A Novel Approach to Measuring Interventricular Dependence

Steven R. Bruhl MD, MSResearch Conference

April 19th, 2010

The Continuity Equation

• Flow in one area must equal the flow in a second area provided no shunts are present.

• Most frequently used to calculate aortic valve areas, but also applies to blood flow between the right and left ventricles.

The Hypothesis• In healthy subjects, blood flow between the RV and

the LV circuits should be nearly identical.

• However, blood flowing from the right ventricle (RV) to the left ventricle (LV) and LV back to the RV is dependent on right and left ventricular function

• Acute changes in RV or LV function might be expected to abruptly alter this delicate interventricular relation.

Study Rational:

If a method could be developed to accurately and reproducibly assess this relationship:

– Knowing this interventricular relationship could add diagnostic or prognostic information to chronic RV, LV, or even pulmonary diseases. (PAH, Scleroderma, Restrictive CM, ILD, COPD etc.)

– Acute changes in this interventricular relationship might aid in the diagnostic, prognostic or treatment decisions of acute RV or LV or pulmonary diseases. (LV or RV infarcts, cardiac tamponade, PE)

Study Objective• Develop a simple and reproducible method for

assessing this systolic interventricular relationship by:

– Selecting a relatively easy, validated and reproducible measurement for assessing and directly comparing LV and RV systolic function.

– Using this method, establish what is the “normal” systolic interventricular relationship and compare this relationship across age, by gender and BMI.

Difficulties of RV Functional Assessment

(J Am Soc Echocardiogr 2009;22:776-792.)

Potential Options for Assessing RV Function

• Cardiac MRI: Gold Standard• RV RNA Blood Pool Scanning (MUGA)• Gated RV SPECT• 3D Echocardiography• 2D Echocardiography

– Fractional area change– Tissue Doppler Techniques– Speckle Tracking Techniques– M-mode derived Tricuspid Annular Plane of Systolic

Excursion (TAPSE)

(J Am Soc Echocardiogr 2009;22:776-792.)

Cardiac MRI

Gated RV RNA Scan

Color Doppler Tissue Imaging

(J Am Soc Echocardiogr 2009;22:776-792.)

Pulsed Wave Tissue Doppler

TAPSE

Validation of TAPSE• TAPSE is Feasible:

– TAPSE measured in all 900 pts in a mean time of 3 ± 1 min. Inter- and intra-observer variabilities were very low for TAPSE (0.24±1.3 and 0.17±1.4 mm, respectively) (Int J Cardiol. 2007 Jan 31;115(1):86-9)

• TAPSE is Accurate: – TAPSE Correlated significantly with RV EF when compared to cardiac

MRI (75 mixed pts) (r=0.62 p<0.01) (n=150) (Eur Radiol. 2008 Nov;18(11):2399-405)

• TAPSE is Superior: – TAPSE by 2D echo is superior to 3D echo and preferable over gated

SPECT for the measurement of RV function when compared to MRI. (34 mixed pts) (Eur J Echocardiogr. 2006 Dec;7(6):430-8)

TAPSE Declines in RV Disease• Survival in pulmonary hypertension:

– 63 consecutive PH pts referred for RHC• TAPSE>18mm: 1 yr (94%) and 2 yr (88%) survival• TAPSE<18mm: 1 yr (60%) and 2 yr (50%) survival(Am J Respir Crit Care Med 2006 Nov 1;174(9):1034-41)

• Detects early RV dysfunction in scleroderma– 22 Scleroderma pts without PH vs 22 age matched controls

• TAPSE 23.2 +/- 4.1mm • 26.5 +/- 2.9, P<0.006(Cardiovasc Ultrasound. 2010 Jan 22;8:3)

• Pulmonary Embolism– TAPSE has good correlation with surrogate markers for morbidity and

mortality in APE and seemed to perform as well as the standard echo parameters used to assess RV function

(J Thromb Thrombolysis. 2009 Nov;28(4):506-12. Epub 2009 Mar 13.)

TAPSE Declines in LV Disease• Predicts Death in STEMI with Shock

– 70 of 184 consecutive pts with STEMI and Shock:– Cox-regression analysis revealed a hazard ratio of 2.1 (95% CI 1.3–3.4, P

= 0.002) for RV dysfunction when adjusted for age, glucose on admission, and LVEF < 40%. In patients with and without RV dysfunction, the right coronary artery was the infarct-related artery in 41 and 28% of patients, respectively (P = 0.06). (Eur J Heart Fail (2010) 12 (3): 276-282)

• Predicts CRT Response: – TAPSE (<14mm) prior to CRT predicts a decreased response to CRT

regardless of degree of inter or intra-ventricular dyssynchrony. (76% vs 14% P<0.001) (Pacing Clin Electrophysiol. 2009 Aug;32(8);1040-9)

• Predicts Death or Transplant in Systolic HF– Among 140 consecutive pts with chronic CHF and EF<35%, NYHA Class

III or IV + TAPSE <14 combined were the best 2 predictors of death or need for Tx. (Am J Cardiol. 2000 Apr 1;85(7):837-42)

Pulsed Wave Doppler Tissue Imaging

• Peak systolic velocities of the tricuspid valve are affected by pericardial pressure: RV TD S' velocities were reduced by 43% +/- 17% (P < .001) within 5 min of pericardial incision. (Am Heart J. 2010 Feb;159(2):314-22.)

