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Background: Some aspects of prognosis are not reflected by cumulative survival estimates. These aspects include information on the time already survived by the patient and the patient's survival compared with the general population. Conditional survival (ie, conditional on having survived a certain period of time already) and relative conditional survival (ie, compared with the general population) do incorporate these aspects. We investigated these measures of prognosis in patients undergoing percutaneous coronary intervention.Methods and Results: We studied 17 903 consecutive patients undergoing percutaneous coronary intervention between 2000 and 2014. Cumulative survival was estimated for patients with ST-segment-elevation myocardial infarction (n=5996, 853 deaths), non-ST-segment-elevation myocardial infarction (n=5371, 901 deaths), and stable angina pectoris (n=6536, 965 deaths) in 4 age categories. One-year conditional and relative conditional survival up to 10 years post-percutaneous coronary intervention was calculated. The results demonstrated that 1-year cumulative survival for patients with ST-segment-elevation myocardial infarction aged ≥76 years was 83%. One-year conditional survival, conditional on surviving the first month, was 92% in this group, and relative conditional survival (relative to the general population) was 99%. In younger age categories and in patients with non-ST-segment-elevation myocardial infarction and stable angina pectoris , similar patterns were found albeit less pronounced. Five-year relative conditional rendered similar results.Conclusions: Relative conditional survival provides a comprehensive picture of patient prognosis, particularly for older patients with ST-segment-elevation myocardial infarction. Although, as expected, their cumulative survival is low, once they survive the first month after percutaneous coronary intervention, their prognosis is comparable to that of the general population. Therefore, relative conditional survival estimates provide an important, meaningful addition when discussing prognosis with patients. [ABSTRACT FROM AUTHOR]

Background: Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk. Methods: TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling. Results: Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78–2.57) unadjusted, 1.96 (1.49–2.53) after adjustment for clinical confounders and 1.44 (1.05–1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78–3.33) and 1.52 (1.15–2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785). Conclusions: Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice. Registration: URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.) [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Fractional flow reserve (FFR)-guided treatment has been demonstrated to improve percutaneous coronary intervention (PCI) results. However, little is known on the long-term impact of low post-PCI FFR. Methods: This is a large prospective all comers study evaluating the impact of post-PCI FFR on clinical outcomes. All patients undergoing successful PCI were eligible for enrollment. FFR measurements were performed immediately after PCI when the operator considered the angiographic result acceptable and final. No further action was undertaken based on the post-PCI result. Suboptimal post-PCI FFR was defined as FFR<0.90. The primary end point was major adverse cardiac events, a composite of cardiac death, any myocardial infarction, or any revascularization at 2-year follow-up. Secondary end points were target vessel revascularizations and stent thrombosis and the separate components of the primary end point. Results: A total of 1000 patients were enrolled. Post-PCI FFR was successfully measured in 1165 vessels from 959 patients. A poststenting FFR<0.90 was observed in 440 vessels (37.8%). A total of 399 patients had at least 1 vessel with FFR<0.90 post-PCI. At 2-year follow-up, a patient level analysis showed no association between post-PCI FFR and major adverse cardiac event (hazard ratio [HR], 1.08 [95% CI, 0.73–1.60], P =0.707), cardiac death (HR, 1.55 [95% CI, 0.72–3.36], P =0.261), any myocardial infarction (HR, 1.53 [95% CI, 0.78–3.02], P =0.217). A vessel level analysis showed a higher rate of target vessel revascularization (HR, 1.91 [95% CI, 1.06–3.44], P =0.030) and a tendency toward higher rate of stent thrombosis (HR, 2.89 [95% CI, 0.88–9.48], P =0.081) with final post-PCI FFR<0.90. Conclusions: Suboptimal post-PCI FFR has only a moderate impact on major adverse cardiac event but coronary arteries with a post-PCI FFR<0.90 have a higher rate of target vessel revascularization. [ABSTRACT FROM AUTHOR]

Background: Instantaneous wave–free ratio (iFR) offers a reliable non–hyperemic assessment of coronary physiology but requires dedicated proprietary software with a fully automated algorithm. We hypothesized that dPR (diastolic pressure ratio), calculated with novel universal software, has a strong correlation with iFR, similar diagnostic accuracy relative to resting distal coronary artery pressure/aortic pressure and fractional flow reserve (FFR). Methods and Results: The dPR study is an observational, retrospective, single-center cohort study including patients who underwent iFR or FFR. Dedicated software was used to calculate the dPR from Digital Imaging and Communications in Medicine (DICOM) pressure waveforms. The flat period on the pressure difference between sample (dP) to the time difference between the same sample points (dt) signal was used to detect automatically the period, where the resistance is low and constant, and to calculate the dPR, which is an average over 5 consecutive heartbeats. The software was validated by correlating iFR results with dPR. Software validation was done by comparing 78 iFR measurements in 44 patients who underwent iFR. Mean iFR and dPR were 0.91±0.10 and 0.92±0.10, respectively, with a significant linear correlation (R =0.997; P <0.001). Diagnostic accuracy was tested in 100 patients who underwent FFR. Mean FFR, resting distal coronary artery pressure/aortic pressure, and dPR were 0.85±0.09, 0.94±0.05, and 0.93±0.07, respectively. There was a significant linear correlation between dPR and FFR (R =0.77; P <0.001). Both distal coronary artery pressure/aortic pressure and dPR had good diagnostic accuracy in the identification of lesions with an FFR ≤0.80 (area under the curve, 0.84; 95% CI, 0.76–0.92 and 0.86; 95% CI, 0.78–0.93, respectively). Conclusions: dPR, calculated by a novel validated software tool, showed a strong linear correlation with iFR. dPR correlated well with FFR with a good diagnostic accuracy to identify positive FFR. [ABSTRACT FROM AUTHOR]

