Age and functional relevance of coronary stenosis: a post hoc analysis of the ADVISE II trial.

BACKGROUND: The influence of age-dependent changes on fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) and the response to pharmacological hyperaemia has not been investigated. AIMS: We investigated the impact of age on these indices. METHODS: This is a post hoc analysis of the ADVISE II trial, including a total of 690 pressure recordings (in 591 patients). Age-dependent correlations with FFR and iFR were calculated and adjusted for stenosis severity. Patients were stratified into three age terciles. The hyperaemic response to adenosine, calculated as the difference between resting and hyperaemic pressure ratios, and the prevalence of FFR-iFR discordance were assessed. RESULTS: Age correlated positively with FFR (r=0.08, 95% CI: 0.01 to 0.15, p=0.015), but not with iFR (r=-0.03, 95% CI: -0.11 to 0.04, p=0.411). The hyperaemic response to adenosine decreased with patient age (0.12±0.07, 0.11±0.06, 0.09±0.05, for the 1st [33-58 years], 2nd [59-69 years] and 3rd [70-94 years] age tertiles, respectively, p<0.001) and showed significant correlation with age (r=-0.14, 95% CI: -0.21 to -0.06, p<0.001). The proportion of patients with FFR ≤0.80+iFR >0.89 discordance doubled in the first age tercile (14.1% vs 7.1% vs 7.0%, p=0.005). CONCLUSIONS: The hyperaemic response of the microcirculation to adenosine administration is age dependent. FFR values increase with patient age, while iFR values remain constant across the age spectrum. These findings contribute to explaining differences observed in functional stenosis classification with hyperaemic and non-hyperaemic coronary indices.

Usefulness of Routine Fractional Flow Reserve for Clinical Management of Coronary Artery Disease in Patients With Diabetes.

Importance: Approximately one-third of patients considered for coronary revascularization have diabetes, which is a major determinant of clinical outcomes, often influencing the choice of the revascularization strategy. The usefulness of fractional flow reserve (FFR) to guide treatment in this population is understudied and has been questioned. Objective: To evaluate the usefulness and rate of major adverse cardiovascular events (MACE) of integrating FFR in management decisions for patients with diabetes who undergo coronary angiography. Design, Setting, and Participants: This cross-sectional study used data from the PRIME-FFR study derived from the merger of the POST-IT study (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease [March 2012-November 2013]) and R3F study (French Study of FFR Integrated Multicenter Registries Implementation of FFR in Routine Practice [October 2008-June 2010]), 2 prospective multicenter registries that shared a common design. A population of all-comers for whom angiography disclosed ambiguous lesions was analyzed for rates, patterns, and outcomes associated with management reclassification, including revascularization deferral, in patients with vs without diabetes. Data analysis was performed from June to August 2018. Main Outcomes and Measures: Death from any cause, myocardial infarction, or unplanned revascularization (MACE) at 1 year. Results: Among 1983 patients (1503 [77%] male; mean [SD] age, 65 [10] years), 701 had diabetes, and FFR was performed for 1.4 lesions per patient (58.2% of lesions in the left anterior descending artery; mean [SD] stenosis, 56% [11%]; mean [SD] FFR, 0.81 [0.01]). Reclassification by FFR was high and similar in patients with and without diabetes (41.2% vs 37.5%, P = .13), but reclassification from medical treatment to revascularization was more frequent in the former (142 of 342 [41.5%] vs 230 of 730 [31.5%], P = .001). There was no statistical difference between the 1-year rates of MACE in reclassified (9.7%) and nonreclassified patients (12.0%) (P = .37). Among patients with diabetes, FFR-based deferral identified patients with a lower risk of MACE at 12 months (25 of 296 [8.4%]) compared with those undergoing revascularization (47 of 257 [13.1%]) (P = .04), and the rate was of the same magnitude of the observed rate among deferred patients without diabetes (7.9%, P = .87). Status of insulin treatment had no association with outcomes. Patients (6.6% of the population) in whom FFR was disregarded had the highest MACE rates regardless of diabetes status. Conclusions and Relevance: Routine integration of FFR for the management of coronary artery disease in patients with diabetes may be associated with a high rate of treatment reclassification. Management strategies guided by FFR, including revascularization deferral, may be useful for patients with diabetes.

[Diabetes Screening in Patients with Macrovascular Coronary Disease: Are the New European Guidelines a Step Backwards?] / Rastreio da Diabetes em Doentes com Doença Macrovascular Coronária: As Novas Guidelines Europeias são um Retrocesso?

