Effects of Percutaneous Transluminal Angioplasty on Diastolic Function in Patients With Chronic Occlusion of Lower-Extremity Artery

Abstract: Objective. We investigated whether successful revascularization of total occlusion of a large lower-extremity artery is associated with improvement of left ventricular (LV) diastolic function. Background. Total occlusion of a large lower-extremity artery might affect the systemic vascular resistance and increase the afterload, because the left ventricle must work harder to eject blood into a smaller vascular bed. Chronic elevation of afterload is a cause of LV diastolic dysfunction. Methods. This is a single-center retrospective analysis of 20 patients (10 men, age 69.6 ± 12.3 years) with chronic total occlusions (CTOs) of the aorto-iliac and femoropopliteal segments who underwent a successful endovascular revascularization. Baseline and postprocedural evaluation of diastolic function was performed, and the primary endpoint was improvement in LV diastolic function, which was defined as any decrease of the baseline E/E’ ratio or any increase of the baseline E’ velocity after the index procedure. Results. There was a significant effect of successful revascularization on the E/A ratio (from 1.5 ± 1.1 to 1.0 ± 0.3; P=.046) because of a significant increase of A velocity (from 86.3 ± 30.4 cm/s to 98.3 ± 21.8 cm/s; P=.03). The E’ velocity (from 7.4 ± 2.0 cm/s to 8.3 ± 2.3 cm/s; P=.07) did not show a significant increase, but there was a significant reduction in E/E’ ratio (from 14.6 ± 3.9 to 12.4 ± 3.3; P=.02). Logistic regression analysis did not identify possible predictors of improvement in LV diastolic function. Conclusion. Our results showed that a successful revascularization was associated with improvement in the echocardiographic parameters of LV diastolic function in patients with CTO of large lower-extremity artery, and these changes may be related to the afterload reduction.

J INVASIVE CARDIOL  2016;28(12):498-504. Epub 2016 October 15.

Key words: chronic total occlusion, diastolic dysfunction, lower-extremity disease

Left ventricular (LV) diastolic dysfunction (DD) is caused by impaired myocardial relaxation and/or increased ventricular stiffness and is characterized by elevated LV filling pressures.¹ When treating a patient with DD, it is important to reduce cardiac afterload to establish hemodynamic optimization.^2,3 The benefits of optimizing hemodynamics include improving LV filling, reducing blood pressure, and improvement in exercise capacity and quality of life.⁴ Medical therapies with beta-blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), calcium-channel blockers (CCB), and diuretics have been independently associated with improvement of DD.^4-6 Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis. Risk factors for PAD are nearly the same as those for coronary artery disease (CAD). In addition, the hemodynamics and underlying mechanisms for PAD in the lower extremity are very similar to those found in CAD. Based on Poiseuille’s equation, a decrease in vessel radius will increase the resistance by a power of four.^7,8 Considering that systemic vascular resistance (SVR) is often used clinically as a measure of afterload,⁹ we hypothesized that total occlusion of a large lower-extremity artery might affect the SVR and subsequently increase the LV afterload, because the LV must work harder to eject blood into a smaller vascular bed. Since chronic elevation of afterload is a cause of LV-DD, it might infer that successful percutaneous transluminal angioplasty (PTA) of a totally occluded large lower-extremity artery would be a useful modality in terms of improvement in LV-DD due to its afterload reducing effects. In real clinical practice, our institution has seen that heart failure (HF)-related signs and symptoms such as dyspnea and fatigue improved after successful PTA in some patients with PAD and DD. However, it remains unknown in the published scientific literature whether successful PTA improves DD in patients with PAD, and if so, whether the effect is attributable to the attenuation of DD. The present study was designed to evaluate the effect of successful revascularization with PTA (in particular on LV diastolic function) in patients with total occlusion of a large lower-extremity artery, and to confirm the presence or absence of its beneficial effect.

