study aimed to investigate the association of CIAKI with long-term cardiovascular adverse events. METHODS: In total, 980 patients undergoing coronary angiography/PCI were assessed in this prospective cohort study. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) and cardiac death (CVD) during an 8-year follow-up. Glomerular filtration rate change during the follow-up was the secondary endpoint.CIAKI was defined as a serum creatinine increase at least 0.3 mg/dl in 48 h or at least 50% in 7 days. RESULTS: CIAKI was observed in 69 patients (7%). Chronic kidney disease [relative risk (RR) = 4, P < 0.01], reduced ejection fraction (RR = 2.88, P < 0.01), CIAKI risk score at least 4 (RR = 2.64, P = 0.02), and emergency coronary angiography/PCI (RR = 3.87, P < 0.01) increased CIAKI risk, whereas statins were protective (RR = 0.32, P < 0.01).Patients with CIAKI had higher rates of 8-year cardiovascular adverse events: 54 versus 15% MACCE (RR = 6.67, P < 0.01), 38 versus 4% CVD (RR = 15.73, P < 0.01). Among other factors, CIAKI was the strongest predictor of 8-year MACCE (RR = 3.16, P < 0.01) and CVD (RR = 7.34, P < 0.01).During the follow-up, glomerular filtration rate declined drastically in CIAKI patients: 70 versus 39% had chronic kidney disease stage worsening (P < 0.01) and 8 versus 0.3% started hemodialysis (P < 0.01). CONCLUSION: We found a strong correlation between CIAKI and poor long-term cardiac outcomes. Apparently showing up as a transient, functional impairment of kidney function, CIAKI implies an organic damage with structural modifications leading to significant kidney deterioration over time, responsible for an increased risk of long-term cardiac events. Statins significantly reduced CIAKI occurrence. A careful management of high-risk patients is needed to limit long-term complications of coronary angiography/PCI.

AKIGUARD (Acute Kidney Injury GUARding Device) trial: in-hospital and one-year outcomes.

AIMS: Contrast-induced acute kidney injury (CIAKI) in patients with chronic kidney disease undergoing coronary angiography or percutaneous coronary intervention is a common iatrogenic complication associated with increased morbidity and mortality. This study compares sodium bicarbonate/isotonic saline/N-acetylcysteine/vitamin C prophylaxis (BS-NAC) against high-volume forced diuresis with matched hydration in CIAKI prevention. METHODS: One-hundred and thirty-three consecutive patients undergoing coronary angiography or percutaneous coronary intervention with estimated glomerular filtration rate less than 60 mL/min/1.73m were randomized to the study group receiving matched hydration (MHG) or to the control group receiving BS-NAC. MHG received in vein (i.v.) 250 mL isotonic saline bolus, followed by a 0.5 mg/kg furosemide i.v. bolus to forced diuresis. A dedicated device automatically matched the isotonic saline i.v. infusion rate to the urinary output for 1 h before, during and 4 h after the procedure. RESULTS: MHG had the lowest incidence of CIAKI (7 vs. 25%, P = 0.01), major adverse cardiac and cerebrovascular events at 1 year (7 vs. 32%, P < 0.01) and readmissions to cardiology/nephrology departments (8 vs. 25%, P = 0.03; hospitalization days 1.0 ±â€Š3.8 vs. 4.9 ±â€Š12.5, P = 0.01). Three months after the procedure the decrease in the estimated glomerular filtration rate was 0.02% for MHG versus 15% for the control group. CONCLUSION: Matched hydration was more effective than BS-NAC in CIAKI prevention. One-year follow-up showed that matched hydration was associated also with limited chronic kidney disease progression, major adverse cardiac and cerebrovascular events and hospitalizations.

Impact of contrast-induced acute kidney injury definition on clinical outcomes.

BACKGROUND: Contrast-induced acute kidney injury (CIAKI) is a frequent complication after infusion of contrast media in patients undergoing percutaneous coronary intervention. A wide range of CIAKI rates occurs after intervention between 3% and 30%, depending on the definition. The aim of this study was to identify which methodology was more effective at recognizing patients at high risk for in-hospital and out-of-hospital adverse events. METHODS AND RESULTS: Serum creatinine increases, after contrast agent infusion, were evaluated in 755 consecutive and unselected patients. Incidences of CIAKI diagnosed by 2 common definitions varied from 6.9% (creatinine increase of ≥0.5 mg/dL, CIAKI-0.5) to 15.9% (creatinine increase of ≥25%, CIAKI-25%). Significant differences appeared between the 2 definitions of sensitivity to predict renal failure according to receiver operating characteristic curve analysis (98% for CIAKI-0.5 and 62% for CIAKI-25%), using a cutoff value of postprocedural glomerular filtration rate of 60 mL/min. Both definitions of CIAKI were related to composite adverse events, but CIAKI-0.5 showed a stronger predicting value (odds ratio 2.875 vs 1.802, P = .036). In multivariate linear regression, only CIAKI-0.5 was a predictive variable of death (odds ratio 3.174, 95% CI 1.368-7.361). CONCLUSIONS: An increase in serum creatinine of ≥0.5 mg/dL is more sensitive because it recognizes more selectively those patients with a higher risk of mortality and morbidity. Serum creatinine increases of ≥25% overestimate CIAKI by including many patients without postprocedural relevant deterioration of renal function and affected by a lower risk of adverse events at follow-up.

Concurrent G-CSF and GM-CSF administration for the induction of bone marrow-derived cell mobilization in patients with acute myocardial infarction: a pilot study evaluating feasibility, safety and efficacy.

AIMS: To verify feasibility and safety of bone marrow stem cells (BMC) mobilization in patients (pts) with acute myocardial infarction (AMI) and to monitor the clinical effects of BMC mobilization in terms of myocardial perfusion and function. METHODS AND RESULTS: Eight male pts (median age: 50.5 years) treated with a primary PTCA were enrolled. The mobilization regimen consisted of G-CSF 5 microg/kg/12 h from day 0 to day +2 and GM-CSF 2.5 microg/kg/24 h. All pts underwent coronary angiography, intracoronary doppler flow study, echocardiography, and nuclear thallium scan before treatment and at 6 months. All pts showed increased values of WBC and circulating CD34+ following cytokine administration. No patient died. All patients completed a 6-months follow-up: target lesion revascularization rate was 12,5%, target vessel revascularization rate was 37.5%, angiographic mean ejection fraction increased from 49.8+/-11.9 to 55.4+/-8.7 (p=NS), mean coronary flow reserve from 1.63+/-0.42 to 2.5+/-0.4 (p=0.001), mean Thallium uptake raised from 55.56+/-16.42% to 67.56+/-13.66% (p=0.01), and normally perfused segments from 16% to 52% (p=0.01). CONCLUSION: Cytokine-induced BMC mobilization is feasible in AMI pts. Improvements of myocardial perfusion can be expected after PTCA associated with G-CSF and GM-CSF induced mobilization. Further studies are required to define the role of BMC-mobilization and the most effective cytokine combination.