Processes of Care After Hospital Discharge for Survivors of Acute Kidney Injury: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Survivors of acute kidney injury (AKI) are at high risk of adverse outcomes. Monitoring of kidney function, screening for proteinuria, use of statins and renin-angiotensin-aldosterone system (RAAS) inhibitors, and nephrology follow-up among survivors have not been fully characterized. We examined these processes of care after discharge in survivors of hospitalized AKI. STUDY DESIGN: Population-based retrospective cohort study. SETTING & PARTICIPANTS: Adults in Alberta, Canada, admitted to the hospital between 2009 and 2017, then followed from their discharge date until 2019 for a median follow-up of 2.7 years. EXPOSURE: Hospital-acquired AKI diagnostically conforming to Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria for stage 2 or stage 3 disease, or the need for acute dialysis. OUTCOME: Outcomes after hospital discharge included the proportion of participants who had evaluation of kidney function, were seen by a specialist or general practitioner, and received postdischarge prescriptions for recommended medications for chronic kidney disease (CKD). ANALYTICAL APPROACH: Cumulative incidence curves to characterize the proportion of participants who received each process of care outcome within the first 90 days and subsequent 1-year follow-up period after hospital discharge. To avoid risks associated with multiple hypothesis testing, differences were not statistically compared across groups. RESULTS: The cohort (n=23,921) included 50.2% men (n=12,015) with a median age of 68.1 [IQR, 56.9-78.8] years. Within 90 days after discharge, 21.2% and 8.6% of patients with and without pre-existing CKD, respectively, were seen by a nephrologist; 60.1% of AKI survivors had at least 1 serum creatinine measured, but only 25.5% had an assessment for albuminuria within 90 days after discharge; 52.7% of AKI survivors with pre-existing CKD, and 51.6% with de novo CKD were prescribed a RAAS inhibitor within 4-15 months after discharge. LIMITATIONS: Retrospective data were collected as part of routine clinical care. CONCLUSIONS: The proportion of patients receiving optimal care after an episode of AKI in Alberta was low and may represent a target for improving long-term outcomes for this population. PLAIN-LANGUAGE SUMMARY: A study in Alberta, Canada, examined the care received by patients with acute kidney disease (AKI) during hospitalization and after discharge between 2007 and 2019. The results showed that a low proportion of patients with moderate to severe AKI were seen by a kidney specialist during hospitalization or within 90 days after discharge. Fewer than 25% of AKI patients had their kidney function monitored with both blood and urine tests within 90 days of discharge. Additionally, about half of AKI survivors with chronic kidney disease (CKD) were prescribed guideline recommended medications for CKD within 15 months after discharge. There is potential to improve health care delivery to these patients both in hospital and after hospital discharge.

Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial.

