Subacute saphenous vein graft stent thrombosis due to unusual drug interaction: a case report.

Background: Stent thrombosis is a potentially lethal complication of coronary angioplasty and responsible for 20% of all post-angioplasty myocardial infarctions. Unusual causes may be overlooked and difficult to identify. Case summary: A 70-year-old male with history of triple aortocoronary bypass presented with acute inferolateral ST-segment elevation myocardial infarction (STEMI). Critical stenosis of the vein graft to the right coronary artery was revealed, and with the use of distal embolic protection device, successful angioplasty with stent was performed under double antiplatelet treatment with aspirin and ticagrelor. Two weeks later, he presented again at the emergency department with an acute inferolateral STEMI. Subacute stent thrombosis with complete occlusion of the stented vein graft was evident. Repeated balloon dilatations restored the flow stabilizing the patient; optical coherence tomography showed good stent expansion and apposition. Scrutinizing the patient's history, we discovered comedication with carbamazepine that is a CYP3A4 inducer and reduces ticagrelor's effect. Switching to prasugrel ensured potent antiplatelet treatment, and the patient was discharged 5 days later. The 6-month follow-up was uneventful and free of symptoms. Discussion: Stent thrombosis has dire consequences, and the precipitating factors should always be investigated. Inadequate platelet inhibition secondary to non-compliance to therapy or resistance and suboptimal stent expansion/apposition are its main causes. Drug interactions are an underrecognized factor that may significantly alter the potency of antiplatelet drugs and also lead to stent thrombosis; thus, treatment is essential to be tailored to each patient comedication.

SAGE Score in Normotensive and Pre-Hypertensive Patients: A Proof of Concept. / Escore SAGE em Normotensos e Pré-Hipertensos: Uma Prova de Conceito.

BACKGROUND: The SAGE score was developed to detect individuals at risk for increased pulse wave velocity (PWV). So far, studies have been focused on hypertensive patients. OBJECTIVE: To assess the ability of the score to detect non-hypertensive and pre-hypertensive patients at risk for increased PWV. METHODS: Retrospective cross-sectional study of analysis of central blood pressure data and calculation of the SAGE score of non-hypertensive and pre-hypertensive patients. Each score point was analyzed for sensitivity, specificity, positive and negative predictive values, using the cut-off point for positive diagnosis a PVW ≥ 10m/s, ≥9.08 m/s (75thpercentile) and ≥7.30 m/s (50thpercentile). A p<0.05 was considered statistically significant. RESULTS: The sample was composed of 100 normotensive and pre-hypertensive individuals, with mean age of 52.64 ± 14.94 years and median PWV of 7.30 m/s (6.03 - 9.08). The SAGE score was correlated with age (r=0.938, p<0.001), glycemia (r=0.366, p<0.001) and glomerular filtration rate (r=-0.658, p<0.001). The area under the ROC curve was 0.968 (p<0.001) for PWV ≥ 10 m/s, 0.977 (p<0.001) for PWV ≥ 9.08 m/s and 0.967 (p<0.001) for PWV ≥ 7.30 m/s. The score 7 showed a specificity of 95.40% and sensitivity of 100% for PWV≥10 m/s. The cut-off point would be of five for a PWV≥9.08 m/s (sensitivity =96.00%, specificity = 94.70%), and two for a PWV ≥ 7.30 m/s. CONCLUSION: The SAGE score could identify individuals at higher risk of arterial stiffness, using different PWV cutoff points. However, the development of a specific score for normotensive and pre-hypertensive subjects is needed.

