Statins: Cardiovascular Risk Reduction in Percutaneous Coronary Intervention—Basic and Clinical Evidence of Hyperacute Use of Statins

Reduction of LDL-cholesterol concentration in serum, blocking the isoprenylation of GTPases and the activation of myocyte-protective enzyme systems are three mechanisms that currently explain the lipid and non-lipid effects of statins. However, the decrease of LDL-cholesterol, the reduction of inflammation biomarkers and even the atheroregresion, as surrogate effects to the mechanisms of action of statins would be irrelevant if not accompanied by a significant decrease in the incidence of cardiovascular events. Statins like no other pharmacological group have proven to reduce the incidence of cardiovascular events and prolong life in any clinical scenario. This article review the basic and clinical evidence that support a new indication for HMG-CoA reductase inhibitors “pharmacological myocardial preconditioning before anticipated ischemia” or hyperacute use of statins in subjects with any coronary syndrome eligible for elective, semi-urgent or primary percutaneous coronary intervention: ARMYDA-Original, NAPLES I-II, ARMYDA-ACS, ARMYDA-RECAPTURE, Non-STEMI-Korean, Korean-STEMI trials

The Avantgarde Carbostent in Patients Scheduled for Undelayable Noncardiac Surgery

Background. Treatment of patients who need coronary revascularization before undelayable non-cardiac surgery is challenging. Methods. We assessed the safety and efficacy of percutaneous coronary interventions (PCI) using the Avantgarde TM Carbostent (CID, Italy) in patients undergoing PCI before undelayable non-cardiac surgery. The Multiplate analyzer point-of-care was used to assess residual platelet reactivity. One major cardiac events (MACE, defined as death, myocardial infarction, and stent thrombosis and major bleeding) were assessed. Results. 42 consecutive patients were analyzed. Total stent length ≥25 mm was observed in 16 (37%) patients. Multivessel stenting was performed in 11 (31.5%) patients. Clopidogrel was interrupted 5 days before surgery in 35 patients, whereas it was stopped the day of the surgery in 7 patients. Surgery was performed after 27 ± 9 (7–42) days from PCI. MACE occurred in one patient (2.4%; 95% confidence interval: 0.01–13%), who had fatal acute myocardial infarction 3 days after abdominal aortic aneurysm surgery and 12 days after stent implantation. No case of major bleeding in the postoperative phase was observed. Conclusions. The present pilot study suggests that, although at least 10–14 days of dual antiplatelet therapy remain mandatory, the Avantgarde TM stent seems to have a role in patients requiring undelayable surgery

Cardiorenal syndrome type 3: pathophysiologic and epidemiologic considerations

Cardiorenal syndrome (CRS) type 3 is a subclassification of the CRS whereby an episode of acute kidney injury (AKI) precipitates and contributes to the development of acute cardiac injury. There is limited understanding of the pathophysiologic mechanisms of how AKI contributes to acute cardiac injury and/or dysfunction. An episode of AKI may have effects that depend on the severity and duration of AKI and that both directly and indirectly predispose to an acute cardiac event. Moreover, baseline susceptibility will modify the subsequent risk for cardiac events associated with AKI. Experimental data suggest cardiac injury may be directly induced by inflammatory mediators, oxidative stress, apoptosis and activation of neuroendocrine systems early after AKI. Likewise, AKI may be associated with physiologic derangements (i.e. volume overload; metabolic acidosis, retention of uremic toxins, hyperkalemia; hypocalcemia), alterations to coronary vasoreactivity, and ventricular remodeling and fibrosis that indirectly exert negative effects on cardiac function. AKI may also adversely impact cardiac function by contributing to alternations in drug pharmacokinetics and pharmacodynamics. Additional experimental and translational investigations coupled with epidemiologic surveys are needed to better explore that pathophysiologic mechanisms underpinning acute cardiac events associated with AKI and their impact on outcomes

RenalGuard system in high-risk patients for contrast-induced acute kidney injury.

