Hung Q. Ly

Contrast-Induced Nephropathy: From Pathophysiology to Preventive Strategies

Contrast-induced nephropathy (CIN) is a frequent cause of acute kidney injury in hospitalized patients. CIN is most commonly defined as either an absolute (≥ 0.5 mg/dL; ≥ 44 μmol/L) or relative (≥ 25%) increase in serum creatinine levels at 48-72 hours after exposure to iodinated contrast media (CM). Its occurrence is associated with worsened clinical outcomes. Patients undergoing cardiac catheterization and percutaneous coronary intervention are particularly vulnerable to CIN. The complex pathophysiology of CIN involves different mechanisms, such as vasoconstriction, oxidative stress, medullary ischemia, and the direct toxic effects of CM. In CIN pathophysiology, both patient-related and procedure-related risk factors have been identified. The risk for CIN can be reliably estimated with clinical scores such as that proposed by Mehran. Because no definitive treatment exists for CIN, the most effective strategy remains prevention. Several interventions have been investigated--from hydration to various pharmacologic agents and mechanical devices. In this state-of-the-art article, we review the pathophysiology, diagnosis, risk stratification, and preventive strategies for CIN.

The Benefits Conferred by Radial Access for Cardiac Catheterization Are Offset by a Paradoxical Increase in the Rate of Vascular Access Site Complications With Femoral Access : The Campeau Radial Paradox

OBJECTIVES The purpose of this study was to assess whether the benefits conferred by radial access (RA) at an individual level are offset by a proportionally greater incidence of vascular access site complications (VASC) at a population level when femoral access (FA) is performed. BACKGROUND The recent widespread adoption of RA for cardiac catheterization has been associated with increased rates of VASCs when FA is attempted. METHODS Logistic regression was used to calculate the adjusted VASC rate in a contemporary cohort of consecutive patients (2006 to 2008) where both RA and FA were used, and compared it with the adjusted VASC rate observed in a historical control cohort (1996 to 1998) where only FA was used. We calculated the adjusted attributable risk to estimate the proportion of VASC attributable to the introduction of RA in FA patients of the contemporary cohort. RESULTS A total of 17,059 patients were included. At a population level, the VASC rate was higher in the overall contemporary cohort compared with the historical cohort (adjusted rates: 2.91% vs. 1.98%; odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.17 to 1.89; p = 0.001). In the contemporary cohort, RA patients experienced fewer VASC than FA patients (adjusted rates: 1.44% vs. 4.19%; OR: 0.33, 95% CI: 0.23 to 0.48; p < 0.001). We observed a higher VASC rate in FA patients in the contemporary cohort compared with the historical cohort (adjusted rates: 4.19% vs. 1.98%; OR: 2.16, 95% CI: 1.67 to 2.81; p < 0.001). This finding was consistent for both diagnostic and therapeutic catheterizations separately. The proportion of VASCs attributable to RA in the contemporary FA patients was estimated at 52.7%. CONCLUSIONS In a contemporary population where both RA and FA were used, the safety benefit associated with RA is offset by a paradoxical increase in VASCs among FA patients. The existence of this radial paradox should be taken into consideration, especially among trainees and default radial operators.

Association of a history of systemic hypertension with mortality, thrombotic, and bleeding complications following non-ST-segment elevation acute coronary syndrome

Chronic hypertension is a well established risk factor for the development of cardiovascular disease; however, its prognostic significance after a non‐ST‐segment elevation acute coronary syndrome remains to be established. Data from 15,414 patients included in six randomized Thrombolysis in Myocardial Infarction (TIMI) trials (TIMI 3B, TIMI11 A, TIMI 11B, TIMI 12, the Orbofiban in Patients With Unstable Coronary Syndromes [OPUS]‐TIMI 16, and the Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy [TACTICS]‐TIMI 18) were analyzed. A history of hypertension was present in 10,998 (71.35%) patients; comorbidities and higher TIMI risk scores were more likely in these patients. However, positive troponin and ST‐segment deviations were less frequent among hypertensive patients. After multivariate analysis, the history of hypertension was associated with more adverse outcomes, specifically the composite end point of death/myocardial infarction at 30 days and 1 year (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.31–1.81; p<0.001 at 1 year) than in patients without this history. An independent relationship was also observed with mortality (OR 1.70, 95% CI 1.34–2.16; p<0.001 at 1 year), myocardial infarction (OR 1.50, 95% CI 1.23–1.82; p<0.001 at 1 year), recurrent ischemia (OR 1.24, 95% CI 1.11–1.38; p<0.001 at 1 year), and major bleeding (OR 1.45, 95% CI 1.03–2.06; p=0.036 at 30 days). It was concluded that chronic hypertension remains an independent marker for major short‐ and long‐term cardiac adverse outcomes after non‐ST‐segment elevation acute coronary syndrome.

