K.M. Cherian MS FRACS DSc (Hons) DSc (HC) Frontier Lifeline & Dr.K.M.Cherian Heart Foundation, Chennai Experience with Ross Procedure in India Frontier Lifeline Chennai Ross Summit II - 2009 Atlanta

India is a country full of paradoxes. Be it economic stratas in the society, culture, climate or the terrain. A nation of 1.2 billion people with contradictions, that is India. Parumala , Chennai

India is a country full of paradoxes. Be it economic stratas in the society, culture, climate or the terrain. A nation of 1.2 billion people with contradictions, that is India.

Top 10 Economies Ranking Country Approximate GDP- Purchasing Power Parity 1 USA $13,860,000,000,000 2 China $7,043,000,000,000 3 Japan $4,305,000,000,000 4 India $2,965,000,000,000 5 Germany $2,833,000,000,000 6 United Kingdom $2,147,000,000,000 7 Russia $2,076,000,000,000 8 France $2,067,000,000,000 9 Brazil $1,838,000,000,000 10 Italy $1,800,000,000,000

Below Poverty Line is a benchmark used by the Government of India to indicate economic disadvantage Internationally, an income of < $1 / day/head of PPP is defined as extreme poverty – 37% of Indians are extremely poor and therefore below the poverty line

Below Poverty Line is a benchmark used by the Government of India to indicate economic disadvantage

Internationally, an income of < $1 / day/head of PPP is defined as extreme poverty – 37% of Indians are extremely poor and therefore below the poverty line

Our experience Special situations RVOT Reconstruction with xenografts

Our experience

Special situations

RVOT Reconstruction with xenografts

Mr.Donald Ross conducted the first workshop for us in September 1987 (Chennai) CLASSICAL ROSS Procedures (2) Top hat for Tricuspid valve replacement (for SBE) (1)

Mr.Donald Ross conducted the first workshop for us in September 1987 (Chennai)

CLASSICAL ROSS Procedures (2)

Top hat for Tricuspid valve replacement (for SBE) (1)

Frontier Conclave 2005 Frontier Conclave 2006 Prof Zohair Al-Halees 7 Ross Procedures & 1 Ross Kono in 2 days with no mortality

Severe Aortic Valve diseases in: New born infants Children Young adults Women of child bearing age Patients with infective endocarditis Patients with complex LVOT obstruction

Severe Aortic Valve diseases in:

New born infants

Children

Young adults

Women of child bearing age

Patients with infective endocarditis

Patients with complex LVOT obstruction

16 th December 1974 Mr. Donald Ross arrange but at the age of 23, I would be much happier putting in a homograft valve and would certainly use it if it were my own son.

“ COST CONTAINMENT”

“ COST CONTAINMENT”

DOS:22.12.1995

From 1990 till date No. of patients 160 Age 3 months - 51 years Males 121 Females 39

From 1990 till date

No. of patients 160

Age 3 months - 51 years

Males 121

Females 39

Aortic stenosis - 65 pts Aortic stenosis with Regurgitation - 45 “ Aortic regurgitation - 40 “ Associated CAD - 4 “ Mitral Valve Repair ( MV repair 2 and OMV 1 ) - 3 “ VSD Closure - 2 “ Cong.AS with previous BAV - 1 “

Aortic stenosis - 65 pts

Aortic stenosis with Regurgitation - 45 “

Aortic regurgitation - 40 “

Associated CAD - 4 “

Mitral Valve Repair ( MV repair 2 and OMV 1 ) - 3 “

VSD Closure - 2 “

Cong.AS with previous BAV - 1 “

CPB time Range:101 - 325 minutes Mean: 124 . 19 minutes ACC time Range; 59 - 129 minutes Mean: 86.46 minutes Re-exploration within 24 hrs : 12 patients Delayed sternal closure : 8 patients Additional CABG for suspected coronary insufficiency : 7 patients Mortality : 6 patients