Background: Previous studies on the association between cytomegalovirus (CMV) infection and cardiac allograft vasculopathy (CAV) were conducted on patients transplanted in the prevalganciclovir prophylaxis era. The aim of our study is to evaluate this relation in heart transplantation (HTx) recipients treated according to current prophylactic and immunosuppressive regimens., Methods: This single-center retrospective study included all consecutive adult patients that underwent HTx between January 1, 2000, and May 31, 2018. Clinically relevant CMV infection was defined as either plasma CMV DNAemia ≥ 1000 IU/mL with/without clinical symptoms or <1000 IU/mL with symptoms. The primary endpoint was first manifestation of CAV diagnosed by coronary angiography. For statistical analysis, the cause-specific hazard regression model was applied, with clinically relevant CMV infection and any CMV infection as time-dependent variables., Results: In total, 260 patients were included in the analysis. The median (interquartile range) follow-up was 7.88 (4.21-12.04) years. During the follow-up, clinically relevant CMV infection was diagnosed in 96 (37%) patients and CAV in 149 (57%) patients. In the multivariate regression analysis, independent predictors of CAV were: number of rejection episodes (cause-specific hazard ratio [95% confidence interval]: 1.18 [1.04-1.34], P = 0.01), hypertension (1.61 [1.11-2.34], P = 0.01), treatment with mycophenolate mofetil (0.68 [0.47-0.97], P = 0.03). No significant association was observed between CMV infection and CAV, except for patients who experienced a breakthrough CMV infection (n = 24) during prophylaxis (1.94 [1.11-3.40], P = 0.02)., Conclusions: In the era of contemporary immunosuppression and valganciclovir prophylaxis, a significant effect of CMV infection on the risk of CAV was seen only among HTx recipients with CMV breakthrough infection.

Objective: Previous proteomics experiments have demonstrated that several proteins are differentially expressed in vulnerable human carotid plaques compared with stable plaques. This study aims to investigate the prognostic value of 13 such circulating biomarkers in patients with coronary artery disease., Approach and Results: Between 2008 and 2011, 768 patients who underwent coronary angiography for acute coronary syndrome or stable angina pectoris were included in a prospective biomarker study. Plasma concentrations of 13 biomarkers were measured in 88 patients who experienced a major adverse cardiovascular event (MACE) within 1 year and 176 control patients without MACE who were matched on age, sex, and number of diseased coronary vessels. MACE comprised all-cause mortality, acute coronary syndrome, unplanned coronary revascularization, and stroke. After adjustment for established cardiovascular risk factors, osteoglycin (OGN; odds ratio per SD increase in ln-transformed OGN, 1.53; 95% confidence interval, 1.11-2.11; P=0.010) and neutrophil gelatinase-associated lipocalin/matrix metalloproteinase 9 (NGAL/MMP9; odds ratio per SD increase in ln-transformed NGAL/MMP9, 1.37; 95% confidence interval, 1.01-1.85; P=0.042) complex were independently associated with MACE during follow-up. These associations were independent of C-reactive protein levels. Adding OGN or NGAL/MMP9 to a model containing conventional risk factors did not significantly improve discriminatory power (OGN: area under receiver operating characteristic curve, 0.75 versus 0.67; NGAL/MMP9: 0.73 versus 0.67) but did significantly improve risk reclassification (OGN: net reclassification index=0.29; 95% confidence interval, 0.05-0.53; P<0.019; NGAL/MMP9: net reclassification index=0.44; 95% confidence interval, 0.20-0.69; P<0.001)., Conclusions: Circulating OGN and NGAL/MMP9 complex are promising biomarkers that are expressed in vulnerable atherosclerotic plaques and may have incremental value for prediction of MACE within 1 year after coronary angiography.

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) may be a new and independent predictor of cardiovascular events. The effect of Lp-PLA2 may be exerted through effects of the enzyme on the development of atherosclerosis. Therefore, we investigated the association between Lp-PLA2 activity and measures of extracoronary atherosclerosis., Methods and Results: Lp-PLA2 activity was determined in a random sample of 1820 participants from the Rotterdam Study, a population-based cohort study in men and women > or =55 years. Common carotid intima-media thickness, carotid plaques, ankle-arm index, and aortic calcification were examined. Atherosclerosis status could be assigned in 1609 participants. The age-adjusted odds ratio of having atherosclerosis at any site for the highest versus the lowest tertile of Lp-PLA2 activity was 1.86 (95% CI, 1.01 to 3.43) in men and 1.60 (95% CI, 1.08 to 2.37) in women. After additional adjustment for cholesterol, these associations attenuated or even disappeared. The odds ratios of having atherosclerosis at specific sites (carotid arteries and aortic-iliac-femoral tract) followed a similar pattern., Conclusions: Although Lp-PLA2 has been found to be independently associated with cardiovascular events, the association with measures of subclinical extracoronary atherosclerosis found in this study strongly attenuated or even disappeared after adjustment for cholesterol.