Volume 3 Number 2A publication of Cardiology Associates • Mobile,Alabama

CT Angiograms Coming toCardiology AssociatesBy J. Andrew Morrow, Jr., M.D., F.A.C.C.

How the Successes ofInterventional CardiologyHave Advanced theScope of EPBy Stephanie D. Grosz, M.D., F.A.C.C.

Beyond theHeart, Part 2

By Frank T. Bunch, M.D., F.A.C.C.

Beyond theHeart, Part 2

By Frank T. Bunch, M.D., F.A.C.C.

CT Angiograms Coming toCardiology AssociatesBy J. Andrew Morrow, Jr., M.D., F.A.C.C.

How the Successes ofInterventional CardiologyHave Advanced theScope of EPBy Stephanie D. Grosz, M.D., F.A.C.C.

N O W A V A I L A B L E

©2002 Scios Inc. All rights reserved. P0100101Sept 2002

820 West Maude AvenueSunnyvale, CA 94085

FROM

3

Gerry M. Phillips, M.D., FACCKenneth E. Francez, Jr., M.D., FACCJ. Andrew Morrow, Jr., M.D., FACC

Frank T. Bunch, M.D., FACCM. Wail Hashimi, M.D., FACC

Richard J. Chernick, M.D., FACCBrian D. Dearing, M.D., FACCWilliam J. Hayes, M.D., FACCErik A. Eways, M.D., FACC

Charles W. Parrott, M.D., FACCKenneth M. Burnham, M.D., FACC

Elia Abboud, M.D., FACCDavid T. Trice, M.D., FACC

James R. Stinebaugh, Jr., M.D., FACCMichael W. Monson, M.D.Karl V. Hakmiller M.D.

Ralph S. Buckley, M.D., FACCJason H. Cole, M.D.

ElectrophysiologyStephanie D. Grosz, M.D., FACC

D. Scott Kirby, M.D.

Pediatric CardiologyDavid C. Mayer, M.D., FACC, FAAP

Anne M. Hackman, M.D. FACC, FAAPLynn Arnold Batten, M.D., FACC, FAAP

Cholesterol and Lipid DisordersMary H. Honkanen, M.D.

Terence E. Hale, M.D., FACC(1955-2000)

Vance M. Chunn, FACHECEO/Administrator

6701 Airport BoulevardSuite D-330 Mobile, AL 36608

(251) 607-9797 Fax (251) 639-0940

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1721 North McKenzie StreetFoley, AL 36535

(251) 943-4100 Fax (251) 943-3794www.cardassoc.com

1-800-842-4009EditorErik A. Eways, M.D., F.A.C.C.

Cover Photograph byVance M. Chunn, F.A.C.H.E.

Edition 8

Created by Publishing Concepts, Inc.Virginia Robertson, President • vrobertson@pcipublishing.com

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December 2004

In this issue of Cardiology Currents, our physicians take a look at the ever

changing and evolving nature of cardiovascular disease. The amazing advances made

in the areas of interventional and preventive cardiology are helping to keep patients

alive for longer and with expectations for better quality of life. Many of these

patients, as they survive and thrive, may eventually find themselves in need of “sec-

ondary cardiology services” – electrophysiology, or treatment of peripheral vascular

disease or heart failure.

In her article, Stephanie Grosz, M.D. demonstrates how the successes experienced

in one field of cardiology translate into a need for new treatment options that elec-

trophysiologists can provide to their patients. She highlights the tremendous strides

made in the areas of device therapy and the evolution and advancement of catheter

based ablation.

Frank Bunch , M.D. has written the second article in his series on Peripheral

Vascular Disease. Again, we find that many patients who initially present with coro-

nary disease or symptoms they believe are related to coronary disease, are often at

risk for the secondary complications of peripheral vascular disease. In this issue, Dr.

Bunch focuses on symptoms and treatment options for aortic, iliac and lower

extremity vessel disease.

Drew Morrow, M.D. shares details about how CT angiography will benefit the

patients of Cardiology Associates and discusses the arrival of a 64 slice CT scanner

in our city.

As we approach the holidays, all of us here at Cardiology Associates wish you and

yours a blessed season.

Sincerely

Gerry M. Phillips, M.D., F.A.C.C.

