Pacemaker
Therapy
in Congestive
Abdulmassih S. Iskandrian,
he armamentarium of pharmacologic agents used in the treatment of congestive heart failure (CHF) continues to expand and provide symptomatic improvement to many such patients. It is clear that short-term responsesto drug therapy do not always predict long-term effect; hemodynamic improvement doesnot always translate to symptomatic improvement and an increasein exerciseperformance doesnot always predict a better prognosis. Most patients with CHF have severeleft ventricular (LV) dysfunction with a decreasein ejection fraction (EF) and dilatation at both end-diastoleand end-systole;isolated diastolic dysfunction is uncommon. Further, improvement in symptoms with drug therapy often occurs with no or only modest improvement in EF.im3 The Frank-Starling curve depicting the LV function in patients with CHF is shifted to the right and is often flat. Hence, considerable changes in end-diastolic volume may occur with only modest changesin stroke volume. Thus, the left ventricle appearsto have exhausted the preload reserve and is very sensitive to changes in afterload. Decrease of the inappropriately high afterload in CHF has been the mainstay of vasodilator therapy becauseof the inverse relation between afterload and systolic performance. It is possible that symptomatic improvement with vasodilator therapy in part is also due to a decreasein secondary mitral regurgitation because of decrease in LV size and thus, in the size of the mitral valve annu~us.~,~The decrease in mitral regurgitation improves the forward cardiac output, although the EF may not change. In studies using rapid atria1 pacing, we and others have observeda decreasein LV size that is explained by the decreasein diastolic filling period.6-8In normal subjects, the decreasein end-diastolic volume is accompanied by a decreasein stroke volume, but no change in cardiac output becauseof the proportional increase in heart rate. The decreasein end-diastolic volume is accompanied by a decreasein end-diastolic pressure. In patients with coronary artery disease,pacing-induced ischemia may, however, cause increased LV stiffness and an increase in end-diastolic pressure. In 1986, we hypothesized that pacing may be beneficial in some patients with CHF for 2 reasons.’ In pa-
T
From the Philadelphia Heart Institute, Presbyterian Medical Center of Philadelphia, Philadelphia, Pennsylvania. Manuscript received and accepted February 23, 1990. Address for reprints: Abdulmassih S. Iskandrian, MD, Philadelphia Heart Institute, Presbyterian Medical Center of Philadelphia, 39th and Market Streets, Philadelphia, Pennsylvania 19104.
Heart
Failure
MD
tients with dilated cardiomyopathy due to coronary artery disease,segmentsremote from the infarcted myocardium show wall motion abnormality, although the coronary artery supplying these segmentsis patent and the perfusion pattern by thallium imaging is normal, indicating cellular viability. The possiblereason for this dysfunction may be slippageof the myofibrils and overstretching of the sarcomeresbeyond the L-max resulting in a decreasein tension and force and velocity of shortening. The secondreason is that a decreasein LV end-diastolic volume is probably more than the decrease in stroke volume because of the flat nature of the Frank-Starling curve. Such a small decreasein stroke volume is more than compensatedby the pacing tachycardia and by any improvement in the velocity and extent of shortening resulting from better alignment and overlap between the thick and thin filaments. The decrease in end-diastolic volume will result in a decrease in LV filling pressure.Further, since pacing also causes a decreasein right ventricular end-diastolic volume, and hence, in right ventricular filling pressure,such a reduction may additionally decreasethe LV filling pressure via the interaction between the 2 ventricles through the common septum and the pericardium. Obviously, patients who will benefit from pacing therapy should not have severeCAD and thus may be at risk of developing myocardial ischemia, even at the modest pacing rate of approximately 100 beats/min. The decreasein end-diastolic volume may also result in a decreasein the secondary mitral regurgitation and tricuspid regurgitation and improvement in forward cardiac output. Third, to benefit from pacing, patients should have a resting bradycardia, either due to sinus node dysfunction or secondary to drug therapy. We also hypothesized