Direct Stenting Versus Pre‐Dilation in ST‐Elevation Myocardial Infarction: A Systematic Review and Meta‐Analysis

OBJECTIVES This study aimed at comparing direct stenting (DS) versus stenting with pre-dilation (SP) in patients with ST-elevation myocardial infarction (STEMI), using a systematic review and meta-analysis of published evidence. BACKGROUND There is conflicting evidence whether stenting strategy impacts clinical outcomes in patients with STEMI. METHODS We searched EMBASE, MEDLINE, and CENTRAL, from inception to December 2014. The primary endpoint was mortality. Secondary endpoints included major adverse cardiac events (MACEs), ST-segment resolution, and angiographic outcomes. RESULTS A total of 9,331 patients enrolled in 12 studies (3 randomized controlled trials, RCTs; 9 non-randomized studies, NRSs) were included. DS was associated with lower mortality (OR 0.55; 95%CI: 0.33-0.94; P = 0.03) in NRSs, and overall (OR 0.56; 95%CI: 0.37-0.86; P = 0.008). Mortality was non-significantly reduced in RCTs (OR 0.56; 95%CI: 0.26-1.23; P = 0.15). DS was also associated with lower MACE rate (OR 0.71; 95%CI 0.60-0.84; P < 0.0001) in NRSs, but not in RCTs (OR 0.99; 95%CI: 0.61-1.60; P = 0.96). ST-segment resolution, no reflow, final thrombolysis in myocardial infarction (TIMI) flow and final TIMI myocardial perfusion or blush grade were significantly better with DS in NRSs, and non-significantly better in RCTs. CONCLUSIONS The available evidence suggests that DS in STEMI might be associated with better clinical and procedural outcomes, as compared with SP. However, the fact that RCTs account for the minority of available data and that most of the available studies poorly reflect current clinical practice, as well as the existence of publication bias, preclude drawing definitive conclusions.

Transradial Percutaneous Coronary Interventions in Acute Coronary Syndrome

Transradial access (TRA) is becoming increasingly used worldwide for percutaneous coronary intervention (PCI) after acute coronary syndromes (ACS). TRA compared with transfemoral access has been noted to improve clinical outcomes in clinical trials and large registry cohort studies. However, much of the benefits of TRA PCI are noted in patients with ST elevation myocardial infarction (STEMI) undergoing primary PCI, where TRA PCI has been associated with reductions in major bleeding events and potentially lower short- and long-term mortality rates. Although much less data exist for TRA PCI in unstable angina and/or non-ST elevation myocardial infarction, similar reductions in bleeding and mortality have not been consistently described. Differences in outcome benefit with TRA PCI among various ACS subtypes may be attributable to the potentially increased inherent risk of periprocedural bleeding in STEMI compared with unstable angina and/or non-ST elevation myocardial infarction. Pre- and intra-procedural factors associated with STEMI treatment, such as use of pharmacoinvasive therapy and aggressive antithrombotic regimens likely increase bleeding risk in patients. In conclusion, this review describes the evidence for TRA PCI across the spectrum of ACS and highlights why differences in clinical benefit may exist among ACS subtypes.

Effect of Radial-to-Femoral Access Crossover on Adverse Outcomes in Primary Percutaneous Coronary Intervention

We aimed to describe the impact of the vascular access used when patients are treated with primary percutaneous coronary intervention (PPCI) and to assess whether this translates into differences in angiographic outcomes. Patients with ST-elevation myocardial infarction who underwent PPCI were divided into 3 groups: successful radial access (RA), successful femoral access (FA), and Crossover (failed RA with need for bailout FA) groups. Vascular access-related time (VART) was defined as the delay in PPCI that can be attributed to vascular access-related issues. Study end point was the final corrected Thrombolysis In Myocardial Infarction frame count. Multivariable analysis was used to identify predictors of RA failure (RAF: FA + Crossover). We included 241 patients (RA, n = 172; FA, n = 49; Crossover, n = 20). Mean VART was longer in Crossover (10.3 [8.8 to 12.4] minutes), relative to RA (4.1 [3.2 to 5.5] minutes) and FA (4.6 [3.4 to 8.4] minutes, p <0.001). A similar situation was found for time-to-first device (Crossover 22.5 [20.3 to 32.0], RA 15.0 [12.0 to 19.8]; FA 17.9 [13.5 to 22.3] minutes, p <0.001) and total procedure time (Crossover 60.3 [51.6 to 71.5], RA 46.8 [38.1 to 59.7], FA 52.3 [41.9 to 74.7] minutes, p <0.001). No differences in corrected Thrombolysis In Myocardial Infarction frame count were observed (Crossover 26 [18 to 32] frames, RA 24 [18 to 32] frames, FA 25 [16 to 34] frames, p = 0.625). Killip class IV (odds ratio [OR] 3.628, 95% confidence interval [CI] 1.098 to 11.981, p = 0.035), cardiopulmonary resuscitation before arrival (OR 3.572, 95% CI 1.028 to 12.407, p = 0.045), and glomerular filtration rate (OR 0.861, 95% CI 0.758 to 0.978, p = 0.021) were independent predictors of RA failure. In conclusion, in the setting of PPCI, radial-to-FA crossover can lead to VART delays that do not affect angiographic outcomes, in comparison with successful RA.