4

Cardiology Associates expects to have its GE 64slice CT scanner operational in the first quarter of2005. It is anticipated to be the first scanner of itstype in Mobile. The scans will offer new possibili-ties in caring for our patients. CT angiography is adeveloping technology with promise to improvethe evaluation of several types of vessel disease.The current generation of 16 slice scanners hasshown promise- particularly in the area of periph-eral vascular disease. The new generation of 64slice scanners will advance the technology andexpand its use to more patients and more types ofcardiovascular abnormalities- especially thoseinvolving the heart. The faster scanner will allowimaging of the beating heart with higher resolutionand with much shorter breath holds by the patient.

CT angiography uses approximately the sameamount of radiation and slightly less contrast “dye”as invasive angiography in the hospital. The majoradvantages are that there is no need for an arterialpuncture and no need to manipulate catheters tofind the arteries. This reduces the risk of the proce-dure and eliminates the need for a hospital visit- aswell as the need for bed rest and observation afterthe procedure. The patient spends about an hour atthe scan and then goes home. An IV line is requiredfor administration of the contrast agent. The heart-beat is monitored by EKG leads so that the scanscan be timed to the cardiac cycle.

CT angiography provides excellent peripheralarterial studies. In most patients the scanner canevaluate any large peripheral artery as well as a tra-ditionally invasive angiogram. Studies of large por-tions of the peripheral arterial tree can be done withless X ray contrast than in the invasive angiography

suite. Interventions in the invasive lab can be “target-ed” to already demonstrated blockages.

The new generation of scanners will have moreapplicability for cardiac evaluations. The breathhold for a cardiac scan will be reduced from 20 to30 seconds down to 5 to 8 seconds. There will be abit more tolerance for higher heart rates and heartrate variability. The new scanner will have higherresolution around the edges of its field. Theseadvances will allow scans to be obtained in morepatients- and allow more patients to benefit fromthis new technology.

The CT angiograms are very sensitive and easilydemonstrate the presence or absence of plaquebuildup in the coronary arteries. CT angiogramsalso show “blood clots in the lungs” - or pulmonaryembolisms well. In addition, dissections or “tears”in the aorta are easily seen. Thus one test is able toevaluate three of the most serious or dangerouscauses of chest pain. Other causes of chest painsuch as pericardial effusions and hiatal hernias maybe demonstrated as well. A great deal of informa-tion is available in one scan.

CT angiography is not as precise as a heartcatheterization for defining the fine details ofbypasses, stents, and exact percentage of blockage incoronary arteries. The CT angiograms do not showthe amount of flow disturbance from fat buildup inthe arteries- best seen with a stress test. The CTangiogram is a new test which complements ratherthan replaces our current diagnostic modalities.

The physicians and staff of Cardiology Associatesare excited about the opportunities available withthis new technology. Look for more information infuture issues of Cardiology Currents.

CT Angiograms Coming toCardiology Associates

by J. Andrew Morrow, Jr., M.D., F.A.C.C.

As research and technologicaldevelopments continue toadvance the detection and

treatment of coronary artery diseaseand heart attacks, the demand forservices and treatment options inthe field of electrophysiology grows

proportionally.Our success in treating patients with coronary

artery disease and improving life expectancy in thesepatients has resulted in a new and exponentially grow-ing need to help those people who have either sur-vived a cardiac arrest or are at risk for a life threaten-ing rhythm disturbance. Expanding areas of applica-tion for radiofrequency ablation, particularly for atrialfibrillation, has provided exciting focus for the field,and help for these patients, many of whom are debili-tated by their disease. Improved device therapy withthe addition of biventricular devices to the armamen-tarium of treatment for congestive heart failure hasimproved both quality of life and mortality in thissubgroup of patients.

Deaths from heart attacks have been cut nearly inhalf over the last 20 years. Conversely, since 1980, thedeath rate from arrhythmias has increased from 27.6per 100,000 to 69.8 per 100,000. Fortunately, inmany areas of arrhythmia management and treatment,new and emerging options continue to be exploredand utilized with great success. The new technologiesfrequently complement with treatments that havebecome standard of care, such as electrophysiologystudies, catheter ablation, and device therapy. Theseadvances will be reviewed in this article.

