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results of this study suggested superiority of CABG over PCI inelderly patients, this is counterintuitive and these results may notbe generalizable to the majority of patients requiring coronaryrevascularization. Those patients with a higher risk profile werelikely to be excluded from randomization because of proceduralrisks associated with CABG (3). The advantage of PCI in theelderly patients could therefore not be identified in this pooledanalysis.

Furthermore, long-term survival of young patients with morecomplex coronary artery disease is best realized through surgicalrevascularization with a left internal mammary artery (IMA) tothe left anterior descending artery and additional arterial grafts(preferably the right IMA) to other major coronaries. This willoptimize long-term survival due to excellent graft patency (4),which is critical, especially in young patients with a relativelylong life expectancy (5). Young patients who undergo PCI willhave a high risk of multiple repeat revascularizations and aresusceptible to the associated procedural risks.

The ancillary benefit of PCI over CABG is its lesser invasive-ness and shorter initial hospitalization (6). However, in younger,fitter patients, CABG is appealing because of low complicationrates, short lengths of stay, and little time needed to resume normalactivities of daily living. The benefit of PCI over CABG inyounger patients may therefore be small, whereas long-termefficacy is clearly superior in the majority of young patients; thetreatment of choice should therefore be CABG.

*Stuart J. Head, MScRuben L. J. Osnabrugge, MScA. Pieter Kappetein, MD, PhD

*Department of Cardiothoracic SurgeryErasmus University Medical CenterP.O. Box 20403000 CA Rotterdamthe NetherlandsE-mail: s.head@erasmusmc.nl

http://dx.doi.org/10.1016/j.jacc.2012.11.078

EFERENCES

1. Flather M, Rhee JW, Boothroyd DB, et al. The effect of age onoutcomes of coronary artery bypass surgery compared with balloonangioplasty or bare-metal stent implantation among patients withmultivessel coronary disease: a collaborative analysis of individualpatient data from 10 randomized trials. J Am Coll Cardiol 2012;60:2150–7.

2. Kappetein AP, Feldman TE, Mack MJ, et al. Comparison of coronarybypass surgery with drug-eluting stenting for the treatment of left mainand/or three-vessel disease: 3-year follow-up of the SYNTAX trial. EurHeart J 2011;32:2125–34.

3. Head SJ, Holmes DR Jr., Mack MJ, et al. Risk profile and 3-yearoutcomes from the SYNTAX percutaneous coronary intervention andcoronary artery bypass grafting nested registries. J Am Coll Cardiol Intv2012;5:618–25.

4. Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events.N Engl J Med 1986;314:1–6.

5. Kieser TM, Lewin AM, Graham MM, et al. Outcomes associated withbilateral internal thoracic artery grafting: the importance of age. AnnThorac Surg 2011;92:1269–75.

6. Head SJ, Kaul S, Bogers AJ, Kappetein AP. Non-inferiority studydesign: lessons to be learned from cardiovascular trials. Eur Heart J

2012;33:1318–24.

Prognostic Value ofMultidetector Coronary ComputedTomography AngiographyCho et al. (1) should be commended for their recent attempt toanswer an important question in an ongoing debate on theprognostic value of coronary computed tomography angiography(CCTA). In their retrospective cohort study from a single center,they concluded that CCTA provided improved discrimination forfuture major adverse cardiovascular events over the exercise stresstest (1). However, it should be noted that:

1. Results of the current study were predominantly based on aclinician-driven outcome—revascularization, which is moreamenable to change and should be interpreted with greatcaution. The difference in prognostic value of the exercise stresstest and CCTA (for both negative and positive tests) failed toachieve statistical significance for more relevant clinical out-comes—cardiac death and nonfatal myocardial infarction.Thus, the CCTA-based approach led to a higher rate ofrevascularization, but it remains unclear whether the CCTA-guided therapeutic decision-making process led to improve-ment in outcomes in terms of hard clinical endpoints.

2. The researchers censored the outcomes by excluding revascu-larizations that occurred �90 days after the index test to avoida confounding effect of CCTA driving the study endpoint.However, such selective removal of patients creates treatmentselection bias and results in greater observed risk reductionamong patients with obstructions as compared with thosewithout obstructions.

Despite the high radiation exposure, higher cost, unprovenclinical benefits, and inability to provide useful clinical informationin the settings of high heart rate, coronary calcification, andobesity—which are rampant among patients with coronary arterydisease (2)—should we really advocate CCTA as a first-line testfor more than 5 million Americans who present to the emergencydepartment every year with chest pain (3)?

*Abhishek Sharma, MD

*Maimonides Medical Center1016 50th Street #2CBrooklyn, New York 11219E-mail: abhisheksharma4mamc@gmail.com

http://dx.doi.org/10.1016/j.jacc.2012.11.077

EFERENCES

1. Cho I, Shim J, Chang HJ, et al. Prognostic value of multidetectorcoronary computed tomography angiography in relation to exerciseelectrocardiogram in patients with suspected coronary artery disease.J Am Coll Cardiol 2012;60:2205–15.

2. Arbab-Zadeh A, Miller JM, Rochitte CE, et al. Diagnostic accuracy ofcomputed tomography coronary angiography according to pre-testprobability of coronary artery disease and severity of coronary arterialcalcification. The CORE-64 (Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography) interna-

tional multicenter study. J Am Coll Cardiol 2012;59:379–87.