BACKGROUND: The SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial showed the safety but not efficacy of the Symplicity system (Medtronic, Santa Rosa, CA, USA) at 6 months follow-up in patients with treatment-resistant hypertension. This final report presents the 36-month follow-up results. METHODS: SYMPLICITY HTN-3 was a single-blind, multicentre, sham-controlled, randomised clinical trial, done in 88 centres in the USA. Adults aged 18-80 years, with treatment-resistant hypertension on stable, maximally tolerated doses of three or more drugs including a diuretic, who had a seated office systolic blood pressure of 160 mm Hg or more and 24 h ambulatory systolic blood pressure of 135 mm Hg or more were randomly assigned (2:1) to receive renal artery denervation using the single electrode (Flex) catheter or a sham control. The original primary endpoint was the change in office systolic blood pressure from baseline to 6 months for the renal artery denervation group compared with the sham control group. Patients were unmasked after the primary endpoint assessment at 6 months, at which point eligible patients in the sham control group who met the inclusion criteria (office blood pressure ≥160 mm Hg, 24 h ambulatory systolic blood pressure ≥135 mm Hg, and still prescribed three or more antihypertensive medications) could cross over to receive renal artery denervation. Changes in blood pressure up to 36 months were analysed in patients in the original renal artery denervation group and sham control group, including those who underwent renal artery denervation after 6 months (crossover group) and those who did not (non-crossover group). For comparisons between the renal artery denervation and sham control groups, follow-up blood pressure values were imputed for patients in the crossover group using their most recent pre-crossover masked blood pressure value. We report long-term blood pressure changes in renal artery denervation and sham control groups, and investigate blood pressure control in both groups using time in therapeutic blood pressure range analysis. The primary safety endpoint was the incidence of all-cause mortality, end stage renal disease, significant embolic event, renal artery perforation or dissection requiring intervention, vascular complications, hospitalisation for hypertensive crisis unrelated to non-adherence to medications, or new renal artery stenosis of more than 70% within 6 months. The trial is registered with ClinicalTrials.gov, NCT01418261. FINDINGS: From Sep 29, 2011, to May 6, 2013, 1442 patients were screened, of whom 535 (37%; 210 [39%] women and 325 [61%] men; mean age 57·9 years [SD 10·7]) were randomly assigned: 364 (68%) patients received renal artery denervation (mean age 57·9 years [10·4]) and 171 (32%) received the sham control (mean age 56·2 years [11·2]). 36-month follow-up data were available for 219 patients (original renal artery denervation group), 63 patients (crossover group), and 33 patients (non-crossover group). At 36 months, the change in office systolic blood pressure was -26·4 mm Hg (SD 25·9) in the renal artery denervation group and -5·7 mm Hg (24·4) in the sham control group (adjusted treatment difference -22·1 mm Hg [95% CI -27·2 to -17·0]; p≤0·0001). The change in 24 h ambulatory systolic blood pressure at 36 months was -15·6 mm Hg (SD 20·8) in the renal artery denervation group and -0·3 mm Hg (15·1) in the sham control group (adjusted treatment difference -16·5 mm Hg [95% CI -20·5 to -12·5]; p≤0·0001). Without imputation, the renal artery denervation group spent a significantly longer time in therapeutic blood pressure range (ie, better blood pressure control) than patients in the sham control group (18% [SD 25·0] for the renal artery denervation group vs 9% [SD 18·8] for the sham control group; p≤0·0001) despite a similar medication burden, with consistent and significant results with imputation. Rates of adverse events were similar across treatment groups, with no evidence of late-emerging complications from renal artery denervation. The rate of the composite safety endpoint to 48 months, including all-cause death, new-onset end-stage renal disease, significant embolic event resulting in end-organ damage, vascular complication, renal artery re-intervention, and hypertensive emergency was 15% (54 of 352 patients) for the renal artery denervation group, 14% (13 of 96 patients) for the crossover group, and 14% (10 of 69 patients) for the non-crossover group. INTERPRETATION: This final report of the SYMPLICITY HTN-3 trial adds to the totality of evidence supporting the safety of renal artery denervation to 36 months after the procedure. From 12 months to 36 months after the procedure, patients who were originally randomly assigned to receive renal artery denervation had larger reductions in blood pressure and better blood pressure control compared with patients who received sham control. FUNDING: Medtronic.

Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial.

BACKGROUND: Renal denervation has been shown to lower blood pressure in the presence of antihypertensive medications; however, long-term safety and efficacy data from randomised trials of renal denervation are lacking. In this pre-specified analysis of the SPYRAL HTN-ON MED study, we compared changes in blood pressure, antihypertensive drug use, and safety up to 36 months in renal denervation versus a sham control group. METHODS: This randomised, single-blind, sham-controlled trial enrolled patients from 25 clinical centres in the USA, Germany, Japan, the UK, Australia, Austria, and Greece, with uncontrolled hypertension and office systolic blood pressure between 150 mm Hg and 180 mm Hg and diastolic blood pressure of 90 mm Hg or higher. Eligible patients had to have 24-h ambulatory systolic blood pressure between 140 mm Hg and less than 170 mm Hg, while taking one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned (1:1) to radiofrequency renal denervation or a sham control procedure. Patients and physicians were unmasked after 12-month follow-up and sham control patients could cross over after 12-month follow-up completion. The primary endpoint was the treatment difference in mean 24-h systolic blood pressure at 6 months between the renal denervation group and the sham control group. Statistical analyses were done on the intention-to-treat population. Long-term efficacy was assessed using ambulatory and office blood pressure measurements up to 36 months. Drug surveillance was used to assess medication use. Safety events were assessed up to 36 months. This trial is registered with ClinicalTrials.gov, NCT02439775; prospectively, an additional 260 patients are currently being randomly assigned as part of the SPYRAL HTN-ON MED Expansion trial. FINDINGS: Between July 22, 2015, and June 14, 2017, among 467 enrolled patients, 80 patients fulfilled the qualifying criteria and were randomly assigned to undergo renal denervation (n=38) or a sham control procedure (n=42). Mean ambulatory systolic and diastolic blood pressure were significantly reduced from baseline in the renal denervation group, and were significantly lower than the sham control group at 24 and 36 months, despite a similar treatment intensity of antihypertensive drugs. The medication burden at 36 months was 2·13 medications (SD 1·15) in the renal denervation group and 2·55 medications (2·19) in the sham control group (p=0·26). 24 (77%) of 31 patients in the renal denervation group and 25 (93%) of 27 patients in the sham control group adhered to medication at 36 months. At 36 months, the ambulatory systolic blood pressure reduction was -18·7 mm Hg (SD 12·4) for the renal denervation group (n=30) and -8·6 mm Hg (14·6) for the sham control group (n=32; adjusted treatment difference -10·0 mm Hg, 95% CI -16·6 to -3·3; p=0·0039). Treatment differences between the renal denervation group and sham control group at 36 months were -5·9 mm Hg (95% CI -10·1 to -1·8; p=0·0055) for mean ambulatory diastolic blood pressure, -11·0 mm Hg (-19·8 to -2·1; p=0·016) for morning systolic blood pressure, and -11·8 mm Hg (-19·0 to -4·7; p=0·0017) for night-time systolic blood pressure. There were no short-term or long-term safety issues associated with renal denervation. INTERPRETATION: Radiofrequency renal denervation compared with sham control produced a clinically meaningful and lasting blood pressure reduction up to 36 months of follow-up, independent of concomitant antihypertensive medications and without major safety events. Renal denervation could provide an adjunctive treatment modality in the management of patients with hypertension. FUNDING: Medtronic.