that atria1 pacing is the preferred method of pacing because it maintains the atria1 contribution to ventricular filling and maintains the sequenceof activation of both ventricles. Regional asynergy and a decreasein EF has been observedin patients with ventricular pacing and fixed as well as rate-related left bundle branch block. In this issueof the journal, Hechleitener et allo report symptomatic improvement in 16 patients with CHF using atrioventricular-sequential pacing. Their patients were apparently refractory to conventional therapy and were in New York Heart Association functional classesIII and IV. They noted an increasein LVEF by radionuclide angiography (but no change in fractional shortening by 2-dimensional echocardiography) and a modest decreasein LV, right ventricular and left atria1 dimensions.However, only 4 of their 16 patients had an increasein heart rate with pacing. The mean heart rate THE AMERICAN
JOURNAL
OF CARDIOLOGY
JULY 15, 1990
223
for the group actually decreased after pacing, but the authors did not provide the heart rates during Holter monitoring. They concluded that the improvement in symptoms was mainly due to a decrease in atrioventricular conduction delay (set by the pacer at 100 ms), which decreased mitral regurgitation and also preserved atria1 systole. This study has the following limitations: there are no quantitative exercise data; there are no serial measurements to compare atria1 vs atrioventricularsequential pacing and to determine the optimum pacing rate and the optimum atrioventricular conduction delay; there are no quantitative data of the degree of mitral and tricuspid regurgitation (at rest and during exercise); there are no data on importance of atria1 contribution to LV filling; and there are no LV volume measurements, no measurements of right ventricular function and volume; and the prognostic data are not adequately defined. Answers to these questions are important to our understanding of relative role of pacing in CHF. Although the work by Hechleitener et allo is preliminary, the authors are to be congratulated for taking the first step using a new approach in patients with refractory CHF. Acknowledgment: The author wishes to thank Phyllis H. Stubbs for secretarial assistance.
224
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
66
REFERENCES 1. Packer M, Meller J, Medina N, Gorlin R, Herman MV. Importance of left ventricular chamber size in determining the response to hydralazine in severe chronic heart failure. N Engl J Med /980;303;250-255. 2. The Consensus Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (Consensus). N Engl J Med 1987:316:1429~1435. 3. Massie B, Kramer BL, Topic N, Henderson SG. Hemodynamic and radionuelide effects of acute Captopril therapy for heart failure: changes in left and right ventricular volumes and function at rest and during exercise. Circulation 1982,65:1734-1781. 4. Stevenson LW, Brunken RC, Belil D, Grover-McKay M, Schwaiger M, Schelbert HR, Tillish JH. Afterload reduction with vasodilators and diuretics decreases mitral regurgitation during upright exercise in advanced heart disease. JACC 1990;15:174-180. 5. Yoran C, Yellin EL, Becker RM, Gabbay S, Frater RWM, Sonnerblick EH. Dynamic aspects of acute mitral regurgitation: effects of ventricular volume, pressure and contractility on the effective regurgitant orifice area. Circulation 1979,60:170-l 76. 6. Iskandrian AS, Hakki AH, Bemis CE, Kane SA, Boston B, Amenta A. Left ventricular end-systolic pressure-volume relation: a combined radionuclide and hemodynamic study. Am J Cardiol 1983;51:1057-1061. 7.lskandrian AS, Bemis CE, Hakki AH, Heo J, Kimbiris D, Mintz GS. Ventricular systolic and diastolic impairment during pacing-induced myocardial ischemia in coronary artery disease: simultaneous hemodynamic, electrocardiographic and radionuclide angiographic evaluation. Am Heart J 1986;/ /2:382-391. 9. Aroesty JM, McKay RG, Heller GV, Royal HD, Als AV, Grossman W. Simultaneous assessment of left ventricular systolic and diastolic dysfunction during pacing-induced ischemia. Circulation 1985:7/:889~900. 9. Iskandrian AS, Mintz GS. Pacemaker therapy in congestive heart failure: a new concept based on excessive utilization of the Frank-Starling mechanism. Am Heart J 1986;112:867-870. 10. Hechleitener M, Zechmann W, Hiirtnagl H, Ng C-K, Hiirtnagl H, Gschnitzer F. Physiological dual-chamber pacing: alternative for drug resistant dilated cardiomyopathy. Am J Cardiol 1990,66:.
