Cardiovascular Effects of Space Flight Richard J. Cohen, M.D., P h .D. Har v ar d- MIT Di vision of Healt h S c iences and T e chnol ogy Cardiovascular Problems Associated with Space Flight ? O rthostatic Intolerance upon Re-entry ?A r r h y t h m i a s ? L oss of Cardiac Mass ? R educed Exercise Capacit y ? M anifest a tion of Pre- existi ng Car d i o vascul ar Disease Post Flight Orthostatic Intolerance ? A ppears to be mor e severe t h e l o nger the durati on of s p ace flight. ? W omen are more sever e ly affected t h an men, but virt uall y all ar e aff ected aft e r l o ng durati on flight. ? C urrent countermeasures of salt and water loading and use of a G suit are not adequate Cardiovascular Problems Associated with Space Flight V e no us Resis t a n ce Micr ovasc ular Res i stance ? R esi s t a nc e B aror ef l e x ? V a s or eac tivit y ? α? S y mp ath e ti c I nput ? AVP ? R e n in- A n g iot e nsin Sy s t e m ? N itr ic Ox ide V e no us Com p l i ance ? α -S y m p a th eti c I nput ? M uscle Mass/Ton e A r ter i a l Com p lia nce Heart ? I not rop y ?H RB a r o r e f l e x ? P aras y m p a the t i c I nput ? β? S y mp athe tic I nput ? A rrh y t hm i a s ? C ardi ac At roph y ?Ang iot e nsin In tra v asc u la r V ol um e ? S a l t a n d Wa te r I n ta ke ? AVP ? ANP ? M i n er al oco r t i coi d s Human Studie s Hu m a n Studies Cor e - W illia m s Alter a tion in Car d iovascular Regulation - C ohen Renal and C ar dio-E ndocr i ne Responses - W illia m s Ventricular A rr hyth m ias - Cohen Rode nt Studie s Car d iovascular Deconditioning - S ho ukas Car d iac Atr ophy - S chneider Comp u t er Mod e lin g Ka mm Cardiovascular Problems Decondition i ng Atroph y Arrh y t hmias Acti on s Determine Magn itude of Problem Identif y M echan is m s Propose Counter measures Te st Counte rmea sure s Effects of Microgravity on Cardiovascular, Hormonal and Renal Response to Posture Inve stiga t or s : Ric ha r d Co h en, M.D., P h.D Cr ai g R a m s d e ll, M. D., Tom M ullen, Ph.D., N a ta l i e Sh eynb erg , M.D . Gor d o n Will ia ms, M. D. Disciplines: Ca rd io logy, End o c r in olo g y, Sp ac e Me dicine Primar y Source N a tiona l Spa c e Bi omedi cal Re se arch of Fu ndin g : Instit ute GCRC Site Visit Experiment Protocol 2 Days Extens iv e CV & Endocrine Testing 3 Days Extens iv e CV & Endocrine Testing 16 Days 4o HDT Bed rest Controlled Diet, NA, K and Fluid Intake ? S upine-Stand Tests ? C ardiov ascu lar System ID ? A II Infusions ? T W a ve Alternans ? E le c t ro ly tes ? L eg Com p liance S t ud ies ? N orepi I nfusions ? E chocardiogram s ? O thers ... Cardiovascular System Identification S y st em Ident i f i cat ion Res u lts AB P (Finapres ) ECG A/ D (Resp itrac e ) ILV A m plifier System Id en tificatio n CSI Effect of Autonomic Blockade CSI Effect of Autonomic Neuropathy HR Barororeflex Sensitivity Effect of Midodrine Kaplan-Meier Syncope-Free Survival 0 40 80 120 160 0 10 20 30 40 50 60 70 80 90 100 Con t rol Mi do drine P = 0.021 Time (Min u t es) Sy ncop e-Free Survival Arrhythmias in Space ? A necdotal reports of ventricular arrhythm ias during spa ceflight ? R uns of ventricular tachycardia recorded from m e m b ers of Skylab and Mir ? T wo Russi an Mir c osm onauts reportedl y