ABLATION

One of the biggest breakthroughs in the field of EPand certainly within the realm of ablation isPulmonary Vein Isolation or Ablation for AtrialFibrillation (AFIB). This arrhythmia affects more thanhalf of the 4 million Americans currently diagnosed

with a rhythm disorder. Many cardiovascular abnor-malities can contribute to AFIB including coronaryartery disease, valvular heart disease, heart failure,hypertension, dilated cardiomyopathy, as well as non-cardiac disease such as thyrotoxicosis and a variety ofpulmonary diseases. Prior to AFIB ablation, the onlyoption available for this large segment of patient pop-ulation was drug therapy. Standard medical regimensusually consist of an anticoagulant to prevent stroke,and a rhythm control medication with or without arate control drug. These are chronic suppressive regi-mens, not considered curative. Atrial fibrillationbreakthrough on medical therapy is not uncommon,and can occur in as many as 50% of patients.

AFIB ablation is an alternative treatment option inselect groups of patients with atrial fibrillation whohave not done well on medical therapy. Research hasshown that if the electrical triggers that set off anabnormal rhythm can be localized to the pulmonaryveins (the veins that drain the lungs to the left side ofthe heart), and these veins can be isolated from theheart electrically with ablation, then the triggers that“send” the heart into AFIB can never reach the heart.The procedure is evolving, and has mixed resultsreported in the literature. As many as 50-70% ofpatients may have long term “cure” of AFIB, in thatthey may be able to discontinue antiarrhythmic med-ications. The therapy is not without morbidity, and isnot indicated for all patients with AFIB, but it is agood alternative for some patients.

continued on the next page

9

by Stephanie D. Grosz,M.D., F.A.C.C.

How the Successes of

INTERVENTIONAL CARDIOLOGYHave Advanced the Scope of EP

Deaths from heart attacks have beencut nearly in half over the last 20

years. Conversely, since 1980, thedeath rate from arrhythmias has

increased from 27.6 per 100,000 to69.8 per 100,000.

10

DEVICE THERAPY

Two subspecialty fields of cardiology-Electrophysiology and Heart Failure- meet in an effortto treat the millions of patients who are now survivingheart attacks and cardiovascular events because ofimprovements in treatments in the areas of coronarydisease. Almost every type of cardiovascular event orrisk factor can damage the heart and eventually lead toone or both of these subspecialty fields of cardiology.One of the ways the two disciplines work together isin the area of coronary disease, and left ventriculardysfunction. Currently, the mortality for patients withcoronary disease and Ejection Fraction (EF) of < 30%is high, 20% at 2 years despite treatment with optimalmedical therapy-ACE inhibitors, beta blockers, digox-in, and diuretics. Part of the mortality in this high riskgroup of patients is due to arrhythmia. 400,000 peo-ple in the United States per year experience suddencardiac death, caused largely by ventricular arrhyth-mias. The mortality of out of hospital cardiac arrestremains extremely high so much recent research hasfocused on identifying high risk patients to preventsudden death from arrhythmias.

One of the primary treatments for this group ofpatients is defibrillator therapy. A defibrillator is surgi-cally and fluoroscopically implanted in the cardiaccatheterization lab. The device “watches” the patient’srhythm at all times, automatically detecting any signif-icant arrhythmia, and will shock and abort a suddendeath event quickly and effectively. Defibrillatorshave been indicated for patients who have shownmalignant arrhythmias, such as sudden death survivorsand those who have ventricular, or “bottom chamber”arrhythmias. Based on new studies, defibrillator thera-py has now expanded to include high risk patients

who have not yet shown ventricular arrhythmias.MADIT 2 was a landmark study in EP that showedimproved life expectancy in patients with EF<30%who had defibrillators placed vs. those treated withmedical therapy. These patients had not shown anyarrhythmias yet. Cardiology Associates participated inthis trial that now supports prophylactic defibrillatortherapy for patients with coronary disease andimpaired LV function.