FUNDAMENTO: O SAGE foi desenvolvido para identificar hipertensos com chance de velocidade de onda de pulso (VOP) aumentada. Até o momento, as publicações do escore foram em hipertensos. OBJETIVO: Verificar a capacidade do SAGE de identificar os normotensos ou pré-hipertensos com chance de aumento da VOP. MÉTODOS: Transversal retrospectivo, incluiu exames de normotensos e pré-hipertensos que realizaram a medida central da pressão arterial e apresentavam os parâmetros para o cálculo do escore. Para cada pontuação do escore, foi analisada a sensibilidade, especificidade, valor preditivo positivo e negativo utilizando como ponto de corte para o diagnóstico positivo VOP ≥ 10m/s, ≥9,08 m/s (percentil 75) e ≥7,30 m/s (percentil 50). Um valor de p<0,05 foi adotado como estatisticamente significante. RESULTADOS: A amostra foi de 100 participantes normotensos ou pré-hipertensos, com média (DP) de 52,64 (14,94) anos e VOP mediana de 7,30 m/s (6,03 ­ 9,08). O SAGE apresentou correlação com idade (r=0,938, p<0,001), glicemia (r=0,366, p<0,001) e taxa de filtração de glomerular (r=-0,658, p<0,001). A área sob a curva ROC foi de 0,968 (p<0,001) para VOP≥10 m/s, 0,977 (p<0,001) para VOP≥9,08 m/s e 0,967 (p<0,001) para VOP≥7,30 m/s. O escore 7 apresentou especificidade de 95,40% e sensibilidade de 100% para VOP≥10 m/s. O ponto de corte seria cinco para VOP≥9,08 m/s (s=96,00%, e= 94,70%), e dois para VOP≥7,30 m/s. CONCLUSÃO: O SAGE foi capaz de identificar indivíduos com maior chance de apresentar rigidez arterial, utilizando diferentes pontos de corte de VOP. Entretanto, o desenvolvimento de um escore específico para normontensos e pré-hipertensos faz-se necessário.

Escore SAGE em Normotensos e Pré-Hipertensos: Uma Prova de Conceito / SAGE Score in Normotensive and Pre-Hypertensive Patients: A Proof of Concept

Resumo Fundamento O SAGE foi desenvolvido para identificar hipertensos com chance de velocidade de onda de pulso (VOP) aumentada. Até o momento, as publicações do escore foram em hipertensos. Objetivo Verificar a capacidade do SAGE de identificar os normotensos ou pré-hipertensos com chance de aumento da VOP. Métodos Transversal retrospectivo, incluiu exames de normotensos e pré-hipertensos que realizaram a medida central da pressão arterial e apresentavam os parâmetros para o cálculo do escore. Para cada pontuação do escore, foi analisada a sensibilidade, especificidade, valor preditivo positivo e negativo utilizando como ponto de corte para o diagnóstico positivo VOP ≥ 10m/s, ≥9,08 m/s (percentil 75) e ≥7,30 m/s (percentil 50). Um valor de p<0,05 foi adotado como estatisticamente significante. Resultados A amostra foi de 100 participantes normotensos ou pré-hipertensos, com média (DP) de 52,64 (14,94) anos e VOP mediana de 7,30 m/s (6,03 - 9,08). O SAGE apresentou correlação com idade (r=0,938, p<0,001), glicemia (r=0,366, p<0,001) e taxa de filtração de glomerular (r=-0,658, p<0,001). A área sob a curva ROC foi de 0,968 (p<0,001) para VOP≥10 m/s, 0,977 (p<0,001) para VOP≥9,08 m/s e 0,967 (p<0,001) para VOP≥7,30 m/s. O escore 7 apresentou especificidade de 95,40% e sensibilidade de 100% para VOP≥10 m/s. O ponto de corte seria cinco para VOP≥9,08 m/s (s=96,00%, e= 94,70%), e dois para VOP≥7,30 m/s. Conclusão O SAGE foi capaz de identificar indivíduos com maior chance de apresentar rigidez arterial, utilizando diferentes pontos de corte de VOP. Entretanto, o desenvolvimento de um escore específico para normontensos e pré-hipertensos faz-se necessário.

