Background
It is uncertain that chronic heart failure (CHF) patients are susceptible to renal tubular damage with that of worsening renal function (WRF) preceding clinical outcomes.
Hypothesis
...Changes in tubular damage biomarkers are stronger predictors of subsequent clinical events than changes in creatinine (Cr), and both have different clinical determinants.
Methods
During 2.2 years, we repeatedly simultaneously collected a median of 9 blood and 8 urine samples per patient in 263 CHF patients. We determined the slopes (rates of change) of the biomarker trajectories for plasma (Cr) and urinary tubular damage biomarkers N‐acetyl‐β‐d‐glucosaminidase (NAG), and kidney‐injury‐molecule (KIM)‐1. The degree of tubular injury was ranked according to NAG and KIM‐1 slopes: increase in neither, increase in either, or increase in both; WRF was defined as increasing Cr slope. The composite endpoint comprised HF‐hospitalization, cardiac death, left ventricular assist device placement, and heart transplantation.
Results
Higher baseline NT‐proBNP and lower eGFR predicted more severe tubular damage (adjusted odds ratio, adj. OR 95%CI, 95% confidence interval per doubling NT‐proBNP: 1.26 1.07‐1.49; per 10 mL/min/1.73 m2 eGFR decrease 1.16 1.03‐1.31). Higher loop diuretic doses, lower aldosterone antagonist doses, and higher eGFR predicted WRF (furosemide per 40 mg increase: 1.32 1.08‐1.62; spironolactone per 25 mg decrease: 1.76 1.07‐2.89; per 10 mL/min/1.73 m2 eGFR increase: 1.40 1.20‐1.63). WRF and higher rank of tubular injury individually entailed higher risk of the composite endpoint (adjusted hazard ratios, adj. HR 95%CI: WRF 1.9 1.1‐3.4, tubular 8.4 2.6‐27.9; when combined risk was highest 15.0 2.0‐111.0).
Conclusion
Slopes of tubular damage and WRF biomarkers had different clinical determinants. Both predicted clinical outcome, but this association was stronger for tubular injury. Prognostic effects of both appeared independent and additive.
Despite the growing burden of heart failure (HF), there have been no recommendations for use of any of the primary prevention models in the existing guidelines. HF was also not included as an outcome ...in the American College of Cardiology/American Heart Association (ACC/AHA) risk score.
Among 2743 men and 3646 women aged ≥ 55 years, free of HF, from the population-based Rotterdam Study cohort, 4 Cox models were fitted using the predictors of the ACC/AHA, ARIC and Health-ABC risk scores. Performance of the models for 10-year HF prediction was evaluated. Afterwards, performance and net reclassification improvement (NRI) for adding NT-proBNP to the ACC/AHA model were assessed.
During a median follow-up of 13 years, 429 men and 489 women developed HF. The ARIC model had the highest performance c-statistic (95% confidence interval CI): 0.80 (0.78; 0.83) and 0.80 (0.78; 0.83) in men and women, respectively. The c-statistic for the ACC/AHA model was 0.76 (0.74; 0.78) in men and 0.77 (0.75; 0.80) in women. Adding NT-proBNP to the ACC/AHA model increased the c-statistic to 0.80 (0.78 to 0.83) in men and 0.81 (0.79 to 0.84) in women. Sensitivity and specificity of the ACC/AHA model did not drastically change after addition of NT-proBNP. NRI(95%CI) was - 23.8% (- 19.2%; - 28.4%) in men and - 27.6% (- 30.7%; - 24.5%) in women for events and 57.9% (54.8%; 61.0%) in men and 52.8% (50.3%; 55.5%) in women for non-events.
Acceptable performance of the model based on risk factors included in the ACC/AHA model advocates use of this model for prediction of HF risk in primary prevention setting. Addition of NT-proBNP modestly improved the model performance but did not lead to relevant discrimination improvement in clinical risk reclassification.
The study sought to assess whether treatment with ticagrelor, as compared with prasugrel and clopidogrel, improves endothelium-dependent dilation throughout the course of the treatment and other ...vascular biomarkers, including systemic adenosine plasma levels.
The in vivo off-target effects of ticagrelor in post-acute coronary syndrome (ACS) patients remain poorly characterized.