brought back early due to hea r t rhythm disturbanc es ? T wo primates died suddenly following landing ? N o deaths from ventricular arrhythm ias during space flight Arrhythmias in Space ? I t is not known whether or not s p acef light incr eases the ris k of vent ri cular arr h ythmias. ? If s p acefl i ght does increase the risk of ventricul a r arr h yt hmi a s, it could be of concern for long term space flight such as duri ng a mission t o Mars. Use of Microvolt T-Wave Alternans Testing to Reduce Risk of Sudden Cardi ac Deat h Richard J. Cohen M.D., P h.D. Harvard-MIT Division of Health Sciences and Technology Sudden Cardiac Death A Major Public Health Proble m ? 1 /2 of al l car diac deat hs ? 1 /7 of al l deaths ( t housan ds) (m il li o n s ) Popula t i on S i ze SCD Perc en t / Year T o t al SCD / Year (percen t ) High Risk Groups for SCD Popula t i on S i ze SCD Perc en t / Year T o t al SCD / Year High Cor onar y High Cor onar y RiskRisk Post M I Post M I Heart Fa il ure/ Heart Fa il ure/ E F < 35 % ) E F < 35 % ) Pre v ious Pre v ious VF / VTVF / VT S y ncope / S y ncope / Heart DiseaseHeart Disease 00 10 0 10 0 20 0 20 0 30 0 30 0 5050 00 1010 2020 5050 11 22 55 00 1010 11 22 55 2020 (m il li o n s ) (percen t ) ( t housan ds) A d ap ted f r o m M y e rbur g Heart Failure Patient With “Lightheadedness” A 63-year-old man arrived in the hospital for suspected VT foll owi n g a bout of light headedness. His hist ory reveal ed a diagnosis of coronary artery disease, NYHA class II heart failure, previ o us cor o nar y bypass gr aft s u r g er y, and his L V EF was measured at 26%. Patient with Non-Ischemic Dilated Cardiomyopathy A 54-year-old woman arrived in the hospital following a syncopal episode. Her history revealed diagnoses of non-ischemic dilated cardiomyopathy, NYHA class I heart failure, and a previously measured LVEF was 25%. VT in Patient with Acute MI A 68 year old man presented with a chief complaint of three s y ncopal episodes on the day of presentat i on. EC G reveal ed VT at a rat e of 150 b pm and car d i ac enzymes conf ir med acut e myocar dial infarction. Subsequent cardiac catheterization revealed two-vessel CAD and normal ventricular functi on. Patient with Prior MI and Renal Failure A 64 year old man with a 20 year history of renal f a il ure, and a hist or y of an MI 12 years pri o r to admission, pr esented with a new anterior myocar dial i n farct i on. His LVEF was 40% and he had NYHA class II heart failure. Syncope & Family History of SCD A 25-year-old male was evaluated for abr u pt l o ss of conscious ness. A family history of sudden death prompted the need for further evaluation. His LVEF was nor m al. 1. Herring H: Experimentelle Stud ien an Saugetieren uber d a s Electr ocardiogramm Ztchr fd ges exp e r M e d 1909 ; 7 : 363. 2. Lewis T: Notes upon alternation of the hear t. Quart J Me d 1910; 4 : 141 - 144. 3. Kleinfeld M, Ro zans k i J: Altern a n s of the ST seg m ent in P r in zm etal 's ang i na. Cir c 1977; 55:574 - 57 7. 4. Schwartz PJ, Mallian i : A. Ele c tric al al terna tio n of th e T - wave: Clin ica l and exp e rim e ntal evidence of its r e lationship with the s y mp athetic nervous s y stem and with the lon g Q - T s y ndrome. AM Heart J 1975 ; 89 :45 - 50. 