46. Pulmonary Hypertension and Cardiac Resynchronization Therapy

Published on 26/02/2015 by admin

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Last modified 22/04/2025

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History

The patient was referred from another center for consideration of cardiac resynchronization therapy (CRT) for long-standing ischemic cardiomyopathy and progressive heart failure symptoms. At time of referral he described New York Heart Association (NYHA) class III symptoms despite optimal medical therapy.
The patient’s history included ischemic heart disease, first diagnosed at 40 years of age. At that time he also had exertional angina. A 12-lead electrocardiogram (ECG) showed left bundle branch morphology. Echocardiography and left ventriculography demonstrated impaired left ventricular function with a left ventricular ejection fraction of 40%. Coronary angiography demonstrated severe three-vessel coronary artery disease. He underwent coronary bypass grafting at 40 years of age, with left internal mammary grafting to the left anterior descending artery and saphenous vein grafts to the lateral circumflex and posterior descending arteries. He then remained asymptomatic until ventricular fibrillation arrest occurred while driving in a car race at 50 years of age. Coronary bypass grafts were intact, with no new native coronary lesions suitable for percutaneous intervention. Left ventricular function remained mildly impaired. Treatment with amiodarone was initiated, and he underwent implantation of an implantable cardioverter-defibrillator at that time. He had no further ventricular arrhythmias or device therapies delivered, but over the ensuing 8 years he developed progressive symptoms of heart failure accompanied by a decline in left ventricular systolic function. At the time of referral for CRT, he had no symptoms of ischemic heart disease and coronary angiography demonstrated patent grafts but diffuse native coronary disease.
Apart from hyperlipidemia, the patient had no history of other significant medical conditions.

Current Medications

The patient was taking spironolactone 25 mg daily, furosemide 120 mg daily, atorvastatin 20 mg daily, carvedilol 12.5 mg twice daily, enalapril 5 mg twice daily, amiodarone 200 mg daily, and enteric coated aspirin 100 mg daily.

Comments

Although the patient practiced good adherence to guideline–based heart failure medications, maximal doses of carvedilol and enalapril were not tolerated because of hypotension and azotemia. Occasional additional midday furosemide doses were self-administered by the patient according to an action plan based on weight and symptoms.

Current Symptoms

The patient experienced NYHA class III symptoms of shortness of breath and fatigue and occasional orthopnea and paroxysmal nocturnal dyspnea. He had no syncope, palpitations, or anginal symptoms.

Physical Examination

Laboratory Data

Comments

Hematologic investigations were within normal limits. Biochemical testing revealed mild renal dysfunction consistent with prerenal azotemia, with no evidence of intrinsic renal disease on subsequent testing.

Electrocardiogram

Findings

The ECG in Figure 46-1 shows a sinus rhythm of 60 bpm, left bundle branch block, and QRS duration of 190 ms.

Echocardiogram

Findings

The echocardiogram showed severe left ventricular dilation with an end-diastolic volume of 484 mL, end-systolic volume of 380 mL, with severe global systolic dysfunction and calculated ejection fraction of 21% (Figure 46-2).

Comments

In addition to severe systolic dysfunction, evidence of mechanical dyssynchrony with a prolonged left ventricular preejection time of 190 ms was noted (Figure 46-3).
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FIGURE 46-1 Resting electrocardiogram.

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FIGURE 46-2 Apical four-chamber view of the left ventricle. LV, Left ventricle.

Findings

The echocardiogram also showed normal mitral valve leaflets, tenting of leaflets resulting from left ventricular dilation, severe functional mitral regurgitation, effective regurgitant orifice 0.5 cm2, and the regurgitant volume of 72 mL by the proximal isovelocity surface area method.

Comments

The findings on echocardiography were consistent with those of severe functional mitral regurgitation as a consequence of ischemic cardiomyopathy with severe ventricular dilation (Figure 46-4).
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FIGURE 46-3 Apical long axis view of the mitral valve.

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FIGURE 46-4 Apical four-chamber view of the tricuspid valve.

Findings

Moderately severe functional tricuspid regurgitation, with peak velocity of 3.8 ms, consistent with estimated right ventricular systolic pressure of 58 mm Hg above right atrial pressure.

Physiologic Tracings

Findings

The initial hemodynamic recordings demonstrated elevated pulmonary artery pressures (Figures 46-5 through 46-8). The pulmonary capillary wedge pressure was elevated, and the waveform demonstrated large c-V waves consistent with mitral regurgitation. The transpulmonary gradient was 9 mm Hg, and the calculated pulmonary vascular resistance was 2.5 Wood units. After administration of intravenous nitroglycerin, a significant fall in pulmonary artery and pulmonary capillary wedge pressure occurred. Abolition of the prominent c-V wave was also seen on the pulmonary capillary wedge tracing.