Methods

The study protocol was developed in accordance with the Declaration of Helsinki and was approved by the institutional review board. All consecutive patients admitted to our institution between January 2005 and December 2014 who underwent PTA for chronic total occlusion (CTO) of large lower-extremity arteries (aorto-iliac arteries or femoropopliteal arteries [FPAs]) were evaluated. Patients were suitable for inclusion if they had undergone successful PTA for CTO of iliac artery or FPA and preserved left ventricular ejection fraction (LVEF), which was defined as LVEF ≥50% on baseline echocardiogram.¹⁰ Echocardiograms performed within 1 month before the index procedure (baseline) and within 3 months after a successful revascularization (post procedural) were eligible for this analysis. Patients were excluded if they had a history of cardiac ischemic insult on heart such as acute myocardial infarction (AMI) prior to postprocedural echocardiogram, evidence of critical limb ischemia (CLI) with poor tibial run-off vessels, and significant LV hypertrophy at baseline (LV wall thickness ≥13 mm). To best limit potential confounding factors, we excluded all patients presenting significant valvular heart diseases (more than or equal to moderately severe valve diseases), reduced LVEF (<50%), end-stage renal disease (ESRD) with dialysis, and permanent atrial fibrillation. 

The primary endpoint was improvement in LV diastolic function, which was defined as any decrease of the baseline E/E’ ratio or any increase of the baseline E’ velocity after the index procedure. The secondary endpoints included changes in pulsed-wave Doppler (PWD)-derived transmitral filling indices (E and A velocities, E/A ratio, deceleration time) and tissue Doppler imaging (TDI)-derived indices (E’ velocity and A’ velocity) from baseline to follow-up.

Two-dimensional (2D) measurements included LV dimensions at end diastole and end systole from the apical four-chamber and two-chamber views, and LVEF calculated using the biplane method.¹¹ Left atrial (LA) diameter was measured in the parasternal long-axis view. The PWD-derived transmitral velocities were obtained at the mitral leaflet tips according to American Society of Echocardiography guidelines.¹² Measurements included the E velocity (early diastolic peak mitral inflow velocity) and A velocities, the E/A ratio, and the E deceleration time (ms). TDI-derived indices were acquired in the apical four-chamber view and PWD mode for determination of systolic (S’), early mitral annulus diastolic velocity (E’), and late diastolic (A’) velocities. For all parameters, the average of three consecutive heartbeats was recorded, and velocities were recorded at end-expiration. For TDI evaluation, gain and filters were adjusted as needed to eliminate background noise and to allow for a clear tissue signal. The tissue Doppler signals were recorded at a sweep speed of 100 mm/s. From the apical four-chamber view, a 5 mm sample volume was placed at the lateral and septal corners of the mitral annulus, and we calculated the averaged peak early (E’) diastolic velocity at the mitral annulus, and the ratio between early wave mitral flow and mitral annulus early diastolic velocity (E/E’).¹³ Also, E/E’ ratio was calculated to determine LV filling pressure. DD refers to a disturbance in ventricular relaxation, distensibility or filling, regardless of whether the LVEF is normal or depressed and whether the patient is asymptomatic or symptomatic.¹⁴ In the present study, DD was defined when the ratio of E/E’ was >15 or E’ velocity <8 cm/s.^15,16 

Successful revascularization was defined to achieve a residual pressure gradient of <10 mm Hg, residual stenosis with <30%, or no flow-limiting dissection after nitinol stent implantation according to Trans-Atlantic Inter-Society Consensus (TASC) II classification as published.¹⁷

Statistical analysis. Categorical variables were expressed as percentages and continuous data were expressed as mean ± standard deviation. Logistic regression analysis was performed to identify possible predictors of improvement of diastolic function. A P-value of <.05 was considered to be statistically significant. The analyses were performed using the SPSS version 13 software (SPSS, Inc).

Results

We identified 659 patients who underwent a successful endovascular revascularization for totally occluded aorto-iliac or FPA. With review of the exclusion criteria, 20 patients (10 men and 10 women; age 69.6 ± 12.3 years) were included in the analysis (Figure 1). Baseline clinical characteristics for the study population are shown in Table 1. No patients died, developed serious cardiovascular events such as acute coronary syndrome or cardiac arrest, or were readmitted to the hospital during the study period. Sixteen patients (72.7%) had diabetes, 19 patients (86.4%) had hypertension, 6 patients (27.3%) had a history of tobacco smoking. A history of percutaneous coronary intervention was present in 4 patients (18.2%). Seven patients (31.8%) had concomitant CAD. Fifteen patients (75.0%) had a total occlusion of FP artery in 1 limb, and a patent FP artery in the contralateral limb. Three patients (15%) showed a CTO of unilateral iliac artery. One patient (5%) had bilateral iliac artery occlusion, and 1 patient had bilateral FPA occlusion. Baseline echocardiogram was performed at 16.1 ± 12.5 days before the revascularization procedure, and the interval between the revascularization procedure and follow-up (postprocedural) echocardiograms averaged 46.6 ± 45.79 days. Chronic loading medication during the study included diuretics in 6 patients (30.0%), beta-blockers in 10 patients (50.0%), ACEI or ARB in 7 patients (35.0%), and CCB in 4 patients (20.0%). There were no patients taking sildenafil continuously. 