Therapy
in Congestive
Abdulmassih S. Iskandrian,
he armamentarium of pharmacologic agents used in the treatment of congestive heart failure (CHF) continues to expand and provide symptomatic improvement to many such patients. It is clear that short-term responsesto drug therapy do not always predict long-term effect; hemodynamic improvement doesnot always translate to symptomatic improvement and an increasein exerciseperformance doesnot always predict a better prognosis. Most patients with CHF have severeleft ventricular (LV) dysfunction with a decreasein ejection fraction (EF) and dilatation at both end-diastoleand end-systole;isolated diastolic dysfunction is uncommon. Further, improvement in symptoms with drug therapy often occurs with no or only modest improvement in EF.im3 The Frank-Starling curve depicting the LV function in patients with CHF is shifted to the right and is often flat. Hence, considerable changes in end-diastolic volume may occur with only modest changesin stroke volume. Thus, the left ventricle appearsto have exhausted the preload reserve and is very sensitive to changes in afterload. Decrease of the inappropriately high afterload in CHF has been the mainstay of vasodilator therapy becauseof the inverse relation between afterload and systolic performance. It is possible that symptomatic improvement with vasodilator therapy in part is also due to a decreasein secondary mitral regurgitation because of decrease in LV size and thus, in the size of the mitral valve annu~us.~,~The decrease in mitral regurgitation improves the forward cardiac output, although the EF may not change. In studies using rapid atria1 pacing, we and others have observeda decreasein LV size that is explained by the decreasein diastolic filling period.6-8In normal subjects, the decreasein end-diastolic volume is accompanied by a decreasein stroke volume, but no change in cardiac output becauseof the proportional increase in heart rate. The decreasein end-diastolic volume is accompanied by a decreasein end-diastolic pressure. In patients with coronary artery disease,pacing-induced ischemia may, however, cause increased LV stiffness and an increase in end-diastolic pressure. In 1986, we hypothesized that pacing may be beneficial in some patients with CHF for 2 reasons.’ In pa-
T
From the Philadelphia Heart Institute, Presbyterian Medical Center of Philadelphia, Philadelphia, Pennsylvania. Manuscript received and accepted February 23, 1990. Address for reprints: Abdulmassih S. Iskandrian, MD, Philadelphia Heart Institute, Presbyterian Medical Center of Philadelphia, 39th and Market Streets, Philadelphia, Pennsylvania 19104.
Heart
Failure
MD
tients with dilated cardiomyopathy due to coronary artery disease,segmentsremote from the infarcted myocardium show wall motion abnormality, although the coronary artery supplying these segmentsis patent and the perfusion pattern by thallium imaging is normal, indicating cellular viability. The possiblereason for this dysfunction may be slippageof the myofibrils and overstretching of the sarcomeresbeyond the L-max resulting in a decreasein tension and force and velocity of shortening. The secondreason is that a decreasein LV end-diastolic volume is probably more than the decrease in stroke volume because of the flat nature of the Frank-Starling curve. Such a small decreasein stroke volume is more than compensatedby the pacing tachycardia and by any improvement in the velocity and extent of shortening resulting from better alignment and overlap between the thick and thin filaments. The decrease in end-diastolic volume will result in a decrease in LV filling pressure.Further, since pacing also causes a decreasein right ventricular end-diastolic volume, and hence, in right ventricular filling pressure,such a reduction may additionally decreasethe LV filling pressure via the interaction between the 2 ventricles through the common septum and the pericardium. Obviously, patients who will benefit from pacing therapy should not have severeCAD and thus may be at risk of developing myocardial ischemia, even at the modest pacing rate of approximately 100 beats/min. The decreasein end-diastolic volume may also result in a decreasein the secondary mitral regurgitation and tricuspid regurgitation and improvement in forward cardiac output. Third, to benefit from pacing, patients should have a resting bradycardia, either due to sinus node dysfunction or secondary to drug therapy. We also hypothesized