Pacing in cardiomyopathy.

Permanent cardiac pacing is an established treatment for the prevention of syncope or sudden death in patients with heart block or sinus node disease. Recent observations underscore the use of pacing in patients with various forms of cardiomyopathy, i.e. hypertrophic, dilated and tachycardia-induced cardiomyopathy. The evidence favouring the use of pacing in patients with cardiomyopathy is mainly derived from retrospective and uncontrolled investigations and the data from the scarce randomized investigations are rather disappointing. Therefore, the indications for pacing remain controversial.

Failure of myocardial inactivation: a clinical assessment in the hypertrophied heart.

BACKGROUND: Abnormal intracellular calcium handling is observed in hypertrophied cardiac muscle and in end-stage heart failure muscle. This abnormal calcium handling results in prolongation of the calcium transient and in a biphasic calcium transient with prominent late component. In the present studies, the mechanical correlates of abnormal calcium handling were investigated in the hypertrophied human left ventricle by analysis of: 1) isovolumic left-ventricular relaxation kinetics after drastic left-ventricular unloading in patients with severe aortic stenosis after sequential balloon aortic valvuloplasty-arterial vasodilation; and 2) morphology of the diastolic left-ventricular pressure signal in patients with aortic stenosis and hypertrophic cardiomyopathy. METHODS AND RESULTS: Drastic left-ventricular unloading in patients with severe aortic stenosis by sequential aortic valvuloplasty-arterial vasodilation resulted in a slow and dyssynchronous left-ventricular relaxation pattern, as evident from a prolongation of the time constant of left-ventricular pressure decay from 46.6 +/- 12.5 to 73.2 +/- 23.3 ms (p < 0.01), and from the development of a convex downward negative dP/dt upstroke pattern. Abnormal diastolic left-ventricular pressure wave forms consisting of continuous left-ventricular pressure decay throughout diastole and/or a secondary pressure rise in mid-diastole were observed in patients with aortic stenosis and with hypertrophic cardiomyopathy. Postextrasystolic potentiation caused further slowing of this abnormal diastolic left-ventricular pressure decay, as evident from the decrease in phase of the first harmonic of a Fourier transform applied to the diastolic left-ventricular pressure wave. When an abnormal diastolic left-ventricular pressure wave form was observed at rest or after postextrasystolic potentiation, a simultaneously recorded left-ventricular monophasic action potential signal revealed the occurrence of delayed afterdepolarizations. CONCLUSIONS: The mechanical correlates of abnormal calcium handling or of inactivation failure in the hypertrophied human left ventricle consist of slow and dyssynchronous left-ventricular isovolumic relaxation after left-ventricular unloading and of diastolic left-ventricular aftercontractions, which hinder left-ventricular filling and which are accompanied by delayed afterdepolarizations.

Wide-range load shift of combined aortic valvuloplasty-arterial vasodilation slows isovolumic relaxation of the hypertrophied left ventricle.