Polymer-based or Polymer-free Stents in Patients at High Bleeding Risk.

BACKGROUND: Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS: In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS: A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority). CONCLUSIONS: Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.).

Cardiovascular outcomes in children with Kawasaki disease: a population-based cohort study.

BACKGROUND: The risk of cardiovascular events after Kawasaki disease (KD) remains uncertain. Our objective was to determine the risk of cardiovascular events and mortality after KD. METHODS: Population-based retrospective cohort study using Ontario health administrative databases (0-18 years; 1995-2018). EXPOSURE: pediatric KD hospitalizations. Each case was matched to 100 non-exposed controls. PRIMARY OUTCOME: major adverse cardiac events (MACE; cardiovascular death, myocardial infarction, or stroke composite). SECONDARY OUTCOMES: composite cardiovascular events and mortality. We determined incidence rates and adjusted hazard ratios (aHR) using multivariable Cox models. RESULTS: Among 4597 KD survivors, 79 (1.7%) experienced MACE, 632 (13.8%) composite cardiovascular events, and 9 (0.2%) died during 11-year median follow-up. The most frequent cardiovascular events among KD survivors were ischemic heart disease (4.6 events/1000 person-years) and arrhythmias (4.5/1000 person-years). KD survivors were at increased risk of MACE between 0-1 and 5-10 years, and composite cardiovascular events at all time periods post-discharge. KD survivors had a lower mortality risk throughout follow-up (aHR 0.36, 95% CI 0.19-0.70). CONCLUSION: KD survivors are at increased risk of post-discharge cardiovascular events but have a lower risk of death, which justifies enhanced cardiovascular disease surveillance in these patients. IMPACT: Among 4597 Kawasaki disease (KD) survivors, 79 (1.7%) experienced major adverse cardiac events (MACE) and 632 (13.8%) had composite cardiovascular events during 11-year median follow-up. KD survivors had significantly higher risks of post-discharge MACE and cardiovascular events versus non-exposed children. Only nine KD survivors (0.2%) died during follow-up, and the risk of mortality was significantly lower among KD survivors versus non-exposed children. Childhood KD survivors should receive preventative counseling and cardiovascular surveillance, aiming to mitigate adult cardiovascular disease.

Incidence of cardiovascular disease and mortality in childhood solid organ transplant recipients: a population-based study.

