An intracorporeal (abdominal) left ventricular assist device. Initial clinical trials

We have initiated clinical trials with an intracorporeal (abdominal) partial artificial heart and ten preterminal postcardiotomy patients have been studied. During profound left ventricular failure, the device captures the entire cardiac output from the apex of the left ventricle at low pressures (20 to 40 mm Hg) and ejects (at 80 to 150 mm Hg) into the infrarenal abdominal aorta; the biological aortic valve opens only intermittently and the entire systemic circulation is pump generated. The device is six to ten times more effective than intra-aortic balloon pumping in man and has maintained systemic perfusion during clinical asystole and ventricular fibrillation. We have documented that the profoundly depressed postcardiotomy left ventricle, initially incapable of ejection, can recover during total left ventricular unloading with the abdominal left ventricular assist device support over a seven-day period.     

Beta-adrenergic blockade as adjunctive oral therapy in patients with chronic atrial fibrillation

In many patients with chronic atrial fibrillation, it is difficult to prevent an excessive ventricular rate under stress, even with high levels of digoxin in the blood. The effect of adding beta-adrenergic blockade with practolol to digoxin on the heart rate at rest and during low-grade controlled exercise was investigated in 28 patients with chronic atrial fibrillation and in ten normal control subjects who were receiving maintenance dosages (0.25 to 0.75 mg) of digoxin. In atrial fibrillation, therapy with practolol decreased the mean heart rate at rest from 99.8 beats per minute to 77.5 beats per minute (23 percent reduction; P less than 0.01) and during mild exercise from 148.9 beats per minute to 105.4 beats per minute (29 percent) reduction (P less than 0.001). Fifteen patients had clinically significant heart failure; therapy with practolol did not worsen it. Reversible side effects were detected in two patients. When therapy with digoxin is not sufficient to control atrial fibrillation, the addition of a beta-adrenergic blocking agent is recommended as adjunctive treatment in selected patients.     

Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins

BACKGROUND: Atrial fibrillation, the most common sustained cardiac arrhythmia and a major cause of stroke, results from simultaneous reentrant wavelets. Its spontaneous initiation has not been studied. METHODS: We studied 45 patients with frequent episodes of atrial fibrillation (mean [+/-SD] duration, 344+/-326 minutes per 24 hours) refractory to drug therapy. The spontaneous initiation of atrial fibrillation was mapped with the use of multielectrode catheters designed to record the earliest electrical activity preceding the onset of atrial fibrillation and associated atrial ectopic beats. The accuracy of the mapping was confirmed by the abrupt disappearance of triggering atrial ectopic beats after ablation with local radio-frequency energy. RESULTS: A single point of origin of atrial ectopic beats was identified in 29 patients, two points of origin were identified in 9 patients, and three or four points of origin were identified in 7 patients, for a total of 69 ectopic foci. Three foci were in the right atrium, 1 in the posterior left atrium, and 65 (94 percent) in the pulmonary veins (31 in the left superior, 17 in the right superior, 11 in the left inferior, and 6 in the right inferior pulmonary vein). The earliest activation was found to have occurred 2 to 4 cm inside the veins, marked by a local depolarization preceding the atrial ectopic beats on the surface electrocardiogram by 106+/-24 msec. Atrial fibrillation was initiated by a sudden burst of rapid depolarizations (340 per minute). A local depolarization could also be recognized during sinus rhythm and abolished by radiofrequency ablation. During a follow-up period of 8+/-6 months after ablation, 28 patients (62 percent) had no recurrence of atrial fibrillation. CONCLUSIONS: The pulmonary veins are an important source of ectopic beats, initiating frequent paroxysms of atrial fibrillation. These foci respond to treatment with radio-frequency ablation.     