To assess the effects of left ventricular (LV) load on isovolumic relaxation rate of the hypertrophied LV, wide range LV load shifts were imposed by the sequential use of balloon aortic valvuloplasty (BAV) and arterial vasodilation in 14 patients with severe sclerocalcific aortic stenosis (aortic valve area, 0.45 +/- 0.16 cm2). Micromanometer tip-catheter LV pressure recordings (n = 14) and simultaneous LV angiograms (n = 9) were obtained before BAV, during nitroprusside infusion (NIT) before BAV, 48 hours after BAV, and 48 hours after BAV during NIT. LV peak systolic pressure (LVPSP) decreased from 237 +/- 33 mm Hg before BAV to 200 +/- 33 mm Hg (p less than 0.01) during NIT before BAV, to 201 +/- 27 mm Hg (p less than 0.01) after BAV and to 165 +/- 26 mm Hg (p less than 0.01) during NIT after BAV.LV end-systolic volume (LVESV) decreased from 55 +/- 34 ml before BAV to 25 +/- 23 ml (p less than 0.01) during NIT before BAV, to 30 +/- 32 ml (p less than 0.025) after BAV and to 15 +/- 12 ml (p less than 0.025) during NIT after BAV. LV end-systolic wall stress (LVESs) decreased from 90 +/- 30.10(3) dyne/cm2 before BAV to 41 +/- 13.10(3) dyne/cm2 (p less than 0.01) during NIT before BAV, to 55 +/- 16.10(3) dyne/cm2 (p less than 0.025) after BAV and to 26 +/- 6.10(3) dyne/cm2 (p less than 0.01) during NIT after BAV. Only after sequential BAV-NIT was the time of LV electromechanical systole (LVEST), which marked the onset of the LV isovolumic relaxation period, significantly reduced (from 419 +/- 26 msec before BAV to 363 +/- 28 msec after BAV-NIT [p less than 0.01]). The time constants of LV pressure decay with zero or nonzero asymptote pressure (TO and TPB) remained unchanged after BAV and during NIT before BAV. At the lowest LVPSP, LVESV, and LVESs after sequential BAV-NIT, both TO and TPB significantly prolonged from 35.7 +/- 6.3 to 46.7 +/- 12.6 msec (p less than 0.025) and from 46.6 +/- 12.5 to 73.2 +/- 23.3 msec (p less than 0.01). Phase-plane plots (LV dP/dt vs. LVP) of the LV pressure (P) signal during isovolumic relaxation were constructed for the four different loading states by matching corresponding LVP and LV dP/dt points. For a given LVP value, the corresponding LV dP/dt values on the phase plane plots were comparable before BAV, during NIT before BAV, and after BAV. The corresponding LV dP/dt value was higher during NIT after BAV, impling a slower relaxation rate at the same LVP after sequential BAV-NIT. A shift in the control of isovolumic LV relaxation kinetics from myofilamentary detachment to myoplasmic calcium removal, which proceeds slower in hypertrophied myocardium, could explain the observed slowing of LV isovolumic relaxation after drastic LV unloading of sequential BAV-NIT.

Implantation of a dual chamber pacemaker in a patient with persistent left superior vena cava.

A patient underwent dual chamber pacemaker implantation by puncture of the left subclavian vein. During the procedure we observed persistence of the left superior vena cava. A "J-shaped" atrial lead was used for ventricular pacing with excellent long-term results. This technique can be a valuable alternative when confronted with the problem of persistent left superior vena cava during pacemaker implantation.

Atrial pacing bigeminy: a manifestation of crosstalk.

Atrial pacing bigeminy, defined as atrial pacing with alternating short and long cycle lengths, was recorded in two out of five DDD-pacemaker implants. Another fascinating feature, the lowering of the effective pacing rate after programming to a higher rate, occurred in one patient. Both phenomena can be explained by crosstalk; appropriate programming resulted in normal DDD-function in all cases. These observations in our patients have led to some interesting conclusions regarding multiprogrammability and nominal settings.

Temporary AVI pacing by chest wall stimulation.

Temporary atrial pacing (coded AVI pacing) has recently been proposed to assess atrial capture in patients with unipolar dual chamber pacemakers. This pacing mode can usually be achieved by programming the ventricular output to a subthreshold value. In patients with noncommitted bifocal pacemakers, AVI pacing can also be obtained by prolonging the programmed AV delay allowing for spontaneous conduction after atrial capture. However, in patients with prolonged AV conduction and a low aventricular stimulation threshold, ventricular stimulation cannot be prevented using the forementioned procedures. Using chest wall stimulation, we developed and tested a new method of temporary AVI pacing in patients with noncommitted DDD or DVI pacemakers.

Relaxation properties of mammalian atrial muscle.

The properties of relaxation, particular the sensitivity of relaxation to load, were analyzed in isolated intact atrial muscle and in manually dissected, detergent-treated cellular preparations from cat, dog, and rat atria. Force and length traces under increasing afterloads and following load clamps were obtained using an electromagnetic lever-force transducer system for the intact muscles and a capacitance transducer system for the cellular preparations. In both types of preparations, the time course of relaxation was hardly affected by the load or by alterations in load (load clamps), unlike intact mammalian ventricular muscle. This load independence of relaxation, which was hardly influenced by variations of initial muscle length, resembled relaxation in intact frog ventricular muscle and in detergent-treated mammalian ventricular single cells. As relaxation of these ventricular preparations with poorly developed (frog) or absent (detergent-treated single cells) calcium-sequestering systems was shown to be governed by the dissipation of activation, these results suggest a similar control mechanism for relaxation in mammalian atrial muscle. Furthermore, load independence of relaxation of mammalian atrial muscle in late diastole may promote optimal filling of the ventricle.

