Association between mid-term worsening renal function and mortality after transcatheter aortic valve replacement in patients with chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD), acute kidney injury (AKI) and worsening renal function at 30 days after transcatheter aortic valve replacement (TAVR) portend poor outcomes. We sought to evaluate the association between worsening renal function at 3-6 months and mortality among patients with baseline renal dysfunction undergoing TAVR. METHODS: This is a retrospective study of patients with glomerular filtration rate (GFR) < 60 ml/min undergoing TAVR between June 2011 and March 2019 at the Regional Cardiac Catheterization Lab at Kaiser Permanente Los Angeles. Worsening renal function at 3-6 months post-TAVR was defined as: increase in serum creatinine >1.5 times compared to baseline, absolute increase of ≥0.3 mg/dl, or initiation of dialysis. RESULTS: Of 683 patients reviewed, 176 were included in the analysis (median age 84 [IQR 79-88] years, 56% female). Of these, 27 (15.3%) had worsening renal function. AKI post-TAVR (OR 2.9, 95% CI 1.1-7.4, p = .03) and transfusion of ≥4 units red blood cells (OR 8.4, 95% CI 1.2-59, p = .03) were independent predictors of worsening renal function. Worsening renal function increased risk for mortality (HR 2.2, 95% CI 1.17-4.27, p = .015) at a median follow-up of 691 days. Those with improved/stable function with baseline GFR < 60 ml/min had comparable mortality risk to those with baseline GFR ≥ 60 ml/min (18% vs. 16.5%; HR 1.1, 95% CI 0.72-1.75, p = .62). CONCLUSION: Among patients with baseline renal dysfunction, only 15% developed worsening renal function at 3-6 months after TAVR, which was associated with increased mortality. Predictors for worsening renal function include AKI and blood transfusions. Preventative measures peri-procedurally and continued monitoring post-discharge are warranted to improve outcomes.

The role of neighborhood disadvantage in predicting mortality in patients after transcatheter aortic valve replacement.

BACKGROUND: Neighborhoods have a powerful impact on health. Prior investigations into disparities associated with transcatheter aortic valve replacement (TAVR) have focused on race and access to the procedure. We sought to investigate the role of neighborhood disadvantage on mortality post-TAVR. METHODS: Patients who underwent TAVR at Kaiser Permanente Los Angeles Medical Center between June, 2011 and March, 2019 were evaluated. Neighborhood disadvantage was defined using the area deprivation index, an established and validated index that considers multiple socioeconomic metrics. Cutoffs used for disadvantage were national percentile ≥25% and state decile ≥6. Cox proportional hazards regression analysis was used to assess outcomes. RESULTS: A total of 668 patients (age 82.1 ± 7.5 years, 49% female) were included, of which 215 (32.2%) were from disadvantaged neighborhoods by state decile, and 167 (25%) by national percentile. At a median follow-up of 18.8 months (interquartile range 8.7-36.5 months), neighborhood disadvantage was independently associated with increased all-cause mortality (National percentile: hazard ratio [HR] 1.91, 95% confidence interval [CI] 1.35-2.69; state decile: HR 1.68, 95% CI 1.21-2.34). On propensity scored analysis, neighborhood disadvantaged remained independently associated with increased all-cause mortality (National percentile: IPTW HR 1.86, 95% CI 1.52-2.28, PSM HR 1.67, 95% CI 1.11-2.51; state decile: IPTW HR 1.55, 95% CI 1.26-1.91, PSM HR 2.0, 95% CI 1.33-2.99). CONCLUSION: Living in a disadvantaged neighborhood was independently associated with increased mortality post-TAVR on multivariate and propensity score matched analysis. Further investigations into the role of neighborhood disadvantage are needed to address disparities and improve outcomes post-TAVR.

Trends in statin utilization among adults with severe peripheral artery disease including critical limb ischemia in an integrated healthcare delivery system.