Prognostic impact of the residual SYNTAX score on in-hospital outcomes in patients undergoing primary percutaneous coronary intervention

This study sought to assess the impact of residual coronary artery disease (CAD), using the residual SYNTAX score (rSS), on in‐hospital outcomes after primary percutaneous intervention (PPCI). The study also aimed to determine independent predictors for high rSS. Residual CAD has been associated with worsened prognosis in patients undergoing PCI for non‐ST acute coronary syndromes. The rSS is a systematic angiographic score that measures the extent and complexity of residual CAD after PCI.

Collectively Operated Fellow-Initiated Research as a Novel Teaching Model to Bolster Interest and Increase Proficiency in Academic Research

Research is a core aspect of training in academic medicine, but fellows face many challenges thwarting their ability to perform clinically meaningful projects. The concept of a multicentre clinical trial collectively operated by fellows, and integrated longitudinally into training, has never been described. In this article, the authors expose the key principles of Collectively Operated Fellow-Initiated Research (COFIR) that they put in place. The aim of COFIR is to introduce a cohort of fellows to the career of clinician-scientists by conducting a longitudinal research project integrated into the curriculum of their clinical fellowship at a level they would not have access to as single individuals. First, fellows must formulate the research hypothesis to generate a patient-oriented research idea that resonates with a large group of trainees. Second, fellows must be actively involved in the multifaceted aspects of research under the mentorship of clinical scientists. Third, fellows must document and disseminate the newly acquired methodological know-how. Finally, fellows must put the safety of patients above any other consideration. Examples of how these principles were applied in a research project are provided in this article; it represents a call to action for fellows to collectively contribute to the production of significant medical research.

Bioresorbable Vascular Scaffold During ST-Elevation Myocardial Infarction: A Systematic Review.

BACKGROUND The bioresorbable vascular scaffold (BVS) represents a novel technology designed to overcome the long-term limitations of metallic coronary stent implantation in percutaneous coronary intervention. In this context, primary percutaneous coronary intervention in ST-elevation myocardial infarction (STEMI) could be a preferred scenario for BVS implantation. Nevertheless, data on efficacy and safety are lacking in this specific subset of patients. METHODS We conducted a systematic review to examine the safety and efficacy of BVS use in STEMI patients. We searched PubMed, EMBASE, and the Cochrane Library through June 2016 for studies that included outcome data for BVS implantation in STEMI patients. Outcomes of interest included cardiac death, myocardial infarction, scaffold thrombosis, target lesion revascularization, restenosis, and composite end points. RESULTS We identified 9 eligible articles, which included 1 randomized controlled trial and 8 cohort studies (5 controlled), for a total of 846 patients. These studies varied in size (11-290) and follow-up duration (1-24 months). The incidence of major cardiac events ranged from 1.1% to 13%, with no statistically significant difference between BVS and control groups in studies that included a comparison group. Although there was a trend toward an increase in scaffold thrombosis in the largest controlled registries, no statistically significant increase was found. CONCLUSIONS Current clinical data are scarce, but suggest that BVS might represent a reasonable alternative to drug-eluting stents in STEMI patients. The lack of large randomized controlled trials with extended follow-up periods and the scaffold thrombosis signal are limiting factors for widespread use before additional large-scale trials are available.

Clinical outcomes of bioresorbable vascular scaffold to treat all-comer patients. Are patients with acute coronary syndrome better candidate for bioresorbable vascular scaffold?

BACKGROUND Scaffold thromboses (ST) and adverse events and have been associated with bioresorbable vascular scaffolds (BVS) at long-term, but their mechanism remains unclear. We sought to evaluate patient and lesion characteristics associated with mid- to long-term outcomes in patients treated with BVS. METHODS This is an observational single-center, single-arm, retrospective study evaluating the performance of BVS in an all-comer population, including complex lesions (chronic total occlusions, long lesions), small vessels, and acute coronary syndromes (ACS). RESULTS From May 2013 to June 2015, we included 482 patients (580 lesions) that were treated with BVS implantation including 71.2% treated for ACS in the present analysis. Mean follow-up period was 816.2 ± 242.6 days. The primary endpoint was device oriented cardiac events (DOCE), defined as a composite of target-lesion revascularization (TLR), ST, target vessel myocardial infarction (TVMI) and cardiac death. Using Kaplan-Meier methods, the DOCE and ST rates at 36 months were 9.4% and 2.3%, respectively. No ST occurred between 2 and 3 years and ST occurred after 3 years, in one patient. Using multivariate analysis, ACS was the only significant predictor of lower rates of DOCE (p = 0.04, HR: 0.47, 95% CI: 0.23-0.96). CONCLUSIONS In this large all-comers real-world cohort, lesions treated with BVS had non-negligible rates of DOCE and ST, in line with previous published randomized trials. The occurrence of very late event was very low after 24 months. ACS patients had lower rates of DOCE.