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Background There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. Objectives The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. Methods The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. Results The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months’ extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). Conclusions In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555 )

International audience; Background: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. Methods: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). Conclusion: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.

International audience; This cross-sectional study evaluates the association of major adverse cardiac events (MACE) integrated with fractional flow reserve as the management strategy for diabetes with outcomes in patients with ambiguous lesions who undergo angiography.Key PointsQuestionWhat are the usefulness, rate of major adverse cardiovascular events (MACE), and clinical outcomes of routinely integrating fractional flow reserve in the management strategy for patients with diabetes who undergo coronary angiography? FindingsIn this cross-sectional study of 1983 patients, overall reclassification by fractional flow rate was high and similar in patients with diabetes (41.2%) and patients without diabetes (37.5%); however, reclassification from medical treatment to revascularization was more frequent among patients with diabetes. The rate of 1-year MACE was similar in reclassified (9.7%) and nonreclassified (12.0%) patients with diabetes, and the rate of MACE of patients deferred based on fractional flow reserve was similar among those with and without diabetes. MeaningThe findings suggest that management strategies guided by fractional flow reserve, including revascularization deferral, may be useful for patients with diabetes.ImportanceApproximately 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. ObjectiveTo 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 ParticipantsThis 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 MeasuresDeath from any cause, myocardial infarction, or unplanned revascularization (MACE) at 1 year. ResultsAmong 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 RelevanceRoutine 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.

Background: In the ARCTIC trial (Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting), treatment adjustment following platelet function testing failed to improve clinical outcomes. However, high-on-treatment platelet reactivity (HPR) is considered as a predictor of poor ischemic outcome. This prespecified substudy evaluated clinical outcomes according to the residual platelet reactivity status after antiplatelet therapy adjustment. Methods: We analyzed the 1213 patients assigned to the monitoring arm of the ARCTIC trial in whom platelet reactivity was evaluated by the VerifyNow P2Y 12 test before percutaneous coronary intervention and during the maintenance phase (at 14 days). HPR was defined as platelet reaction unit≥235U. The primary ischemic end point, a composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization and the safety end point of major bleeding were assessed according to the platelet reactivity status. Results: Before percutaneous coronary intervention, 35.7% of patients displayed HPR (n=419). During the acute phase, between percutaneous coronary intervention and the 14-day platelet function testing, ischemic (adjusted hazard ratio, 0.94 [95% CI, 0.74–1.18]; P =0.58) and safety outcomes (hazard ratio, 1.28 [95% CI, 0.22–7.59]; P =0.78) were similar in HPR and non-HPR patients. During the maintenance phase, the proportion of HPR patients (n=186, 17.4%) decreased by 56%. At 1-year, there was no difference for the ischemic end point (5.9% versus 6.0%; adjusted hazard ratio, 0.79 [95% CI, 0.40–1.58]; P =0.51) and a nonsignificant higher rate of major bleedings (2.7% versus 1.0%, hazard ratio, 2.83 [95% CI, 0.96–8.41]; P =0.06) in HPR versus non-HPR patients. Conclusions: The proportion of HPR was halved after platelet function testing and treatment adjustment but without significant ischemic benefit at 1 year. HPR seems more as a modifiable risk marker than a risk factor of ischemic outcome. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00827411.

