PATHOPHYSIOLOGY ,NATURAL HISTORY OF VSD

PATHOPHYSIOLOGY ,HEMODYNAMICS AND NATURAL HISTORY OF VSD

1. PATHOPHYSIOLOGY, HEMODYNAMICS AND NATURAL HISTORY OF VSD

2. EMBYOLOGY OF IVS

3. Parts of IVS : Membranous septum : Ventriculoatrial + Interventricular components Muscular septum : Inlet septum(lightly trabeculated ) Trabecular septum(heavily trabeculated ) Infundibular septum(non- trabeculated )

4. VSD - m.c. congenital malformation of the heart(excluding BAV) – 20-30% of children in India with CHD - Saxena , et al .: Indian Guidelines for Management of CHDs - Annals of Pediatric Cardiology / Volume 12 / Issue 3 / Sept-Dec 2019 Classification of VSD : - initiated by Soto et al in 1980 - further modified by Anderson, VanPraagh , Casteneda and others

5. Morphologic Classification of Ventricular Septal Defect

6. PATHOPHYSIOLOGY L eft  Right shunt Large pulmonary flow(↑ Qp ) LA/LV Enlarged (Stage I) ↑ Qp with PAH Biventricular Enlargement (Stage II) Severe PAH(Muscle hypertrophy + Intimal proliferation and fibrosis) Shunt reversal (R  L) LA/LV Normal size (Stage III)

7. Factors that influence the hemodynamics of VSD The size of the VSD Pressure gradient across RV/LV P ulmonary vascular resistance VSD may not be apparent at birth because of the nearly equal pressures in the right and left ventricles and a lack of shunting . With increasing shunt corresponding to the increasing pressure difference between the ventricles, these defects become clinically apparent .

8. RVSP PA PVR SHUNT HEMODYNAMICS RESTRICTIVE VSD < 1/3 rd of Ao Orifice NORMAL NORMAL NORMAL SMALL(1.5 : 1) SYSTOLIC NORMAL (LV PRESSURES are not transmitted to RV) MOD.RESTRICTIVE VSD 1/3 rd - 3/4 th of Ao Orifice > NORMAL SUB-SYSTEMIC LOW VARIABLE MODERATE(1.5-2.2 : 1) SYSTOLIC, DIASTOLIC (LV VOO) LV - ↑ VOO RV - ↑ POO NON-RESTRICTIVE VSD - HIGH & VARIABLE PVR ≥ 3/4 th of Ao Orifice RVSP ≈ LVSP COMMON CHAMBER PA ≈ Ao HIGH VARIABLE PERSISTENTLY LARGE (>2.2 : 1) PVR dependent FLOW LV - ↑↑↑ VOO -SYSTOLIC DYSFUNCTION RV - ↑↑↑ POO(SYSTEMIC AFTERLOAD) PVR-HIGH NON-RESTRICTIVE VSD – HIGH & FIXED PVR RVSP > LVSP PA > Ao HIGH FIXED RIGHT LEFT EISENMENGERISATION of pulmonary vasculature

9. Restrictive VSD - Small (≤1.4 : 1) shunt due to significant pressure gradient between LV and RV(pulmonary-to-aortic systolic pressure ratio < 0.3 ) Moderately restrictive VSD - moderate shunt ( Qp /Qs of 1.4 to 2.2 : 1) with a pulmonary-to-aortic systolic pressure ratio <0.66 Large or nonrestrictive VSD - large shunt ( Qp /Qs > 2.2) and a pulmonary-to-aortic systolic pressure ratio >0.66 . Eisenmenger VSD has a systolic pressure ratio of 1 and Qp /Qs less than 1 : 1 or a net right-to-left shunt.

10. CLINICALLY RESTRICTIVE VSD : Asymtomatic and lives long Systolic murmur CXR and ECG may be completely normal IE is a usual risk d/t effect of shunt jet on STL More chances of Spontaneous closure

11. MODERATELY RESTRICTIVE VSD : Symptomatic d/t ↑ Qp – Easy fatiguability Cough while feeding Excessive Sweating Restless on recumbent position and poor sleep Gets better with Isotonic exercise d/t fall in SVR Delayed onset of murmur because delayed fall in PVR and can lead to CCF Thrill and Hyperactive precardium

12. CXR shows Cardiomegaly, increased pulmonary vascularity with prominent PA segment is suggestive of significant left‑to‑right flow . ECG shows LV VOO, LVH, LAE or BiVH Risk of IE and CCF because of LV VOO Rarely reaches adulthood, if not intervened