Evidence suggests that statin therapy in patients with peripheral artery disease (PAD) is beneficial yet use remains suboptimal. We examined trends in statin use, intensity, and discontinuation among adults aged ⩾ 40 years with incident severe PAD and a subset with critical limb ischemia (CLI) between 2002 and 2015 within an integrated healthcare delivery system. Discontinuation of statin therapy was defined as the first 90-day gap in treatment within 1 year following PAD diagnosis. We identified 11,059 patients with incident severe PAD: 31.1% (n = 3442) with CLI and 68.9% (n = 7617) without CLI. Mean (SD) age was 68.6 (11.3) years, 60.5% were male, 54.2% white, 23.2% Hispanic, and 16.2% black. Statin use in the year before diagnosis increased from 50.4% in 2002 to 66.0% in 2015 (CLI: 43.7% to 68.0%; without CLI: 53.1% to 64.2%, respectively). The proportion of patients on high-intensity statins increased from 7.3% in 2002 to 41.9% in 2015 (CLI: 7.2% to 39.4%; without CLI: 7.4% to 44.2%, respectively). Of the 40.5% (n = 4481) who were not on a statin in the year before diagnosis, 13.5% (n = 607) newly initiated therapy within 1 month (CLI: 10.1% (n = 150); without CLI: 15.3% (n = 457)). Following diagnosis, 12.5% (n = 660) discontinued statin therapy within 1 year (CLI: 15.5% (n = 202); without CLI: 11.5% (n = 458)). Although use of statins increased from 2002 to 2015, a substantial proportion of the overall PAD and CLI subpopulation remained untreated with statins, representing a significant treatment gap in a population at high risk for cardiovascular events and adverse limb outcomes.

Open Versus Endovascular or Hybrid Thoracic Aortic Aneurysm Repair.

Thoracic aortic aneurysms are associated with significant morbidity and mortality. There are multiple underlying etiologies, including genetic abnormalities, that have important implications in their natural history. The variable histologic, anatomic, and clinical presentations necessitate careful consideration of available treatment options. Surgical repair of these aneurysms has been the mainstay of treatment; however, these approaches can carry a relatively high risk of morbidity and mortality. Endovascular approaches have now become first-line therapy for descending thoracic aneurysms, and with advancements in graft technology, endovascular approaches are being increasingly employed for hybrid repairs of the aortic arch and even the ascending aorta. However, to date, clinical outcomes from randomized trials and long-term follow-up are limited. As technology continues to advance, there is the potential for further integration of surgical and endovascular treatments so that patients have the best opportunity for a favorable outcome.

Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial.

BACKGROUND: The administration of intravenous fluid remains the cornerstone treatment for the prevention of contrast-induced acute kidney injury. However, no well-defined protocols exist to guide fluid administration in this treatment. We aimed to establish the efficacy of a new fluid protocol to prevent contrast-induced acute kidney injury. METHODS: In this randomised, parallel-group, comparator-controlled, single-blind phase 3 trial, we assessed the efficacy of a new fluid protocol based on the left ventricular end-diastolic pressure for the prevention of contrast-induced acute kidney injury in patients undergoing cardiac catheterisation. The primary outcome was the occurrence of contrast-induced acute kidney injury, which was defined as a greater than 25% or greater than 0·5 mg/dL increase in serum creatinine concentration. Between Oct 10, 2010, and July 17, 2012, 396 patients aged 18 years or older undergoing cardiac catheterisation with an estimated glomerular filtration rate of 60 mL/min per 1·73 m(2) or less and one or more of several risk factors (diabetes mellitus, history of congestive heart failure, hypertension, or age older than 75 years) were randomly allocated in a 1:1 ratio to left ventricular end-diastolic pressure-guided volume expansion (n=196) or the control group (n=200) who received a standard fluid administration protocol. Four computer-generated concealed randomisation schedules, each with permuted block sizes of 4, were used for randomisation, and participants were allocated to the next sequential randomisation number by sealed opaque envelopes. Patients and laboratory personnel were masked to treatment assignment, but the physicians who did the procedures were not masked. Both groups received intravenous 0·9% sodium chloride at 3 mL/kg for 1 h before cardiac catheterisation. Analyses were by intention to treat. Adverse events were assessed at 30 days and 6 months and all such events were classified by staff who were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT01218828. FINDINGS: Contrast-induced acute kidney injury occurred less frequently in patients in the left ventricular end-diastolic pressure-guided group (6·7% [12/178]) than in the control group (16·3% [28/172]; relative risk 0·41, 95% CI 0·22-0·79; p=0·005). Hydration treatment was terminated prematurely because of shortness of breath in three patients in each group. INTERPRETATION: Left ventricular end-diastolic pressure-guided fluid administration seems to be safe and effective in preventing contrast-induced acute kidney injury in patients undergoing cardiac catheterisation. FUNDING: Kaiser Permanente Southern California regional research committee grant.