Background— Fractional flow reserve (FFR) is not firmly established as a guide to treatment in patients with acute coronary syndromes (ACS). Primary goals were to evaluate the impact of integrating FFR on management decisions and on clinical outcome of patients with ACS undergoing coronary angiography, as compared with patients with stable coronary artery disease. Methods and Results— R3F (French FFR Registry) and POST-IT (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease), sharing a common design, were pooled as PRIME-FFR (Insights From the POST-IT and R3F Integrated Multicenter Registries - Implementation of FFR in Routine Practice). Investigators prospectively defined management strategy based on angiography before performing FFR. Final decision after FFR and 1-year clinical outcome were recorded. From 1983 patients, in whom FFR was prospectively used to guide treatment, 533 sustained ACS (excluding acute ST-segment–elevation myocardial infarction). In ACS, FFR was performed in 1.4 lesions per patient, mostly in left anterior descending (58%), with a mean percent stenosis of 58±12% and a mean FFR of 0.82±0.09. In patients with ACS, reclassification by FFR was high and similar to those with non-ACS (38% versus 39%; P =NS). The pattern of reclassification was different, however, with less patients with ACS reclassified from revascularization to medical treatment compared with those with non-ACS ( P =0.01). In ACS, 1-year outcome of patients reclassified based on FFR (FFR against angiography) was as good as that of nonreclassified patients (FFR concordant with angiography), with no difference in major cardiovascular event (8.0% versus 11.6%; P =0.20) or symptoms (92.3% versus 94.8% angina free; P =0.25). Moreover, FFR-based deferral to medical treatment was as safe in patients with ACS as in patients with non-ACS (major cardiovascular event, 8.0% versus 8.5%; P =0.83; revascularization, 3.8% versus 5.9%; P =0.24; and freedom from angina, 93.6% versus 90.2%; P =0.35). These findings were confirmed in ACS explored at the culprit lesion. In patients (6%) in whom the information derived from FFR was disregarded, a dire outcome was observed. Conclusions— Routine integration of FFR into the decision-making process of ACS patients with obstructive coronary artery disease is associated with a high reclassification rate of treatment (38%). A management strategy guided by FFR, divergent from that suggested by angiography, including revascularization deferral, is safe in ACS.

BACKGROUND Fractional flow reserve (FFR) is defined by the maximal coronary flow ratio with and without stenosis. AIMS We hypothesized that guiding catheter intubation in coronary ostia during FFR measurements may underestimate FFR value by limiting the increase of coronary flow during maximal hyperaemia. METHODS Between June 2013 and January 2014, we prospectively included all patients with i.v. adenosine FFR measurements. FFR was measured with the guiding catheter intubated in the coronary ostia (FFRint) and extubated in the aorta (FFRext). We calculated the ratio between coronary ostium assessed by quantitative coronary angiography and guiding catheter surfaces, defined as the free ostial lumen ratio. RESULTS In total, 151 lesions in 104 patients were included; 121 lesions and 88 patients were eligible for analysis. Mean±SD FFRext was significantly lower compared with FFRint; 0.82±0.08 and 0.84±0.08, respectively (P

Background Recently developed microcatheters can be used instead of pressure wire for fractional flow reserve (FFR) measurement. We sought to assess the hemodynamic and clinical impacts of using larger profile device to measure FFR. Methods and results Our prospective registry included 99 consecutive patients who underwent invasive FFR measurements of intermediate coronary stenoses between June 2015 and July 2016. FFR values were obtained first using a pressure wire only (FFRw), second using a Navvus microcatheter (FFRmc), and finally using the wire with the microcatheter still in the stenosis (FFRw-mc) during intravenous adenosine infusion. Eighty-eight stenoses were suitable for a thorough head-to-head comparison. Mean FFRw (0.83 ± 0.08) was significantly higher than mean FFRmc (0.80 ± 0.10) and FFRmc-w (0.80 ± 0.10). Mean FFRmc and FFRmc-w did not significantly differ. Bland–Altman analysis showed a bias of −0.03 ± 0.05 for lower FFRMC values compared to FFRw values. Using a threshold of 0.80 for FFR, the indication for revascularization would have differed when based on FFRmc versus FFRw in 20/88 (23%) of the lesions and 18/77 (23%) of the patients ( Fig. 1 ). Conclusions FFR measured using a microcatheter overestimates stenosis severity, leading to erroneous indication for revascularization in a sizable proportion of cases.

Background Platelet function testing offers the possibility to individualize antiplatelet therapy in coronary artery disease patients but failed to improve clinical outcomes in randomized trials. However, high-on-treatment platelet reactivity (HPR) remains a risk factor for recurrent ischemic events and low-on-treatment platelet reactivity (LPR) is a risk factor for bleedings. Methods We collected data of patients assigned to the monitoring arm of the randomized ARCTIC and ANTARCTIC trials that evaluated the platelet reactivity by the VerifyNow P2Y12 test two weeks after coronary stenting. HPR was defined by PRU ≥ 208, LPR by PRU ≤ 85 and optimal platelet reactivity (OPR) by 85. Results Among the 1418 patients included, HPR was present in 269 patients (18.9%), OPR was reached in 681 patients (48.0%) and LPR in 468 patients (33.0%). The primary composite endpoint occurred in 9.7%, 11.5% and 14.3% respectively. There was no significant difference in the net clinical benefit between HPR and OPR patients (adjusted HR: 0.91(0.48–1.72); P = 0.77) and between LPR and OPR patients (adjusted HR: 1.13 (0.67–1.90); P = 0.64). There were no difference in the individual clinical endpoints between the three groups. ROC curve analysis demonstrated that PRU when used for treatment adjustment has a limited ability to discriminate net clinical benefit, ischemic or bleeding complications (curve–c index = 0.55, 0.51 or 0.59, respectively). Conclusion Two weeks after stenting, an optimal platelet reactivity was obtained in less than half of the population. The net clinical benefit of these patients was not different from that of patients with HPR and LPR who had treatment adjustment.