Table 2 summarizes periprocedural echocardiographic and Doppler variables (baseline and follow-up echocardiographic outcomes). There was no significant difference in magnitude of the change in LV end-diastolic dimension, LV end-systolic dimension, LVEF, LA diameter, and E velocity between baseline and follow-up. The baseline E velocity was 104.2 ± 25.2 cm/s and the follow-up E velocity was 101.1 ± 30.0 cm/s (P=.46), but a successful revascularization procedure yielded a significant increase of A velocity from 86.3 ± 30.4 cm/s to 98.3 ± 21.8 cm/s (P=.03). Overall, there was a significant effect of successful revascularization procedure on the E/A ratio, the most commonly used diastolic function variable (from 1.5 ± 1.1 to 1.0 ± 0.3; P=.046). The E’ velocity (from 7.4 ± 2.0 cm/s to 8.3 ± 2.3 cm/s; P=.07) and A’ velocity (from 8.1 ± 2.0 cm/s to 9.2 ± 3.3 cm/s; P=.42) showed no significant changes during the study period (Figure 1). However, there was a significant difference in magnitude of the changes in E/E’ ratio (from 14.6 ± 3.9 to 12.4 ± 3.3; P=.02) (Figure 2). The highest decrease of E/E’ ratio was observed in a patient with unilateral FPA total occlusion. In this patient, the E/E’ ratio decreased from 24.1 cm/s to 10.8 cm/s. The proportion of patients with DD decreased after a successful revascularization procedure (from 70.0% at baseline to 45.0% at follow-up, but did not reach statistical significance [P=.10]). 

Univariate analysis was performed to identify possible predictors of improvement of diastolic function. However, we did not observe significant variables associated with an increased odds of an improvement in LV diastolic function, thus multivariate analysis was not conducted (Table 3). 

Discussion

In the present study, successful revascularization was performed in patients with total occlusion of large lower-extremity artery (aorto-iliac or FPA) and the following results were obtained: (1) three echocardiographic parameters – A velocity, E/A ratio, and in particular E/E’ ratio – were significantly changed; however, there were no significant changes observed in LV end-diastolic, end-systolic dimensions, LVEF, LA diameter, E velocity, and E’ velocity; and (2) there was a significant difference in magnitude of the changes in E/E’ ratio (from 14.6 ± 3.9 to 12.4 ± 3.3; P=.02) with the successful revascularization procedure.

The presence of PAD may be considered part of polyvascular diseases including ischemic heart disease and cerebrovascular diseases along with systemic inflammation, oxidative stress, endothelial dysfunction, greater arterial stiffness, sympathetic nervous system, activated renin-angiotensin aldosterone system, and so on.¹⁸ In addition, PAD is recognized as systemic vascular dysfunction and atherosclerosis, the common cause of development of DD. Under experimental conditions, it is well known that aortic clamping increases afterload. The degree of increase in afterload is dependent predominantly on the level of clamping. With higher clamping, greater increases in afterload are seen.^9,19 In an animal study (even in the absence of CAD), the increase of afterload accompanying aortic cross-clamping led to increases in both myocardial oxygen demand and limitation of myocardial oxygen supply. Moreover, marked increases in preload were also seen in response to aortic clamping.²⁰ Judging by experimental and clinical studies, it’s not surprising that PAD (particularly, total occlusion of a large artery), which can be regarded as a clamping condition in the experimental setting, is associated with DD with afterload increase. 