Coronary occlusion site as a determinant of the cardiac rhythm effects of atropine and vagotomy

We have previously demonstrated that atropine pretreatment increases the incidence of fatal ventricular arrhythmias induced by left anterior descending coronary artery (LAD) occlusion. The purpose of the present study was to determine whether the deleterious effect of atropine also applies to arrhythmias induced by right coronary artery (RCA) occlsusion. Occlusion of the RCA resulted in ventricular arrhythmias in all 20 animals studied, followed by ventricular fibrillation in three animals (15 per cent). Right coronary occlusion also resulted in bradycardia (-30.3 +/- 5.1 beats per minute) and hypotension (-23.1 +/- 4.9 mm. Hg). Pretreatment of 15 animals with atropine caused no significant increase in the incidence of ventricular fibrillation (i.e., 20 per cent). In addition, atropine pretreatment had no effect on the fall in heart rate and hypotension associated with RCA ligation. Sectioning the vagus nerves produced results similar to atropine pretreatment with the exception that a significant portion of the bradycardia was prevented. These results indicate that the increase in deaths after atropine observed in animals undergoing experimental LAD occlusion in not demonstrated with RCA occlusion. The results also indicate that the potential for deleterious effects of atropine in acute infarction might depend on the anatomic location of the involved myocardium.     

Propranolol in mitral stenosis during sinus rhythm

Patients with early symptomatic mitral stenosis usually suffer from pulmonary congestion on the basis of left atrial and pulmonary venous hypertension. They are often in sinus rhythm, and cardiac output is usually well maintained. Symptoms occur most often when heart rate, cardiac output, or both are increased. In this study, intravenous propranolol administered to patients with pure mitral stenosis in sinus rhythm resulted in significant reductions in mitral diastolic gradient (-7.1 mm. Hg +/- 1.6 SED), mean pulmonary wedge pressure (--6.9 mm. Hg +/- 1.2) and mean pulmonary artery pressures (--9.0 mm. Hg +/- 1.2). This was due to simultaneous reduction of heart rate (--13.0 beats/minute +/- 2.6 and cardiac output (--0.5 L./minute +/- 0.2). A small associated reduction of left ventricular systolic pressure (--5.1 mm. Hg +/- 2.6) was not accompanied by adverse clinical effects. A potential role for propranolol in medical management of pure mitral stenosis in the presence of sinus rhythm is suggested.     

Hemodynamic effects of intravenous prenalterol in severe heart failure

Nine patients with chronic severe low output heart failure (radionuclide left ventricular ejection fraction 17 +/- 5 percent [mean +/- standard deviation], left ventricular filling pressure 26 +/- 6 mm Hg, cardiac index 1.9 +/- 0.4 liters/min per m2, left ventricular stroke work index 18 +/- 6 g-m/m2) from various causes were treated with intravenous prenalterol (a new catecholamine-like inotropic agent) in doses of 1,4 and 8 mg. Significant hemodynamic improvement occurred as measured by increased left ventricular ejection fraction (to 26 +/- 4 percent), decreased left ventricular filling pressure (to 21 +/- 8 mm Hg) and increased cardiac index (to 2.4 +/- 0.6 liters/min per m2) and left ventricular stroke work index (to 25 +/- 8 g-m/m2). Significant increases in heart rate (from 87 +/- 18 to 91 +/- 18 beats/min) and mean systemic arterial pressure (from 87 +/- 8 to 92 +/- 7 mm Hg) also occurred. Peak hemodynamic response occurred at various doses. Significant adverse effects associated with prenalterol consisted of increased ventricular ectopic beats in two patients and asymptomatic ventricular tachycardia in two patients. Thus, intravenous prenalterol produces hemodynamic improvement in patients with a chronic severe low output state but may be associated with increased ventricular ectopic activity.     

Cardiac responses to moderate training in rats

Left ventricular (LV) performance was studied in 30 rats conditioned by swimming and in 27 sedentary controls. Hearts were studied in the open chest both during sinus rhythm and during atrial pacing. Afterload was increased by occlusion of the aorta. Sinus rates were 328 beats/min in sedentary and 300 in conditioned animals (P less than 0.01). During ejection (E), peak left ventricular systolic pressure (PLVSP) and maximum LV dP/dt were significantly higher in conditioned than in sedentary animals. When data from hearts matched for similar heart rates were compared, increased LV performance was still seen during aortic obstruction in conditioned animals. Performance at pacing rates up to 400 beats/min was similar in hearts from conditioned and sedentary animals. At pacing rates above 400 beats/min cardiac performance was less in sedentary than in the conditioned animals. These data illustrate that although base-line cardiac performance may be the same in rats conditioned by a moderate swimming program and in sedentary animals, cardiac reserve is improved by the swimming program.     

