Urinary podocyte mRNAs precede microalbuminuria as a progression risk marker in human type 2 diabetic nephropathy.

Earlier detection of progression risk in diabetic nephropathy will allow earlier intervention to reduce progression. The hypothesis that urinary pellet podocyte mRNA is a more sensitive progression risk marker than microalbuminuria was tested. A cross sectional cohort of 165 type 2 diabetics and 41 age and sex-matched controls were enrolled. Podocyte stress (Urinary pellet podocin:nephrin mRNA ratio), podocyte detachment (Urinary pellet podocin mRNA:creatinine ratio: UPPod:CR) and a tubular marker (Urinary pellet aquaporin 2:creatinine ratio) were measured in macro-albuminuric, micro-albuminuric and norm-albuminuric groups. eGFR was reassessed after 4 years in 124 available diabetic subjects. Urinary pellet podocyte and tubular mRNA markers were increased in all diabetic groups in cross-sectional analysis. After 4 years of follow-up univariable and multivariate model analysis showed that the only urinary markers significantly related to eGFR slope were UPPod:CR (P < 0.01) and albuminuria (P < 0.01). AUC analysis using K-fold cross validation to predict eGFR loss of ≥ 3 ml/min/1.73m2/year showed that UPPod:CR and albuminuria each improved the AUC similarly such that combined with clinical variables they gave an AUC = 0.70. Podocyte markers and albuminuria had overlapping AUC contributions, as expected if podocyte depletion causes albuminuria. In the norm-albuminuria cohort (n = 75) baseline UPPod:CR was associated with development of albuminuria (P = 0.007) and, in the tertile with both normal kidney function (eGFR 84 ± 11.7 ml/min/1.73m2) and norm-albuminuria at baseline, UPPod:CR was associated with eGFR loss rate (P = 0.003). In type 2 diabetics with micro- or macro-albuminuria UPPod:CR and albuminuria were equally good at predicting eGFR loss. For norm-albuminuric type 2 diabetics UPPod:CR predicted both albuminuria and eGFR loss.

Long-term clinical outcomes in patients with ST-segment elevation acute myocardial infarction complicated by cardiogenic shock due to acute pump failure.

BACKGROUND:: Cardiogenic shock remained the leading cause of death in ST-segment elevation acute myocardial infarction (STEMI) patients even in the primary percutaneous coronary intervention era. METHODS:: Among 3942 STEMI patients with primary percutaneous coronary intervention within 24 h after symptom-onset in the Coronary Revascularization Demonstrating Outcome Study in Kyoto acute myocardial infarction registry, the study population of the current analysis consisted of 466 STEMI patients who were complicated by cardiogenic shock due to acute pump failure. RESULTS:: The cumulative incidence of all-cause death of cardiogenic shock due to acute pump failure was 25.4% at 30 days, 38.7% at one year, and 51.4% at five years. Cumulative five-year incidence of all-cause death in patients with left main coronary artery culprit lesion was extremely high (left main coronary artery: 70.4%, left anterior descending artery: 52.5%, left circumflex artery: 50.6%, and right coronary artery; 44.3%, respectively, log-rank p<0.001). The cumulative five-year incidence of all-cause death in patients with onset-to-balloon time ⩽3 h as well as those with door-to-balloon time ⩽90 min were significantly lower than those without (43.3% versus 55.5%, log-rank p=0.008, and 44.9% versus 55.8%, log-rank p=0.003, respectively). After adjusting for confounders, onset-to-balloon time ⩽3 h and door-to-balloon time ⩽90 min were independently associated with lower long-term risk for all-cause death (hazard ratio: 0.69, 95% confidence interval: 0.49-0.96, p=0.03, and hazard ratio: 0.73, 95% confidence interval: 0.53-0.98, p=0.04, respectively). CONCLUSIONS:: The long-term mortality of STEMI patients complicated by cardiogenic shock due to acute pump failure remains high even in the current clinical practice. In this high-risk category of patients, shorter onset-to-balloon and door-to-balloon time were associated with significantly lower long-term risk for mortality.

Adaptive servoventilation versus oxygen therapy for sleep disordered breathing in patients with heart failure: a randomised trial.