Background High urine flow rate (UFR) has been suggested as a target for effective prevention of contrast-induced acute kidney injury (CI-AKI). The RenalGuard therapy (saline infusion plus furosemide controlled by the RenalGuard system) facilitates the achievement of this target. Methods Four hundred consecutive patients with an estimated glomerular filtration rate ≤30 mL/min per 1.73 m 2 and/or a high predicted risk (according to the Mehran score ≥11 and/or the Gurm score >7%) treated by the RenalGuard therapy were analyzed. The primary end points were (1) the relationship between CI-AKI and UFR during preprocedural, intraprocedural, and postprocedural phases of the RenalGuard therapy and (2) the rate of acute pulmonary edema and impairment in electrolytes balance. Results Urine flow rate was significantly lower in the patients with CI-AKI in the preprocedural phase (208 ± 117 vs 283 ± 160 mL/h, P P = .009). The best threshold for CI-AKI prevention was a mean intraprocedural phase UFR ≥450 mL/h (area under curve 0.62, P = .009, sensitivity 80%, specificity 46%). Performance of percutaneous coronary intervention (hazard ratio [HR] 4.13, 95% CI 1.81-9.10, P P = .012), and total furosemide dose >0.32 mg/kg (HR 5.03, 95% CI 2.33-10.87, P Conclusions RenalGuard therapy is safe and effective in reaching high UFR. Mean intraprocedural UFR ≥450 mL/h should be the target for optimal CI-AKI prevention

The Influence of Body Mass Index on Clinical Interpretation of Established and Novel Biomarkers in Acute Heart Failure

Background: Body mass index (BMI) is a known confounder for natriuretic peptides, but its influence on other biomarkers is less well described. We investigated whether BMI interacts with biomarkers’ association with prognosis in patients with acute heart failure (AHF).Methods and Results: B-type natriuretic peptide (BNP), high-sensitivity cardiac troponin I (hs-cTnI), galectin-3, serum neutrophil gelatinase-associated lipocalin (sNGAL), and urine NGAL were measured serially in patients with AHF during hospitalization in the AKINESIS (Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic Heart Failure) study. Cox regression analysis was used to determine the association of biomarkers and their interaction with BMI for 30-day, 90-day and 1-year composite outcomes of death or HF readmission. Among 866 patients, 21.2%, 29.7% and 46.8% had normal (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) or obese (≥ 30 kg/m2) BMIs on admission, respectively. Admission values of BNP and hs-cTnI were negatively associated with BMI, whereas galectin-3 and sNGAL were positively associated with BMI. Admission BNP and hs-cTnI levels were associated with the composite outcome within 30 days, 90 days and 1 year. Only BNP had a significant interaction with BMI. When BNP was analyzed by BMI category, its association with the composite outcome attenuated at higher BMIs and was no longer significant in obese individuals. Findings were similar when evaluated by the last-measured biomarkers and BMIs.Conclusions: In patients with AHF, only BNP had a significant interaction with BMI for the outcomes, with its association attenuating as BMI increased; hs-cTnI was prognostic, regardless of BMI.</p

Short-term prognostic implications of serum and urine neutrophil gelatinase-associated lipocalin in acute heart failure:findings from the AKINESIS study