Abstract Background The SAGE score was developed to detect individuals at risk for increased pulse wave velocity (PWV). So far, studies have been focused on hypertensive patients. Objective To assess the ability of the score to detect non-hypertensive and pre-hypertensive patients at risk for increased PWV. Methods Retrospective cross-sectional study of analysis of central blood pressure data and calculation of the SAGE score of non-hypertensive and pre-hypertensive patients. Each score point was analyzed for sensitivity, specificity, positive and negative predictive values, using the cut-off point for positive diagnosis a PVW ≥ 10m/s, ≥9.08 m/s (75thpercentile) and ≥7.30 m/s (50thpercentile). A p<0.05 was considered statistically significant. Results The sample was composed of 100 normotensive and pre-hypertensive individuals, with mean age of 52.64 ± 14.94 years and median PWV of 7.30 m/s (6.03 - 9.08). The SAGE score was correlated with age (r=0.938, p<0.001), glycemia (r=0.366, p<0.001) and glomerular filtration rate (r=-0.658, p<0.001). The area under the ROC curve was 0.968 (p<0.001) for PWV ≥ 10 m/s, 0.977 (p<0.001) for PWV ≥ 9.08 m/s and 0.967 (p<0.001) for PWV ≥ 7.30 m/s. The score 7 showed a specificity of 95.40% and sensitivity of 100% for PWV≥10 m/s. The cut-off point would be of five for a PWV≥9.08 m/s (sensitivity =96.00%, specificity = 94.70%), and two for a PWV ≥ 7.30 m/s. Conclusion The SAGE score could identify individuals at higher risk of arterial stiffness, using different PWV cutoff points. However, the development of a specific score for normotensive and pre-hypertensive subjects is needed.

Magmaris Resorbable Magnesium Scaffold Versus Conventional Drug-Eluting Stent in ST-Segment Elevation Myocardial Infarction: 1-Year Results of a Propensity-Score-Matching Comparison.

Magmaris® (Biotronik AG, Switzerland) is the first RMS and early experience has shown promising results in stable coronary artery disease. Acute coronary syndromes have been hypothesized as a potential target group for bioresorbable scaffolds, but the efficacy and safety of RMS has not been extensively studied in ST-segment elevation myocardial infarction (STEMI). BEST-MAG is a prospective multicenter trial designed to evaluate optical coherence tomography (OCT-)guided implantation of resorbable magnesium scaffold (RMS) in STEMI. Consecutive STEMI patients fulfilling inclusion/exclusion criteria were treated with RMS following a standardized OCT-based implantation technique including systematic pre- and post-dilatation, and baseline plus final OCT imaging. The primary endpoint was a device oriented composite endpoint (DOCE) including cardiac death, target vessel myocardial infarction (TV-MI) and target lesion revascularization (TLR) within 12 months. Clinical outcomes were compared after propensity score matching (PSM) to the results of the randomized controlled BIOSTEMI trial comparing biodegradable polymer sirolimus eluting (BP-SES) and durable polymer everolimus eluting stents (DP-EES) in STEMI. Between 15th February 2019 and 25th May 2020, 30 patients were included in 5 centers. Procedural success was achieved in all cases based on OCT control with final scaffold expansion of 82 ± 11%. At twelve-months, DOCE rate was 13.3% (n = 4), including 4 cases of TLR (13.3%) and one case of TV-MI (3.3%). No cardiac death occurred, and no scaffold thrombosis (ScT) was observed. Using PSM, DOCE rates in BP-SES and DP-EES groups were 10% and 6% respectively and TLR rates were 3.3% and 0.0%. In this study, OCT-guided RMS implantation in selected STEMI patients appeared feasible but was associated with numerically higher rates of TLR as compared with conventional drug-eluting stents, although the limited number of patients included in this analysis does not allow drawing statistically significant conclusions.

A SAGE score cutoff that predicts high-pulse wave velocity as measured by oscillometric devices in Brazilian hypertensive patients.

We aimed to identify the optimal cutoff SAGE score for Brazilian hypertensive patients who had their pulse wave velocity (PWV) measured with oscillometric devices. A retrospective analysis of patients who underwent central blood pressure measurement using a validated oscillometric device, the Mobil-O-Graph® (IEM, Stolberg, Germany), between 2012 and 2019 was performed. Patients with arterial hypertension and available data on all SAGE parameters were selected. An ROC curve was constructed using the Youden index to define the best score to identify patients at high risk for high PWV. A total of 837 patients met the criteria for SAGE and diagnosis of hypertension. The median age was 59.0 years (interquartile range [IQR]: 47.0-68.0), and 50.7% of the patients were women. The following comorbidities and conditions were present: dyslipidemia (37.4%), diabetes (20.7%), a body mass index score ≥30 kg/m2 (36.6%), use of antihypertensive drugs (69.5%), and smoking (18.3%). The median peripheral blood pressure was 128 mmHg (IQR: 117-138 mmHg) for systolic and 81 mmHg (IQR: 73-90 mmHg) for diastolic blood pressure. The median PWV was 8.3 m/s (7.1-9.8 m/s), and the prevalence of high PWV (≥10 m/s) was 22.9% (192 patients). A cutoff SAGE score ≥8 was effective at identifying a high risk of PWV ≥ 10 m/s, achieving 67.19% sensitivity (95% CI: 60.1-73.8) and 93.95% specificity (95% CI: 91.8-95.7). With this cutoff point, 1 out of every 5 treated hypertensive patients would be referred for a PWV measurement. A SAGE score of ≥8 identified Brazilian hypertensive patients with a high risk of future cardiovascular events (PWV ≥ 10 m/s).