CPB time

Range:101 - 325 minutes

Mean: 124 . 19 minutes

ACC time

Range; 59 - 129 minutes

Mean: 86.46 minutes

Re-exploration within 24 hrs : 12 patients

Delayed sternal closure : 8 patients

Additional CABG for suspected coronary insufficiency : 7 patients

Mortality : 6 patients

Antibiotics for 3 days Aspirin for 6 months Blood culture on 5 th post-operative day Follow up echo at 7 days, 3 months and at annual check up Penicillin prophylaxis till 45 years of age for RHD patients

Antibiotics for 3 days

Aspirin for 6 months

Blood culture on 5 th post-operative day

Follow up echo at 7 days, 3 months and at annual check up

Penicillin prophylaxis till 45 years of age for RHD patients

Seventh post-op day Acceptable aortic valve function Acceptable pulmonary valve function

Seventh post-op day

Acceptable aortic valve function

Acceptable pulmonary valve function

Three months old child weighing 3.2 kg Ross with reconstruction of RVOT using aortic homograft Two years later came back with severe PR Underwent replacement of the homograft with decelluarised xenograft

Three months old child weighing 3.2 kg

Ross with reconstruction of RVOT using aortic homograft

Two years later came back with severe PR

Underwent replacement of the homograft with decelluarised xenograft

11 year old boy Aortic regurgitation Both coronaries arising from posterior sinus Intraluminal angioscopic view showing the orifice of coronaries

11 year old boy

Aortic regurgitation

Both coronaries arising from posterior sinus

19 year old female Severe calcific AS with root disease Abscess cavity projecting into RVOT Abscess cavity exteriorized with indigenous bovine pericardium and Ross procedure performed

19 year old female

Severe calcific AS with root disease

Abscess cavity projecting into RVOT

Abscess cavity exteriorized with indigenous bovine pericardium and Ross procedure performed

Post-op Echo

50 year old man 5 years post-op Ross Chest x-ray : widened aortic shadow 2-D Echocardiogram : Normally functioning autograft valve, normally functioning pulmonary homograft and dilated ascending aorta 64-slice CT delineated the aneurysm of the autograft with dissection Coronary arteries : normal autograft

50 year old man

5 years post-op Ross

Chest x-ray : widened aortic shadow

2-D Echocardiogram : Normally functioning autograft valve, normally functioning pulmonary homograft and dilated ascending aorta

64-slice CT delineated the aneurysm of the autograft with dissection

Coronary arteries : normal autograft

Intra-operatively, the dissection flap was extending from the level of previous aortotomy to the sino-tubular junction The left and right coronary buttons were intact The valve leaflets and the annulus were normal The native ascending aorta beyond the autograft was normal Valve sparing root replacement with 28mm Hemashield Dacron graft was performed

Intra-operatively, the dissection flap was extending from the level of previous aortotomy to the sino-tubular junction

The left and right coronary buttons were intact

The valve leaflets and the annulus were normal

The native ascending aorta beyond the autograft was normal

Valve sparing root replacement with 28mm Hemashield Dacron graft was performed

Histological examination of the excised autograft wall showed focal loss of elastic fibres and proteoglycan deposition Presence of a suture line between the native aorta and the pulmonary autograft as well as around the coronary buttons limits the extension of the dissection Conclusion: Dissection of the pulmonary autograft can occur without neo-aortic valve involvement. Valve sparing root replacement can be done in this situation

Histological examination of the excised autograft wall showed focal loss of elastic fibres and proteoglycan deposition

Presence of a suture line between the native aorta and the pulmonary autograft as well as around the coronary buttons limits the extension of the dissection

Conclusion: Dissection of the pulmonary autograft can occur without neo-aortic valve involvement. Valve sparing root replacement can be done in this situation

The number of Ross procedures performed all over the world is declining due to scarcity or non- availability of Homografts The Redfern Report, which investigated postmortem practices at Alder Hey Children’s Hospital, identified malpractice

The number of Ross procedures performed all over the world is declining due to scarcity or non- availability of Homografts