Hemodynamic benefits of right ventricular outflow tract pacing: comparison with right ventricular apex pacing

To assess optimal hemodynamics in relation to stimulation site during right ventricular pacing, 17 consecutive patients who underwent cardiac catheterization were studied. In all patients, right ventricular apex and right ventricular outflow tract stimulation was performed at 85, 100, and 120 beats/min. Cardiac index at both pacing sites was compared using the left ventricular outflow tract continuous wave Doppler technique. Comparison of the two stimulation sites demonstrated that right ventricular outflow tract pacing resulted in a higher cardiac index at 85 beats/min (2.42 +/- 1.2 vs 2.04 +/- 1.0 L/min per m2, P < 0.002) at 100 beats/min (2.78 +/- 1.4 vs 2.35 +/- 1.1 L/min per m2, P < 0.001) and 120 beats/min (3.00 +/- 1.5 vs 2.61 +/- 0.9 L/min per m2, P < 0.001). From a total of 51 paired observations, 45 showed an increase in cardiac index during outflow tract pacing as compared to apex pacing. Right ventricular outflow tract pacing at 120 beats/min resulted in a lower cardiac index than right ventricular apex pacing in patients with significant coronary artery disease and/or impaired left ventricular function (ejection fraction < or = 50%), whereas right ventricular outflow tract pacing produced higher cardiac indices in the absence of these abnormalities. Right ventricular outflow tract pacing resulted in higher cardiac indices as compared to apex pacing in all other subgroups at all other pacing sites tested. It is concluded that stimulation of the right ventricular outflow tract offers a significant hemodynamic benefit during single chamber pacing as compared to conventional apex pacing, particularly in the absence of significant coronary artery disease and/or left ventricular dysfunction.     

Pathophysiological considerations concerning uni- and biventricular mechanical cardiac assist

Mechanical assisted circulation by the means of cardiac assist devices is a routine procedure in modern cardiac surgery and cardiology. We investigated the impact of mechanical unloading on regional myocardial "stunning" and the influence of assisted circulation on left heart and right heart failure persevered by an ultimate addition of pulmonary hypertension in experimental set ups. We found that mechanical unloading either during ischemia or in the early reperfusion phase attenuates stunning and enhances the return of synchronous heart performance. In our global dysfunction model we showed that the right heart is dispensable. Sufficient inflow to the left heart is provided unless pulmonary hypertension is present. Also additional left heart support can not overcome the deleterious situation and in select cases only additional right heart support can prevent the "low LVAD output" syndrome. We conclude that mechanical assisted circulation and mechanical unloading are beneficial in case of regional and global dysfunction persevered by pulmonary hypertension, however, the knowledge about interactions of assist systems and the circulation has to be improved in order to optimize clinical assist device performance.     

Method of increasing the effectiveness of veno-arterial perfusion

Under study was the efficacy of heart unloading in different variants of asynchronous peripheral veno-arterial perfusion (VAP). In 12 experiments VAP was accomplished in association with the left ventricle decompression. Due to the latter, complete or nearly complete exsanguination of the left ventricle was gained in 11 experiments. In fibrillation of caridac ventricles no lung edema was noted in these cases. The elaborated technic was successfully employed twice in animals being in the state of "cardiogenic shock", induced by myocardiac infarction lasting for a day.     

Functional correlation of molecular electronic properties with potency of synthetic carbinolamine antimalarial agents