that atria1 pacing is the preferred method of pacing because it maintains the atria1 contribution to ventricular filling and maintains the sequenceof activation of both ventricles. Regional asynergy and a decreasein EF has been observedin patients with ventricular pacing and fixed as well as rate-related left bundle branch block. In this issueof the journal, Hechleitener et allo report symptomatic improvement in 16 patients with CHF using atrioventricular-sequential pacing. Their patients were apparently refractory to conventional therapy and were in New York Heart Association functional classesIII and IV. They noted an increasein LVEF by radionuclide angiography (but no change in fractional shortening by 2-dimensional echocardiography) and a modest decreasein LV, right ventricular and left atria1 dimensions.However, only 4 of their 16 patients had an increasein heart rate with pacing. The mean heart rate THE AMERICAN
JOURNAL
OF CARDIOLOGY
JULY 15, 1990
223
for the group actually decreased after pacing, but the authors did not provide the heart rates during Holter monitoring. They concluded that the improvement in symptoms was mainly due to a decrease in atrioventricular conduction delay (set by the pacer at 100 ms), which decreased mitral regurgitation and also preserved atria1 systole. This study has the following limitations: there are no quantitative exercise data; there are no serial measurements to compare atria1 vs atrioventricularsequential pacing and to determine the optimum pacing rate and the optimum atrioventricular conduction delay; there are no quantitative data of the degree of mitral and tricuspid regurgitation (at rest and during exercise); there are no data on importance of atria1 contribution to LV filling; and there are no LV volume measurements, no measurements of right ventricular function and volume; and the prognostic data are not adequately defined. Answers to these questions are important to our understanding of relative role of pacing in CHF. Although the work by Hechleitener et allo is preliminary, the authors are to be congratulated for taking the first step using a new approach in patients with refractory CHF. Acknowledgment: The author wishes to thank Phyllis H. Stubbs for secretarial assistance.
224
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
66
REFERENCES 1. Packer M, Meller J, Medina N, Gorlin R, Herman MV. Importance of left ventricular chamber size in determining the response to hydralazine in severe chronic heart failure. N Engl J Med /980;303;250-255. 2. The Consensus Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (Consensus). N Engl J Med 1987:316:1429~1435. 3. Massie B, Kramer BL, Topic N, Henderson SG. Hemodynamic and radionuelide effects of acute Captopril therapy for heart failure: changes in left and right ventricular volumes and function at rest and during exercise. Circulation 1982,65:1734-1781. 4. Stevenson LW, Brunken RC, Belil D, Grover-McKay M, Schwaiger M, Schelbert HR, Tillish JH. Afterload reduction with vasodilators and diuretics decreases mitral regurgitation during upright exercise in advanced heart disease. JACC 1990;15:174-180. 5. Yoran C, Yellin EL, Becker RM, Gabbay S, Frater RWM, Sonnerblick EH. Dynamic aspects of acute mitral regurgitation: effects of ventricular volume, pressure and contractility on the effective regurgitant orifice area. Circulation 1979,60:170-l 76. 6. Iskandrian AS, Hakki AH, Bemis CE, Kane SA, Boston B, Amenta A. Left ventricular end-systolic pressure-volume relation: a combined radionuclide and hemodynamic study. Am J Cardiol 1983;51:1057-1061. 7.lskandrian AS, Bemis CE, Hakki AH, Heo J, Kimbiris D, Mintz GS. Ventricular systolic and diastolic impairment during pacing-induced myocardial ischemia in coronary artery disease: simultaneous hemodynamic, electrocardiographic and radionuclide angiographic evaluation. Am Heart J 1986;/ /2:382-391. 9. Aroesty JM, McKay RG, Heller GV, Royal HD, Als AV, Grossman W. Simultaneous assessment of left ventricular systolic and diastolic dysfunction during pacing-induced ischemia. Circulation 1985:7/:889~900. 9. Iskandrian AS, Mintz GS. Pacemaker therapy in congestive heart failure: a new concept based on excessive utilization of the Frank-Starling mechanism. Am Heart J 1986;112:867-870. 10. Hechleitener M, Zechmann W, Hiirtnagl H, Ng C-K, Hiirtnagl H, Gschnitzer F. Physiological dual-chamber pacing: alternative for drug resistant dilated cardiomyopathy. Am J Cardiol 1990,66:.