Guiding Myocardial Revascularization by Algorithmic Interpretation of FFR Pullback Curves: A Proof of Concept Study.

Background: Coronary artery disease distribution along the vessel is a main determinant of FFR improvement after PCI. Identifying focal from diffuse disease from visual inspections of coronary angiogram (CA) and FFR pullback (FFR-PB) are operator-dependent. Computer science may standardize interpretations of such curves. Methods: A virtual stenting algorithm (VSA) was developed to perform an automated FFR-PB curve analysis. A survey analysis of the evaluations of 39 vessels with intermediate disease on CA and a distal FFR <0.8, rated by 5 interventional cardiologists, was performed. Vessel disease distribution and PCI strategy were successively rated based on CA and distal FFR (CA); CA and FFR-PB curve (CA/FFR-PB); and CA and VSA (CA/VSA). Inter-rater reliability was assessed using Fleiss kappa and an agreement analysis of CA/VSA rating with both algorithmic and human evaluation (operator) was performed. We hypothesize that VSA would increase rater agreement in interpretation of epicardial disease distribution and subsequent evaluation of PCI eligibility. Results: Inter-rater reliability in vessel disease assessment by CA, CA/FFR-PB, and CA/VSA were respectively, 0.32 (95% CI: 0.17-0.47), 0.38 (95% CI: 0.23-0.53), and 0.4 (95% CI: 0.25-0.55). The raters' overall agreement in vessel disease distribution and PCI eligibility was higher with the VSA than with the operator (respectively, 67 vs. 42%, and 80 vs. 70%, both p < 0.05). Compared to CA/FFR-PB, CA/VSA induced more reclassification toward a focal disease (92 vs. 56.2%, p < 0.01) with a trend toward more reclassification as eligible for PCI (70.6 vs. 33%, p = 0.06). Change in PCI strategy did not differ between CA/FFR-PB and CA/VSA (23.6 vs. 28.5%, p = 0.38). Conclusions: VSA is a new program to facilitate and standardize the FFR pullback curves analysis. When expert reviewers integrate VSA data, their assessments are less variable which might help to standardize PCI eligibility and strategy evaluations. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT03824600.

Global Fractional Flow Reserve Value Predicts 5-Year Outcomes in Patients With Coronary Atherosclerosis But Without Ischemia.

Background Global fractional flow reserve (FFR) (ie, the sum of the FFR values in the 3 major coronary arteries) is a physiologic correlate of global atherosclerotic burden. The objective of the present study was to investigate the value of global FFR in predicting long-term clinical outcome of patients with stable coronary artery disease but no ischemia-inducing stenosis. Methods and Results We studied major adverse cardiovascular events (MACEs: all-cause death, myocardial infarction, and any revascularization) after 5 years in 1122 patients without significant stenosis (all FFR >0.80; n=275) or with at least 1 significant stenosis successfully treated by percutaneous coronary intervention (ie, post-percutaneous coronary intervention FFR >0.80; n=847). The patients were stratified into low, mid, or high tertiles of global FFR (≤2.80, 2.80-2.88, and ≥2.88). Patients in the lowest tertile of global FFR showed the highest 5-year MACE rate compared with those in the mid or high tertile of global FFR (27.5% versus 22.0% and 20.9%, respectively; log-rank P=0.040). The higher 5-year MACE rate was mainly driven by a higher rate of revascularization in the low global FFR group (16.4% versus 11.3% and 11.8%, respectively; log-rank P=0.038). In a multivariable model, an increase in global FFR of 0.1 unit was associated with a significant reduction in the rates of MACE (hazard ratio [HR], 0.988; 95% CI, 0.977-0.998; P=0.023), myocardial infarction (HR, 0.982; 95% CI, 0.966-0.998; P=0.032), and revascularization (HR, 0.985; 95% CI, 0.972-0.999; P=0.040). Conclusions Even in the absence of ischemia-producing stenoses, patients with a low global FFR, physiologic correlate of global atherosclerotic burden, present a higher risk of MACE at 5-year follow-up.