Fifty-four stable post-ACS patients were sequentially exposed to each of the 3 oral P2Y
inhibitors following a 3-period balanced Latin square crossover design with 4 weeks per treatment in 5 European centers. The primary endpoint was the assessment of endothelial function with pulse amplitude tonometry and expressed as reactive hyperemia index at treatment steady state. Secondary endpoints included reactive hyperemia index after loading or before maintenance regimen, systemic adenosine plasma levels, a wide set of vascular biomarkers, and ticagrelor or AR-C124910XX plasma levels throughout each ticagrelor period. In 9 patients, the evaluation of endothelial function was performed simultaneously by pulse amplitude tonometry and flow-mediated dilation.
Reactive hyperemia index did not differ after ticagrelor (1.970 ± 0.535) as compared with prasugrel (2.007 ± 0.640; p = 0.557) or clopidogrel (2.072 ± 0.646; p = 0.685), nor did systemic adenosine plasma levels or vascular biomarkers at any time points. P2Y
platelet reactivity units were lower after ticagrelor as compared with clopidogrel at all time points and after maintenance dose as compared with prasugrel. Flow-mediated dilatation did not differ after the maintenance dose of ticagrelor as compared with clopidogrel and prasugrel.
Ticagrelor did not improve endothelial function or increased systemic adenosine plasma levels as compared with prasugrel and clopidogrel in stabilized patients who suffered from an ACS. (Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function in Humans HI-TECH; NCT02587260).
Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) is useful in the evaluation of cardiac allograft vasculopathy (CAV) in heart transplant (HTx) recipients. ...The current study evaluated the long-term prognostic value of stress SPECT MPI for predicting all-cause mortality and cardiac events in HTx recipients.
The study population consisted of 166 HTx recipients (mean age 54 ± 10 years, 84% male) who underwent exercise or dobutamine stress 99mTc-tetrofosmin SPECT MPI for the assessment of CAV. An abnormal SPECT MPI was defined as the presence of a fixed or a reversible perfusion defect. Endpoints were all-cause mortality, cardiac mortality, and non-fatal myocardial infarction (MI).
MPI abnormalities were detected in 55 patients (33%), including fixed defects in 28 patients (17%), partially reversible in 17 patients (10%), and completely reversible defects in 10 patients (6%). During a median follow-up of 12.8 years (range 0-15, mean follow-up 9.5 years), 109 (66%) patients died (all-cause mortality), of which 67 (40%) were due to cardiac causes. A total of 5 (3%) patients experienced a non-fatal MI. HTx recipients with a normal stress 99mTc-tetrofosmin SPECT MPI had a significantly better prognosis as compared with those with an abnormal study, up to 5 years after the initial test. The presence of a reversible perfusion defect was a significant predictor of all-cause mortality, cardiac mortality, and major cardiac events, during the entire follow-up period.
Stress 99mTc-tetrofosmin SPECT MPI provides valuable prognostic information for the prediction of long-term outcome in HTx recipients. Patients with a normal stress 99mTc-tetrofosmin SPECT MPI have a significantly better prognosis as compared with those with an abnormal study, up to 5 years after initial testing.
Aims
This study aimed to investigate the left ventricular (LV) remodelling and long‐term prognosis of patients with new‐onset acute heart failure (HF) with reduced ejection fraction who were ...pharmacologically managed and survived until hospital discharge. We compared patients with ischaemic and non‐ischaemic aetiology.
Methods and results
This cohort study consisted of 111 patients admitted with new‐onset acute HF in the period 2008–2016 62% non‐ischaemic aetiology, 48% supported by inotropes, vasopressors, or short‐term mechanical circulatory devices, and left ventricular ejection fraction (LVEF) at discharge 28% (interquartile range 22–34). LV dimensions, LVEF, and mitral valve regurgitation were used as markers for LV remodelling during up to 3 years of follow‐up. Both patients with non‐ischaemic and ischaemic HF had significant improvement in LVEF (P < 0.001 and P = 0.004, respectively) with significant higher improvement in those with non‐ischaemic HF (17% vs. 6%, P < 0.001). Patients with non‐ischaemic HF had reduction in LV end‐diastolic and end‐systolic diameters (6 and 10 mm, both P < 0.001), but this was not found in those with ischaemic HF +3 mm (P = 0.09) and +2 mm (P = 0.07), respectively. During a median follow‐up of 4.6 years, 98 patients (88%) did not reach the composite endpoint of LV assist device implantation, heart transplantation, or all‐cause mortality, with no difference between with ischaemic and non‐ischaemic HF hazard ratio 0.69 (95% confidence interval 0.19–2.45).
