Left ventricular mechanics in dilated cardiomyopathy

The influence of altered chamber shape on the evaluation of left ventricular (LV) mechanics in idiopathic dilated cardiomyopathy (IDC) is unknown. Nine patients with IDC and 7 subjects with normal LV function were studied with simultaneous LV pressure and M-mode echographic recordings in order to derive LV meridional wall stress. The major axis of the left ventricle, determined from the left ventriculogram at rest, allowed for derivation of circumferential wall stress. The IDC group was characterized by larger end-diastolic and end-systolic LV volumes, increased LV mass, depressed angiographic ejection fraction and more spherical LV chamber shape. Both end-systolic meridional (114 +/- 30 kdyne/cm2) and circumferential (251 +/- 73 kdyne/cm2) wall stresses were elevated in patients with IDC, although the ratio of these stresses was less than normal (2.2 +/- 0.1 vs 2.7 +/- 0.2, respectively). LV load alteration with phenylephrine or nitroglycerin allowed for construction of end-systolic stress-minor-axis dimension and end-systolic stress-minor-axis shortening relations. Similar mean slopes of the meridional end-systolic stress-dimension relation were noted in IDC and normal subjects, although the line was displaced to the right in IDC. The slope of the circumferential end-systolic stress-dimension relation was, however, decreased in patients with IDC. Moreover, the end-systolic stress-fractional minor-axis shortening relation in patients with IDC was displaced downward from the normal relation supporting depressed contractile function in these IDC patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanics of pulsus alternans in aortic valve stenosis

Differences in the mechanics of strong and weak contractions during sustained pulsus alternans were studied in 4 patients with aortic valve stenosis (AS). No significant difference was observed between strong (S) and weak (W) beats in M-mode echographic end-diastolic minor-axis dimension or end-diastolic meridional wall stress. Peak systolic meridional stress (S:225 X 10(3) dynes/cm2; W:205 X 10(3) dynes/cm2), the time integral of left ventricular (LV) meridional systolic stress (S:5,000 X 10(3) dynes/cm2; W:4,500 X 10(3) dynes/cm2) and the area of a stress dimension loop (S:202 X 10(3) dyne/cm; W 165 X 10(3) dyne/cm) were all greater for strong beats. However, end-systolic meridional stress (S:100 X 10(3) dynes/cm2; W:115 X 10(3) dynes/cm2) and end-systolic minor-axis dimension (S:4.75 cm; W:5.0 cm) were significantly greater for weak beats. Stress-length relations, derived from resting and postnitroglycerin determinations, revealed higher end-systolic dimensions for weak beats at any level of limiting afterload, suggesting diminished contractile performance of weak beats. Additionally, fractional minor-axis shortening for weak beats was diminished, at any level of end-systolic stress, in comparison with that for strong beats. The results are supportive of theories suggesting alternating contractile performance during pulsus alternans.     

Exercise intolerance in patients with chronic left heart failure: Relation to oxygen transport and ventilatory abnormalities

Circulatory, metabolic, and ventilatory responses to maximal and submaximal symptom-limited exercise were studied in 13 patients with chronic stable heart failure. Maximal exercise was sustained 6.5 ± 0.6 minutes (mean ± standard error of the mean) and increased minute oxygen consumption (VO₂) to 940 ± 65 ml/min, whereas submaximal exercise was sustained for 15.4 ± 2.3 minutes and increased VO₂ to 825 ± 49 ml/min (both p < 0.01 compared with maximal exercise). Both exercise protocols were terminated because of fatigue and both were associated with reduced cardiac output relative to VO₂, marked systemic oxygen extraction (80 ± 2% maximal versus 78 ± 2% submaximal) and similarly elevated blood lactate concentrations (37 ± 4 mg/dl maximal versus 36 ± 4 mg/dl submaximal), suggesting inadequate oxygen delivery to working muscle. Minute ventilation during both types of exercise was also more than twice normal relative to carbon dioxide production. However, during submaximal exercise, dyspnea was noted in only 3 patients despite these ventilatory abnormalities. During maximal exercise, dyspnea was noted in 11 patients but did not force termination of exercise or preclude achievement of marked systemic oxygen extraction and lactate production. These data suggest that patients with chronic stable cardiac failure are limited during both maximal and submaximal exercise primarily by inadequate oxygen transport to working muscle.     