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3. Pitts SR, Niska RW, Xu J, Burt CW. National Hospital AmbulatoryMedical Care Survey: 2006 emergency department summary. NatlHealth Stat Report 2008;7:1–38

Relationship of Cardiac Outputto Respiratory Pattern andPressures in Patients WithFontan CirculationWe congratulate Shafer et al. (1) on their recent publication. Wewould like to raise some points and would be grateful to theresearchers if clarification could be provided to better understandtheir methodology and results. With regards to the patientpopulation, we were somewhat surprised to see that young pa-tients, seemingly undergoing operations in the last decade or so, allunderwent atriopulmonary Fontan. Total cavopulmonary connec-tion has been the surgery of choice in the last 2 decades because itprovides a better hemodynamic profile and reduces the risk ofarrhythmia generated by an enlarging right atrium.

The results of this study were obtained in young and asymp-tomatic patients a few years post-Fontan operation. We wonderwhether the conclusions can be generalized to the whole popula-tion of patients with Fontan circulation, including those with verylarge right atria and those with a “failing Fontan.”

The inert gas rebreathing method is indeed one of the mostaccurate methods for noninvasive assessment of cardiac output.This method requires appropriate and strict adjustment of respi-ratory pattern. A rebreathing bag of a volume of 1.5 to 2.5 litersshould be used for several breaths and should be emptied at eachbreath for the technique to provide accurate results (2). Suchadjustment of breathing pattern during exercise produces littlechange in cardiac output in healthy individuals but could signifi-cantly affect cardiac output in patients with Fontan circulation. Infact, an optimal respiratory breathing pattern during exercise hasbeen suggested in Fontan patients, resulting in the most efficientpulmonary augmentation of blood flow (3). The lack of a signif-icant increase in cardiac index from “exercise” to “exercise plusinspiratory load,” as seen in this study, would appear to contradictprevious data on the beneficial effects of negative inspiratorypressure in Fontan patients (4). We wonder whether this relates tothe technique used for measuring cardiac output.

Furthermore, it appears unclear to us whether the increase instroke volume in these patients was accounted for entirely by theskeletal muscle and ventilatory pumps. Complete separation of theeffects of the muscle and ventilatory pumps is difficult to achieve,even with such a carefully designed protocol such as the one usedin this paper, as demonstrated by the change in minute ventilationin both patients and controls on “zero-resistance cycling” (Fig. 4 oftheir paper [1]). The latter proved to be statistically nonsignificant,but we wonder whether this was due to the Bonferroni post hocadjustment for multiple comparisons, which is known to inflatetype II errors.

*Aleksander Kempny, MDRafael Alonso-Gonzalez, MD, MSc

Konstantinos Dimopoulos, MD, MSc, PhD F

*Adult Congenital Heart CentreRoyal Brompton and Harefield NHS Foundation TrustSydney StreetLondon SW3 6NPUnited KingdomE-mail: a.kempny@rbht.nhs.uk

http://dx.doi.org/10.1016/j.jacc.2013.01.081

EFERENCES

1. Shafer KM, Garcia JA, Babb TG, Fixler DE, Ayers CR, Levine BD.The importance of the muscle and ventilatory blood pumps duringexercise in patients without a subpulmonary ventricle (Fontan opera-tion). J Am Coll Cardiol 2012;60:2115–21.

2. Damgaard M, Norsk P. Effects of ventilation on cardiac outputdetermined by inert gas rebreathing. Clin Physiol Funct Imaging2005;25:142–7.

3. Fogel MA. Ventricular Function and Blood Flow in Congenital HeartDisease. Malden, MA: Blackwell Futura, 2005.

4. Shekerdemian LS, Bush A, Shore DF, Lincoln C, Redington AN.Cardiopulmonary interactions after Fontan operations: augmentation ofcardiac output using negative pressure ventilation. Circulation1997;96:3934–42.

Reply

We appreciate the interest and thoughtful comments regarding ourrecently published paper and are pleased to take this opportunity todiscuss our techniques and data further (1).

As stated, our study was performed exclusively in patients withthe atriopulmonary connection (APC) Fontan. Although this isnot the more contemporary type of Fontan circulation, our designdid allow for study of a relatively homogenous population, limitingthe amount of unmeasured confounding. Although there is evi-dence of less efficient flow dynamics at rest and lower effectivepulmonary blood flow at peak exercise in the APC Fontan versusthe total cavopulmonary connection (TCPC), the changes duringexercise as they would apply to our findings are unknown (2,3). Wegree that there is a need for additional investigation of our resultsn the TCPC Fontan and hope to do so in the future.

In part because of the work of Shekerdemian et al. (4), thenspiratory load was included in our study and designed to impose annhancing and inhibitory (from the expiratory load) stimulus on theentilatory pump. However, it is worth highlighting a few keyifferences between the Shekerdemian et al. (4) study and ours. First,heir patients were intubated and paralyzed and thus by definitionithout thoracic or skeletal muscle pump activity. Their study showed

hat negative-pressure ventilation was able to counteract some of thentoward effects of positive-pressure ventilation in the absence ofespiratory muscle pump activity. It is important to emphasize that wehowed a decline in stroke volume even in the presence of muscle pumpctivity, highlighting the need for caution when using this type ofentilatory support. Although our study failed to show significantdditional benefit of negative intrathoracic pressure during exercisebove the increase in stroke volume due to the muscle pump, we agreehat the design did not evaluate the ventilatory pump withoutimultaneous action of the muscle pump. If we had added an isocapnicyperpnea condition in the absence of zero resistance cycling to ourtudy, we could have commented more fully on this concept. Withur data, we would suggest that unless antagonized, the effects ofhange in intrathoracic pressure are less critical than the muscle pumpn maintaining the stroke volume in the nonparalyzed patient with

ontan circulation.