Two-year results from Onyx ONE clear in patients with high bleeding risk on one-month DAPT with and without intracoronary imaging.

BACKGROUND: Patients with high bleeding risk (HBR) are often treated with abbreviated dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) to reduce bleeding risk, however this strategy is associated with an increase in ischemic events, especially if the acute PCI result is suboptimal. We compared clinical outcomes among patients with HBR treated with 1-month DAPT who underwent intravascular ultrasound (IVUS)- or optical coherence tomography (OCT)-guided PCI versus those who underwent angiography-guided PCI without intravascular imaging. METHODS: The Onyx ONE Clear study includes patients with HBR from the Onyx ONE US/Japan and Onyx ONE randomized studies who were treated with the Resolute Onyx zotarolimus-eluting stent. The primary endpoint was the composite of cardiac death (CD) or myocardial infarction (MI) between 1 month and 2 years after PCI. Propensity-score adjustments and matching were performed for differences in baseline and procedural characteristics between groups. RESULTS: Among the 1507 patients in Onyx ONE Clear, 271 (18.0 %) had IVUS or OCT used during PCI (Imaging-guided group) and 1236 (82.0 %) underwent Angiography-guided PCI (Angio-guided group). Imaging-guided patients were less likely to present with atrial fibrillation, acute coronary syndrome, and left ventricle ejection fraction ≤35 %. Conversely, Imaging-guided patients were more likely to have complex (ACC/AHA type B2/C), longer, and heavily calcified lesions. Between 1 month and 2 years, the composite rate of CD or MI was similar between Imaging-guided and Angio-guided patients (9.9 % vs. 12.4 %, P = 0.33). There was also no difference between groups after adjustment; (P = 0.56). However, CD was significantly lower among Imaging-guided patients (2.7 % vs. 6.1 %, P = 0.048). There were no between-group differences in MI or stent thrombosis. Propensity score matching results were similar. CONCLUSION: Despite higher lesion complexity, using intravascular imaging guidance for PCI between 1-month and 2-years follow-up had comparable outcomes with angiographic guidance alone in patients with HBR treated with 1-month DAPT. (ClinicalTrials.gov: Identifier: NCT03647475 and NCT03344653). NON-STANDARD ABBREVIATIONS AND ACRONYMS: BARC: Bleeding Academic Research Consortium; DAPT: dual antiplatelet therapy; DES: drug-eluting stent; HBR: high bleeding risk; IVUS: intravascular ultrasound; OCT: optical coherence tomography; SAPT: single antiplatelet therapy.

Controversies in the use & implementation of drug-eluting stent technology.

The introduction of drug eluting stents has resulted in dramatic reductions in the rates of restenosis and the need for repeat revascularization. In the last several years, concern has been raised regarding the long-term safety of this technology, particularly in the area of late restenosis and stent thrombosis. The development of newer anti-restenotic drug coatings, biodegradable polymers and even completely bioabsorbable stents offer the potential to address these limitations. Additional questions that have recently come to the forefront include the optimal duration of dual antiplatelet therapy, the use of platelet reactivity assays and genetic testing and drug eluting stent use in the treatment of acute myocardial infarction. This article will attempt to address these and other areas of controversy in the use and implementation of drug eluting stents.

The Prognostic Utility of Invasive Right Heart Catheterization in Patients Prior to Transcatheter Aortic Valve Replacement.