Dual chamber rate responsive pacing incorporating a mode switching option is increasingly used in patients with chronic paroxysmal atrial fibrillation and high degree AV block. Single-lead VDDR pacemakers have rarely used for this indication. The purpose of this study was to determine their reliability of atrial sensing during atrial fibrillation, the percentage of atrial synchronous ventricular pacing, and the behavior of the sinus rate outside the phases of atrial fibrillation. We studied ten patients with a single-lead VDDR pacemaker implanted for this indication. Follow-up visits were performed at predischarge and after 1, 3, 6, 12, 18, and 24 months. During the mean follow-up period of 18.9 +/- 6.9 months, the atrial sensing thresholds in sinus rhythm remained stable. Atrial synchronous ventricular stimulation was achieved in 68.7 +/- 31.2% (median 82.5%) of the whole follow-up time. All patients showed an adequate atrial rate response during sinus rhythm. Atrial fibrillation was detected by the pacemakers in 24.0 +/- 29.8% of time. In 3 of 10 patients the duration of atrial fibrillation showed a steady increase from visit to visit. The sensed amplitudes of atrial fibrillation ranged from 0.1-1.0 mV. A programmed atrial sensitivity of 0.1 mV was necessary to achieve complete sensing of atrial fibrillation. None of the patients experienced tachycardias with optimized pacemaker programming. Single-lead VDDR pacing incorporating a mode-switching option is useful in patients with high degree AV block and paroxysmal atrial fibrillation, since it provides atrial synchronous ventricular pacing in more than two-thirds of follow-up time. In a subgroup of patients, a progressive increase of the time during atrial fibrillation was demonstrated. A reliable detection of paroxysmal atrial fibrillation requires the programming of the atrial sensitivity to its most sensitive value.     

Effects of pulsatile and nonpulsatile coronary perfusion on performance of the canine left ventricle

This study compares the effect of pulsatile (Group C, Fib/P) and nonpulsatile (Group B, Fib/NP) coronary perfusion on myocardial performance during 2 hours of normothermic ventricular fibrillation. Group A (BH/NP), used as a base-line observation, consisted of 2 hours of nonpulsatile coronary perfusion in beating hearts. The assessment of ventricular performance included diastolic ventricular compliance, myocardial oxygen consumption and lactate extraction, regional myocardial blood flow, and histology. After 120 minutes of ventricular fibrillation, Group C showed normal ventricular diastolic compliance as compared to a 50 per cent decrease in Group B (p less than 0.01). Myocardial oxygen consumption was not significantly different from that in Group B. Because of a 70 per cent increase in oxygen extraction above Group B (p less than 0.05), total left ventricular myocardial blood flow was reduced (103 +/- 23 versus 260 +/- 36 ml. per 100 Gm. per minute, p less than 0.05) and had near-constant resistance. Lactate extraction was significantly greater and more stable as compared to Group B (9.28 +/- 1.33 versus 1.8 +/- 1.08, p less than 0.05). Left ventricular endocardial/epicardial flow ratio was greater in Group C (1.21 +/- 0.08 versus 1.06 +/- 0.06, p less than 0.05). Minimal subendocardial histologic changes were present as compared to the marked patchy subendocardial ischemic changes seen in Group B. The results demonstrate that the addition of pulsatile flow to coronary perfusion minimized the deleterious effects of prolonged ventricular fibrillation on myocardial performance.     

Reflex vascular capacity reduction in the dog

The maximum degree and time course of active reflex venoconstriction in chloralose-anesthetized dogs was studied. The mean circulatory filling pressure (Pmc) was measured by fibrillating the heart and rapidly pumping blood from the aorta to the vena cava until the systemic arterial pressure equaled the central venous pressure. Ventricular fibrillation was continued for 1 minute and was assumed to induce maximal sympathetic discharge to the capacity vessels. Blood was removed to maintain the Pmc constant at the level determined at 8 seconds after the start of fibrillation. It was necessary to remove 13.8 ml/kg by the end of 1 minute. After autonomic nervous system blockade by hexamethonium only 4.8 ml/kg were removed to hold the Pmc constant. Thus, in conclusion, the maximal degree of active venoconstriction induced by circulatory arrest was 9.0 ml/kg during the 1st minute of cardiac fibrillation. A basal capacity vessel tone was present, equivalent to 10 ml/kg under the experimental conditions used.     