5. Redd y CVR, Kiok J P , K h an RG , El - She r if N: Re polariz ation a lter n ans as s o cia t ed with alcoholism and h y pomagnesemia . A m J Card iol 1984; 53:390 - 39 1. Relaxed Em o t i o n a l Excite m e n t Historical References 1. Herring H: Experimentelle Stud ien an Saugetieren uber d a s Electr ocardiogramm Ztchr fd ges exp e r M e d 1909 ; 7 : 363. 2. Lewis T: Notes upon alternation of the hear t. Quart J Me d 1910; 4 : 141 - 144. 3. Kleinfeld M, Ro zans k i J: Altern a n s of the ST seg m ent in P r in zm etal 's ang i na. Cir c 1977; 55:574 - 57 7. 4. Schwartz PJ, Mallian i : A. Ele c tric al al terna tio n of th e T - wave: Clin ica l and exp e rim e ntal evidence of its r e lationship with the s y mp athetic nervous s y stem and with the lon g Q - T s y ndrome. AM Heart J 1975 ; 89 :45 - 50. 5. Redd y CVR, Kiok J P , K h an RG , El - She r if N: Re polariz ation a lter n ans as s o cia t ed with alcoholism and h y pomagnesemia . A m J Card iol 1984; 53:390 - 39 1. Relaxed Em o t i o n a l Excite m e n t (Schwartz & M alli ani. A m He art J 1975; 89:45-50) Historical References ? K alter H H (Electrical Alternans, N. Y. State J. M., 1948) reviewed 46 cases of electrical alternans reported in the world literature ? I ncidence approxim ately 1 in 1000 EC G’s ? M ortalit y 61% Mechanism Linking TWA to Ventricular Arrhythmias Long APD S h or t AP D Lon g A P D Shor t APD Lon g A P D R e gi on Sh or t AP D Regi o n Action Po ten t i a l Altern ans Lead s to T-Wav e Alt e rn ans Sp atially Discordan t Altern ans Leads t o Di spe r si on o f R ecove ry , Wave F r ont F r act i o nat i on , a n d R eent r y T-Wave Alternans Visible Visible Microvolt Microvolt Level Level T-Wave Alternans Measurement: Spectral Method ECG 128 Beats TIME SERIES SPECTRUM 0 10 20 30 40 50 Spect r u m ( μμμμ V 2 ) Re s p P e da l i ng Al t e r n a n s 10 0 12 0 14 0 16 0 18 0 20 0 T W a v e Le vel ( μμμμ V) FFT 0 2 0 4 0 6 0 8 0 1 00 12 0 0. 0 0 . 1 0. 2 0 . 3 0. 4 0 . 5 B eat N u m b e r F r e q u e n c y ( C ycl es / B ea t ) T-Wave Alternans Measurement: Spectral Method ECG 128 Beats FFT Av g 0 . 0 0 .1 0 . 2 0 .3 0 . 4 0 .5 F r eq u e n c y ( C yc le s/ B e a t ) 0 10 20 30 40 50 0. 0 0 . 1 0 . 2 0 . 3 0. 4 0 . 5 Fr e que ncy ( C y c l e s/ B e a t ) Spe c t r um ( μμμμ V 2 ) Re s p P e d a lin g Al t e r n a n s T-Wave Alternans Measurement: Spectral Measures Alte rnans V o ltage ( Alte rnans V o ltage ( VV altalt )) 0 10 20 30 40 50 0. 0 0 . 1 0. 2 0 . 3 0. 4 0 . 5 Freq ue n c y (C y c le s/ Beat ) Spec trum ( μμμμ V 2 ) Nois e B a n d Al t e r n a n s P o w e r Noise Le v e l Alte rnans R a tio (k ) Alte rnans R a tio (k ) k Altern an s Po we r Noise Std. De v. ==== V alt = (Altern an s Po wer) ? Heart Rate Dependence of TWA Heart Rate Dependence of TWA VT PATIENT VT PATIENT H H H H H J J J J J J 0 10 20 30 40 ALTERNANS ( μμμμ V ) CONT ROL CONT ROL 80 100 120 140 HEART RATE (BPM) Ro sen baum , e t a l Measurement of T-Wave Alternans During Exercise Stress Micro-V Alternans Sensors MGH/MIT Clinical Study ? 