• RV infarcts reduce peak tricuspid velocities: 24 hours after STEMI, tricuspid annular velocities were significantly reduced in patients with ST elevation in V4R compared to those without (11.1 vs. 13.7 cm/sec, P < 0.01). <13 cm/sec has a sensitivity of 89% and specificity of 71% for identifying patients with ST elevation in V4R. (Echocardiography. 2010 Feb;27(2):139-45. Epub 2009 Aug 31.)

Methods of LV functional Assessment

• Gated blood pool RNA Scanning• Cardiac MRI• Gated LV SPECT • 3D Echo• Volumetric Approaches (Simpson’s Rule)• Mitral Annular Plane of Systolic Excursion (MAPSE)• Pulsed Wave Tissue Doppler• Visual Estimation

Measurements of LV Function• MAPSE as a surrogate of LV Function: MAPSE

<12mm by MME has a 90% sensitivity, 88% specificity and 89% accuracy for detection of LVEF<50% (Eur J Echocardiography (2006) 7, 187-198)

• MAPSE and TAPSE by MRI: In 116 pts, each Correlated well with LVEF and RVEF respectively (r = 0.64 and 0.52 resp. p < 0.001). (Journal of Cardiovascular Magnetic Resonance 2008, 10(Suppl 1):A238)

Methods• 51 “healthy” volunteers and patients were included in

the study population.• All Participants had:

– Normal sinus rhythm without complete right or left bundle branch blocks.

– No known history of pulmonary hypertension, atrial fibrillation, pacemakers, defibrillators, a history of heart failure, myocardial infarction, previous cardiac surgery.

– No more than mild valvular disease, normal LV and RV size and function, a left atrial index <28cc/m².

Methods

• Baseline variables:– Age, BSA, gender, left ventricular ejection fraction

(LVEF), left ventricular interventricular septal thickness, left atrial volume index, and right ventricular systolic pressure (RVSP).

• Divided by Age:<30, 30-50, and <50 years old.

• Divided by Gender:

Results

• Average peak values:– TAPSE: 22.1 ± 2.9– SPSE: 12.6 ± 2.2 – MAPSE: 14.3 ± 2.6

• MAPSE/TAPSE, SPSE/MAPSE, and SPSE/TAPSE ratios were also calculated: all measurements were further subdivided by age and sex as seen in Table 2.

Figure 1. Linear regression analysis of MAPSE/TAPSE by age and BSA subdivided by gender as well as LVs/RVs by age and BSA also subdivided by gender.

Pulsed Wave Tissue Doppler Results

• On average, RVs was 33.4% greater than LVs.

• The peak LVs/RVs ratio was 0.76 +0.14 and remained relatively constant with little variation across age (P=0.89), gender (P=0.80) or BSA (P=0.46)

TAPSE and MAPSE Results• On average, TAPSE was over 54.5% greater than MAPSE with a

MAPSE/TAPSE ratio of 0.66 ± 0.14.

• This relationship remained relatively consistent across the population and did not vary significantly regardless of age (P=0.51), gender (P=0.19), or BSA (P=0.78).

• Considering the cavity size of the RV is significantly less than that of the LV, it stands to reason that the RV would need to decrease its end systolic volume greater through increased tricuspid annular motion than that of the larger LV in order to maintain an equal stroke volume.

• Since MAPSE is a surrogate of LV function just as TAPSE is a surrogate of RV function; a MAPSE/TAPSE is a numerical representation of this systolic interventricular relationship.

Putting it all Together

Normal LV/RVInterventricular

Relationship

TAPSE/MAPSE=0.66 +0.14

Primary RV DiseaseTAPSE ↓ while

MAPSE remains constant

(TAPSE/MAPSE ratio decreases)

Primary LV DiseaseTAPSE ↓ and MAPSE also ↓

(TAPSE/MAPSE ratio remains constant)

Conclusion

• Unlike the diastolic interventricular relationship, the relative consistency of the MAPSE/TAPSE as well as the LVs/RVs ratio across age, gender and BSA make these measurements attractive for evaluation and monitoring of patients with both acute or chronic diseases that might interfere with this interventricular relationship.