Number of functioning homograft banks in the country: 3

Restrictions from government Delays in post mortem examination Third party insurance necessitates “request” for autopsy from Police as the body belongs to state Unacceptable mortuary conditions Medico legal cases only come for post mortem Multi religious, multiracial, multilingual and Superstitious society

Restrictions from government

Delays in post mortem examination

Third party insurance necessitates “request” for autopsy from Police as the body belongs to state

Unacceptable mortuary conditions

Medico legal cases only come for post mortem

Multi religious, multiracial, multilingual and Superstitious society

We have used indigenously prepared xenografts for RVOT reconstruction in 23 patients undergoing ROSS so far. The hemodynamic performance, in-hospital results and follow up results are comparable to homograft

We have used indigenously prepared xenografts for RVOT reconstruction in 23 patients undergoing ROSS so far.

The hemodynamic performance, in-hospital results and follow up results are comparable to homograft

Tensile strength testing Stress, strain, Young’s modulus Burst test Differential scanning calorimetry FT-IR Microscopy To prove acellularity, collagen architecture, shelf life determination etc H & E staining Von Giessons staining High resolution optical microscopy Confocal microscopy Transmission electron microscopy Scanning electron

Tensile strength testing Stress, strain, Young’s modulus

Burst test

Differential scanning calorimetry

FT-IR

Microscopy

To prove acellularity, collagen architecture, shelf life determination etc

H & E staining

Von Giessons staining

High resolution optical microscopy

Confocal microscopy

Transmission electron microscopy

Scanning electron

Cytotoxicity studies In vivo In vitro Guinea pig maximization studies Retrovirus detection by genomic studies Acellularity studies by DNA detection Large animal experiment proving autologous cell deposition and trizonation of the fibrous matrix Thrombogenicity studies shows no thrombosis Collagenase digestion tests - resistant to digestion

Cytotoxicity studies

In vivo

In vitro

Guinea pig maximization studies

Retrovirus detection by genomic studies

Acellularity studies by DNA detection

Large animal experiment proving autologous cell deposition and trizonation of the fibrous matrix

Thrombogenicity studies shows no thrombosis

Collagenase digestion tests - resistant to digestion

DSC showing collagen stability of Tissue (>80 ° C)

FT-IR Showing largely collagen conformity by presence of amide (CO=NH at 1450-1650 range and non heparin treated BP has shown presence of large spike at 1740 suggesting free-COOH group(arrow) No spike at 1740-BP(H+) BP( H-)

FT-IR Showing largely collagen conformity by presence of amide (CO=NH at 1450-1650 range and non heparin treated BP has shown presence of large spike at 1740 suggesting free-COOH group(arrow)

Operative photograph showing processed BP implanted as an interposition graft in the internal jugular vein of sheep Group A explanted from the sheep after 6 months showing thickening of the vessel wall

TESI VIIIth annual congress in Shanghai, China. 2005 October (22nd – 25th) Decellularization of xenografts for clinical use. Soma Guhathakurta, Susan Verghese, Sushma Nayar, Ravi Agarwal, B S Murthy, S Veerappan, P Padmaja, V Balasubramanian, KM Cherian S. Guhathakurta, S Verghese, V Balasubramanian R Agarwal, BS Murthy, S. Veerappan, P Padmaja, KM Cherian “ Technique to process xenogenic tissues for cardiovascular implantation – preliminary report”, Current Science, Volume 91 No.8, 25 October 2006. Cherian K M ., Soma Guhathakurta., Susan Verghese., Murthy B S., Ravi Agarwal., Versatile Use Of Indigenously Prepared Bovine Jugular Vein Conduit In Pediatric Cardiac Surgery; 4th World Congress Of Pediatric Cardiology And Cardiac Surgery, Sept. 18-22,2005. Buenos Aires Argentina R Balasundari, E Kurien, R Gupta, S Veerappan, S Warrier, V Balasubramanian, K M Cherian, S Guhathakurta, “ Post processing complete microbe free Porcine xenograft suitable for clinical use&quot; IJTCVS2007;23:240-245. Radha Chandrasekaran ,Balasundari Ramesh Veerappan Sivasubramanian, Cherian Kotturathu Mammen, Vijaya Nayak , Soma Guhathakurta: Cytotoxicity and Sensitization Studies of Processed Porcine Xenografts IJTCVS2007;23:240-245. S Guhathakurta, V Balasubramanian, B.V.R Tata, KM Cherian, “Effect of Gamma Irradiation on Xenogenic Tissue Property ” (Revised manuscript under review) S. Guhathakurta “Processing Of Xenografts for Cardiovascular use”- Nagarjun University-Stem 2006- Society for Regenerative Medicine &Tissue Engineering