Mechanisms for increasing stroke volume during static exercise with fixed heart rate in humans

Ten patients with preserved inotropic function having a dual-chamber (right atrium and right ventricle) pacemaker placed for complete heart block were studied. They performed static one-legged knee extension at 20% of their maximal voluntary contraction for 5 min during three conditions: 1) atrioventricular sensing and pacing mode [normal increase in heart rate (HR; DDD)], 2) HR fixed at the resting value (DOO-Rest; 73 +/- 3 beats/min), and 3) HR fixed at peak exercise rate (DOO-Ex; 107 +/- 4 beats/min). During control exercise (DDD mode), mean arterial pressure (MAP) increased by 25 mmHg with no change in stroke volume (SV) or systemic vascular resistance. During DOO-Rest and DOO-Ex, MAP increased (+25 and +29 mmHg, respectively) because of a SV-dependent increase in cardiac output (+1.3 and +1.8 l/min, respectively). The increase in SV during DOO-Rest utilized a combination of increased contractility and the Frank-Starling mechanism (end-diastolic volume 118-136 ml). However, during DOO-Ex, a greater left ventricular contractility (end-systolic volume 55-38 ml) mediated the increase in SV.     

Thoracotomy for postchemotherapy resection of pulmonary residual tumor mass in patients with nonseminomatous testicular germ cell tumors: aggressive surgical resection is justified

BACKGROUND: Atrioventricular association is a key criterion for arrhythmia diagnosis. Its use in a defibrillator should significantly reduce the incidence of inappropriate shocks. Therefore, we evaluated the diagnostic accuracy of an algorithm that uses dual-chamber sensing and analysis of atrioventricular association to discriminate ventricular from supraventricular arrhythmias in a prototype of an implantable defibrillator. METHODS AND RESULTS: The algorithm performed a stepwise analysis of arrhythmias. The rhythm was first classified on the basis of cycle lengths. Each episode was then classified as supraventricular or ventricular in origin on the basis of the stability of cycle lengths and atrioventricular association. This algorithm was evaluated in 156 episodes of induced sustained tachycardias. Eighty-nine tachycardias were taken from the Ann Arbor electrogram library; the others were recorded in 50 patients during electrophysiological studies. The atrial and ventricular signals were stored on an external recorder and then injected into an external prototype of a defibrillator system. The algorithm correctly diagnosed 96% of ventricular tachycardia episodes, 100% of ventricular fibrillation episodes, and 92% of double-tachycardia episodes. The mean detection time for ventricular tachycardia was 2.6 +/- 0.8 seconds, and for ventricular fibrillation, it was 2.1 +/- 0.4 seconds. The positive predictive values for the diagnoses of atrial fibrillation and atrial flutter were 92% and 86%, respectively. For ventricular tachycardia and ventricular fibrillation, the values were 95% and 100%, respectively. CONCLUSIONS: Analysis of atrioventricular association promotes reliable differentiation between ventricular and supraventricular tachycardias and should enhance the diagnostic capabilities of implantable defibrillators.     

Circulatory support with a left-heart assist device after intracardiac operation: design concepts and management techniques

A simple left-heart assist device was developed to reduce left ventricular preload while simultaneously increasing total systemic blood flow. It consists of special cannulas connected to a simple extracorporeal tubing loop and roller pump, designed to permit bypass of as much as 5 liters of blood per minute from left atrium to ascending aorta. Employed in 15 patients with advanced heart disease who were in low cardiac output following repair, the system was proven effective. An asset of the device is the ability to subsequently separate the patient from the device without need to reenter the thorax or abdomen.     

Misplacement of a transvenous lead from an implantable cardioverter-defibrillator into the left ventricle via a patent foramen ovale

HISTORY AND CLINICAL FINDINGS: 24-hour ECG monitoring in a 64-year-old man revealed self-limited (< 30 s) ventricular tachycardias (VT) of > 200/min. He had triple-vessel coronary artery disease with both anterior and posterior wall infarctions treated by three aortocoronary venous grafts. Physical examination was unremarkable except for a well healed thoracotomy scar. INVESTIGATIONS: Programmed ventricular stimulation induced prolonged monomorphic VT of 320 beats/min, despite aminodarone treatment. Left-heart catheterization demonstrated the three patent aortocoronary grafts and a left-ventricular ejection fraction of only 20%. TREATMENT AND COURSE: Because of the inducible and prolonged VT, despite antiarrhythmic treatment with amiodarone, a cardioverter-defibrillator was implanted (ICD). During threshold measurements of the pacemaker integrated into the ICD the pacemaker impulse was noted to produce a right bundle branch block pattern, the ICD lead having erroneously been placed in the left ventricle via a patent foramen ovale. The lead was left in place, because the ICD was functioning well and lead removal with the possible need of a thoracotomy carried a high risk. CONCLUSION: Extreme caution is needed to avoid malpositioning an implantable cardioverter-defibrillator. If the lead tip is unwittingly fixed in the left ventricle but functions well it should be left in place under prophylactic anticoagulation, because of the potentially high risk of its operative removal.     