BACKGROUND: The new European guidelines on diabetes mellitus and cardiovascular diseases propose that the FINnish Diabetes RIsk SCore should be used to evaluate the risk of diabetes mellitus and that diabetes mellitus screening in coronary artery disease patients should be based on fasting glucose and HbA1c. The 2 hour oral glucose tolerance test, recommended for all pts in the previous guidelines, is now only recommended for 'inconclusive' cases. We aimed to evaluate this new strategy. MATERIAL AND METHODS: Fasting glucose, HbA1c and glucose tolerance test (75 g, 2h) were prospectively evaluated in a consecutive group of pts with coronary artery disease. ADA criteria (both glucose tolerance test and HbA1c) were used to define diabetes mellitus and pre-diabetes mellitus. Diabetes mellitus risk was evaluated according to the FINnish Diabetes RIsk SCore. RESULTS: A total of 135 patients were included (mean age 62.3 +/- 13.1 years, 99 males). Glucose tolerance test and HbA1c together diagnosed 18 (13.3%) new cases of diabetes mellitus and 77 (57.0%) patients with pre-diabetes mellitus. Fasting glucose + HbA1c (guidelines strategy) identified 12/18 patients with diabetes mellitus (Sens 66.7%; negative predictive value 95.1%; Kappa 0.78; p < 0.0001) and 83/95 patients with glucose anomalies (pre- diabetes mellitus + diabetes mellitus) (Sens 87.4%; negative predictive value 76.9%). Performing glucose tolerance test in the 29 patients with an elevated FINnish Diabetes RIsk SCore would allow identifying 15/18 patients with diabetes mellitus (Sens 83.3%; negative predictive value 97.5%; Kappa 0.85; p < 0.0001) and 86/95 patients with glucose anomalies (Sens 90.5%; negative predictive value 81.6%). DISCUSSION: Although this strategy improved the screening accuracy, one in each six patients with diabetes mellitus would still remain undiagnosed, as compared to measuring HbA1c and performing an glucose tolerance test in all patients. CONCLUSION: Using the FINnish Diabetes RIsk SCore to select candidates to additional glucose tolerance test improves the accuracy for identifying diabetic patients, as compared with fasting glucose + HbA1c alone. However, 1/6 patients diabetes mellitus is still left undiagnosed with this strategy proposed by the current guidelines.

Introdução: As novas recomendações europeias de diabetes mellitus tipo 2 e doença cardiovascular sugerem que o risco de diabetes mellitus tipo 2 deve ser avaliado através do score de risco FINnish Diabetes RIsk SCore e que o rastreio de diabetes mellitus tipo 2 na população com doença arterial coronária deve ser efetuado apenas com a glicemia plasmática em jejum e a HbA1, remetendo a prova de tolerância oral à glicose para os casos 'inconclusivos'. Pretendemos avaliar os resultados desta estratégia, que difere da previamente defendida nas guidelines. Material e Métodos: A glicemia plasmática em jejum, HbA1c e a prova de tolerância oral à glicose (75 g, 2 horas) foram avaliadas prospectivamente num grupo de doentes consecutivos submetidos a intervenção coronária percutânea, sendo usada a classificação da ADA para pré-diabetes mellitus tipo 2 e diabetes mellitus tipo 2. O risco de diabetes foi avaliado de acordo com o FINnish Diabetes RIsk SCore. Resultados: Foram incluídos 135 doentes (idade média 62,3 +/- 13,1 anos; 99 homens). Usando a prova de tolerância oral à glicose e a HbA1c, foram diagnosticados 18 (13,3%) novos casos de diabetes mellitus tipo 2 e 77 (57,0%) casos de pré-diabetes mellitus tipo 2. A glicemia plasmática em jejum + HbA1c identificou 12/18 doentes com diabetes mellitus tipo 2 (Sens 66,7%; valor preditivo negativo 95,1%; Kappa 0,78; p < 0,0001) e 83 do total (pré-diabetes mellitus tipo 2/ diabetes mellitus tipo 2) de 95 doentes com distúrbios da glucose (Sens 87,4%; valor preditivo negativo 76,9%). Realizar adicionalmente prova de tolerância oral à glicose nos 29 doentes com um FINnish Diabetes RIsk SCore elevado permitiu diagnosticar 15/18 doentes com diabetes mellitus (Sens 83,3%; valor preditivo negativo 97,5%; Kappa 0,85; p < 0,0001) e 86/95 dos doentes com distúrbios da glucose (Sens 90,5%; valor preditivo negativo 81,6%). Discussão: Apesar da melhoria diagnóstica, um em cada seis doentes com diabetes mellitus tipo 2 não seria diagnosticado por esta estratégia. Conclusão: A utilização do FINnish Diabetes RIsk SCore como forma de selecionar os doentes candidatos a rastreio com prova de tolerância oral à glicose melhora a capacidade diagnóstica, quando comparada com a simples avaliação da glicemia plasmática em jejum e da HbA1c. No entanto, um em cada seis doentes com diabetes mellitus tipo 2 não é identificado com esta metodologia.