Conclusions
Patients with new‐onset acute HF with reduced ejection fraction discharged on optimal medical treatment have a good prognosis. We observed a considerable LV remodelling with improvement in LV function and dimensions, starting already at 6 months in patients with non‐ischaemic HF but not in their ischaemic counterparts.
Renal dysfunction and anaemia are common in patients with acute heart failure (HF). It is not known whether their combined presence has additive prognostic value. We investigated their prognostic ...value separately and in combination, on prognosis in acute HF patients. Furthermore, we examined whether the improvement in prognosis was comparable between patients with and without renal dysfunction.
This prospective registry includes 1783 patients admitted to the (Intensive) Coronary Care Unit for acute HF in the period of 1985-2008. The outcome measure was the composite of all-cause mortality, heart transplantation and left ventricular assist device implantation. In patients without renal dysfunction, anemia was associated with worse 30-day outcome (HR 2.91; 95% CI 1.69-5.00), but not with 10-year outcome (HR 1.13 95% CI 0.93-1.37). On the contrary, anemia was found to influence prognosis in patients with renal dysfunction, both at 30 days (HR 1.93 95% CI 1.33-2.80) and at 10 years (HR 1.27 95% CI 1.10-1.47). Over time, the 10-year survival rate improved in patients with preserved renal function (HR 0.73 95% CI 0.55-0.97), but not in patients with renal dysfunction.
The long-term prognosis of acute HF patients with a preserved renal function was found to have improved significantly. However, the prognosis of patients with renal dysfunction did not change. Anemia was a strong prognosticator for short-term outcome in all patients. In patients with renal dysfunction, anemia was also associated with impaired long-term prognosis.
While the efficacy of the intracardiac defibrillators (ICDs) for primary prevention is not disputed, the relevant studies were carried out a long time ago. Most pertinent trials, including MADIT‐II, ...SCD‐Heft, and DEFINITE, recruited patients more than 20 years ago. Since then, improved therapeutic modalities including, in addition to cardiac resynchronization therapy, mineralocorticoid receptor antagonists, angiotensin receptor‐neprilysin inhibitors, and, most recently, inhibitors of sodium‐glucose cotransporter 2, have lowered present‐day rates of mortality and of sudden cardiac death. Thus, nowadays, ICD therapy may be less effective than previously reported, and not as beneficial as many people currently believe. However, criteria for ICD implantation remain very inclusive. The patient must (only) be symptomatic and have ejection fraction (EF) ≤ 35%. The choice of EF 35% is notable because the average EF in all large trials was much lower, and clinical benefit was mainly limited to EF ≤ 30%. This EF cut‐off value defines a substantial portion of potential ICD recipients. It seems therefore reasonable to limit ICD eligibility criteria in the EF range 30–35% to patients at highest risk only. We discuss and present some rational criteria to assist the clinician in improving risk stratification for preventive ICD implantation.
Background Amongst the 3 approved oral P2Y12 inhibitors for the treatment of patients with acute coronary syndrome (ACS), ticagrelor, but not prasugrel or clopidogrel, has been associated to ...off-target properties, such as improved endothelial-dependent vasomotion and increased adenosine plasma levels. Methods The Hunting for the off-target propertIes of Ticagrelor on Endothelial function and other Circulating biomarkers in Humans (HI-TECH) study ( NCT02587260 ) is a multinational, randomized, open-label, cross-over study with a Latin squares design, conducted at 5 European sites, in which patients free from recurrent ischemic or bleeding events ≥30 days after a qualifying ACS were allocated to sequentially receive a 30 ± 5-day treatment with prasugrel, clopidogrel, and ticagrelor in random order. The primary objective was to evaluate whether ticagrelor, at treatment steady state (i.e. after 30 ± 5 days of drug administration), as compared with both clopidogrel and prasugrel, is associated with an improved endothelial function, assessed with peripheral arterial tonometry., Thirty-six patients undergoing evaluable endothelial function assessment for each of the assigned P2Y12 inhibitor were needed to provide 90% power to detect a 10% relative change of the reactive hyperemia index (RHI) in the ticagrelor group. Conclusion The HI-TECH study is the first randomized, cross over study aiming to ascertain whether ticagrelor, when administered at approved regimen in post-ACS patients, improves endothelial function as compared with both clopidogrel and prasugrel.
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