13. LVH – Voltage criteria ( S in V1 + R in V5/V6 > 35mm or R in V5/V6 > 25mm) Left Axis Deviation LV strain pattern – ST depressions in V5/V6 with corresponding ST elevations in V1/V2/V3, U waves in V1-V4

14. Radiological features : Based on grades of PAH Grade Mean PA pressure Systolic PA pressure Pacifico classification (Ratio of PA systolic & systemic systolic) Radiological features Mild 25-40 25-49 1/3-1/2 MPA dilatation Moderate 41-55 50-69 1/2- 2/3 MPA dilatation Rt Descending PA dilatation (>14-16 mm) Mild peripheral pruning Severe >55 >70 >2/3 Severe MPA dilatation ( +calcification) Severe Hilar prominence Severe pruning RV enlargement ( Loss of retrosternal space)

15. MPA dilatation Rt Descending PA dilatation Mild peripheral pruning

16. Severe MPA dilatation ( +calcification) Severe Hilar prominence Severe pruning RV enlargement ( Loss of retrosternal space)

17. Non-Restrictive VSD : Present in infancy with CCF Symptomatology - Poor growth and development Laboured breathing Frequent URTI Difficulty feeding and diaphoresis Dyspnoea and irritability on lying down-improves with sitting

18. Suck-Rest-Suck cycles

19. EISENMENGER’S SYNDROME Regulation of shunt through a Non-restrictive VSD with amelioration of symptoms is almost always a result of rise in PVR    Eisenmenger’s syndrome Victor Eisenmenger first identified and published in 1897”Congenital Defects of the Ventricular Septum” Maude Abbott , a Canadian physician, named the condition as Eisenmenger’s complex(1936) Paul Wood, a British Cardiologist, defined this pulmonary HTN with reversed shunt as Eisenmenger’s syndrome(1958)

20. It is a multisystem disorder involving : Red cell mass, Hemostasis Systemic vascular bed CNS Bilirubin kinetics Coronary circulation and Myocardium Uric acid Clearence Kidney Respiratory system Digits and long bones Gynecologic endocrinology

21. PATHOPHYSIOLOGY Right  Left shunt Cyanosis + ↓Tissue Oxygenation Arterial Hypoxemia Adaptive Erythrocytosis ↑ Hematocrit ↑ RBC turnover & Hemolysis Indirect Bilirubinemia +Gall Stones EXTRAMURAL CORONARY ECTASIA Iron Deficiency(≤ 4 yrs ) CEREBRAL VENOUS THROMBOSIS Paradoxical Emboli STROKE Thrombocytopenia(≥ 50yrs) + Abnormal vWF Muco -cutaneous bleeding Easy Bruising, Epistaxis, Gingival bleeding, Menorrhagia, PULM.HEMORRHAGE(MOST SERIOUS) SUDDEN DEATH ↑ Shear stress in blood vessels ↑ NO,PGs SYSTEMIC VASCULAR DILATION SYNCOPE Dilation of Hilar Arterioles + Glomerular Capillaries ↑ PGDF,TGF β PROTENURIA + GLOMERULOPATHY Remodelling of Coronary Microvasculature ↓ CORONARY VASCULAR RESERVE CLUBBING+HYPERTROPHIC OSTEOARTHROPATHY Hyperuricemia Renal Calculi,Gouty Arthritis

22. GERBODE DEFECT ~0.08% of CHD LV–RA communications - congenital >> acquired-Post-MI, trauma, surgical, IE First mentioned in 1838  by Thurnam J . On aneurisms of the heart with cases (Autopsy report) First diagnosed by Kirby et al in a living patient directly on O.T table,18 Jan.1956 and closed it successfully through right thoracotomy by inflow occlusion + Hypothermia In 1958, Gerbode et al   successfully performed surgery on five patients with this anomaly and named it   Gerbode defect Caused by an anatomic deficiency of the membranous septum The Gerbode Defect: Left Ventricular to Right Atrial Communication—Anatomic, Hemodynamic, and Echocardiographic Features - SILBIGER, ET AL - ECHOCARDIOGRAPHY: A Jrnl . of CV Ultrasound & Allied Tech - 2009

23. Modified Riemenschneider and Moss Classification 1/3 rd cases associated with other anomalies – most common being ASD(PFO/ Secumdum ASD)