BACKGROUND: With improved survival among children after transplantation, our understanding of the risk for developing other comorbidities is improving, yet little is known about the long-term risk of cardiovascular events and mortality after solid organ transplantation. METHODS: In a cohort study using health administrative data, we compared cardiovascular events in children (n = 615) with liver, lung, kidney, small bowel, or multi-organ transplant at the Hospital for Sick Children, Toronto, Canada, with asthmatic children (n = 481,697) between 1996 and 2014. Outcomes included non-fatal cardiovascular events, cardiovascular death, all-cause mortality, and a composite of non-fatal and fatal cardiovascular events. Time-stratified Cox proportional hazards models were used. RESULTS: Among 615 children, 317 (52%) were recipients of kidneys, 253 (41%) of livers, and the remaining 45 (7%) had lung, small bowel, or multi-organ transplants. Median follow-up was 12.1 [7.2, 16.7] years. Non-fatal incident cardiovascular events were 34 times higher among solid organ transplant recipients than non-transplanted children (incidence rate ratio (IRR) 34.4, 95% CI: 25.5, 46.4). Among transplant recipients, the cumulative incidence of non-fatal and fatal cardiovascular events was 2.3% and 13.0%, 5 and 15 years after transplantation, respectively. CONCLUSIONS: Increased rate of cardiovascular events in children after transplantation highlights the need for surveillance during transition into adulthood and beyond. A higher resolution version of the Graphical abstract is available as Supplementary information.

Transplantation of Patients With Long Dialysis Vintage in the Current Deceased Donor Kidney Allocation System (KAS).

RATIONALE & OBJECTIVE: In 2014 the wait-time calculation for deceased donor kidney transplantation in the United States was changed from the date of first waitlisting to the date of first maintenance dialysis treatment with the aim of minimizing disparities in access to transplantation. This study examined the impact of this policy on access to transplantation, patient survival, and transplant outcomes among patients treated with maintenance dialysis for a prolonged duration before waitlisting. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients identified in the US Renal Data System between 2008 and 2018 aged 18-70 years and in the 95th percentile of dialysis treatment duration (≥6.5 years) before waitlisting. EXPOSURE: Waitlisting for transplantation before versus after implementation of the policy. OUTCOME: Time from date of waitlisting to deceased donor transplantation and death, and from date of transplantation to all cause graft loss. ANALYTICAL APPROACH: Univariate and multivariable time to event analyses. RESULTS: Patients waitlisted after the policy change had a higher likelihood of deceased donor transplantation (HR, 3.12 [95% CI, 2.90-3.37]) and lower risk of death (HR, 0.74 [95% CI, 0.63-0.87]). The risk of graft loss was lower in the post-kidney allocation system (KAS) cohort (HR, 0.66 [95% CI, 0.55-0.80]). The proportion of adult patients treated with dialysis ≥6.5 years who were never waitlisted for transplantation remained high (73%) and did not decrease after the policy implementation. LIMITATIONS: Cannot determine causality in this observational study. CONCLUSIONS: The policy change was associated with an increase in deceased donor transplantation and marked improvement in patient survival for patients waitlisted after long periods of dialysis treatment without decreasing the utility of available deceased donor kidney supply. The policy was not associated with increased waitlisting of this disadvantaged population.

Outcomes among CMV-mismatched and highly sensitized kidney transplants recipients who develop neutropenia.

Limited data exist on the incidence and clinical outcomes of neutropenia among kidney transplant recipients. Our study included 572 adults who received a kidney transplant at the University of California, San Francisco Medical Center between 2012 and 2018, and were CMV-mismatched or had a PRA ≥ 80%. Recipients with HIV, Hepatitis B and C, and primary non-function were excluded. Participants were followed for at least 1 year after transplantation. Neutropenia was defined as absolute neutrophil count < 1000 cells/µl. Cox proportional hazards regression models using neutropenia as a time-varying predictor were used to determine the risk of mycophenolic acid and valganciclovir changes, rejection, hospitalizations and use of granulocyte colony stimulating factor. Models were adjusted for demographics and transplant characteristics. Mean follow-up was 3.7 (SD, 1.8) years. The mean age of the cohort was 50.4 (13.1) years, and 57.5% were female. A total of 208 (36.3%) participants had neutropenia. Neutropenia was associated with an increased risk of valganciclovir or MPA dose reductions or discontinuations [adjusted hazard ratio, aHR: 7.78, 95% CI: 4.73-12.81], rejection [aHR 2.00, 95% CI: 1.10-3.64] and hospitalizations [aHR 3.32, 95% CI: 2.12-5.19]. Neutropenia occurs frequently after kidney transplantation and leads to more medication changes and adverse clinical outcomes.

Association between Longer Travel Distance for Transplant Care and Access to Kidney Transplantation and Graft Survival in the United States.