AIMS: Kidney impairment has been associated with worse outcomes in acute heart failure (AHF), although recent studies challenge this association. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker of kidney tubular injury. Its prognostic role in AHF has not been evaluated in large cohorts. The present study aimed to determine if serum NGAL (sNGAL) or urine NGAL (uNGAL) is superior to creatinine for predicting short-term outcomes in AHF. METHODS AND RESULTS: The study was conducted in an international, multicentre, prospective cohort consisting of 927 patients with AHF. Admission and peak values of sNGAL, uNGAL and uNGAL/urine creatinine (uCr) ratio were compared to admission and peak serum creatinine (sCr). The composite endpoints were death, initiation of renal replacement therapy, heart failure (HF) readmission and any emergent HF-related outpatient visit within 30 and 60 days, respectively. The mean age of the cohort was 69 years and 62% were male. The median length of stay was 6 days. The composite endpoint occurred in 106 patients and 154 patients within 30 and 60 days, respectively. Serum NGAL was more predictive than uNGAL and the uNGAL/uCr ratio but was not superior to sCr (area under the curve [AUC]; admission sNGAL 0.61 [95% confidence interval (CI) 0.55-0.67] and 0.59 [95% CI 0.54-0.65], peak sNGAL 0.60 [95% CI 0.54-0.66] and 0.57 [95% CI 0.52-0.63], admission sCr 0.60 [95% CI 0.54-0.64] and 0.59 [95% CI 0.53-0.64] [area under the curve: admission sNGAL 0.61, 95% confidence interval (CI) 0.55-0.67, and 0.59, 95% CI 0.54-0.65; peak sNGAL: 0.60, 95% CI 0.54-0.66, and 0.57, 95% CI 0.52-0.63; admission sCr: 0.60, 95% CI 0.54-0.64, and 0.59, 95% CI 0.53-0.64, at 30 and 60 days, respectively], peak sCr 0.61 [95% CI 0.55-0.67] and 0.59 [95% CI 0.54-0.64] at 30 and 60 days, respectively). NGAL was not predictive of the composite endpoint in multivariate analysis. CONCLUSIONS: Serum NGAL outperformed uNGAL but neither was superior to admission or peak sCr for predicting adverse events

Potential Utility of Cardiorenal Biomarkers for Prediction and Prognostication of Worsening Renal Function in Acute Heart Failure

Background: Multiple different pathophysiologic processes can contribute to worsening renal function (WRF) in acute heart failure. Methods and Results: We retrospectively analyzed 787 patients with acute heart failure for the relationship between changes in serum creatinine and biomarkers including brain natriuretic peptide, high sensitivity cardiac troponin I, galectin 3, serum neutrophil gelatinase-associated lipocalin, and urine neutrophil gelatinase-associated lipocalin. WRF was defined as an increase of greater than or equal to 0.3 mg/dL or 50% in creatinine within first 5 days of hospitalization. WRF was observed in 25% of patients. Changes in biomarkers and creatinine were poorly correlated (r < 0.21) and no biomarker predicted WRF better than creatinine. In the multivariable Cox analysis, brain natriuretic peptide and high sensitivity cardiac troponin I, but not WRF, were significantly associated with the 1-year composite of death or heart failure hospitali-zation. WRF with an increasing urine neutrophil gelatinase-associated lipocalin predicted an increased risk of heart failure hospitalization. Conclusions: Biomarkers were not able to predict WRF better than creatinine. The 1-year outcomes were associated with biomarkers of cardiac stress and injury but not with WRF, whereas a kidney injury bio-marker may prognosticate WRF for heart failure hospitalization

Relation of Decongestion and Time to Diuretics to Biomarker Changes and Outcomes in Acute Heart Failure

Prompt treatment may mitigate the adverse effects of congestion in the early phase of heart failure (HF) hospitalization, which may lead to improved outcomes. We analyzed 814 acute HF patients for the relationships between time to first intravenous loop diuretics, changes in biomarkers of congestion and multiorgan dysfunction, and 1-year composite end point of death or HF hospitalization. B-type natriuretic peptide (BNP), high sensitivity cardiac troponin I (hscTnI), urine and serum neutrophil gelatinase-associated lipocalin, and galectin 3 were measured at hospital admission, hospital day 1, 2, 3 and discharge. Time to diuretics was not correlated with the timing of decongestion defined as BNP decrease >= 30% compared with admission. Earlier BNP decreases but not time to diuretics were associated with earlier and greater decreases in hscTnI and urine neutrophil gelatinase-associated lipocalin, and lower incidence of the composite end point. After adjustment for confounders, only no BNP decrease at discharge was significantly associated with mortality but not the composite end point (p = 0.006 and p = 0.062, respectively). In conclusion, earlier time to decongestion but not the time to diuretics was associated with better biomarker trajectories. Residual congestion at discharge rather than the timing of decongestion predicted a worse prognosis. (C) 2021 The Authors. Published by Elsevier Inc