Development of a paracorporeal left ventricular assist pump system: an experimental study

Experiments were designed to compare the hemodynamic performance and metabolic effect of a paracorporeal left ventricular assist pump system (PLVAPS) with those of intra-aortic balloon pumping (IABP) in a series of 35 dogs with and without myocardial infarction (MI). The animals were subjected to a three-hour period of pumping seven days after implantation of catheters and loose left anterior descending coronary (LAD) snares. MI was produced by closed-chest snaring of the LAD 13 hours before the onset of pumping. Measurements in addition to blood chemistry included aortic, pulmonary, atrial and ventricular pressures, ECG, cardiac index, left ventricular stroke work index (LVSWI) and endocardial viability ratio (EVR). The hemodynamic effects of PLVAPS assistance in normal control dogs and dogs with induced MI closely paralleled those observed with IABP. Both assist devices significantly increased systemic perfusion, decreased LVSWI, and increased EVR by reducing the oxygen demand. Infarct sizes were not significantly reduced with the two modes of pumping. The parameters measured indicate that in our experimental infarct model there is no significant differences between PLVAPS and IABP.     

Asynchronous volume changes of the two ventricles after Fontan operation in patients with a biventricular heart

Coordinated contraction of the ventricle is an important determinant of pump function, which seems to be particularly important in Fontan circulation with one pumping ventricle. We analyzed the synchronism of contraction of the two ventricles in 11 patients with a biventricular heart who had undergone Fontan operation. Curves representing ventricular volume changes in a cardiac cycle measured on angiograms were smoothed and divided into 20 segments. We calculated the number of segments of the same directional volume changes (synchronous changes) between the two ventricles (synchronous ratio). We also calculated the total volume of the two ventricles (the two as one whole ventricle) by adding their volumes in each segment and calculated the ratio (stroke volume ratio) of the aortic stroke volume from the whole ventricle to the sum of stroke volumes of the morphological right and left ventricles. If the two ventricles ejected the blood in a completely synchronous manner, these ratios should be 1.0. In seven patients with synchronous ratios of 0.75 or greater and a stroke volume ratio of greater than 0.95, the cardiac index was 3.2 +/- 0.3 l/min/m2, the maximum total volume (corresponding to end-diastolic volume) was 106 +/- 45% normal, and the ejection fraction was 0.44 +/- 0.10. In four patients with ratios of less than 0.70 and 0.95, respectively, the parameters were 2.4 +/- 0.5 (P < 0.05), 193 +/- 92%, and 0.33 +/- 0.08, respectively. The synchronous ratio was inversely correlated with cardiac output. In conclusion, synchronism of the cardiac cycle of the two ventricles affects Fontan circulation in patients with a biventricular heart.     

Effects of unilateral stellate ganglion blockade on the arrhythmias associated with coronary occlusion

In anesthetized dogs the circumflex and/or the anterior descending coronary artery were briefly occluded (10 to 90 seconds) and ectopic beats occurring during the occlusion or for 60 seconds following release were counted. Control occlusions were alternated with occlusions performed during complete, reversible, unilateral blockade of either the right or the left stellate ganglion. This was achieved with thermodes through which coolant was circulated. In this way the shortcomings associated with stellectomy, which is irreversible, are avoided. Blockade of the right stellate ganglion increased the number of ectopic beats associated with coronary occlusion. The occurrence of episodes of ventricular tachycardia and fibrillation was also greater. By contrast, blockade of the left stellate ganglion reduced or abolished occlusion-induced arrhythmias. These effects are independent of changes in heart rate or vegal activity; they depend solely upon unilateral alteration in sympathetic tone, and are not demonstrable when such tone is low. We suggest that the right and left cardiac sympathetic nerves have a different influence upon cardiac excitability.