BACKGROUND: Transplant candidates may gain an advantage by traveling to receive care at a transplant center that may have more favorable characteristics than their local center. Factors associated with longer travel distance for transplant care and whether the excess travel distance (ETD) is associated with access to transplantation or with graft failure are unknown. METHODS: This study of adults in the United States wait-listed for kidney transplantation in 1995-2015 used ETD, defined as distance a patient traveled beyond the nearest transplant center for initial waiting list registration. We used linear regression to examine patient and center characteristics associated with ETD and Fine-Gray models to examine the association between ETD (modeled as a spline) and time to deceased or living donor transplantation or graft failure. RESULTS: Of 373,365 patients, 11% had an ETD≥50 miles. Traveling excess distance was more likely among patients who were of non-Black race or those whose nearest transplant center had lower annual living donor transplant volume. At an ETD of 50 miles, we observed a lower likelihood of deceased donor transplantation (subhazard ratio [SHR], 0.85; 95% confidence interval [95% CI], 0.84 to 0.87) but higher likelihood of living donor transplantation (SHR, 1.14; 95% CI, 1.12 to 1.16) compared with those who received care at their nearest center. ETD was weakly associated with higher risk of graft failure. CONCLUSIONS: Patients who travel excess distances for transplant care have better access to living donor but not deceased donor transplantation and slightly higher risk of graft failure. Traveling excess distances is not clearly associated with better outcomes, especially if living donors are unavailable.

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial.

BACKGROUND: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. METHODS: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. FINDINGS: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months. INTERPRETATION: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. FUNDING: Medtronic.

Incidence and short-term outcomes of Kawasaki disease.

OBJECTIVE: Kawasaki disease (KD) is a childhood vasculitis with conflicting reported North American trends in incidence and patient characteristics. OBJECTIVES: (1) determine KD incidence between 1995 and 2017; (2) compare patient characteristics by era and age group; (3) determine complication and cardiovascular follow-up rates. METHODS: We used population-based health administrative data to identify children (0-18 yr) hospitalized with KD in Ontario, Canada between 1995 and 2017. We excluded children with prior KD diagnosis or incomplete records. We determined the annualized incidence and follow-up trends. RESULTS: KD was diagnosed in 4,346 children between 1995 and 2017. Annual KD incidence was 22.0 (<5 yr), 6.1 (5-9 yr), and 0.6 (10-18 yr) per 100,000 children. KD incidence increased significantly for all age groups, including from 18.4 to 25.0 cases per 100,000 children <5 yr. Ninety-day mortality occurred in ≤5 children (≤0.1%). Coronary artery aneurysm (CAA) occurred in 106 children (2.4%, 95% confidence interval 2.0-2.9) during admission and 151 (3.5%, 95% confidence interval 3.0-4.1) during 11-year median follow-up. Children 10-18 yr had longer hospitalizations (4.3 vs. 3.5 days, p = 0.003) and more CAA (7.4% vs. 3.4%, p = 0.007). By 1-year post-diagnosis, 3970 (91.3%) and 2576 (59.3%) children had echocardiography and cardiology follow-up, respectively. CONCLUSIONS: KD incidence is increasing in Ontario, with greater healthcare utilization from hospitalizations and subsequent follow-up. IMPACT: 4346 children were hospitalized for Kawasaki disease over 22 years in Ontario, and Kawasaki disease incidence increased significantly for all age groups, males and females. Older children (10-18 years) had longer hospital length of stay, more PICU admissions and more frequent coronary artery aneurysms. Nearly all children with Kawasaki disease had follow-up echocardiography within 1 year.

Achieved blood pressure post-acute kidney injury and risk of adverse outcomes after AKI: A prospective parallel cohort study.

BACKGROUND: There has recently been considerable interest in better understanding how blood pressure should be managed after an episode of hospitalized AKI, but there are scant data regarding the associations between blood pressure measured after AKI and subsequent adverse outcomes. We hypothesized that among AKI survivors, higher blood pressure measured three months after hospital discharge would be associated with worse outcomes. We also hypothesized these associations between blood pressure and outcomes would be similar among those who survived non-AKI hospitalizations. METHODS: We quantified how systolic blood pressure (SBP) observed three months after hospital discharge was associated with risks of subsequent hospitalized AKI, loss of kidney function, mortality, and heart failure events among 769 patients in the prospective ASSESS-AKI cohort study who had hospitalized AKI. We repeated this analysis among the 769 matched non-AKI ASSESS-AKI enrollees. We then formally tested for AKI interaction in the full cohort of 1538 patients to determine if these associations differed among those who did and did not experience AKI during the index hospitalization. RESULTS: Among 769 patients with AKI, 42 % had subsequent AKI, 13 % had loss of kidney function, 27 % died, and 18 % had heart failure events. SBP 3 months post-hospitalization did not have a stepwise association with the risk of subsequent AKI, loss of kidney function, mortality, or heart failure events. Among the 769 without AKI, there was also no stepwise association with these risks. In formal interaction testing using the full cohort of 1538 patients, hospitalized AKI did not modify the association between post-discharge SBP and subsequent risks of adverse clinical outcomes. CONCLUSIONS: Contrary to our first hypothesis, we did not observe that higher stepwise blood pressure measured three months after hospital discharge with AKI was associated with worse outcomes. Our data were consistent with our second hypothesis that the association between blood pressure measured three months after hospital discharge and outcomes among AKI survivors is similar to that observed among those who survived non-AKI hospitalizations.

Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial.

BACKGROUND: Previous catheter-based renal denervation studies have reported variable efficacy results. We aimed to evaluate safety and blood pressure response after renal denervation or sham control in patients with uncontrolled hypertension on antihypertensive medications with drug adherence testing. METHODS: In this international, randomised, single-blind, sham-control, proof-of-concept trial, patients with uncontrolled hypertension (aged 20-80 years) were enrolled at 25 centres in the USA, Germany, Japan, UK, Australia, Austria, and Greece. Eligible patients had an office systolic blood pressure of between 150 mm Hg and 180 mm Hg and a diastolic blood pressure of 90 mm Hg or higher; a 24 h ambulatory systolic blood pressure of between 140 mm Hg and 170 mm Hg at second screening; and were on one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned to undergo renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were masked to randomisation assignments. The primary efficacy endpoint was blood pressure change from baseline (measured at screening visit two), based on ambulatory blood pressure measurements assessed at 6 months, as compared between treatment groups. Drug surveillance was used to assess medication adherence. The primary analysis was done in the intention-to-treat population. Safety events were assessed through 6 months as per major adverse events. This trial is registered with ClinicalTrials.gov, number NCT02439775, and follow-up is ongoing. FINDINGS: Between July 22, 2015, and June 14, 2017, 467 patients were screened and enrolled. This analysis presents results for the first 80 patients randomly assigned to renal denervation (n=38) and sham control (n=42). Office and 24 h ambulatory blood pressure decreased significantly from baseline to 6 months in the renal denervation group (mean baseline-adjusted treatment differences in 24 h systolic blood pressure -7·0 mm Hg, 95% CI -12·0 to -2·1; p=0·0059, 24 h diastolic blood pressure -4·3 mm Hg, -7·8 to -0·8; p=0.0174, office systolic blood pressure -6·6 mm Hg, -12·4 to -0·9; p=0·0250, and office diastolic blood pressure -4·2 mm Hg, -7·7 to -0·7; p=0·0190). The change in blood pressure was significantly greater at 6 months in the renal denervation group than the sham-control group for office systolic blood pressure (difference -6·8 mm Hg, 95% CI -12·5 to -1·1; p=0·0205), 24 h systolic blood pressure (difference -7·4 mm Hg, -12·5 to -2·3; p=0·0051), office diastolic blood pressure (difference -3·5 mm Hg, -7·0 to -0·0; p=0·0478), and 24 h diastolic blood pressure (difference -4·1 mm Hg, -7·8 to -0·4; p=0·0292). Evaluation of hourly changes in 24 h systolic blood pressure and diastolic blood pressure showed blood pressure reduction throughout 24 h for the renal denervation group. 3 month blood pressure reductions were not significantly different between groups. Medication adherence was about 60% and varied for individual patients throughout the study. No major adverse events were recorded in either group. INTERPRETATION: Renal denervation in the main renal arteries and branches significantly reduced blood pressure compared with sham control with no major safety events. Incomplete medication adherence was common. FUNDING: Medtronic.

Rationale and design of the Onyx ONE global randomized trial: A randomized controlled trial of high-bleeding risk patients after stent placement with 1 month of dual antiplatelet therapy.