DISENGAGE Registry.

BACKGROUND: During fractional flow reserve (FFR) measurement, the simple presence of the guiding catheter (GC) within the coronary ostium might create artificial ostial stenosis, affecting the hyperemic flow. We aimed to investigate whether selective GC engagement of the coronary ostium might impede hyperemic flow, and therefore impact FFR measurements and related clinical decision-making. METHODS: In the DISENGAGE (Determination of Fractional Flow Reserve in Intermediate Coronary Stenosis With Guiding Catheter Disengagement) registry, FFR was prospectively measured twice (with GC engaged [FFReng] and disengaged [FFRdis]) in 202 intermediate stenoses of 173 patients. We assessed (1) whether ΔFFReng-FFRdis was significantly different from the intrinsic variability of repeated FFR measurements (test-retest repeatability); (2) whether the extent of ΔFFReng-FFRdis could be clinically significant and therefore able to impact clinical decision-making; and (3) whether ΔFFReng-FFRdis related to the stenosis location, that is, proximal and middle versus distal coronary segments. RESULTS: Overall, FFR significantly changed after GC disengagement: FFReng 0.84±0.08 versus FFRdis 0.80±0.09, P<0.001. Particularly, in 38 stenoses (19%) with FFR values in the 0.81 to 0.85 range, GC disengagement was associated with a shift from above to below the 0.80 clinical cutoff, resulting into a change of the treatment strategy from medical therapy to percutaneous coronary intervention. The impact of GC disengagement was significantly more pronounced with stenoses located in proximal and middle as compared with distal coronary segments (ΔFFReng-FFRdis, proximal and middle 0.04±0.03 versus distal segments 0.03±0.03; P=0.042). CONCLUSIONS: GC disengagement results in a shift of FFR values from above to below the clinical cutoff FFR value of 0.80 in 1 out of 5 measurements. This occurs mostly when the stenosis is located in proximal and middle coronary segments and the FFR value is close to the cutoff value.

Usefulness of the SAGE score to predict elevated values of brachial-ankle pulse wave velocity in Japanese subjects with hypertension.

The score based on the office systolic blood pressure, age, fasting blood glucose level, and estimated glomerular filtration rate (SAGE score) has been proposed as a useful marker to identify elevated values of carotid-femoral pulse wave velocity (PWV). The present cross-sectional study was conducted to examine whether the SAGE score is also a useful marker to identify subjects with elevated brachial-ankle PWV values in Japanese subjects with hypertension. We measured the brachial-ankle PWV and calculated the SAGE score in a total of 1019 employees of a Japanese company with hypertension and 817 subjects with hypertension derived from a multicenter study cohort. The analyses in this study were based on data from these two study groups as well as on a composite population of the two (n = 1836). The receiver operating characteristic curve analysis showed that the area under the curve to identify subjects with brachial-ankle PWV values of ≥1800 cm/s was over 0.70 in each of the three study groups. Even after adjustments, a SAGE score ≥7 had a significant odds ratio for identifying subjects with brachial-ankle PWV values ≥1800 cm/s in the 1836 study subjects from the composite occupational and multicenter study cohort (odds ratio = 2.1, 95% confidence interval = 1.4-3.0, P < 0.01). Thus, in Japanese subjects with hypertension, the SAGE score may be a useful marker for identifying subjects with elevated brachial-ankle PWV values.

Procedural microvascular activation in long lesions treated with bioresorbable vascular scaffolds or everolimus-eluting stents: the PROACTIVE trial.