Relation between site of origin of ventricular tachycardia and relative left ventricular myocardial perfusion and wall motion

To assess the relation between the site of origin of ventricular tachycardia (VT) and relative myocardial perfusion and wall motion, 18 patients with a history of recurrent sustained VT underwent cardiac catheterization, invasive electrophysiologic study with endocardial mapping, and resting radionuclide ventriculography. In addition, 6 patients had exercise and redistribution thallium-201 scintigraphy, whereas the remaining 12 patients had resting thallium scans. The site of origin of VT (determined by catheter and intraoperative endocardial mapping) was correlated with relative myocardial perfusion (thallium) and left ventricular (LV) wall motion. All patients had significant (>50% narrowing) coronary artery disease and 16 had LV aneurysms.Twenty sites of origin of VT (28 morphologies) were identified in these 18 patients. Of the 9 patients with multiple VT morphologies, the VT originated at disparate sites in 2 patients. All 18 patients had thallium defects at rest and 3 patients had additional reversible (ischemic) defects on exercise. Of the 20 sites of origin of VT, 16 were at the periphery of the thallium defect, 1 was adjacent to it, and 3 were in the center of it. In the 16 patients with LV aneurysm, there were 18 sites of origin: 15 at the border of the aneurysm, 1 adjacent to it, and 2 within it.The data suggest that in patients with VT and coronary artery disease the site of origin is usually the periphery of a resting thallium defect, and in patients with LV aneurysm the site is the border of the aneurysm.     

Anatomic and electrophysiologic correlates of ventricular tachycardia requiring left ventricular stimulation

In 108 patients with reproducible initiation of ventricular tachycardia by programmed ventricular stimulation, the ventricular tachycardia was initiated only by left ventricular stimulation in 12 (11 percent). Programmed ventricular stimulation included single and double extrastimuli at three cycle lengths and bursts of rapid pacing to cycle lengths of 250 ms. Clinical, electrocardiographic, angiographic, hemodynamic and electrophysiologic data were available in 74 of 96 patients with ventricular tachycardia initiated by right ventricular stimulation (Group A) and in all 12 patients with ventricular tachycardia initiated only by left ventricular stimulation (Group B). There were no significant differences between Groups A and B in clinical characteristics, hemodynamics or presence and site of infarction or aneurysm. Comparison of electrophysiologic variables revealed no significant differences between Groups A and B in mean A-H interval (92 ± 22 versus 89 ± 15 ms, respectively), H-V interval (59 ± 15 versus 59 ± 15 ms) or right ventricular (241 ± 38 versus 260 ± 40 ms) or left ventricular (232 ± 28 versus 251 ± 42 ms) effective refractory period. Ventricular tachycardia with right bundle branch block and superior axis was more prevalent in Group B (92 percent versus 31 percent, p <0.001) but was observed in 32 patients in Group A.It is concluded that 11 percent of patients with clinically documented sustained ventricular tachycardia will require left ventricular programmed stimulation to reproducibly initiate the tachycardia. No clinical, anatomic, electrocardiographic or electrophysiologic features can predict whether left ventricular programmed stimulation will be required. Because initiation of ventricular tachycardia by programmed ventricular stimulation has important prognostic and therapeutic implications in such patients, stimulation should be performed from the left ventricle when the tachycardia is not initiated by stimulation from the right ventricle.     

Two dimensional echographic imaging of the left ventricle: Comparison of mechanical and phased array systems in vitro