BACKGROUND AND RATIONALE: Polymer-free drug-eluting stent (DES) implantation in combination with 1-month dual antiplatelet therapy (DAPT) has shown superior safety and efficacy outcomes compared with bare-metal stents among patients with high-bleeding risk (HBR) treated with 1-month DAPT. The safety and efficacy of the newer-generation durable-polymer DES Resolute Onyx compared with polymer-free DES among HBR patients treated with 1-month DAPT is unknown. TRIAL DESIGN: The Onyx ONE global randomized trial is an international, prospective, randomized, blinded, controlled study enrolling HBR patients undergoing percutaneous coronary intervention. The trial will randomize up to 2,000 patients in a 1:1 fashion to receive either the durable-polymer Resolute Onyx DES or the polymer-free Biosensors BioFreedom DES. After index procedure, patients in both arms will be treated with 1 month of DAPT (aspirin and oral P2Y12 inhibitor), followed by single antiplatelet therapy thereafter. The primary end point is the composite end point of cardiac death, myocardial infarction, or stent thrombosis at 1-year follow-up. The powered secondary end point is target lesion failure (defined as the composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization) at 1 year. Patient follow-up is planned for 1, 2, and 6 months and 1 and 2 years after the procedure. CONCLUSIONS: The Onyx ONE global randomized trial is the first study to directly compare the safety and efficacy of a durable polymer DES (Resolute Onyx) with a polymer-free DES (BioFreedom) in HBR patients treated with 1 month of DAPT.

Bacteremia in kidney transplant recipients: Burden, causes, and consequences.

Bacteremia is an important complication after kidney transplantation. We examined bacteremia and its outcomes in a large cohort of kidney transplant recipients. Kidney transplants from 1-Jul-2004 to 1-Dec-2014 at the Toronto General Hospital were eligible for study inclusion. Bacteremia was defined as two blood culture positives for common skin contaminants or one blood culture positive for other organisms. The cumulative incidence of first bacteremia was estimated using the Kaplan-Meier method, and risk factors were examined in a Cox proportional hazards model. The risk of graft failure or death was assessed in a time-dependent Cox model. Over follow-up, 154 of 1333 patients had at least one bacteremia episode. The cumulative incidence of first bacteremia was 6.8% (6 months) and 11.9% (5 years). Risk factors included recipient diabetes mellitus, time on dialysis, dialysis modality, delayed graft function, donor age, and donor eGFR. Bacteremia increased the risk of total graft failure (hazard ratio 2.11 [95% CI: 1.50, 2.96]), death-censored graft failure (1.73 [0.99, 3.02]), and death with graft function (2.52 [1.63, 3.89]). In conclusion, bacteremia is common after kidney transplantation and impacts both graft and patient survival. Identifying high-risk patients for targeted preventive strategies may reduce the burden and adverse consequences of this important complication.

The East-West late lumen loss study: Comparison of angiographic late lumen loss between Eastern and Western drug-eluting stent study cohorts.

BACKGROUND: Regulatory decisions approving new coronary drug-eluting stent (DES) require mechanistic observations of angiographic late lumen loss (LLL). Patient safety and device approval times could be enhanced if angiographic follow-up data were found to be generalizable across jurisdictions and geographies. The objectives were to assess the comparability of in-segment LLL in Eastern and Western DES populations using the world's largest compilation of follow-up quantitative coronary angiography data. METHODS: Data from 4 manufacturers involving 29 DES clinical trials in Eastern and Western hemispheres were compiled. "East" and "West" cohorts were defined by trial location. Independent core laboratories quantified in-segment LLL for all studies. East and West were compared before and after adjustment for clinical and anatomic covariates known to correlate with LLL via conditioning on propensity score quintiles. An international panel of experts and regulators prospectively established a clinically meaningful difference between East and West mean in-segment LLL of ±0.40 mm. RESULTS: The data set comprised 2,047 East and 4,456 West patients. Unadjusted mean ± SD for West and East in-segment LLL (mm) was 0.25 ± 0.46 and 0.12 ± 0.42, respectively (difference 0.13 mm; 95% CI 0.11-0.16). Propensity score-adjusted in-segment LLL East and West least squares means were 0.11 and 0.26 mm, respectively (difference 0.15 mm; 95% CI 0.13-0.18). CONCLUSIONS: In the world's largest compilation of DES protocol 8- to 13-month angiographic follow-up data, clinically meaningful comparability of in-segment LLL by independent core laboratory quantitative coronary angiography in East and West cohorts was demonstrated in both unadjusted and adjusted comparisons. These findings suggest that DES LLL, once characterized, could be generalized across regulatory jurisdictions over the course of global registration efforts.

Differences in Dynamic Diurnal Blood Pressure Variability Between Japanese and American Treatment-Resistant Hypertensive Populations.