AIMS: Significant platelet activation after long stented coronary segments has been associated with periprocedural microvascular impairment and myonecrosis. In long lesions treated either with an everolimus-eluting bioresorbable vascular scaffold (BVS) or an everolimus-eluting stent (EES), we aimed to investigate (a) procedure-related microvascular impairment, and (b) the relationship of platelet activation with microvascular function and related myonecrosis. METHODS AND RESULTS: Patients (n=66) undergoing elective percutaneous coronary intervention (PCI) in long lesions were randomised 1:1 to either BVS or EES. The primary endpoint was the difference between groups in changes of pressure-derived corrected index of microvascular resistance (cIMR) after PCI. Periprocedural myonecrosis was assessed by high-sensitivity cardiac troponin T (hs-cTnT), platelet reactivity by high-sensitivity adenosine diphosphate (hs-ADP)-induced platelet reactivity with the Multiplate Analyzer. Post-dilatation was more frequent in the BVS group, with consequent longer procedure time. A significant difference was observed between the two groups in the primary endpoint of ΔcIMR (p=0.04). hs-ADP was not different between the groups at different time points. hs-cTnT significantly increased after PCI, without difference between the groups. CONCLUSIONS: In long lesions, BVS implantation is associated with significant acute reduction in IMR as compared with EES, with no significant interaction with platelet reactivity or periprocedural myonecrosis.

Fractional flow reserve in patients with reduced ejection fraction.

AIMS: Fractional flow reserve (FFR) has never been investigated in patients with reduced ejection fraction and associated coronary artery disease (CAD). We evaluated the impact of FFR on the management strategies of these patients and related outcomes. METHODS AND RESULTS: From 2002 to 2010, all consecutive patients with left ventricular ejection fraction (LVEF) ≤50% undergoing coronary angiography with ≥1 intermediate coronary stenosis [diameter stenosis (DS)% 50-70%] treated based on angiography (Angiography-guided group) or according to FFR (FFR-guided group) were screened for inclusion. In the FFR-guided group, 433 patients were matched with 866 contemporary patients of the Angiography-guided group. For outcome comparison, 617 control patients with LVEF >50% were included. After FFR, stenotic vessels per patient were significantly downgraded compared with the Angiography-guided group (1.43 ± 0.98 vs. 1.97 ± 0.84; P < 0.001). This was associated with lower revascularization rate (52% vs. 62%; P < 0.001) in the FFR-guided vs. the Angiography-guided group. All-cause death at 5 years of follow-up was significantly lower in the FFR-guided as compared with Angiography-guided group [22% vs. 31%. HR (95% CI) 0.64 (0.51-0.81); P < 0.001]. Similarly, rate of major adverse cardiovascular and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, revascularization, and stroke) was significantly lower in the FFR-guided group [40% vs. 46% in the Angiography-guided group. HR (95% CI) 0.81 (0.67-0.97); P = 0.019]. Higher rates of death and MACCE were observed in patients with reduced LVEF compared with the control cohort. CONCLUSIONS: In patients with reduced LVEF and CAD, FFR-guided revascularization was associated with lower rates of death and MACCE at 5 years as compared with the Angiography-guided strategy. This beneficial impact was observed in parallel with less coronary artery bypass grafting and more patients deferred to percutaneous coronary intervention or medical therapy.

Association of Estimated Pulse Wave Velocity With Survival: A Secondary Analysis of SPRINT.