Echocardiogram has been used as an important clinical tool providing reliable and useful information on diastolic performance. We applied for two different methods commonly used in the assessment of diastolic heart function: (1) PWD-derived transmitral flow indices; and (2) TDI-derived indices. Through the integrated use of PWD-derived indices and TDI-derived indices, it is possible to obtain a fairly precise picture of diastolic function.^21,22 The PWD-derived transmitral flow velocity pattern (the E/A ratio in particular) has been most widely used to evaluate diastolic function in the clinical setting.²³ The E/A ratio, however, is influenced by loading conditions (particularly preload), resulting in pseudonormalization (E/A ratio >1) of the transmitral flow velocity in patients with elevated LV end-diastolic pressure.²⁴ Since many factors, such as LA pressure, LV myocardial relaxation or compliance, and aortic pressure, are related to LV filling during diastole, there may be a limitation when diastolic function is evaluated by the PWD-derived indices alone.^21,25 On the contrary, TDI allows for direct measurement of the velocity of change in myocardial length, an index of LV relaxation, and in particular, is less sensitive to preload than transmitral flow velocity pattern.^13,16 In addition, TDI has been shown to be a superior evaluation method in patients with impaired LV relaxation, regardless of the mitral inflow velocity flow pattern in comparison with conventional Doppler echocardiogram.²⁶ TDI-derived indices seem to be a more sensitive tool than PWD-derived indices for the detection of afterload-related DD. Because our hypothesis is based on the improvement in LV diastolic function by the effect of afterload reduction, TDI-derived indices seem to be a more appropriate method for our study. In particular, the E/E’ ratio is among the most reproducible echocardiographic parameters to estimate LV filling pressure related to DD, and is the preferred prognostic parameter in many cardiac conditions.

It was interesting to see the E/A ratio obtained from the transmitral flow velocity pattern decreased very much after a successful revascularization procedure, due to increases in A velocity. The reason for that may be due to an increased A velocity as a result of a decreased SVR, and the drop in LV filling pressure induced by the successful revascularization procedure. Besides an increase in A velocity, there was a trend toward a higher value of E’ velocity on follow-up compared with baseline. Certainly, it was the improvement of E’ velocity that contributed to the decreased E/E’ ratio after the successful revascularization procedure. Thus, we suggest that afterload reduction followed by a decrease of LV filling pressure, in conjunction with a successful revascularization procedure, may have been the main facilitating mechanism for our finding. 

One might wonder whether there was any change in the dose of medications like BB, ACEI, ARB, and CCB, since the indices of LV diastolic function might be basically dose dependent.^4-6 In this study, the cohort was small in number (n = 20) and medication use was assessed by patient chart reviews. Changes in the dose or type of these medications during follow-up were not detected.

Aging, hypertension, myocardial ischemia, and volume overload are well-known common risk factors related to DD.^4-6 It is no wonder that 14 patients (70%) had DD at baseline in this study, considering that most patients had a history of hypertension (86.4%) or concomitant CAD (31.8%). The exact causes of DD in those who had DD at baseline have not been fully evaluated. However, we do not suggest that the presence of PAD was the only risk factor of DD in these patients. Rather, our interest is to investigate whether the benefit of successful revascularization on LV diastolic function could be seen in patients with CTO of a large lower-extremity artery.

It should be noted that the circulation distal to an occluded lesion often undergoes collateralization, which reduces resistance and thereby maintains normal resting blood flow despite a reduced perfusion pressure.^27,28 Patients with aortic occlusive disease have the greater peri-aortic collateralization, with the smallest increases in afterload following occlusion of the aorta. Indeed, 1 patient with bilateral iliac artery occlusion in our study did not show a great reduction of E/E’ ratio (from 10.9 at baseline to 10.1 at follow-up). Therefore, the greatest benefit of successful revascularization on LV diastolic function may be seen in patients with acute limb ischemia rather than in patients with chronic limb ischemia. 

Meanwhile, some authors indicate that PAD patients have worse long-term outcomes compared with CAD patients.²⁹ In a recent meta-analysis, it was demonstrated that advanced DD was associated with a greater than two-fold increase in all-cause mortality despite a preserved LVEF.³⁰ It is worthy to note that patients with PAD and no clinical evidence of CAD have the same relative risk of death from cardiac causes as those whose main diagnosis is CAD.³¹ Although beyond the scope of the present analysis, there is a possibility that DD is an important cause of mortality in the aforementioned result. Currently, strategies to treat DD consist of decreasing afterload, normalization of preload, and control of underlying comorbidities such as hypertension, ventricular rate in atrial fibrillation, pulmonary congestion, and peripheral edema.³² Considering the result of our study, successful revascularization of the CTO of a large lower-extremity artery may be a possible way to reduce afterload and to improve DD.