TESI VIIIth annual congress in Shanghai, China. 2005 October (22nd – 25th) Decellularization of xenografts for clinical use. Soma Guhathakurta, Susan Verghese, Sushma Nayar, Ravi Agarwal, B S Murthy, S Veerappan, P Padmaja, V Balasubramanian, KM Cherian

S. Guhathakurta, S Verghese, V Balasubramanian R Agarwal, BS Murthy, S. Veerappan, P Padmaja, KM Cherian “ Technique to process xenogenic tissues for cardiovascular implantation – preliminary report”, Current Science, Volume 91 No.8, 25 October 2006.

Cherian K M ., Soma Guhathakurta., Susan Verghese., Murthy B S., Ravi Agarwal., Versatile Use Of Indigenously Prepared Bovine Jugular Vein Conduit In Pediatric Cardiac Surgery; 4th World Congress Of Pediatric Cardiology And Cardiac Surgery, Sept. 18-22,2005. Buenos Aires Argentina

R Balasundari, E Kurien, R Gupta, S Veerappan, S Warrier, V Balasubramanian, K M Cherian, S Guhathakurta, “ Post processing complete microbe free Porcine xenograft suitable for clinical use&quot; IJTCVS2007;23:240-245.

Radha Chandrasekaran ,Balasundari Ramesh Veerappan Sivasubramanian, Cherian Kotturathu Mammen, Vijaya Nayak , Soma Guhathakurta: Cytotoxicity and Sensitization Studies of Processed Porcine Xenografts IJTCVS2007;23:240-245.

S Guhathakurta, V Balasubramanian, B.V.R Tata, KM Cherian, “Effect of Gamma Irradiation on Xenogenic Tissue Property ” (Revised manuscript under review)

S. Guhathakurta “Processing Of Xenografts for Cardiovascular use”- Nagarjun University-Stem 2006- Society for Regenerative Medicine &Tissue Engineering

Guhathakurta, “ Xenografts For Cardiovascular Implants” ; Frontier Conclave - an International Update in Cardiovascular Medicine. December 2005, International Centre For Cardio Thoracic And Vascular Diseases, Frontier Life Line S. Guhathakurta ,,” Processing Of Xenografts As Alternative Cardiovascular Implants”- INDO-US workshop , Sri Chitra Thirunal Institute of Medical Sciences, Thiruvananthapuram, India, Feb 1-3, 2007 Dr. Soma Guhathakurta, Director, Frontier Lifeline, Chennai, India,CLRI – Diamond Jubilee celebration; international conference on RECENT TRENDS IN COLLAGEN- Session 3: Diseases. Jan24-25, 2008 . Guhathakurta, Soma1; Balasubramanian, Venkatesh2; Agarwal, Ravi1; Cherian,KotturathuMammen1 Indigenously Processed Bovine Pericardium For Cardiovascular Use ) , Oral presentation at the 18th World Congress of the World Society of Cardio-Thoracic Surgeons, held at Kos Island , Greece from April 30th to May 3rd 2008. Soma Guhathakurta, Balasundari R, Sadasiv Santosh Mathapaty, Satish Galla, Ravi Agarwal, Prashant Vyjyanath,K M Cherian, Indigenously processed xenografts for clinical cardiovascular surgical use ;Indo-Aus Biomedical Device Conference, New Delhi,5th March 2009 S. Guhathakurta, V Balasubramanian, B V R Tata, B Anathakrishnan, S Veerappan, R Balasundari, KM Cherian, “Thrombogenicity studies of three different variants of processed bovine pericardium,” Innovation and Technology in Biology and Medicine (in press)IRBM, Volume 29,Issue 4, September 2008, Pages 223 - 230, Elsevier Masson; Science Direct.