83 consec uti v e patie nts referred to EP lab at MGH ? A lternans vs EP and arrhythm ia-free survival ? A lternans measured during atrial pacing ? P atient Characteristics: – A ge (y ea rs ) 57 ± 16 – I nd ication for Stud y ? C ardiac Arre st 20% ? S u s tain ed Vent ricu lar Tach ycard i a 3 1% ? S y n co pe 22 % ? S u p ra ve nt ric u l a r A r r h y t hm ias 1 8 % ?O t h e r 8 % – H eart Disea s e ? C or ona ry A r t e r y Di sease 6 4 % ? D ilated Card i o m y o p a th y 8 % ? M itral Val v e Prolapse 4% Rose nba um , Ja ckson , Smi t h , ? N o O r ga ni c He art Di sea s e 2 4 % G a ra n, Ru sk i n , Co he n. NE JM 199 4;33 0:23 5-4 1 . Electrical Alternans Versus El ectrophysiologic Testing 80 0 20 40 60 LVEF (% ) 0 20 40 60 80 100 MI (% ) S T Altern an s Ratio 0 5 10 15 SH D: St ruct ural Heart Diseas e T Altern an s Ratio 0 5 10 15 -S H D +S HD +S HD Rosenb aum et al ., New England -E P -E P +EP Jo urn a l o f M edi cin e , 33 0, 235 -2 41 , 199 4. MGH / MIT Results Arrhythm ia Free Survival Rose nba um , Ja ckson , Smi t h , G a ra n , Ruski n an d Cohen N E ngl J M e d 199 4 ; 33 0:23 5 - 24 1 MGH / MIT Results Arrhythm ia Free Survival A l te rn an s T e s t EP Study 100 % 80 60 40 20 0 100 % 80 60 40 20 0 Negati ve Positiv e Negati ve Positiv e Arrhy t hm ia-free Survival (%) 0 4 8 1 2 1 6 2 0 0 4 8 12 16 20 Months Months Rose nba um , Ja ckson , Smi t h , G a ra n , Ruski n an d Cohen N E ngl J M e d 199 4 ; 33 0:23 5 - 24 1 Frankfurt ICD Study ? 95 consecutive patients receiving IC D’s ? R isk str a tif ica t ion pr ior to im plant: – T W A , E PS, L V EF, BRS, S A ECG, HRV, Q T Dis p e r si on, QTVI, Mea n RR, NSVT ? E ndpoint: First appropriate ICD firing ? P atien t Characteris t ics – A ge ( y ears) 60 ± 10 – E jec tion Fract io n (%) 36 ± 14 – I ndex Arrh y t hmia ? V entricular Fibr illation 40% ? V T / V F 4 % ? V T 48% ? N onsustained V T with S y ncop e 8 % – H eart Dis e as e ? C oronar y Arter y Disease 75% ? D ilated Card iom y opa th y 17% ? O t h e r 3 % Hohnlo s e r , Klin ge n heb en , Li , Z ab el, ? N one 5% Peeterm a n s , an d C ohe n. JCE 1 9 9 8 ; 9 : 125 8- 126 8 . Frankfurt ICD Study Results 0 10 20 30 40 50 60 70 80 90 10 0 0 4 8 1 0 1 2 1 4 1 6 1 8 Mont hs E ven t F r e e S u r v i v a l EP + EP - 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 1 0 2 1 4 6 1 8 M onths Ev e n t Fre e Surv i v al TW A + TWA - A l te rn an s T e s t EP Study P< 0.006 P< 0.23 Relative R i sk 2.5 Relative R i sk 1.0 2 6 1 1 ? 41 first appropriate ICD firings (34 f o r VT, 7 for VF) ? T WA (relative risk 2.5, p < 0.006) and LVEF (relative risk 1.4, p < 0.04) were the only statistically significant univariate predictors of appropriate ICD firing during follow-up. ? C ox regression analysis revealed that TWA was the only statistically signif i cant independent predictor of appropriate ICD firing. Multi-Center Regulatory Study ? 337 patients referred for EP study, 9 US Centers ? E ndpoints: Ventricular tachyarrhythm ic events(VTE), VTE plus Tota l Mor t ality ? P atient Characteristics – A ge ( y ears) 56 ± 16 – E jec tion Fract io n (%) 44 ± 18 – I ndication for Stud y ? C ardiac Arres t 5% ? S us tained Ven t ri cular Ta ch ycard i a 14% ? S y n cope/Pres y n c ope 41% ? S upraventricu l ar Ta ch ycard i a 31% ? O t h e r 9 % – H eart Dis e as e ? C oronar y Arter y Disease 41% ? O ther S t ruc t ural Heart Dis e as e 29% Gold MR, e t al . (FD A -Clear ed ? N o S t ructura