Study limitations. We acknowledge several limitations in the present study. First, the number of study patients might have been too small to detect a difference, and there may be some recall bias as well. This study was limited to patients with echocardiograms performed within 1 month before the index procedure (baseline) and within 3 months after a successful revascularization. In addition, patients with ischemic event or any coronary intervention during the study period were completely excluded from the analysis. Although the strict exclusion criteria limited eligible candidates for our study (from 620 in the beginning to 20 for the analysis), this study attempted to limit bias and confounding factors. Second, we only obtained baseline and follow-up diastolic parameters, and therefore cannot clarify the variability of the diastolic parameters during the course of the study. There may be concern that diastolic parameters could become altered according to the time of echocardiographic assessment, which was not standardized in this study. Third, we did not take the length and diameter of the occluded lesion into consideration, leading to a heterogeneous sample. Fourth, other useful parameters for detecting DD (such as isovolumetric relaxation time, color M-mode flow propagation (FP) velocity, and LA volume index) were not evaluated. 

PAD has not been regarded as an important variable in the published literature concerning diastolic function. We believe that the present data indicate the importance of diastolic function in patients with PAD. Furthermore, performing a prospective randomized clinical trial to evaluate the effect of the revascularization procedure for improvement on LV diastolic function might be needed in patients with PAD.

Conclusion

Our results showed that a successful revascularization was associated with improvement in the echocardiographic parameters of LV diastolic function in patients with CTO of a large lower-extremity artery, and these changes may have been related to the afterload reduction.

References

1.     Leite-Moreira AF. Current perspectives in diastolic dysfunction and diastolic heart failure. Heart. 2006;92:712-718.

2.     Chen HH, Lainchbury JG, Senni M, Bailey KR, Redfield MM. Diastolic heart failure in the community: clinical profile, natural history, therapy, and impact of proposed diagnostic criteria. J Card Fail. 2002;8:279-287.

3.     Angomachalelis N, Hourzamanis AI, Sideri S, Serasli E, Vamvalis C. Improvement of left ventricular diastolic dysfunction in hypertensive patients 1 month after ACE inhibition therapy: evaluation by ultrasonic automated boundary detection. Heart Vessels. 1996;11:303-309.

4.     Warner JG Jr, Metzger DC, Kitzman DW, Wesley DJ, Little WC. Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise. J Am Coll Cardiol. 1999;33:1567-1572.

5.     Mitsunami K, Inoue S, Maeda K, et al. Three-month effects of candesartan cilexetil, an angiotensin II type 1 (AT1) receptor antagonist, on left ventricular mass and hemodynamics in patients with essential hypertension. Cardiovasc Drugs Ther. 1998;12:469-474.

6.     Philbin EF, Rocco TA Jr, Lindenmuth NW, Ulrich K, Jenkins PL. Systolic versus diastolic heart failure in community practice: clinical features, outcomes, and the use of angiotensin-converting enzyme inhibitors. Am J Med. 2000;109:605-613.

7.     Kuchan MJ, Jo H, Frangos JA. Role of G proteins in shear stress-mediated nitric oxide production by endothelial cells. Am J Physiol. 1994;267:C753-C758.

8.     Frangos JA, Huang TY, Clark CB. Steady shear and step changes in shear stimulate endothelium via independent mechanisms – superposition of transient and sustained nitric oxide production. Biochem Biophys Res Commun. 1996;224:660-665.

9.     Gelman S. The pathophysiology of aortic cross-clamping and unclamping. Anesthesiology. 1995;82:1026-1060.

10.     Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251-259.

11.     Lang RM, Bierig M, Devereux RB, et al; Chamber Quantification Writing Group; American Society of Echocardiography’s Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18:1440-1463.

12.     Quinones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr. 2002;15:167-184.

13.     Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a non-invasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997;30:1527-1533.

14.     Gaasch WH, Zile MR. Left ventricular diastolic dysfunction and diastolic heart failure. Annu Rev Med. 2004;55:373-394.