Importance: Aortic stiffness, as assessed by carotid-femoral pulse wave velocity, is an independent predictor of future events in individuals with hypertension. Recent data suggest a predictive role of estimated pulse wave velocity (ePWV) calculated by previously published equations using age and blood pressure in future events in individuals with hypertension. Objective: To investigate whether ePWV and its response to treatment predict survival in the Systolic Blood Pressure Intervention Trial (SPRINT). Design, Setting, and Participants: This exploratory, hypothesis-generating, post hoc secondary analysis conducted from October 1, 2018, to August 31, 2019, examined data from 9361 participants in SPRINT and calculated ePWV at baseline and at 12 months. Adjusted hazard ratios (HRs) with 95% CIs of ePWV per 1 SD were estimated using Cox proportional hazards regression models. A total of 8450 patients were assigned to 4 groups according to their treatment allocation and their response in ePWV after 12 months. Interventions: Participants were assigned a systolic blood pressure target of less than 120 mm Hg (intensive treatment) or less than 140 mm Hg (standard treatment). Main Outcomes and Measures: The primary composite cardiovascular outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. Results: In the SPRINT population (3332 women and 6029 men; mean [SD] age, 67.9 [9.4] years), ePWV predicted the primary outcome (HR, 1.30 [95% CI, 1.17-1.43]; P < .001) and all-cause death (HR, 1.65 [95% CI, 1.46-1.86]; P < .001) independent of the Framingham Risk Score. Estimated pulse wave velocity improved the C statistic model for the primary outcome from 0.676 (95% CI, 0.65-0.70) to 0.683 (95% CI, 0.66-0.71; P = .049) and improved the C statistic model for all-cause death from 0.67 (95% CI, 0.64-0.69) to 0.69 (95% CI, 0.66-0.72; P = .03). Net reclassification index indicated improvement in risk discrimination for survival compared with the Framingham Risk Score (categorical net reclassification index = 0.111; P < .001). Regarding response to treatment, intensive treatment was superior to standard treatment only when it was accompanied with a response in ePWV at the first year, while, within the standard treatment group, individuals whose ePWV responded to antihypertensive treatment had improved all-cause mortality, with a 42% lower risk of death compared with nonresponders (HR, 0.58 [95% CI, 0.36-0.94]; P = .03); effects were independent of changes in systolic blood pressure. Conclusions and Relevance: These results suggest that, in the SPRINT trial, ePWV predicted outcomes independent of the Framingham Risk Score, indicating an incremental role of markers of aortic stiffness on cardiovascular risk. Better survival of individuals whose ePWV responded to antihypertensive treatment independently of systolic blood pressure reduction suggests a role of markers of aortic stiffness as effective treatment targets in individuals with hypertension.

Association of Improvement in Fractional Flow Reserve With Outcomes, Including Symptomatic Relief, After Percutaneous Coronary Intervention.

Importance: Whether the improvement in myocardial perfusion provided by percutaneous coronary intervention (PCI) is associated with symptomatic relief or improved outcomes has not been well investigated. Objective: To investigate the prognostic value of the improvement in fractional flow reserve (FFR) after PCI (ΔFFR) on patients' symptoms and 2-year outcomes. Design, Setting, and Participants: This study is a post hoc analysis of data from patients undergoing FFR-guided PCI in the randomized clinical trials Fractional Flow Reserve vs Angiography for Multivessel Evaluation (FAME) 1 (NCT00267774; 2009) and FAME 2 (NCT01132495; 2012), with inclusion of 2 years of follow-up data. The FAME 1 trial included patients with multivessel coronary artery disease from 20 medical centers in Europe and the United States. The FAME 2 trial included patients with stable coronary artery disease involving up to 3 vessels from 28 sites in Europe and North America. Lesions from the group in the FAME 1 trial from whom FFR was measured and the group in the FAME 2 trial who received FFR-guided PCI plus medical therapy were analyzed. Data analysis occurred from May 2017 to May 2018. Interventions: Measure of post-PCI FFR. Main Outcomes and Measures: Vessel-oriented clinical events at 2 years, a composite of cardiac death, target vessel-associated myocardial infarction, and target vessel revascularization. Results: This analysis included 639 patients from whom pre-PCI and post-PCI FFR values were available. Of their 837 lesions, 277 were classified into the lowest tertile (ΔFFR≤0.18), 282 into the middle tertile (0.19≤ΔFFR≤0.31), and 278 into the highest tertile (ΔFFR>0.31). Vessel-oriented clinical events were significantly more frequent in the lowest tertile (n = 25 of 277 [9.1%]) compared with the highest tertile (n = 13 of 278 [4.7%]; hazard ratio, 2.01 [95% CI, 1.03-3.92]; P = .04). In addition, a significant association was observed between ΔFFR and symptomatic relief (odds ratio, 1.33 [95% CI, 1.02-1.74]; P = .02). Conclusions and Relevance: In this analysis of 2 randomized clinical trials, the larger the improvement in FFR, the larger the symptomatic relief and the lower the event rate. This suggests that measuring FFR before and after PCI provides clinically useful information.