l H eart Dis eas e 30% Lab eling , C a m b rid g e H e ar t, In c . K N o . – C ongestive Hear t Failure 34% 983 10 2) . JACC, i n pre s s. Multi-Center Regulatory Study Prediction of VT/ V F, ICD Firing and Total Mortality A l ternans Test EP Study RR=4.7 P=0.001 RR=13.9 P<0.001 50 60 70 80 90 10 0 Ev e n t F r e e Su rv iv al TW A + TW A - 50 60 70 80 90 10 0 E vent F r e e S u r v i val EP + EP - 0 2 4 6 8 1 0 1 2 1 4 0 2 4 6 8 1 0 1 2 1 4 Mo nth s Mo nths Gold MR, e t al . (FD A -Clear ed L abeli n g , Ca mbri dg e He ar t, In c. K No . 98 310 2) . JACC, in p r e s s. Frankfurt CHF Study ? 107 consecu tive p a tients with NYHA class II and III heart failure, no recent MI (6 weeks), and no prior history of VT or VF ? T WA, EF, SAECG, Mean RR, HRV, NSVT, BRS tests perform e d ? E nd-point Ventricular T achyarrhythm ic Events (VTE = VT, VF or SCD) ? P atien t Char ac te ris t ics – A ge (y ea rs ) 5 6 ± 1 0 – E ject ion Frac ti on (% ) 2 8±07 – H eart Disea s e ? C or ona ry A r t e r y Di sease 6 7 % ? D ilated Card i o m y o p a th y 3 3% – A C E In hi bi t o rs 93 % Klingenheben T , Zabel M , D’ Agostino – B et a B l ocke rs 42 % RB, Cohen RJ, Ho hnloser SH. T h e Lancet 2000; 35 6: 651- 65 2. Frankfurt CHF Study Results 60 70 80 90 100 3 3 3 0 27 21 16 1 4 11 T W A - TW A - 5 2 4 5 40 32 30 2 6 24 T W A+ TW A + P = 0. 0 036 A r rh yt h m i a - F ree S u rvi val ? 13 Endpoint Events ? Sensitivity 100 % ? PPV 21 % ? TWA the onl y statisticall y significant predictor 0 3 6 9 12 15 18 Klingen he be n T , Co h en RJ , Pee t e r m ans J A ,, M o nt hs Hohnl ose r SH. AHA, 199 8 Klingenheben T , Z a bel M , D ’ A gostino RB, Co hen RJ, Hohnloser SH. T h e L a ncet 2000; 35 6: 651- 652. . Ikeda Post-MI Study Ikeda Post-MI Study ? 119 consecutive pa ti ents with a c ute MI ? T WA, S A ECG, and EF measured ? E ndpoints: sustai ned VT, VF, sudden deat h ? P atient Characteristics – A ge (years) 60±9 – E jection Fraction (%) 49±9 – M yocard i a l Infarc tion ? A nterior 49% ? L ateral 17% ? I nferior 34% – P rim a ry PTCA 98% Iked a, Sak a t a , T a k a mi, Ko nd o, T e zuka, Nak ae, No r o , Enjoji , Ab e, ? T WA test at 20±6 (7 to 30 days) post-MI Sugi, Y a ma guc hi. JA CC 200 0;3 5 :3 :72 2 - 3 0 Ikeda Post-MI Study Results T WA had the highest univariate relative risk (16.8) com p ared to SAECG TW A - TW A + 0 20 40 60 80 100 0 4 8 1 0 1 2 M ont hs E ven t - F ree S u rvi v al ( % ) p = 0 . 0002 2 6 ? (5.7) and EF (4.7). ? T WA had the highest sensitivity (93%) com p ared to SAECG (53%) and EF (60%). ? T WA negative patients had the lowest one-year event rate (2%) com p ared to SAECG (9%) and EF (8%). ? T WA positive patients had a one-year event rate of 28%; the low EF subgroup of these patients had a one-year event rate of 39%. Non-Ischemic DCM Study Results Prelim inary Result s i n 56 patie nts 0 10 20 30 40 50 60 70 80 90 100 TW A - TW A + P = 0.041 Ev ent - F r ee Sur v iv a l ? 56 non-ischemic dila ted cardiom y o pathy patients ? Endpoints : VT, VF, SCD ? All events among TWA+ patients 3 6 Months Klingen he be n T , Cr e dne r SC, B end er B, Cohe n RJ, Hohnl ose r SH. NASPE, 199 9. 