Catheterization

Right heart catheterization was performed to evaluate pulmonary hypertension.
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FIGURE 46-5 Pulmonary artery pressure trace at baseline before cardiac resynchronization therapy.

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FIGURE 46-6 Pulmonary capillary wedge pressure trace at baseline before cardiac resynchronization therapy.

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FIGURE 46-7 Pulmonary artery pressure trace after intravenous nitroglycerin 300 mcg demonstrating a significant fall in mean pulmonary artery pressure.

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FIGURE 46-8 Pulmonary capillary wedge pressure trace after intravenous nitroglycerin 300 mcg demonstrating a significant fall in mean capillary wedge pressure.

Hemodynamics

Focused Clinical Questions and Discussion Points

Question

Is pulmonary hypertension a contraindication to CRT?

Discussion

Pulmonary hypertension in the setting of heart failure is associated with increased risk for adverse outcome and death,2,4 particularly if pulmonary hypertension persists on serial measurement once medical therapy has been optimized.3 The risk is highest in subjects with “precapillary” or “reactive” pulmonary hypertension that reflects pulmonary vascular remodeling either as a consequence of sustained elevation of pulmonary pressures in the context of left heart disease or as a result of collagen vascular disease or other causes.1,4
Pulmonary hypertension has been associated with a worse prognosis after CRT.8,9 However, reductions in pulmonary artery pressures occur frequently after CRT and are associated with improved clinical outcome.7
Pulmonary hypertension was not an exclusion criterion in landmark CRT trials and is not currently considered a contraindication to CRT. However, patients with pulmonary hypertension warrant careful evaluation to confirm the severity of pulmonary artery pressure elevation and response to vasodilator challenge.4 When precapillary or reactive pulmonary hypertension is identified, the risk for implantation and the potential role of alternative therapies such as pulmonary vasodilator agents (e.g., sildenafil) should be carefully considered.4

Question

What is the best way to assess pulmonary hypertension in preparation for CRT?

Discussion

Echocardiography is the best screening test for evaluation of pulmonary hypertension in the setting of left heart disease, but it has limitations.4 Although right ventricular systolic pressure as a surrogate for pulmonary artery systolic pressure can be estimated from Doppler velocity of the tricuspid regurgitation jet, these estimates may be inaccurate in the setting of a suboptimal acoustic window or incomplete tricuspid regurgitation Doppler trace.6 Echocardiography does not allow accurate measurement of the transpulmonary pressure gradient or pulmonary vascular resistance.6
Right heart catheterization is the gold standard for evaluation of pulmonary vascular hemodynamics and can be performed with minimal risk.4,6 Direct measurement of pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output (by thermodilution or Fick method) allows the most accurate calculation of transpulmonary gradient and pulmonary vascular resistance.4 When pulmonary capillary wedge pressure is greater than 15 mm Hg and the transpulmonary gradient is less than 15 to 20 mm Hg or the pulmonary vascular resistance less than 3 Wood units, pulmonary hypertension is consistent with left atrial pressure elevation4 and is likely to improve if left atrial pressure falls after CRT.7 A fall in pulmonary artery pressures after challenge with a vasodilator, such as nitroprusside, also identifies patients in whom pulmonary hypertension is likely to improve if left atrial pressures fall after intervention with CRT. Reactive or precapillary pulmonary hypertension can be identified when the transpulmonary gradient is greater than 20 or pulmonary vascular resistance is greater than 3. A reduction in pulmonary artery pressures after CRT intervention is less likely in this setting and is also unclear for patients in whom pulmonary artery pressures do not fall after an acute vasodilator challenge.

Question

Should all patients who are being considered for CRT undergo right heart catheterization if evidence is present of pulmonary hypertension at the time of echocardiography?

Discussion

Right heart catheterization is not indicated in all patients undergoing CRT, but may be appropriate in patients with more severe elevation of pulmonary artery pressures (mean pulmonary artery pressure >40 mm Hg), patients with suspected reactive pulmonary hypertension who may be less likely to improve with CRT, and those in whom elevation of pulmonary artery pressure appears disproportionate to the severity of left ventricular or valvular dyfunction and in whom an alternative cause for pulmonary hypertension may be present.4,6

Question

Can all patients with pulmonary hypertension secondary to left ventricular dysfunction or functional mitral regurgitation expect to improve after CRT?

Discussion

A reduction in pulmonary artery pressures occurs in many patients after CRT through a variety of mechanisms and is associated with improved clinical outcomes.7,5 A reduction in mitral regurgitation is seen in a large proportion of subjects receiving CRT and is associated with reductions in pulmonary artery pressures (Figures 46-9 and 46-10).5,10
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FIGURE 46-9 Pulmonary artery pressure trace 3 months after cardiac resynchronization therapy.