INTRODUCTION: Invasive right heart catheterization (RHC) provides valuable prognostic information in cases of severe aortic stenosis, but is not done routinely prior to transcatheter aortic valve replacement (TAVR). Therefore, we sought to investigate the prognostic utility of pre-TAVR RHC for assessing outcomes post TAVR. METHODS: This is a single-center, retrospective study of patients who underwent RHC prior to TAVR between June 2011 and March 2019. We evaluated abnormalities in the following variables as predictors of poor outcomes post TAVR: pulmonary capillary wedge pressure (PCWP), systolic pulmonary artery pressure (PASP), mixed venous oxygen saturation (MVO2), right ventricular stroke work index (RVSWI), and right atrial pressure (RAP). Cox proportional hazard regression models were used to assess the primary composite outcome of all-cause mortality and hospitalization for heart failure. RESULTS: A total of 522 patients (mean age, 83.5 ± 4.5 years; 49.4% women) with complete invasive hemodynamic data were included. At a median follow-up of 529.5 days, there were 127 deaths and 59 heart failure hospitalizations. On multivariate analysis, PCWP ≥15 mm Hg (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.02-2.07), PASP ≥50 mm Hg (HR, 1.66; 95% CI, 1.17-2.36), MVO2 ≤60% (HR, 1.42; 95% CI, 1.01-1.98), RVSWI ≥12 g•m/m²/beat (HR, 1.40; 95% CI, 1.004-1.94), and RAP ≥10 mm Hg (HR, 1.66; 95% CI, 1.09-2.51) were independent predictors of death or heart failure hospitalization. CONCLUSIONS: Preprocedural invasive RHC provides useful prognostic information. A comprehensive invasive hemodynamic assessment should be considered for risk stratification in patients undergoing TAVR.

Readmission in Patients With ST-Elevation Myocardial Infarction in 4 Age Groups (<45, >45 to <60, 60 to <75, and >75).

The incidence of ST-elevation myocardial infarction (STEMI) among younger adults is increasing due to an increased prevalence of cardiometabolic risk factors. Readmissions after STEMI in young patients could lead to substantial health care costs and a significant burden on health care resources. Although STEMI readmissions are well studied in elderly patients, limited data are available regarding readmissions after STEMI in young patients and the etiologies remain poorly understood. Because younger patients with STEMI have different sociodemographic profiles th;an older patients with STEMI, one would postulate that the risk factors for readmissions in young patients would differ from that reported in the older patients with STEMI. We performed a contemporary nationwide study using the 2016 and 2017 Nationwide Readmissions Database to identify patterns of readmissions after STEMI in the young adult population. Our analysis of the Nationwide Readmissions Database revealed a total of 243,747 hospitalizations for STEMI between 2016 and 2017. Readmission rates demonstrated a steady increase from discharge, increasing to 7.8% at 30 days and 10.3% at 60 days before relatively plateauing at 12.1% at 90 days. Cardiovascular etiologies were the most common cause of readmission (53.6%). After multivariable analysis, development of cardiogenic shock (adjusted odds ratio 1.48, 95% confidence interval 1.11 to 1.97; p = 0.008) and acute renal failure (adjusted odds ratio 1.46, 95% confidence interval 1.14 to 1.87; p = 0.003) during the index admission were associated with significantly higher rates of readmission. In conclusion, close monitoring in young patients who presented with STEMI and concomitant with cardiogenic shock or acute renal failure, and possibly, aggressive therapy during index admission may be needed. However, this population may be heterogeneous and further research is needed.

Comparison of a Single Versus Double Perclose Technique for Percutaneous Transfemoral Transcatheter Aortic Valve Replacement.

BACKGROUND: The optimal strategy for arterial closure in percutaneous transfemoral transcatheter aortic valve replacement (TF-TAVR) remains under debate. METHODS: Single-center, prospective, observational study of consecutive patients undergoing TF-TAVR between March 2018 and December 2019 who underwent closure with an upfront single vs double Perclose device. Device success, access-site vascular, and bleeding complications were defined according to the Valvular Academic Research Consortium (VARC)-2 criteria. Inverse-probability of treatment weighting (IPTW) was used to balance baseline characteristics between groups. RESULTS: A total of 241 patients (mean age, 81.4 ± 8.5 years, 47% women) were included, of which 127 underwent an upfront single-Perclose (SP) strategy and 114 underwent an upfront double-Perclose (DP) strategy. Fifty-six percent of patients were treated with a CoreValve (Medtronic). The SP group was less likely to be on dialysis and on aspirin, but were more likely to receive a CoreValve, with larger valve sizes and larger delivery sheaths. Baseline characteristics were well balanced after IPTW adjustment. Device success rate was comparable between groups (96% in the SP group vs 93% in the DP group; P=.39). The SP technique was associated with fewer vascular complications (8.7% in the SP group vs 26.3% in the DP group; P<.01; IPTW relative risk [RR], 0.34; 95% confidence Interval [CI], 0.16-0.71) and bleeding complications (2.4% in the SP group vs 12.3% in the DP group; P<.01; IPTW RR, 0.21; 95% CI, 0.06-0.76) compared with the DP technique. There were no differences in 30-day mortality. CONCLUSION: An upfront SP technique is equally efficacious and not associated with increased vascular and bleeding complications compared with an upfront DP technique in patients undergoing percutaneous TF-TAVR.