Summary Background Elderly patients are at high risk of ischaemic and bleeding events. Platelet function monitoring offers the possibility to individualise antiplatelet therapy to improve the therapeutic risk–benefit ratio. We aimed to assess the effect of platelet function monitoring with treatment adjustment in elderly patients stented for an acute coronary syndrome. Methods We did this multicentre, open-label, blinded-endpoint, randomised controlled superiority study at 35 centres in France. Patients aged 75 years or older who had undergone coronary stenting for acute coronary syndrome were randomly assigned (1:1), via a central interactive voice-response system based on a computer-generated permuted-block randomisation schedule with randomly selected block sizes, to receive oral prasugrel 5 mg daily with dose or drug adjustment in case of inadequate response (monitoring group) or oral prasugrel 5 mg daily with no monitoring or treatment adjustment (conventional group). Randomisation was stratified by centre. Platelet function testing was done 14 days after randomisation and repeated 14 days after treatment adjustment in patients in the monitoring group. Study investigators and patients were not masked to treatment allocation, but allocation was concealed from an independent clinical events committee responsible for endpoint adjudication. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularisation, and Bleeding Academic Research Consortium-defined bleeding complications (types 2, 3, or 5) at 12 months' follow-up. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01538446. Findings Between March 27, 2012, and May 19, 2015, we randomly assigned 877 patients to the monitoring group (n=442) or the conventional group (n=435). The primary endpoint occurred in 120 (28%) patients in the monitoring group compared with 123 (28%) patients in the conventional group (hazard ratio [HR], 1·003, 95% CI 0·78–1·29; p=0·98). Rates of bleeding events did not differ significantly between groups. Interpretation Platelet function monitoring with treatment adjustment did not improve the clinical outcome of elderly patients treated with coronary stenting for an acute coronary syndrome. Platelet function testing is still being used in many centres and international guidelines still recommend platelet function testing in high-risk situations. Our study does not support this practice or these recommendations. Funding Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.

Background— Individualizing antiplatelet therapy after platelet function testing did not improve outcome after coronary stenting in the Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting (ARCTIC) study. Whether results are different during the phase of secondary prevention starting after hospital discharge, when periprocedural events have been excluded, is unknown. Methods and Results— In ARCTIC, 2440 patients were randomized before coronary stenting to a strategy of platelet function monitoring (VerifyNow P2Y 12 /aspirin point-of-care assay) with drug adjustment in suboptimal responders to antiplatelet therapy or to a conventional strategy without monitoring and without drug or dose changes. We performed a landmark analysis starting at the time of hospital discharge evaluating the primary end point of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization through 1 year. After discharge, the primary end point occurred in 8.6% of patients in the monitoring arm and 7.9% in the conventional arm (hazard ratio, 1.105; 95% confidence interval, 0.835–1.461; P =0.48). Stent thrombosis or urgent revascularization occurred in 4.4% and 4.5% in the monitoring and conventional arms, respectively ( P =0.99). There was no difference for any of the other ischemic end points. Major bleeding event rates were 1.8% in the monitoring arm and 2.8% in the conventional arm ( P =0.11), whereas major or minor bleeding event rates were 2.3% and 3.4%, respectively ( P =0.10). Conclusions— Detection of platelet hyper-reactivity by platelet function testing in patients undergoing coronary stenting with further therapeutic adjustment does not reduce ischemic recurrences after intervention. On-treatment platelet hyperreactivity cannot be considered as a risk factor requiring intervention for secondary prevention after percutaneous coronary revascularization. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00827411.