Many patients with left ventricular dysfunctionalso have interventricular conduction delay. This caus-es delayed lateral wall contraction, disorganized ven-tricular contraction and decreased pumping efficacy inthese patients. These patients are “asynchronous”.Morbidity and mortality remain high, with intensemedical therapy, inotropic therapy, and transplant theoptions for many. Cardiac Resynchronization Therapy(CRT) has had significant success in improving qualityof life and mortality for this very sick group ofpatients. It brings another tool to the arsenal of theheart failure physician to offer patients to improveoutput of the failing heart. To resynchronize, a patientmust manifest asynchronous conduction. A standarddefibrillator or pacemaker is placed, but a third lead isplaced in the vein that wraps around the back of theheart, the coronary sinus. The lead is placed in a tar-get branch to pace the left side of the heart and all ofthe wires are attached to the pulse generator to paceboth the right and left sides of the heart together. Thedefibrillator device also provides protection againstsudden cardiac death as discussed previously. Themechanisms of CRT are 1)restoration of normalrhythm function 2)coordination of septal and free-wallcontraction and 3)improvement in pumping efficacy.

The field of interventional cardiology has pio-neered many advances that have improved the lifeexpectancy and quality of life of patients that werepreviously “untreatable”. These efforts have led tonew and important challenges for our field ofElectrophysiology. The problems faced by our patientshave changed, and as physicians, we have focused onthese new issues. As the field continues to evolve, wewill review and update our patients with these excit-ing advances.

“Based on new studies, defibrillator therapyhas now expanded to include high riskpatients who have not yet shown ventriculararrhythmias.”

The early warning signs of a heart attackgive you the power to act — but they often go ignored. Why?

It doesn’t always start with chestpain. Each heart is unique, and soare its ways of asking for help.

Learn all the warning signs.

Early Warning Signs of Heart Attack(referred to as the Prodromal Signs. Experi-enced by 60% of all heart attack victims –hours even days before a heart attack)

• A mild discomfort or nagging ache in thecenter of the chest

• Recurrent discomfort; feels like indiges-tion. Discomfort may increase in intensity.More intense pain with exertion that goesaway with rest.

Heart Attack Signs• Pain in the chest, shoulders, neck or arms• Pressure• Fainting• Sweating• Shortness of Breath• Nausea

It’s never too soon to get good news aboutyour heart. And in the event of a heartattack, crucial heart muscle is damagedevery minute you delay.

It’s Your Choice. Make it the Right One.The Chest Pain Center at Providence

Comprehensive Chest Pain Evaluation – 24 Hours a Day – Without an Appointment

Chest Pain Center Located within the Providence Hospital Emergency RoomChest Pain Center Located within the Providence Hospital Emergency Room

Gerry M. Phillips, M.D., FACC

Kenneth E. Francez, Jr., M.D., FACC

J.Andrew Morrow, Jr., M.D., FACC, FACP

Frank T. Bunch, M.D., FACC

M.Wail Hashimi, M.D., FACC

Richard J. Chernick, M.D., FACC

Brian D. Dearing, M.D., FACC

William J. Hayes, M.D., FACC

Erik A. Eways, M.D., FACC

Charles W. Parrott, M.D., FACC

Kenneth M. Burnham, M.D., FACC

Eliyya G.Abboud, M.D., FACC

David T.Trice, M.D., FACC

James R. Stinebaugh, Jr., M.D., FACC

Michael W. Monson, M.D.,

Karl V. Hakmiller, M.D., FACP

Ralph S. Buckley, M.D., FACC

Jason H. Cole, M.D., MSc

Electrophysiology

Stephanie D. Grosz, M.D., FACC

D. Scott Kirby, M.D., FACC

Pediatric Cardiology

David C. Mayer, M.D., FACC, FAAP

Anne M. Hackman, M.D. FACC, FAAP

Lynn Arnold Batten, M.D., FACC, FAAP

Cholesterol and Lipid Disorders

Mary H. Honkanen, M.D.

Gerry M. Phillips, M.D., FACC Kenneth E. Francez, Jr., M.D., FACC

Brian D. Dearing, M.D., FACC William J. Hayes, M.D., FACC

David T. Trice, M.D., FACC

Stephanie D. Grosz, M.D., FACC D. Scott Kirby, M.D., FACC

James R. Stinebaugh, Jr., M.D., FACC

J. Andrew Morrow, Jr., M.D.,FACC, FACP

Frank T. Bunch, M.D., FACC M. Wail Hashimi, M.D., FACC Richard J. Chernick, M.D., FACC

Erik A. Eways, M.D., FACC Charles W. Parrott, M.D., FACC Kenneth M. Burnham, M.D., FACC Elia G. Abboud, M.D., FACC

Michael W. Monson, M.D. Ralph S. Buckley, M.D., FACCKarl V. Hakmiller, M.D., FACP

David C. Mayer, M.D.,FACC, FAAP

Lynn Arnold Batten, M.D.,FACC, FAAP

Mary H. Honkanen, M.D.Anne M. Hackman, M.D.,FACC, FAAP

Jason H. Cole, M.D., MSc

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23

In the United States, there are 12 – 20% of Americans 65years of age or older affected by Peripheral Vascular Disease(PVD) which is manifested mainly in the lower extremities.It is important to note that there is a 4 to 6 fold increase incardiovascular mortality in patients who have PVD.