[The double control system of heart relaxation]. / Double contrôle de la relaxation du coeur.

The systolic performance of the heart is regulated by two separate mechanisms: the first involves an adaptation to load (Frank-Starling), and the second, variations in contractility. Similarly, recent experimental studies have shown a double mechanism of control of the relaxation phase. Cardiac relaxation, as regards the muscle and muscle-pump system, is governed by the constant interrelation of the sensitivity of the contractile system to conditions of load (load dependence) and by the sensitivity to decreasing activation (inactivation dependence). The load dependence of cardiac muscle requires an important and effective intracellular system of calcium sequestration. For given load conditions, relaxation may be modulated by subtle changes in the dissipation of activation. Such variations of dissipation of activation may result from metabolic (coronary circulation), neuro humoral (sympathetic tone), and pharmacological factors (catecholamine, vasodilator therapy, digitalis) affecting the heart as a whole. Also, for a given load dependence, relaxation will be affected by changes in the conditions of load, which are complex in the whole heart (return force, end systolic deformation, arterial impedence, the law of Laplace, increased intra myocardial pressure due to rapid filling of the coronary reservoir). This double system of control of relaxation, with load dependence predominating is very valuable during the rapid filling phase of the heart. In this phase, relaxation is mainly under load and not in activation dependence. This allows perfect return to the presystolic configuration despite the low filling pressures. The continuous interaction of the cardiac load complex during relaxation and its metabolic and neuro humoral control makes it difficult to assess the relative importance of each factor of this double control. The interaction is even more complex in diseased hearts where regional functional abnormalities are often observed. Similarly, any pharmacological intervention may simultaneously affect load and inactivation dependence.

Relaxation of ventricular cardiac muscle.

1. The load bearing capacity during relaxation of ventricular cardiac muscle from various animal species was investigated. 2. The effect of load on the time course of relaxation was analysed either by comparing afterloaded contractions against various loads or by imposing abrupt alterations in load (load clamps). 3. In heart muscle from the mammalian species studied relaxation was sensitive to loading conditions, whereas in frog heart muscle relaxation was largely independent of the loading conditions. The mechanical properties of relaxation of cardiac muscle appear, therefore, governed by the interplay of a load-controlled and an activation-controlled decay mechanism, the relative importance of which differs with species. 4. Load-dependence may be the mechanical expression of the ratio of the number of force generating sites at any time during contraction and relaxation to the load to be carried; this mechanism would predominate in mammalian animal species with a well developed calcium sequestering sarcoplasmic reticulum. Activation-dependence would seem to predominate in animal species, such as frog, in which calcium sequestration appears to be the rate limiting step during relaxation.

Contractility in mammalian heart muscle; calcium and osmolality.

The influence of osmolality of the external medium on the calcium (Ca) dependency of contractility of isolated electrically excited cat papillary muscle was examined. Maximum unloaded velocity of shortening was directly measured by load clamping the muscle from the preload (at the length, Lmax, at which maximum active tension was developed) to zero load (zero load clamp). Peak velocity of shortening at the Lmax preload, peak total force, peak rate of force development, time to peak force, and time to half relaxation were also recorded. The performance-Ca response curves (Ca concentration between 1.25 nM and 10 nM) for maximum unloaded velocity of shortening, peak shortening velocity at Lmax preload, total force, and peak rate of force development were shifted to the left when osmolality was increased (from 290 mosmoles to 410 mosmoles) with sucrose, and to the right when osmolality was increased with NaCl. The sensitivity for Ca, as determined from the slopes of these response curves, appeared essentially unaltered by either sucrose or NaCl, except for the high Ca concentrations (above 5 mM) at the higher osmolalities (above 370 mosmoles) especially with sucrose.