To determine the reliability of two dimensional echographic images of the left ventricle with different two dimensional echographic instruments, two dimensional echographic images of the left ventricle were compared in vitro using two phased array and two mechanical systems to image 22 short axis slices of three postmortem human hearts (one with infarction, one with left ventricular aneurysm, one with mitral regurgitation). Total left ventricular area and left ventricular cavity area were determined with planimetry and myocardial area was derived by subtraction. Comparison of total, myocardial and cavity areas with calibrated photographs of each slice showed excellent correlations for each echographic system (r = 0.93 to 0.97 for total area; 0.90 to 0.94 for cavity area; 0.89 to 0.95 for myocardial area). For total left ventricular area, the ratio of echographic to photographic image size was close to unity (0.95 to 1.08) for one mechanical and two phased array systems, but significantly lower for mechanical system 2 (0.71, p < 0.001). For myocardial area the echographic/photographic ratio was also close to unity (0.96 to 1.15) for two phased array systems and mechanical system 1 but significantly lower for mechanical system 2 (0.77, p < 0.005). In contrast, all systems underestimated left ventricular cavity area with lower, more variable echographic/photographic ratios (0.48 to 0.78), with mechanical system 2 again giving significantly lower values (p < 0.02) than the other systems. Underestimation of left ventricular cavity area appears to result from inaccurate endocardial display. We conclude that accurate left ventricular image quantitation is possible with either phased array or mechanical systems if each variable studied is calibrated against an independent reference standard and echographic results are corrected by the resultant regression equation.     

Temporal relation between onset of cell anoxia and ischemic contractile failure. Myocardial ischemia and left ventricular failure in the isolated, perfused rabbit heart.

Contractile dysfunction is characteristic of the acutely ischemic myocardium. This study was undertaken to assess the temporal relations between the onset of cell anoxia and ischemic contractile failure in isolated, isovolumetric contracting rabbit hearts. High speed epicardial fluorescence photography using reduced nicotinamide adenosine nucleotide (NADH) was used to identify areas of cell anoxia. The onset of ischemia was correlated with deterioration of pressure generation over the course of sequential 60 second coronary arterial occlusions. In the isovolumetric contracting rabbit heart, areas of ischemia were detected 2 seconds after coronary occlusion. Significant reduction in peak systolic pressure occurred at 6 seconds of ischemic time and pressure continued to decrease throughout the 60 second period of coronary occlusion. NADH accumulation indicates imbalance of myocardial oxygen supply and demand and the cessation of oxygen utilization by the mitochondria. The results of this study indicate that ischemia is detectable within 1 to 2 seconds after coronary occlusion and that ischemic ventricular dysfunction occurs several seconds thereafter. Myocardial oxygen reserve is negligible.     

Identifying patients at risk of sudden death after myocardial infarction: Value of the response to programmed stimulation, degree of ventricular ectopic activity and severity of left ventricular dysfunction

The ability of programmed ventricular stimulation to identify risk of sudden death after acute myocardial infarction (MI) was compared with 24-hour electrocardiographic assessment of ventricular ectopic activity and determination of left ventricular (LV) dysfunction. Forty-six patients underwent programmed stimulation 8 to 60 days (mean 22) after documented MI. Programmed stimulation consisted of single and double extrastimuli from the right ventricular apex at 2 times diastolic threshold during ventricular pacing and normal sinus rhythm. Of the 46 patients, 44 underwent electrocardiographic monitoring at least 6 days after MI. In 43 of the 46 patients, LV ejection fraction (EF) and the presence of LV aneurysm were determined. In response to programmed ventricular stimulation, 5 patients had sustained ventricular tachycardia (VT), 5 had nonsustained VT (≥4 beats), 13 had intraventricular reentrant repetitive responses, and 23 had either bundle branch reentrant repetitive responses or no extra responses to programmed ventricular stimulation (negative study).

During a mean follow-up of 18 months, 10 patients died, 6 suddenly. One of the 10 patients with sustained or nonsustained VT died suddenly, compared with 3 of 13 patients with intraventricular reentrant responses and 2 of 23 patients with a negative study (difference not significant). Of 25 patients with Grade 0 to 2 ventricular ectopic activity, 3 died suddenly after MI, compared with 3 of 19 patients with Grade 3 or 4 activity (difference not significant). By comparison, the frequency of sudden death was greater in patients with an LVEF of <40% (5 of 16 versus 1 of 27 patients) or an LV aneurysm (5 of 13 versus 1 of 30 patients).

Thus, using the described protocol, the response to programmed ventricular stimulation is not helpful in identifying patients at risk for sudden death after MI. The presence of an LV aneurysm or EF of <40% appears to provide the greatest prognostic information with respect to risk for sudden cardiac death.     