0 Comparison to Other Risk Markers Prediction of Arrhythm ia-Free Survival Comparison to Other Risk Markers Prediction of Arrhythm ia-Free Survival A r m oundas et al , 1998 H ohnl os er et al , 1 998 Gol d et al , 1999 K l i ngenheben et al , 200 0 NS V T HR V SA ECG TW A * * * * ∞ 0 5 10 15 * p < 0.01 R e l a t i ve R i sk Event Rates Among TWA+ and EP+ Patients Study Pa t i e n t Pop u lati o n Follow-Up (mon t h s) TW A + E P + Ro senb a u m , et a l NEJM , 199 4 E P 20 81% ~ 8 1% Ikeda, et al J A CC, 20 00 P o s t M I 12 28% Go ld M R , et a l F D A , 19 99 E P 13 23% 25 % Go ld M R , et a l F D A , 19 99 J A CC, r e s s K now n o r Sus p ect ed V e n t ric u l a r Arrhy thmia (E P ) 13 26% 25 % Bloo mfi e l d , et a l Circ , 19 99 ( a bs ) Sy ncope (E P ) 13 19% 21 % Kl i n g e n h eb en , e t al T h e L a nc et , 20 00 C H F 1 8 21% Kl i n g e n h eb en , e t al PA CE , 199 9 (abs ) DCM 6 21% Bu xton , et a l NEJM , 200 0 Prior M I , EF ≤ 0.40, NSV T 24 18 % in p Event Rates Among TWA- and EP- Patients Study Pa t i e n t Popu lati o n Fol l o w-Up (mon t h s) TWA EP- R o se n b au m , e t al NEJM , 199 4 E P 20 6% ~6% Ikeda, et al J A CC, 20 00 P o s t M I 12 2% G o l d M R , e t al F D A , 19 99 E P 13 2% 5% Go ld M R , et a l F D A , 19 99 J A CC, in p r ess K now n o r Sus p ect ed Ve nt r i c u l a r A r r h yt h m i a (E P ) 13 3% 8% B l o o m f ie ld , e t al Circ , 19 99 ( a bs ) Sy ncope (E P ) 13 3% 6% Kl i n g e n h eb en , e t al T h e L a nc et , 20 00 CH F 1 8 0 % Kl i n g e n h eb en , e t al PA CE , 199 9 (abs ) DCM 6 0% Bu xton , et a l NEJM , 200 0 Prio r M I , EF ≤ 0. 4 0 , NSV T 24 12% Observations In a variety of populations: ? V entricular tachyarrhythmic event rates among TWA+ patients are elevated and comparable to event rates among EP+ patients. ? V entricular tachyarrhythmic event rates among TWA- patients are reduced to a level bel o w that of EP- p atients. Clinical Applications ? H istory Indicating Increased Risk of Sustained Ventricular Arrhythm ias – S yncope, Presyncope, P a lpitations, Non-Sustained VT, Fam i ly History, VT or VF Associated with T r ansient or Reversible Cause ? L eft Ventricular Dysfuncti on – H eart Failure, Cardiom yopathy, Reduced E j ection Fraction ? Prior Myocardial Infarction ? P atient s Undergoing Electrophysiology Study Heart Failure Patient With “Lightheadedness” Heart Rate T-Wave Alterna n s A 6 3 - y ear - o l d m a n ar ri ve d i n t h e h o spital for su sp ected VT fo ll o w i n g a b o u t of l i gh t h ead e dn ess. i s h i st or y re vealed a dia g nosis of corona ry a r te ry disea s e, NYHA clas s II heart fai l ure, pr evi o us c o r o n a ry by pas s g r af t s u r g e r y , and his LVE F was m easured at 26% . The res u l t s of bo t h T-wa ve al t e r n an s a n d EPS we re p o sit i ve. He was i m planted wi t h an IC D, a n d t h e devi c e f i re d ap prop r i ately eigh t w e ek s later i n H res p on se t o ve nt ri c u l a r t a c h y a r r hy t h m i a. Patient with Non-Ischemic Dilated Cardiomyopathy Heart Rate T-Wave Alterna n s A 54- year-o ld w o m a n ar riv e d in th e ho sp i t a l f o l l ow i n g a sy nc opa l ep isod e. H e r histor y r e v ealed d i ag no ses of no n- i s ch em ic d i lated car diom y opat h y , NYHA c l ass I hea r t fail ure, a n d a pre v ious ly m easured LVEF was 25%. Patient tested T-wav e altern