Predictors of conduction recovery after permanent pacemaker implantation following transcatheter aortic valve replacement.

PURPOSE: Conduction disturbances after transcatheter aortic valve replacement (TAVR) requiring pacemaker (PPM) implantation are a known complication and may be reversible. Therefore, we sought to evaluate the incidence and predictors for atrioventricular (AV) conduction recovery after TAVR. METHODS: A single-center, retrospective study of patients undergoing PPM implantation for conduction disorders after TAVR between June 2011 and March 2019. Conduction recovery was defined as ≤ 1% ventricular pacing (VP) on follow-up PPM interrogation. RESULTS: A total of 110 patients (mean age 83.6 ± 6.6 years, 46.8% female) were included. At a median follow-up of 438 days (interquartile range [IQR] 111-760 days), 35 patients (32%) had conduction recovery, with 50% of these occurring within the first 6 months. On multivariate analysis, predictors of conduction recovery include female sex (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.01-6.4, p = 0.048), non-VP/non-complete heart block rhythm immediately post-TAVR (HR 5.2, 95% CI 1.5-18.1, p = 0.011), normal sinus rhythm 7 days post-TAVR (HR 3.9, 95% CI 1.7-9.2, p = 0.002), and smaller valve size (mm) (HR 0.81, 95% CI 0.7-0.996, p = 0.045). Significant narrowing of the QRS and resolution of new-onset left bundle branch block within 1 month post-TAVR occurred in those with conduction recovery on PPM interrogation. CONCLUSIONS: One-third of patients receiving new PPM implantation have conduction recovery after TAVR, with 50% occurring within the first 6 months. Patient gender, valve size, and rhythm on serial ECGs after TAVR can help identify patients that may recover AV conduction. A conservative approach rather than immediate PPM implantation may be considered in these patients.

Implantable defibrillators improve survival in end-stage renal disease: results from a multi-center registry.

BACKGROUND: Small retrospective analyses suggest that end-stage renal disease (ESRD) patients do not obtain as much of a survival benefit from an implantable cardioverter-defibrillator (ICD) as non-ESRD patients do. We aimed to assess the survival effect of an ICD in ESRD patients with left ventricular dysfunction. METHODS: Data from two registries identified ESRD patients with an ICD and ESRD patients with left ventricular dysfunction (defined as ejection fraction <0.35). Cox proportional hazards regression was performed, including certain predefined covariates to assess the effect of an ICD on survival. RESULTS: Overall survival in the full cohort was a median of 4.7 years with 20 deaths in the ICD group and 29 deaths in the no-ICD group. The median survival in the ICD group was 8.0 years and 3.1 years in the no-ICD group. Crude analysis showed a better survival in the ICD group as compared to the no-ICD group (p = 0.016). The multivariable analysis confirmed that the ICD group had significantly less all-cause mortality compared to the no-ICD group (HR: 0.40; 95% CI: 0.19, 0.82; p = 0.013). CONCLUSION: An ICD is associated with a higher survival in ESRD patients with left ventricular dysfunction. This result merits further study in a larger cohort of patients.

Racial/ethnic differences in the prevalence of atrial fibrillation among older adults--a cross-sectional study.