In lower extremity and aortic PVD, the hallmark symp-tom is intermittent claudication which is fatigue, tightening,squeezing type sensations that occurs anywhere from thelevel of the buttocks down to the foot and is typically pre-dictable. These symptoms tend to occur with exertion,mainly with walking, and are fairly predictable at a certaindistance. Symptoms generally improve with rest and willreoccur at about the same distance. Oftentimes symptomsof claudication are mistaken for musculoskeletal or neuro-logic conditions.

Peripheral arterial occlusive stenoses located in the lowerextremities can be diagnosed with a thorough history aswell as a physical exam. The exam should include palpationof pulses and listening for bruits, the noises that occur inthe arterial vessels when stenosis is present. In addition, arelatively simple and noninvasive test which can be done inthe office is an ankle brachial index (ABI’s). This test meas-ures the systolic blood pressure of the ankle in comparisonto the brachial systolic blood pressure. It is very helpful indelineating the cause of leg pain.

Oftentimes, patients will adjust their overall activity lev-els to accommodate their symptoms. Their symptoms maynot be as prevalent unless one spends some time asking thepatient specific questions. The adjustments are usuallymade gradually and many patients do not realize they havemade the adjustments, to the point that they are highlyinhibited from their normal daily activities. Overall, PVD,besides creating an increase in mortality and secondary car-

Aortic, Iliac and LowerExtremity Peripheral Vascular Disease

Beyond the Heart, Part Two in a FourPart Series on Peripheral Vascular/Arterial Disease

By Frank T. Bunch, M.D., F.A.C.C.

Major BloodVessels in theLower Body

Abdominalaorta

diovascular disease, can also cause aprogressively sedentary lifestylebrought on in part to prevent symp-toms from occurring

Historically, vascular disease inthe aorta and lower extremities hasbeen treated by either medical thera-py, exercise or surgical therapy. Overthe past 15 or so years, there’s been aprogression of catheter-based thera-pies for PVD which have becomemore and more successful. Peoplewho were sedentary are now able toreturn to a more satisfactory lifestylewithout the risk of major surgery.

Aortic Disease is located mostly inthe abdominal aorta, usually at andbelow the level of the renal arteries.The iliacs are the two branches offthe aorta leading into the left andright lower extremities, then to thearteries of the lower extremitiesbelow the level of the hip. These ves-sels can be affected at any leveleither diffusely throughout the vesselor discreet stenosis.

Aortic disease can be brokendown into two types of disease.

One is aortic aneurysmal diseasein which an aortic aneurysm forms (aballooning of the abdominal aorta).This occurrence is secondary to aweakening in the vessel wall due toatherosclerotic changes as well as in

conjunction with hypertension. Thewalls are greatly affected when theaortic aneurysm reaches somewherein the range of 5 cm in diameter. It isrecommended that an aneurysm ofthis size be repaired due to signifi-cant risk of rupture. In certaininstances, the aortic aneurysm can berepaired through percutaneous thera-py without open surgery. This can bedone by placement of a stent graftwhich is a stent covered with a graftlike material that excludes the aorticaneurysm. The usual hospital stay forthis procedure is one to two days,after which the patient should beable to walk out of the hospital. Thisprocedure also prevents them havingmajor surgery.

The second type of aortic disease isstenosis or narrowing of the abdominalaorta. This can narrow to the pointwhere it can become either totallyoccluded, typically occurring at thevery distal portion of the aorta before

it splits into left or right iliac arteries.It can also occur above that level. Inthe past, the surgical therapy for thiswas bypass grafting with aortabifemoral grafting. This now can betreated using a balloon with possiblestenting, if needed. The long termpatency rate of this treatment hasactually been shown to be very favor-able and is again another modalitywhich can be used instead of subject-ing the patient to major abdominalsurgery. Typically the patient will gohome the next day after being treated.