Background Elderly patients are at high risk for both ischemic and bleeding events. Platelet monitoring offers the opportunity to individualized antiplatelet therapy to optimize the therapeutic risk/benefit ratio. Study design The ANTARCTIC study is designed to demonstrate the superiority of a strategy of platelet function monitoring with dose and drug adjustment in patients initially on prasugrel 5 mg as compared with a more conventional strategy using prasugrel 5 mg without monitoring and without adjustment (Conventional Treatment Arm) to reduce the primary end point evaluated 1 year after stent percutaneous coronary intervention in elderly patients presenting with an acute coronary syndrome (ACS). ANTARCTIC is a multicenter, prospective, open-label study with 2 parallel arms. A total of 852 elderly patients (≥75 years) undergoing stent percutaneous coronary intervention for ACS are to be enrolled. The primary end point is the time to first occurrence of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis, urgent revascularization, and bleeding complications (Bleeding Academic Research Consortium definition 2, 3, or 5). Platelet function analyses will be performed 14 days after randomization and repeated 14 days later in patients who require a change in treatment. Conclusion ANTARCTIC is a nationwide, prospective, open-label study testing a strategy of platelet function monitoring with dose and drug adjustment to reduce ischemic and bleeding complications in elderly ACS patients undergoing coronary stenting.

Background— There is no large report of the impact of fractional flow reserve (FFR) on the reclassification of the coronary revascularization strategy on individual patients referred for diagnostic angiography. Methods and Results— The Registre Français de la FFR (R3F) investigated 1075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 French centers. Investigators were asked to define prospectively their revascularization strategy a priori based on angiography before performing the FFR. The final revascularization strategy, reclassification of the strategy by FFR, and 1-year clinical follow-up were prospectively recorded. The strategy a priori based on angiography was medical therapy in 55% and revascularization in 45% (percutaneous coronary intervention, 38%; coronary artery bypass surgery, 7%). Patients were treated according to FFR in 1028/1075 (95.7%). The applied strategy after FFR was medical therapy in 58% and revascularization in 42% (percutaneous coronary intervention, 32%; coronary artery bypass surgery, 10%). The final strategy applied differed from the strategy a priori in 43% of cases: in 33% of a priori medical patients, in 56% of patients undergoing a priori percutaneous coronary intervention, and in 51% of patients undergoing a priori coronary artery bypass surgery. In reclassified patients treated based on FFR and in disagreement with the angiography-based a priori decision (n=464), the 1-year outcome (major cardiac event, 11.2%) was as good as in patients in whom final applied strategy concurred with the angiography-based a priori decision (n=611; major cardiac event, 11.9%; log-rank, P =0.78). At 1 year, >93% patients were asymptomatic without difference between reclassified and nonreclassified patients (Generalized Linear Mixed Model, P =0.75). Reclassification safety was preserved in high-risk patients. Conclusion— This study shows that performing FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent from that suggested by angiography but guided by FFR.

Patients' responses to oral antiplatelet therapy are subject to variation. Bedside monitoring offers the opportunity to improve outcomes after coronary stenting by individualizing therapy.We randomly assigned 2440 patients scheduled for coronary stenting at 38 centers to a strategy of platelet-function monitoring, with drug adjustment in patients who had a poor response to antiplatelet therapy, or to a conventional strategy without monitoring and drug adjustment. The primary end point was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation. For patients in the monitoring group, the VerifyNow P2Y12 and aspirin point-of-care assays were used in the catheterization laboratory before stent implantation and in the outpatient clinic 2 to 4 weeks later.In the monitoring group, high platelet reactivity in patients taking clopidogrel (34.5% of patients) or aspirin (7.6%) led to the administration of an additional bolus of clopidogrel, prasugrel, or aspirin along with glycoprotein IIb/IIIa inhibitors during the procedure. The primary end point occurred in 34.6% of the patients in the monitoring group, as compared with 31.1% of those in the conventional-treatment group (hazard ratio, 1.13; 95% confidence interval [CI], 0.98 to 1.29; P=0.10). The main secondary end point, stent thrombosis or any urgent revascularization, occurred in 4.9% of the patients in the monitoring group and 4.6% of those in the conventional-treatment group (hazard ratio, 1.06; 95% CI, 0.74 to 1.52; P=0.77). The rate of major bleeding events did not differ significantly between groups.This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting, as compared with standard antiplatelet therapy without monitoring. (Funded by Allies in Cardiovascular Trials Initiatives and Organized Networks and others; ARCTIC ClinicalTrials.gov number, NCT00827411.).