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FIGURE 46-10 Pulmonary capillary wedge pressure trace 3 months after cardiac resynchronization therapy.

Reductions in pulmonary artery pressure are less likely to occur in CRT nonresponders, as a consequence of persisting elevation in left atrial pressures or persisting mitral regurgitation. Correction of elevated pulmonary artery pressures after CRT is also less likely in the context of reactive pulmonary hypertension, in which pulmonary vascular remodeling contributes to persisting pulmonary hypertension.

Final Diagnosis

This patient had severe ischemic cardiomyopathy with severe functional mitral regurgitation and secondary pulmonary hypertension, with normal pulmonary vascular resistance.

Plan of Action

The plan for this patient was cardiac resynchronization with consideration of subsequent mitral valve repair, with left ventricular assist device back-up.

Intervention

Cardiac resynchronization therapy with CRT-D was performed.

Outcome

The CRT-D was successfully implanted.

Findings

The patient had a clinical response with improvement to class II. Brain natriuretic peptide improved from 1414 pg/mL to 574 pg/mL. Left ventricular volumes fell to 341/255 mL. Improvement in left ventricular ejection fraction to 25% also was noted. Mitral regurgitation reduced to moderately severe, with an effective regurgitant orifice area of 0.39 cm2 and regurgitant volume of 44 mL using the proximal isovelocity area method.
Improvement was seen at follow-up right heart catheterization performed 3 months after CRT-D, with pulmonary artery pressures of 35/12 mm Hg, mean 24 mm Hg, and pulmonary capillary wedge mean of 12 mm Hg with relatively normal V waves, giving a transpulmonary gradient of 12 mm Hg and calculated pulmonary vascular resistance of less than 3 Wood units.

Comments

CRT-D implantation was associated with beneficial reverse left ventricular remodeling, a reduction in mitral regurgitation, and a reduction in pulmonary artery pressures. Right heart catheterization before CRT-D implantation indicated that pulmonary hypertension was secondary to elevated left atrial pressure as a consequence of severe functional mitral regurgitation. Findings indicated normal pulmonary vascular resistance and reversibility of pulmonary hypertension when left atrial pressure was lowered with acute vasodilator therapy. Follow-up right heart catheterization after implantation confirmed the finding that pulmonary hypertension was reversible and normalized once left atrial pressures fell after implantation.

Selected References

1. Aronson D., Eitan A., Dragu R. et al. Relationship between reactive pulmonary hypertension and mortality in patients with acute decompensated heart failure. Circ Heart Fail.. 2011;4:644–650.

2. Chatterjee N.A., Lewis G.D. What is the prognostic significance of pulmonary hypertension in heart failure? Circ Heart Fail.. 2011;4:541–545.

3. Grigioni F., Potena L., Galie N. et al. Prognostic implications of serial assessments of pulmonary hypertension in severe chronic heart failure. J Heart Lung Transplant. 2006;25:1241–1246.

4. Guazzi M., Borlaug B.A. Pulmonary hypertension due to left heart disease. Circulation. 2012;126:975–990.

5. Liang Y.J., Zhang Q., Fung J.W. et al. Different determinants of improvement of early and late systolic mitral regurgitation contributed after cardiac resynchronization therapy. J Am Soc Echocardiogr. 2010;23:1160–1167.

6. McLaughlin V.V., Archer S.L., Badesch D.B., Barst R.J., Farber H.W.,  et al.Writing Committee, American College of Cardiology Foundation Task Force on Expert Consensus Documents, American Heart Association, American College of Chest Physicians, American Thoracic Society, Pulmonary Hypertension Association, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension. Circulation. 2009;119:2250–2294.

7. Shalaby A., Voigt A., El-Saed A. et al. Usefulness of pulmonary artery pressure by echocardiography to predict outcome in patients receiving cardiac resynchronization therapy heart failure. Am J Cardiolo. 2008;101:238–241.

8. Stern J., Heist E.K., Murray L. et al. Elevated estimated pulmonary artery systolic pressure is associated with an adverse clinical outcome in patients receiving cardiac resynchronization therapy. Pacing Clin Electrophysiol. 2007;30:603–607.

9. Tedrow U.B., Kramer D.B., Stevenson L.W. et al. Relation of right ventricular peak systolic pressure to major adverse events in patients undergoing cardiac resynchronization therapy. Am J Cardiol. 2006;97:1737–1740.

10. van Bommel R.J., Marsan N.A., Delgado V. et al. Cardiac resynchronization therapy as a therapeutic option in patients with moderate-severe functional mitral regurgitation and high operative risk. Circulation. 2011;124:912–919.

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