an s positi ve. receive d a n ICD des p i t e bei n g n o n - i n duc i b l e i n EPS. Three m ont hs po st -i m p l a nt a t i o n , t h e pat i e nt e x per i e n ced a ve nt r i cu l a r tach yarrh yth m ia term in ated by ICD She shock. VT in Patient with Acute MI A 68 year old m a n presented with a chief com p laint of three syncopal episodes on the day of presentation. ECG revealed VT at a rate of 150 bpm and cardiac enzym e s confirm e d acute m yocardial infarction. Subsequent cardiac catheterization revealed two-vessel CAD and norm a l ventricular function. Six weeks post MI patient had a positive T wave alternans test, but refused EPS and further work-up. Patient subsequently presented to the hosp i ta l com p lain ing of an episo d e of ligh t h e adedness an d confusion not associated with slurred speech, weakness or chest pain. Cardiac enzym e s were negative. At this tim e patient agreed to EPS which was positive for inducible VT, and an ICD was im planted. Patient with Prior MI and Renal Failure A 64 year old m a n with a 20 year history of renal failure, and a history of an MI 12 years prior to adm i ssion, presented with a new anterior m yocardial infarction. His LVEF was 40% and he had NYHA class II heart failure. Patien t had a TWA test 3 weeks Heart Rate T-Wave Alterna n s af ter h i s MI which was positiv e. Nine m onths later he died suddenly . Syncope & Family History of SCD Heart Rate T-Wave Alterna n s A 25-year-old m a le was evaluated for abrupt loss of consciousness. ily history of sudden death prom pted the need for further evaluation. norm a l. T-wave alternans testing was negative. onths follow-up, the patient had no A fam His LVEF was At fifteen m ta chya rrhy t h m ic even ts. Conclusions ? T - w ave alternans appears to be a sensitive and specific m a rker of susceptibil ity t o ventricular a rrhythm ias a nd sudde n death in a wide variety of patient populati ons. ? T - w ave alternans can be reliably measured during exercise stress with commerci a lly available equipment. ? E vent rate am ong T-wave alternans negat i ve patie nt s is extremely low. ? T - w ave alternans can be used to identify patients requiring further dia gnostic testing and treatm e nt, thus increa sing the effectiveness of treatment and reducing its cost. Effect of Bed Rest on T Wave Alternans Effect of T Wave Alternans ? T hree of 11 subjects devel o ped T wave alternans post bed rest. T wave alternans resol v ed over t h e next 2- 3 days ? T he onset heart f o r t h e development of T - wave alternans was above t h e standard cut - of f ( 1 10 bpm) f o r clinical s i gni ficance. ? B ed rest appears t o affect cardi ac repolarization processes. Conclusions ? T he cardiovascular system appears to adapt well to conditions of space f light, but loses its ability to cope with gravitationa l forces following landing. ? S pace flight may ad versely affect cardiac electrical stabi l i t y a nd m a y lead to a reduction in c a rdiac m a ss. ? F urther work is required to defi ne the cardiovasc ular risks of space flight, understand m echanism s and develop appropriate c ounterm easures. ? Cardiovascular technologies developed for the spac e program have had spin-off benefits for ci vil i an m e dicine.