15.     Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation. 2000;102:1788-1794.

16.     Garcia MJ, Thomas JD, Klein AL. New Doppler echocardiographic applications for the study of diastolic function. J Am Coll Cardiol. 1998;32:865-875.

17.     Jaff MR, White CJ, Hiatt WR, et al; TASC Steering Committee. An update on methods for revascularization and expansion of the TASC lesion classification to include below-the-knee arteries: a supplement to the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Endovasc Ther. 2015;22:663-677.

18.     Rooke TW, Hirsch AT, Misra S, et al; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society for Vascular Medicine; Society for Vascular Surgery. 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011;58:2020-2045. 

19.     Attia RR, Murphy JD, Snider M, et al. Myocardial ischemia due to infrarenal aortic cross-clamping during aortic surgery in patients with severe coronary artery disease. Circulation. 1976;53:961-965.

20.     Buckberg GD, Fixler DE, Archie JP, Hoffman JI. Experimental subendocardial ischemia in dogs with normal coronary arteries. Circ Res. 1972;30:67-81.

21.     Sohn DW, Kim YJ, Kim HC, et al. Evaluation of left ventricular diastolic function when mitral E and A waves are completely fused: role of assessing mitral annulus velocity. J Am Soc Echocardiogr. 1999;12:203-208.

22.     Takatsuji H, Mikami T, Urasawa K, et al. A new approach for evaluation of left ventricular diastolic function: spatial and temporal analysis of left ventricular filling flow propagation by color M-mode Doppler echocardiography. J Am Coll Cardiol. 1996;27:365-371.

23.     Giannuzzi P, Imparato A, Temporelli PL, et al. Doppler-derived mitral deceleration time of early filling as a strong predictor of pulmonary capillary wedge pressure in postinfarction patients with left ventricular systolic dysfunction. J Am Coll Cardiol. 1994;23:1630-1637.

24.     Oki T, Tabata T, Yamada H, et al. Clinical application of pulsed Doppler tissue imaging for assessing abnormal left ventricular relaxation. Am J Cardiol. 1997;79:921-928.

25.     Onose Y, Oki T, Yamada H, et al. Effect of cilnidipine on left ventricular diastolic function in hypertensive patients as assessed by pulsed Doppler echocardiography and pulsed tissue Doppler imaging. Jpn Circ J. 2001;65:305-309.

26.     Edvardsen T, Urheim S, Skulstad H, Steine K, Ihlen H, Smiseth OA. Quantification of left ventricular systolic function by tissue Doppler echocardiography: added value of measuring pre- and postejection velocities in ischemic myocardium. Circulation. 2002;105:2071-2077. 

27.     Ouriel K. Peripheral arterial desease. Lancet. 2001;358:1257-1264.

28.     Berger SA, Jou L-D. Flows in stenotic vessels. Ann Rev Fluid Mech. 2000;32:347-382.

29.     McDermott MM, Hahn EA, Greenland P, et al. Atherosclerotic risk factor reduction in peripheral arterial diseasea: results of a national physician survey. J Gen Intern Med. 2002;17:895-904.

30.     Møller JE, Whalley GA, Dini FL, et al; the Meta-Analysis Research Group in Echocardiography (MeRGE) AMI Collaborators, Independent prognostic importance of a restrictive left ventricular filling pattern after myocardial infarction: an individual patient meta-analysis: Meta-Analysis Research Group in Echocardiography Acute Myocardial Infarction. Circulation. 2008;117:2591-2598.

31.     Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286:1317-1324.

32.     Aurigemma GP, Gaasch WH. Diastolic heart failure. N Engl J Med. 2004;351:1097-1105.

From the ¹Division of Interventional Radiology and ²Division of Cardiology, Miami Cardiac and Vascular Institute (MCVI), Miami, Florida; ³Department of Medical and Population Health Sciences Research, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; and ⁴Division of Cardiology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, Republic of Korea.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted June 23, 2016, provisional acceptance given September 13, 2016, final version accepted September 19, 2016.

Address for correspondence: Barry T. Katzen, MD, Miami Cardiac and Vascular Institute (MCVI), 8900 N. Kendall Drive, Miami, FL 33176. Email: barryk@baptisthealth.net