Iliac disease usually involves ather-osclerotic changes which causestenoses in the iliacs.

Symptoms of aortic and iliacblockages are similar. Both have but-tock and lower extremity pain whenthey walk and are actually betterwhen they rest. The difference withiliac pain is that it may only affectone side. The sciatic nerve or spinalstenosis can be mistaken for claudi-

(continued on page 30)

Above:Right Iliac

AngioBefore

Right: RightIliac Angio

After

“Historically, vascular dis-ease in the aorta and

lower extremities has beentreated by either medicaltherapy, exercise or surgi-cal therapy. Over the past

15 or so years, there’sbeen a progression of

catheter-based therapies forPVD which have become

more and more successful.”

Highway 59 – foley, al aba ma251-949-3400

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(Opening May 2004)

30

Beyond the Heart, Part 2continued from page 24

to all our co-sponsors forhelping to make ourmagazine a success. If you would like tobecome a co-sponsor

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Thankyou!

Publishing Concepts, Inc.14109 Taylor Loop Road

Little Rock, AR 72223501.221.9986 / 800.561.4686

Volume 3 Number 1

A publication of Cardiology Associates • Mobile,Alabama

New Closure Tec

hnique

Advances the Tre

atment of

Patients with Rec

urrent

StrokeBy Erik

A. Eways, M.D., F.A.C.C.

Cardiac CT Com

es of Age

By M. Wail Hashimi, M.D., F.A.C.C.

Beyond the

Heart, Part 1

By Frank T. Bunch, M.D., F.A.C.C.

cation symptoms in the iliac arteries.Treatment of the iliac arteries is actu-ally one of the more successfulmodes of therapy which includesangioplasty and, if needed, stenting.

In the lower extremities, belowthe level of the hip, there are twotypes of disease which occur either atthe level of the thigh in the superfi-cial femoral artery or below the kneein the tibialperoneal arteries.Multiple treatments have been triedfor this lower extremity disease frombypass surgery to intervention via thepercutaneous route. Percutaneousapproaches include laser therapy,atherectomy (removal of plaque),cutting devices, and angioplasty, aswell as stenting. Different types ofangioplasty are also available – thosethat use cryotherapy which is a coldballoon as well as balloons that havea cutting blade have both been used.Various gradations of success arepresent. Due to the long vessel andthe diffuse nature of the disease,there is somewhat of a higher scartissue formation, or restenosis, rate inthese vessels versus vessels that areabove that level of the thigh. One ofthe advantages to using percutaneoustherapy for lower extremities belowthe level of the hip is that if repeatprocedures need to be performed,very rarely are bridges burned andmultiple modalities can be used again

and ultimately, if needed, bypass sur-gery is not excluded.

Below the level of the knee insmaller vessels, the important consid-erations need to be the changeoverin progression from intermittentclaudication to a more severe formwhich is ischemia and can be classi-fied as critical ischemia when onedevelops a non-healing wound orpain at rest. Revascularization withdifferent types of therapies is indicat-ed and needs to be done to preventamputation of the affected limb.More recently there have been stud-ies using excimer laser which havedemonstrated successful revascular-ization of vessels below the level ofthe knee to the point where thatpatient can heal and save the limb.

Lower extremity atherosclerosis isan entity which is being underserved.Estimates throughout the countryhave been made and it has beenfound that approximately 25 – 30%of peripheral vascular disease patientsare undergoing the therapy which isactually available to them. As withany form of atherosclerosis, risk fac-tor modification is clearly a necessity.Smoking cessation, lowering choles-terol, blood pressure control as wellas controlling diabetes are all verynecessary for successful outcomeslong term.

“In the United States,there are12 – 20% of

Americans 65 years ofage or older affected by

Peripheral VascularDisease (PVD) which is

manifested mainly in thelower extremities.”

Presorted StandardU.S. POSTAGE PAID

Little Rock, ARPermit No. 2437

Cardiology Associates3715 Dauphin Street

Suite 4400

Mobile, AL 36608

Two weeks after his implant, Wade Arledge felt a little sore.

From dancing all night.

Over 30,000 heart failure patients have received Cardiac Resynchronization Therapy.

How many of your patients could benefit from this therapy?

Patient results vary; not every response to therapy is the same.