ConclusionExamples of this might include:• Acute Processes

– Pulmonary emboli– Right ventricular infarction– Tamponade

• Chronic Diseases– Various stages of PAH– COPD, ILD– Scleroderma– Heart failure and cor-pulmonale

Post-Reperfusion Syndrome

Steven R. Bruhl MD, MS

Introduction:• Post-reperfusion syndrome (PRS) is a widely

reported complication that can occur after the reperfusion of an ischemic tissue or organ.

• Originally Defined as:– A decrease in mean arterial pressure, ≥ 30%

from baseline – The hypotension must last for at least 1 minute

within 5 minutes of graft reperfusion.– Mild PRS is defined as the above criteria with a

decrease in MAP that is less than 30%.•Aggarwal S, Kang Y, Freeman JA, Fortunato FL, Pinsky MR. Postreperfusion syndrome: Cardiovascular

collapse following hepatic reperfusion during liver transplantation. Transplant Proc 1987; 119 Suppl 3: 54-5

History of PRS in Liver Transplantation

• First described in association with liver transplantation after the removal of the celiac artery clamp.

• Incidence: estimated at 20% to 30%

• Is associated with significant intra-operative and postoperative morbidity and mortality.

Introduction

• Also been reported to occur during:

– aneurysm repair– release of high pressure in closed body

compartments– cardiopulmonary bypass surgery– release of limb tourniquets.

The True Etiology of PRS?

• Currently, the exact etiology of PRS remains unknown.

• Theories:– Washout of electrolytes and other metabolites,

especially hyperkalemia or hypercalcemia– Sudden acidosis– Sudden decrease in core temperature– Sudden bradycardia caused by one of the above

In a prospective study by Aggarwal involving 69 consecutive patients undergoing liver transplantation, the researchers examined the relationships between the patient’s:

– hemodynamic profiles– core temperatures– potassium levels– calcium levels– serum pH– SVR, CO, PCWP– Development of PRS

What is the Actual Cause of Post-reperfusion Syndrome?

Aggarwal S, Kang Y, Freeman JA, et al: Postreperfusion syndrome: cardiovascular collapse following hepatic reperfusion during liver transplantation. Transplant Proc 119(Suppl 3):54, 1987

• PRS is caused by a combination of systemic arterial dilation and myocardial depression

• “It appears that factors such as vasoactive substances released from the grafted liver may be involved.”

Aggarwal S, Kang Y, Freeman JA, et al: Postreperfusion syndrome: cardiovascular collapse following hepatic reperfusion during liver transplantation. Transplant Proc 119(Suppl 3):54, 1987

Conclusion from Aggerwal

Hypothesis Driving the Current Retrospective Study

• Although the incidence of PRS is likely to be less than during liver transplantation, we predicted that its occurrence is significantly underreported.

• The use of AV nodal blocking agents and a PMHx of HTN, DM or CAD may also be associated with an increased incidence of PRS

• Increased morbidity and mortality associated with PRS in liver transplant patients likely have similar, but unrecognized, effects in renal transplant patients.

Findings

• Out of 150 sequential Renal transplants between 6/06 and 3/08 at UTMC 6 had hemodynamically significant hypotension within 5 minutes of donor kidney reperfusion

• This is an overall incidence of 4%

Findings

• These findings confirm the existence of PRS during renal transplantation.

• This retrospective study suggests that the incidence of PRS is approximately 4%

• The majority of renal events are milder than that typically seen during liver transplantation

Findings

• First study to suggest that advanced age, the use of extended criteria donor kidneys and diabetes mellitus might be risk factors for the development of PRS.

•Perez-Pena J, Rincon D, Banares R, Olmedilla L, Garutti I, Arnal D, Calleja J, Clemente G. Autonomic neuropathy is associated with hemodynamic instability during human liver transplantation. Transplant

Proc. 2003 Aug;35(5):1866-8.

Findings

• Although coronary artery disease showed only showed a strong trend toward statistical significance, we believe that this may have reached statistical significance in a larger patient population.

• Aggarwal et al. showed that patients experiencing PRS had a significantly lower cardiac output 30 seconds after reperfusion despite concomitant decreases in SVR and mean arterial pressure. Although the reason for this is unclear, a history of CAD may be a marker of patients with decreased cardiac reserve due to significant coronary artery stenosis.

Longterm Considerations

• Considering the relatively limited supply of kidneys available for transplant, any significant adverse outcome would likely warrant further investigation to avoid these complications.

Longterm Considerations• Potential interventions might include:

– Retrograde reperfusion of the graft kidney by first anastomosing the portal vein of the graft kidney to the venous circulation and allowing deoxygenated blood to fill the transplant kidney for 10 minutes before unclamping the arterial circulation.

– Pre-flushing graft kidneys with transplant solutions such as the Minnesota solution.

– Pre-treatment of patients with vasopressors prior to unclamping