Guhathakurta, “ Xenografts For Cardiovascular Implants” ; Frontier Conclave - an International Update in Cardiovascular Medicine. December 2005, International Centre For Cardio Thoracic And Vascular Diseases, Frontier Life Line

S. Guhathakurta ,,” Processing Of Xenografts As Alternative Cardiovascular Implants”- INDO-US workshop , Sri Chitra Thirunal Institute of Medical Sciences, Thiruvananthapuram, India, Feb 1-3, 2007

Dr. Soma Guhathakurta, Director, Frontier Lifeline, Chennai, India,CLRI – Diamond Jubilee celebration; international conference on RECENT TRENDS IN COLLAGEN- Session 3: Diseases. Jan24-25, 2008 .

Guhathakurta, Soma1; Balasubramanian, Venkatesh2; Agarwal, Ravi1; Cherian,KotturathuMammen1 Indigenously Processed Bovine Pericardium For Cardiovascular Use ) , Oral presentation at the 18th World Congress of the World Society of Cardio-Thoracic Surgeons, held at Kos Island , Greece from April 30th to May 3rd 2008.

Soma Guhathakurta, Balasundari R, Sadasiv Santosh Mathapaty, Satish Galla, Ravi Agarwal, Prashant Vyjyanath,K M Cherian, Indigenously processed xenografts for clinical cardiovascular surgical use ;Indo-Aus Biomedical Device Conference, New Delhi,5th March 2009

S. Guhathakurta, V Balasubramanian, B V R Tata, B Anathakrishnan, S Veerappan, R Balasundari, KM Cherian, “Thrombogenicity studies of three different variants of processed bovine pericardium,” Innovation and Technology in Biology and Medicine (in press)IRBM, Volume 29,Issue 4, September 2008, Pages 223 - 230, Elsevier Masson; Science Direct.

50 year old male Severe calcific aortic stenosis Ross procedure in February 2004 RVOT reconstruction with porcine xenograft 64 CT MRI Reconstruction on 18/9/09

50 year old male

Severe calcific aortic stenosis

Ross procedure in February 2004

RVOT reconstruction with porcine xenograft

Ross procedure is a suitable alternative for prosthetic valve replacement in young patients and those with contraindications for anticoagulant therapy Our initial learning curve has been traumatic from high incidence of reopening for bleeding, delayed sternal closure and coronary insufficiency At present we have satisfactorily overcome these difficulties

Ross procedure is a suitable alternative for prosthetic valve replacement in young patients and those with contraindications for anticoagulant therapy

Our initial learning curve has been traumatic from high incidence of reopening for bleeding, delayed sternal closure and coronary insufficiency

At present we have satisfactorily overcome these difficulties

Ross Operation - 3 Age - 12 to 15 yrs Mortality - Nil Ideal indication (RHD) with good results (no mortality), in unusual location – a small village (non-metropolis or university hospitals) is now possible

Ross Operation - 3

Age - 12 to 15 yrs

Mortality - Nil

Xenografts: Cost effectiveness makes it suitable for developing nations – US$ 500 as against US$ 2000 No structural failure or SBE so far in this small series Satisfactory mid term follow-up with functions comparable to homografts. Few of the procedures employing xenograft, have also been performed by surgeons from other countries as well, with similar results.

Xenografts:

Cost effectiveness makes it suitable for developing nations – US$ 500 as against US$ 2000

No structural failure or SBE so far in this small series

Satisfactory mid term follow-up with functions comparable to homografts. Few of the procedures employing xenograft, have also been performed by surgeons from other countries as well, with similar results.

‘ Xenowrap’ Electrospun nano reinforcement of conduits Hybrid valved conduit

‘ Xenowrap’

Electrospun nano reinforcement of conduits

Hybrid valved conduit

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