24. Aneurysmal transformation – Wu et al Morphogenetic process for Infra- valvular shunts

25. LV  RA Large Systolic ∆ + Small Diastolic ∆ SHUNT depends on Size & PVR Large Shunt RA/RV Enlarged ↑ RV preload  LV LA/LV Enlarged Severe PAH may develop but uncommon Biventricular overload Acute/Chronic Heart Failure R L shunt caused by ( 1) Diastolic flow reversal across defect (RA LV) (2 ) continuous RA LA shunt across PFO/OS-ASD

26. Asymptomatic to severe heart failure C haracteristic murmur : loud , harsh pansystolic , Grade III–VI, getting softer with inspiration, radiationing posteriorly and often associated with a thrill along the left sternal border – SEA GULL MURMUR Raised JVP, liver pulsation, and peripheral edema indicating RHF

27. NATURAL HISTORY R efers to the progression of a disease process in an individual over time, in the absence of treatment Spontaneous closure Premature death Pulmonary vascular disease Development of aortic incompetence Bacterial endocarditis Development of infundibular PS

28. Spon Closure Rate Rate of spontaneous closure depends on SIZE and LOCATION of VSD Muscular VSDs are more likely to close spontaneously, especially if they are not large Small VSDs have a >50% chance of spontaneous closure by 5 years >80% chance by adolescence Saxena , et al .: Indian Guidelines for Management of CHDs - Annals of Pediatric Cardiology / Volume 12 / Issue 3 / Sept-Dec 2019

29. Perimembranous VSDs (accounted for most of the moderate to large VSDs) 39% required surgical closure 29 % closed spontaneously by 6 years of age Muscular VSDs – 3% required surgical closure 69% closed spontaneously by 6 years of age The natural history of ventricular septal defects - S W Turner, S Hunter, J P Wyllie

30. Most of the VSDs(~75%) close spontaneously within the first two years of life Afterwards , the chance of spontaneous closure diminishes remarkably but extend till adolescence . Muscular and membranous VSDs with diameters < 6 mm have the best chance of spontaneous closure Spontaneous closure of ventricular septal defects in the first year of life - Lin MH et al - J Formos Med Assoc. 2001

31. Age-wise Probability of Spontaneous closure of Small VSD : 34% by 1 year 67% by 5 years 75% by 10.5 years

32. Mech of closure Adherence of tricuspid leaflet , or chordal tissue to the edges of VSD. Growth & hypertrophy of septum around the defect Negative pressure effect exerted by a high velocity stream flowing through the defect Ventricular septal aneurysm Prolapse of aortic cusp Intrusion of a sinus of Valsalva aneurysm

33. VSD unlikely to close Sub-pulmonary Juxta -arterial Inlet Mal-aligned Gerbode defect Very large Saxena , et al .: Indian Guidelines for Management of CHDs - Annals of Pediatric Cardiology / Volume 12 / Issue 3 / Sept-Dec 2019

34. Premature death About 10% of children with large VSDs die in 1st year , primarily due to congestive heart failure Saxena , et al .: Indian Guidelines for Management of CHDs - Annals of Pediatric Cardiology / Volume 12 / Issue 3 / Sept-Dec 2019 Second phase : Second decade onwards death due to Eisenmengerization Hemoptysis Polycythemia Cerebral abscess Cerebral infarction RV failure

35. Pul vascular disease In the historic series of Dr. Paul Wood, 52% of patients with large VSD developed irreversible pulmonary vascular disease with the onset in infancy in four‑fifths of them Common with Subpulmonary VSD Chances of development of PVD with age (PVR > 8 U.m2) YR Probability 10 yr 10 % 20 yr 50 % 30 yr 80 % 40 yr 100 %

36. Updated clinical classification for PAH associated with CHD, Nice, France, 2013.

37. Development of AR – s een in 6% Mechanism : Lack of support to aortic annulus : Diastolic prolapse of unsupported cusp. Venturi effect : Cusp is sucked during systole More with S ubaortic / J uxtaarterial VSD and S maller VSD

38. Bacterial endocarditis : 2-3 decade, on right side Among congenital heart disease, VSD is the most frequent anomaly in right- sided IE One of the important indications for VSD closure The incidence of IE among ventricular septal defects (VSD) was 0.2%- 2% Baumgartner et al.Guidelines for the management of grown- up congenital heart disease (new version 2010). Eur Heart J. 2010.

39. Development of infundibular PS : 13 % pts Gasul Syndrome : VSD with acquired PS, Gasul found that about 5- 10 % VSD patients develop PS in follow up (JAMA 1957, circulation 1963) Progressive right ventricular outflow tract obstruction ( Gasul phenomenon) may develop in 13% and aortic regurgitation (AR) in 6% of patients