BACKGROUND: Atrial fibrillation affects 4% to 8% of individuals over 60 years of age based on studies of predominantly white populations, whether this is true among nonwhite individuals is not clear. This study was undertaken to define racial/ethnic differences in atrial fibrillation prevalence among a large community cohort. METHODS: This is a cross-sectional study. In 2008, there were 430,317 members aged 60 years or older in a large California health maintenance organization. By searching International Classification of Diseases, Ninth Revision codes and electronic electrocardiographic archives, we identified all members in this age group with primary, nonvalvular atrial fibrillation. Race/ethnicity data were assigned using health plan enrollment, service utilization, Asian/Hispanic surname and geocoding methods, and was available for 80.5% of members (79.8% of non-atrial fibrillation and 92% of atrial fibrillation), 99% of which were white, black, Asian, or Hispanic. We assessed the age- and gender-specific atrial fibrillation prevalence rates for each racial/ethnic group. The effect of race/ethnicity on atrial fibrillation was analyzed with logistic regression methods adjusting for potential confounders. RESULTS: The overall atrial fibrillation prevalence was 5.3%. Among members with assigned race/ethnicity data, the prevalence among whites, blacks, Asians, and Hispanics was 8.0%, 3.8%, 3.9%, and 3.6%, respectively. The adjusted odds ratios (95% confidence intervals) of atrial fibrillation among blacks, Asians, and Hispanics with whites as referent were 0.49 (0.47-0.52), 0.68 (0.64-0.72), and 0.58 (0.55-0.61), respectively. CONCLUSIONS: Atrial fibrillation is less prevalent in older nonwhite individuals than whites. White race/ethnicity is associated with significantly greater odds for atrial fibrillation compared to blacks, Asians, and Hispanics, after adjusting for comorbidities associated with the development of atrial fibrillation.

Advances in percutaneous coronary intervention.

Initially developed more than 30 years ago as simple balloon-based dilatation for focal coronary stenoses, the introduction of the coronary stent allowed percutaneous coronary intervention (PCI) to be applied to most patients with coronary artery disease. PCI improves quality of life by relieving angina in patients with stable coronary artery disease and can be life saving in patients with extensive ischemia and acute coronary syndromes. The safety of the PCI procedure has been enhanced significantly by the appropriate application of adjunctive pharmacotherapy, most importantly antithrombotic and antiplatelet agents. The advent of drug-eluting stents has significantly prolonged the durability of PCI. The safety and efficacy of PCI continue to evolve with the development of next-generation stents and safer and improved pharmacologic agents. An extensive evidence base of randomized clinical trials has established PCI as an important strategy with a pivotal role in the management of patients with coronary artery disease.

Racial/Ethnic differences in ischemic stroke rates and the efficacy of warfarin among patients with atrial fibrillation.

BACKGROUND AND PURPOSE: Warfarin reduces stroke risk in studies of predominantly white patients with atrial fibrillation (AF). Whether nonwhites also have lower rates of stroke while treated with warfarin is unclear. METHODS: A multiethnic stroke-free cohort hospitalized with nonrheumatic AF was identified in a large health maintenance organization. Stroke risk factors (advanced age, diabetes, hypertension, and heart failure), warfarin use, and anticoagulation intensity were assessed. Crude ischemic stroke rates were calculated by Poisson regression for each group while using and not using warfarin. Cox proportional hazard models were constructed to assess the independent effect of race/ethnicity on ischemic stroke. RESULTS: Between 1995 and 2000, we identified 18867 AF hospitalizations (78.5% white, 8% black, 9.5% Hispanic, and 3.9% Asian). Over the course of 63204 person-years follow-up (median, 3.3 years), 1226 ischemic strokes were identified. The percent-time on warfarin did not differ by race/ethnicity. The median percent-time on warfarin that international normalized ratio was 2 to 3 was 54.5% overall, but it was lower in blacks at 47.8%, whereas the other groups had a rate of approximately 54%. The rate ratios (95% CI) of ischemic stroke with warfarin compared to without warfarin for whites, blacks, Hispanics, and Asians were 0.79 (0.68 to 0.90), 0.92 (0.65 to 1.30), 0.71 (0.48 to 1.05), and 0.65 (0.34 to 1.23), respectively. CONCLUSIONS: In this cohort, we did not observe a statistically significant lower rate of stroke with warfarin therapy among nonwhites (in particular blacks) with previous AF hospitalizations. The relatively small numbers of nonwhites renders our estimates less than precise and should be interpreted with caution.