BACKGROUND: Both adaptive servoventilation (ASV) and nocturnal oxygen therapy improve sleep disordered breathing (SDB), but their effects on cardiac parameters have not been compared systematically. METHODS AND RESULTS: 43 patients with chronic heart failure (CHF; left ventricular ejection fraction (LVEF) ≤50%) with SDB were randomly assigned to undergo ASV (n=19, apnoea hypopnoea index (AHI)=34.2±12.1/h) or oxygen therapy (n=24, 36.9±9.9/h) for 3 months. More than 70% of SDB events in both groups were central apnoeas or hypopnoeas. Although nightly adherence was less for the ASV group than for the oxygen group (4.4±2.0 vs 6.2±1.8 h/day, p<0.01), the improvement in AHI was larger in the ASV group than in the oxygen group (-27.0±11.5 vs -16.5±10.2/h, p<0.01). The N-terminal pro-brain natriuretic peptide (NT-proBNP) level in the ASV group improved significantly after titration (1535±2224 to 1251±2003 pg/mL, p=0.01), but increased slightly at follow-up and this improvement was not sustained (1311±1592 pg/mL, p=0.08). Meanwhile, the level of plasma NT-proBNP in the oxygen group did not show a significant change throughout the study (baseline 1071±1887, titration 980±1913, follow-up 1101±1888 pg/mL, p=0.19). The significant difference in the changes in the NT-proBNP level throughout the study between the 2 groups was not found (p=0.30). Neither group showed significant changes in echocardiographic parameters. CONCLUSIONS: Although ASV produced better resolution of SDB in patients with CHF as compared with oxygen therapy, neither treatment produced a significant improvement in cardiac function in the short term. Although we could not draw a definite conclusion because of the small number of participants, our data do not seem to support the routine use of ASV or oxygen therapy to improve cardiac function in patients with CHF with SDB. TRIAL REGISTRATION NUMBER: NCT01187823 (http://www.clinicaltrials.gov).

Prevalence and significance of clinically unsuspected pulmonary embolism: detection using coronary computed tomography angiography.

BACKGROUND AND AIM: Clinically unsuspected pulmonary embolism can be detected using coronary computed tomography (CT), but the clinical significance of unsuspected pulmonary embolism remains unclear. METHODS: Pulmonary embolism was assessed using consecutive coronary CT from March 2003 to June 2007 to assess 1077 patients. Coronary CT was performed using a 16-row multidetector CT (MDCT) scanner with ECG-gating. A radiologist and a cardiologist retrospectively assessed the images of pulmonary arteries to arrive at a consensus diagnosis. RESULTS: Unsuspected pulmonary embolism was detected in 32/1,077 (3.0%) patients. No significant difference was observed with regard to death and acute pulmonary embolism between patients with and without unsuspected pulmonary embolism at five years (6.7% vs. 4.1%, p = 0.61). Prior cardiac surgery within three months of diagnosis of pulmonary embolism was an independent risk factor for unsuspected pulmonary embolism, which was detected in 10/89 (11%) of such patients. The absence of anticoagulant therapy was a risk factor (p = 0.015) for unsuspected pulmonary embolism post-cardiac surgery. Although only one out of 10 patients received anticoagulant therapy, none of the 10 experienced critical events. Five of the 10 patients underwent repeated coronary CT, and the embolus disappeared regardless of its size and location in four of the five patients who did not receive anticoagulant therapy. CONCLUSIONS: The prevalence of unsuspected pulmonary embolism detected using coronary CT was 3.0%. Prior cardiac surgery within three months of diagnosing pulmonary embolism was an independent risk factor for unsuspected pulmonary embolism. The long-term clinical outcomes of patients with unsuspected pulmonary embolism were favorable.

Association of onset to balloon and door to balloon time with long term clinical outcome in patients with ST elevation acute myocardial infarction having primary percutaneous coronary intervention: observational study.

OBJECTIVE: To evaluate the relation of symptom onset to balloon time and door to balloon time with long term clinical outcome in patients with ST segment elevation myocardial infarction (STEMI) having primary percutaneous coronary intervention. DESIGN: Observation of large cohort of patients with acute myocardial infarction. SETTING: 26 tertiary hospitals in Japan. PARTICIPANTS: 3391 patients with STEMI who had primary percutaneous coronary intervention within 24 hours of symptom onset. MAIN OUTCOME MEASURES: Composite of death and congestive heart failure, compared by onset to balloon time and door to balloon time. RESULTS: Compared with an onset to balloon time greater than 3 hours, a time of less than 3 hours was associated with a lower incidence of a composite of death and congestive heart failure (13.5% (123/964) v 19.2% (429/2427), P<0.001; relative risk reduction 29.7%). After adjustment for confounders, a short onset to balloon time was independently associated with a lower risk of the composite endpoint (adjusted hazard ratio 0.70, 95% confidence interval 0.56 to 0.88; P=0.002). However, no significant difference was found in the incidence of a composite of death and congestive heart failure between the two groups of patients with short (≤90 minutes) and long (>90 minutes) door to balloon time (16.7% (270/1671) v 18.4% (282/1720), P=0.54; relative risk reduction 9.2%). After adjustment for confounders, no significant difference was seen in the risk of the composite endpoint between the two groups of patients with short and long door to balloon time (adjusted hazard ratio: 0.98, 0.78 to 1.24: P=0.87). A door to balloon time of less than 90 minutes was associated with a lower incidence of a composite of death and congestive heart failure in patients who presented within 2 hours of symptom onset (11.9% (74/883) v 18.1% (147/655), P=0.01; relative risk reduction 34.3%) but not in patients who presented later (19.7% (196/788) v 18.7% (135/1065), P=0.44; -5.3%). Short door to balloon time was independently associated with a lower risk of a composite of death and congestive heart failure in patients with early presentation (adjusted hazard ratio 0.58, 0.38 to 0.87; P=0.009) but not in patients with delayed presentation (1.57, 1.12 to 2.18; P=0.008). A significant interaction was seen between door to balloon time and time to presentation (interaction P=0.01). CONCLUSIONS: Short onset to balloon time was associated with better 3 year clinical outcome in patients with STEMI having primary percutaneous coronary intervention, whereas the benefit of short door to balloon time was limited to patients who presented early. Efforts to minimise onset to balloon time, including reduction of patient related delay, should be recommended to improve clinical outcome in STEMI patients.