BACKGROUND: Dynamic diurnal changes in 24-h ambulatory systolic blood pressure (SBP) are associated with increased cardiovascular risk. We compared ambulatory BP dynamics in Japanese and American black and white populations with treatment-resistant hypertension.Methods and Results:Both HTN-Japan (n=41) and SYMPLICITY HTN-3 (n=384 white and n=140 black patients) enrolled patients with office SBP ≥160 mmHg and 24-h ambulatory SBP ≥135 mmHg while on ≥3 antihypertensive medications. Indices of circadian variation in ambulatory BP, including morning and nighttime dynamic surges, were retrospectively compared. All 3 cohorts had similar baseline office SBP. The Japanese cohort had significantly lower body mass index, less obstructive sleep apnea, and less hypercholesterolemia than the black and white cohorts, but significantly greater morning SBP levels, including moving peak morning SBP (183 vs. 169 vs. 169 mmHg, P<0.001), morning dynamic surge (37.9 vs. 28.6 vs. 24.2 mmHg, P<0.001) and nighttime dynamic surge (24.9 vs. 8.3 vs. 7.7 mmHg, P<0.001). These racial differences in SBP surge parameters persisted despite adjustment for baseline demographic population differences through multivariate regression. CONCLUSIONS: Greater diurnal BP variability, including dynamic surges, in Japanese compared with black and white patients may indicate ethnic differences in the underlying BP regulatory mechanism of resistant hypertension. These differences may be important to take into consideration for more specific drug and device-based therapy strategies based on ethnicity.

Rationale and design of the East-West late lumen loss study: Comparison of late lumen loss between Eastern and Western drug-eluting stent study cohorts.

BACKGROUND: The contemporary evaluation of novel drug-eluting stents (DES) includes mechanistic observations that characterize postdeployment stent behavior. Quantification of late lumen loss due to neointimal hyperplasia 8-13 months after stent implantation, via quantitative coronary angiography (QCA), constitutes such an observation and is required by most regulatory authorities. Late lumen loss, as determined by QCA, has been validated as a surrogate for clinical endpoints such as target vessel revascularization. The mechanistic response to DES has not been directly compared across predominantly Asian or Western populations, whereas understanding their comparability across geographic populations could enhance global DES evaluation. OBJECTIVE: The East-West late lumen loss study is designed to demonstrate whether the residual differences in late lumen loss, as assessed by QCA, is different between Eastern and Western DES recipients from studies with protocol angiography at 8-13 months of follow-up. METHODS: Data from independent core laboratories that have characterized angiographic late lumen loss in DES clinical trials with protocol follow-up angiography will be compiled and dichotomized into Eastern and Western populations. A prospectively developed propensity score model incorporating clinical and anatomic variables affecting late lumen loss will be used to adjust comparisons of QCA measurements. CONCLUSION: Documentation of whether there are clinically meaningful differences in mechanistic response to DES implantation across genetically unique geographies could facilitate both the quality and efficiency of global device evaluation requiring invasive follow-up for novel stent designs.

Impact of Renal Denervation on Patients With Obstructive Sleep Apnea and Resistant Hypertension　- Insights From the SYMPLICITY HTN-3 Trial.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with activation of the sympathetic nervous system, and patients with this condition often experience elevated blood pressure (BP), increased BP variability, and nocturnal BP surges. METHODS AND RESULTS: The SYMPLICITY HTN-3 trial was a large prospective, randomized, blinded, sham-controlled trial of renal denervation for treatment of uncontrolled, apparently treatment-resistant hypertension. In a post hoc analysis, we examined the effect of renal denervation vs. sham control on office and ambulatory (including nocturnal) systolic BP in patients with and without OSA. 26% (94/364) of renal denervation subjects and 32% (54/171) of sham control subjects had OSA. Baseline office and nighttime systolic BP values were similar in both arms, including in subjects with and without OSA. Compared with sham control, renal denervation reduced the 6-month office systolic BP in subjects with (-17.0±22.4 vs. -6.3±26.1 mmHg, P=0.01) but not in subjects without OSA (-14.7±24.5 vs. -13.4±26.4 mmHg, P=0.64), P=0.07 for the interaction between treatment arm and OSA status. In those with sleep apnea, renal denervation was also associated with a reduction in maximum (-4.8±21.8 vs. 4.5±24.6 mmHg, P=0.03) and average peak (-5.6±20.4 vs. 3.2±22.4 mmHg, P=0.02) nighttime systolic BP. CONCLUSIONS: OSA subjects appeared to be responsive to renal denervation therapy. However, this hypothesis requires prospective testing. (Circ J 2016; 80: 1404-1412).