Effect of race/ethnicity on the efficacy of warfarin: potential implications for prevention of stroke in patients with atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice. It affects approximately 6% of persons over 65 years of age and is independently associated with a 4- to 5-fold higher risk of ischaemic stroke and a 2-fold higher risk of death. Randomized controlled trials have shown that treatment with adjusted-dose oral vitamin K antagonists (primarily warfarin with a target international normalized ratio [INR] of 2.0-3.0) reduces the relative risk of ischaemic stroke by two-thirds (an approximately 3% reduction in annual absolute risk), but is associated with a 0.2% excess annual absolute risk of intracranial haemorrhage (ICH). However, in 'real world' studies, the risk reductions in ischaemic stroke with warfarin have been significantly lower (25-50% relative risk reduction) than in selected trial samples. Moreover, more than 90% of patients enrolled in the sentinel trials were White/European. This raises the question of whether the beneficial results of warfarin can be extrapolated to persons of colour. Important differences in stroke risk profile and responsiveness to warfarin exist across racial/ethnic groups, such that one cannot assume a priori that there is a net benefit of warfarin therapy for AF patients of all racial/ethnic groups.Among patients with ischaemic stroke, AF is more likely to be implicated as the cause of stroke in the White population than in other racial/ethnic groups. Furthermore, AF may be a stronger predictor of ischaemic stroke among the White population than in Black or Hispanic/Latino populations. Approximately one-third of strokes in AF patients are noncardioembolic. Warfarin has been shown to be ineffective in preventing recurrent noncardioembolic strokes. Many persons of colour with AF have other risk factors that predispose them to noncardioembolic stroke, which may partially explain why warfarin has been reported to be less efficacious in preventing strokes in non-White patients with AF, even after adjustment for co-morbidities and anticoagulation monitoring. Notably, the background incidence of ICH is higher in Black, Hispanic and Asian patients than in White patients. Any greater than expected increases in bleeding secondary to anticoagulation may potentially offset any benefit gained from cardioembolic stroke reduction, although this has not been fully resolved.Finally, there are racial/ethnic differences in the prevalence of certain polymorphisms in genes that influence warfarin pharmacokinetics and pharmacodynamics (e.g. cytochrome P450 2C9 and vitamin K epoxide reductase). The Asian population generally appear to require the lowest daily dose of warfarin to maintain a given INR target, with the White population requiring an intermediate daily dose and the Black population requiring the highest daily dose. These differences must be taken into account when administering warfarin in order to minimize the risk of under- or over-anticoagulation.In summary, warfarin is highly effective in preventing ischaemic strokes in White patients with AF at a modestly higher risk of ICH. Whether the same net clinical benefit extends to persons of colour is unproven. Given the rapidly changing demographic nationally and internationally, additional research is needed to resolve this important question.

Sodium bicarbonate vs sodium chloride for the prevention of contrast medium-induced nephropathy in patients undergoing coronary angiography: a randomized trial.

CONTEXT: Sodium bicarbonate has been suggested as a possible strategy for prevention of contrast medium-induced nephropathy, a common cause of renal failure associated with prolonged hospitalization, increased health care costs, and substantial morbidity and mortality. OBJECTIVE: To determine if sodium bicarbonate is superior to sodium chloride for preventing contrast medium-induced nephropathy in patients with moderate to severe chronic kidney dysfunction who are undergoing coronary angiography. DESIGN, SETTING, AND PATIENTS: Randomized, controlled, single-blind study conducted between January 2, 2006, and January 31, 2007, and enrolling 353 patients with stable renal disease who were undergoing coronary angiography at a single US center. Included patients were 18 years or older and had an estimated glomerular filtration rate of 60 mL/min per 1.73 m(2) or less and 1 or more of diabetes mellitus, history of congestive heart failure, hypertension, or age older than 75 years. INTERVENTIONS: Patients were randomized to receive either sodium chloride (n = 178) or sodium bicarbonate (n = 175) administered at the same rate (3 mL/kg for 1 hour before coronary angiography, decreased to 1.5 mL/kg per hour during the procedure and for 4 hours after the completion of the procedure). MAIN OUTCOME MEASURE: The primary end point was a 25% or greater decrease in the estimated glomerular filtration rate on days 1 through 4 after contrast exposure. RESULTS: Median patient age was 71 (interquartile range, 65-76) years, and 45% had diabetes mellitus. The groups were well matched for baseline characteristics. The primary end point was met in 13.3% of the sodium bicarbonate group and 14.6% of the sodium chloride group (relative risk, 0.94; 95% confidence interval, 0.55-1.60; P = .82). In patients randomized to receive sodium bicarbonate vs sodium chloride, the rates of death, dialysis, myocardial infarction, and cerebrovascular events did not differ significantly at 30 days (1.7% vs 1.7%, 0.6% vs 1.1%, 0.6% vs 0%, and 0% vs 2.2%, respectively) or at 30 days to 6 months (0.6% vs 2.3%, 0.6% vs 1.1%, 0.6% vs 2.3%, and 0.6% vs 1.7%, respectively) (P > .10 for all). CONCLUSION: The results of this study do not suggest that hydration with sodium bicarbonate is superior to hydration with sodium chloride for the prevention of contrast medium-induced nephropathy in patients with moderate to severe chronic kidney disease who are undergoing coronary angiography. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00312117.