Duration of dual antiplatelet therapy and long-term clinical outcome after coronary drug-eluting stent implantation: landmark analyses from the CREDO-Kyoto PCI/CABG Registry Cohort-2.

BACKGROUND: Optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation has not been yet fully elucidated. METHODS AND RESULTS: We assessed the influence of prolonged thienopyridine therapy on clinical outcomes with landmark analysis at 4 and 13 months after DES implantation. Among 6802 patients with at least 1 DES implantation in the CREDO-Kyoto Registry Cohort-2, 6309 patients (on thienopyridine, 5438 patients; off thienopyridine, 871 patients) and 5901 patients (on thienopyridine, 4098 patients; off thienopyridine, 1803 patients) were eligible for the 4- and 13-month landmark analyses, respectively. The majority of patients had stable coronary artery disease (73%) and received sirolimus-eluting stents (93%), and approximately 90% of thienopyridine was ticlopidine. Patients taking thienopyridine had more complex comorbidities and more complex lesion and procedural characteristics as compared with patients not taking thienopyridine. After adjusting for confounders, thienopyridine use was not associated with decreased risk for death/myocardial infarction/stroke (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.89-1.43, P=0.32 in the 4-month landmark analysis; HR, 1.14; 95% CI, 0.90-1.45, P=0.29 in the 13-month landmark analysis, respectively), whereas the risk for GUSTO moderate/severe bleeding tended to be higher in patients taking thienopyridine (HR, 1.51; 95% CI, 1.00-2.23, P=0.049 in the 4-month landmark analysis; HR, 1.44; 95% CI, 0.99-2.09, P=0.057 in the 13-month landmark analysis, respectively). CONCLUSIONS: Prolonged thienopyridine therapy beyond 4 and 13 months appeared not to be associated with reduction in ischemic events but to be associated with a trend toward increased bleeding. Optimal duration of DAPT after DES implantation might be shorter than the currently recommended 1-year interval.

Systematic evaluation of vascular access by color-Doppler ultrasound decreased the incidence of emergent vascular access intervention therapy and X-ray exposure time: a single-center observational study.

Arteriovenous fistula has superior patency over other accesses, but vascular access intervention therapy (VAIVT) for stenosis or thrombosis still remain major reasons for hospital admission of dialysis patients. The aim of this study was to examine the usefulness of systematic evaluation of vascular access by color-Doppler ultrasound (CDUS). This study was a single-center observational design study. We planned screening CDUS to evaluate all vascular accesses once per year, and additionally, follow-up CDUS of post-interventional patients 1 month, 3 months and 6 months after their recent VAIVT. This systematic evaluation was started from September 2009. The observational period between September 2008 and August 2009 was defined as period A. The observational period between September 2009 and August 2010 was defined as period B. We compared the incidence of emergent VAIVT and X-ray exposure time during the period A to B. 131 patients with AV fistula were assigned. 13 patients were excluded due to death, hospital transfer or re-operation of their accesses. During period A, 57 VAIVTs were carried out, and 37 cases (65%) were emergent. During period B, 42 VAIVTs were carried out, and 11 cases (25%) were emergent. The incidence of emergent intervention therapy was lower during period B than period A (P < 0.001). The amount of X-ray exposure time per patient was decreased in patients who received VAIVT during both periods (P < 0.03). Systematic evaluation of vascular access by CDUS decreased the incidence of emergent VAIVT and X-ray exposure time.