Seventeen consecutive patients, aged 56 +/- 12, were chronically paced in the AAIR mode for a symptomatic sinus node disease with atrial chronotropic incompetence defined by a peak exercise heart rate (HR) less than 75% of the maximal predicted heart rate (MPHR) mean = 65 +/- 10%). Sensors used were activity sensing (n = 7), minute ventilation (n = 6), or respiratory rate (n = 4). Basic pacing rate was programmed at 71 +/- 5 beats/min and the maximal sensor rate at approximately 85% MPHR (143 +/- 10); other sensor parameters were programmed individually. Six months after implant, two standardized and symptom limited exercise tests were performed in random order, AAI and AAIR modes, respectively. AAIR pacing significantly improved peak exercise HR (139 +/- 14 vs 112 +/- 30 beats/min; P less than 0.01), maximal sustained workload (132 +/- 42 vs 110 +/- 38 watts; P less than 0.02), and total exercise duration (724 +/- 299 vs 594 +/- 245 sec; p less than 0.02) compared to the AAI mode. In all 17 patients, HR was continuously sensor driven in the AAIR mode, making it possible to precisely study the adaptation of the stimulus-R interval and of the stimulus-R:RR ratio during exercise. Six patients normally adapted with a progressive shortening. Six others did not adapt at all without any variation of interval. Five patients paradoxically increased their stimulus-R interval (286 +/- 10 msec at peak E vs 220 +/- 19 msec at rest) and their stimulus-R:RR ratio (67 +/- 20% vs 29 +/- 4%), producing P waves occurring immediately after, or even within the R wave of the preceding cycle; two patients complained of severe exercise related symptoms corresponding to the so-called "AAIR pacemaker syndrome." The principal factors involved in the nonadaptation of AV interval to HR were related to the patient (organic heart disease, with the particular problem of the denervated heart; the bradytachy syndrome; and the use of drugs, especially beta blockers and Class I antiarrhythmic drugs) or to the pacemaker ("overstimulation" phenomenon). These observations constitute an additional argument for wider indications of implanting DDDR units in these patients.

CAZEAU, S., ET AL.: Dynamic Electrophysiology of Ventriculoatrial Conduction: Implications for DDD and DDDR Pacing. The behavior of ventriculoatrial conduction (VAC) during exercise remains unknown. In order to determine its characteristics and the consequences it might have on dual chamber pacemaker technology and programming, 17 patients underwent an electrophysiological study (EPS) of atrioventricular conduction (AVC) and of VAC during a protocol including three steps: supine rest, upright position, and finally during cycloergometric exercise; the measurements were done at progressively increasing pacing rates. During a preimplantation EPS, Wenckebach points AVC-W and VAC-W and conduction times, AVCT and VACT (as a function of pacing rate), were measured in ten consecutive patients using temporary leads and an external device. In another study, AVCT, VACT, AVC-W, and VAC-W were measured by telemetric recordings under identical conditions in seven patients implanted earlier with a DDD pacemaker. A 1/1 VAC was observed in 7/17 patients (41%) at rest, and in 13/17 patients (76%) at the end of the protocol; VAC was never observed in 4/17 patients [23%], but occurred in six of the ten patients initially free, three standing at rest and three on exercise. For all patients, the VAC behavior remained of “nodal” type, indicated by a progressive increase in VACT as pacing rate rose up to the VAC-W point. Neither the existence of exercise-induced VAC nor the maximal VACT-W could be predicted from AVC or VAC data obtained at rest. However, at the same pacing rates, standing up and exercise induced a shortening effect on VACT, and improved the VAC-W by an average of 33%. These results suggest that the electrophysiological behavior of VAC does not obey any general rule and cannot be predicted individually. It would thus appear unwise to base pacemaker mediated tachycardia (PMT) protection solely on long postventricular atrial refractory period (PVARP) programming in DDD patients. This work also revealed the potential risks of a rate responsive auto-adaptive PVARP algorithm as proposed in certain new devices.