Effect of a Contrast Modulation System on Contrast Media Use and the Rate of Acute Kidney Injury After Coronary Angiography.

OBJECTIVES: The aim of the AVERT (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN) trial was to test the efficacy of the AVERT system to reduce the contrast media volume (CMV) used during coronary angiographic procedures without impairing image quality and to prevent contrast-induced acute kidney injury (CI-AKI) in patients at risk for CI-AKI. BACKGROUND: CI-AKI is a common complication of percutaneous coronary procedures, associated with increased morbidity and mortality. The AVERT system alters the coronary injection pressure profile by diverting contrast away from the patient during coronary injection. METHODS: The AVERT trial was a prospective, multicenter, 1:1 randomized clinical trial in 578 subjects with either baseline estimated glomerular filtration rate 20 to 30 ml/min/1.73 m2 or estimated glomerular filtration rate 30 to 60 ml/min/1.73 m2 and at least 2 additional risk factors for CI-AKI. Patients undergoing coronary angiography with planned or possible percutaneous coronary intervention (PCI) were randomized to hydration plus the AVERT system (n = 292) or hydration only (n = 286). The primary effectiveness endpoints were: 1) the total CMV used; and 2) the incidence of CI-AKI, defined as a ≥0.3 mg/dl increase in serum creatinine within 5 days post-procedure. RESULTS: Patient demographics were well balanced between the groups, with mean baseline serum creatinine of 1.6 ± 0.4 mg/dl and 64.9% patients with diabetes mellitus. PCI was performed in 42.2% of procedures, with coronary angiography in the remainder. Use of AVERT resulted in a 15.5% relative reduction in CMV overall (85.6 ± 50.5 ml vs. 101.3 ± 71.1 ml; p = 0.02) and a 22.8% relative reduction in CMV among PCI patients (114 ± 55 ml vs. 147 ± 81 ml; p = 0.001). The maximum relative reduction in CMV was 46% (124 ± 48 ml vs. 232 ± 97 ml; p = 0.01) when ≥3 lesions were treated. There were no differences in the rates of CI-AKI (27.0% vs. 26.6%; p = 0.70) between the study groups. CONCLUSIONS: Use of the AVERT system was feasible and safe, with acceptable image quality during coronary angiography and PCI. AVERT significantly reduced CMV, with the extent of CMV reduction correlating with procedural complexity. No significant differences in CI-AKI were observed with AVERT in this trial. (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN [AVERT]; NCT01976299).

Incidence, mortality, and racial differences in peripartum cardiomyopathy.

There are no large population-based studies on the incidence and prognosis of peripartum cardiomyopathy (PC). Between 1996 and 2005, there were 241,497 deliveries within the Southern California Kaiser healthcare system. Among these, we identified 60 cases of PC by searching for an International Classification of Diseases, Ninth Edition diagnosis of heart failure (HF) and detailed chart review. PC was confirmed if all of the following criteria were satisfied: (1) left ventricular ejection fraction <0.50, (2) met the Framingham criteria for HF, (3) new symptoms of HF or initial echocardiographic diagnosis of left ventricular dysfunction occurred in the month before or in the 5 months after delivery, and (4) no alternative cause of HF could be identified. The overall incidence of PC was 1 in 4,025 deliveries. The incidence in whites, African-Americans, Hispanics, and Asians was 1 of 4,075, 1 of 1,421, 1 of 9,861, and 1 of 2,675 deliveries, respectively. The incidence of PC was greatest in African-Americans, which was 2.9-fold higher compared with whites (p = 0.03) and 7-fold that of Hispanics (p <0.001). With a mean follow-up of 4.7 years, the freedom from all-cause death was 96.7% by the Kaplan-Meier method. In conclusion, this large population-based study highlights important racial differences in the incidence of PC. We observed the lowest incidence of PC in Hispanics and the highest in African-Americans. Our findings also suggest that the current mortality associated with PC may be less than reported in older series, perhaps because of the high utilization of modern HF therapy.