Hemodynamic changes induced by cardiac angiography with ioxaglate: comparison with diatrizoate

The hemodynamic and electrocardiographic changes induced by left ventriculography and coronary arteriography with ioxaglate (a new low osmolality angiographic contrast agent) were characterized and compared with the changes induced by a commercial formulation of the commonly used angiographic contrast agent, diatrizoate (Renografin-76). Left ventriculography and coronary arteriography were performed in 25 patients utilizing ioxaglate and in another 25 patients utilizing diatrizoate. Both agents increased left ventricular end-diastolic pressure and decreased arteriovenous oxygen difference after left ventriculography, but the magnitude of the increase caused by ioxaglate was significantly less than that caused by diatrizoate (changes in left ventricular end-diastolic pressure was 5.3 +/- 1.3 mm Hg with ioxaglate and 9.5 +/- 1.5 mm Hg with diatrizoate [p less than 0.02] ). Change in arteriovenous oxygen difference was -0.33 +/- 0.19 ml/100 ml with ioxaglate and -0.85 +/- 0.13 ml/100 ml with diatrizoate (p less than 0.05). Both agents were well tolerated when used for coronary arteriography with no adverse events occurring in either group. Ioxaglate is a well tolerated cardiac angiographic contrast agent that produces less hemodynamic disturbance than diatrizoate. Accordingly, it may be particularly well suited to use in patients with impaired left ventricular function.     

Electrophysiologic approach to therapy of recurrent sustained ventricular tachycardia.

The refinement of the techniques of programmed stimulation and intracardiac recording has led to understanding of the mechanism of ventricular tachycardia and these techniques can be applied clinically to the development of therapeutic regimens. The efficacy of drug therapy can be assessed in sequential studies evaluating the ability of drugs to prevent initiation of the arrhythmia by electrical stimulation. The efficacy of pacemaker therapy can be evaluated by assessing the effects of stimulation during the tachycardia. The recent development of endocardial mapping provides the surgeon with a tool to guide therapeutic surgical ablation of the site of origin of the tachycardia. Such an electrophysiologic approach to recurrent ventricular tachycardia can lead to the rapid development of successful therapy under controlled conditions.     

Contractile mechanics and interaction of the right and left ventricles

The heart and lungs, together with hemoglobin, provide for the transport of oxygen from the atmosphere to the metabolizing tissue. The oxygenation of blood and the circulation of oxygenated blood are precisely synchronized so that the heart and lungs constitute an integrated cardiopulmonary unit. The functional integration of the heart and lungs is fostered by their anatomic arrangement and mechanical interaction.The cardiopulmonary unit consists of the right and left ventricles (two in-series pumps composed of cardiac muscle), which are mechanically coupled by the lungs. The factors that control cardiac muscle shortening (fiber length, afterload and myocardial contractile state) also regulate the pumping behavior of each ventricle. Because the ventricles are aligned in series a perturbation in the mechanical events of one ventricle will influence the behavior of the other ventricle. The interventricular septum and pericardium further promote the mechanical interplay between ventricles. Intrathoracic pressure (the pressure that surrounds the cardiopulmonary unit) creates an additional interaction between the ventricles as well as the heart and lungs.     

Clinical characteristics and long-term follow-up in 119 survivors of cardiac arrest: relation to inducibility at electrophysiologic testing

Electrophysiologic studies were performed in 119 survivors of cardiac arrest. Sustained ventricular arrhythmias were initiated by programmed ventricular stimulation in 72 patients (61%). Coronary artery disease patients with induced sustained ventricular arrhythmias had a higher incidence of prior myocardial infarction (95 versus 72%) and ventricular aneurysm (59 versus 28%) and a lower ejection fraction (37 versus 50%) than those with no inducible sustained ventricular arrhythmias. Of the 72 patients with inducible ventricular arrhythmias, 11 (15%) died suddenly during a mean follow-up of 18 months (range 15 days to 58 months). In this group, 6 of 41 patients (15%) discharged on a successful antiarrhythmic regimen and 5 of 27 patients (19%) discharged on an unsuccessful regimen or without a predischarge study have died suddenly. Of these 27 patients, 1 of 12 patients treated with amiodarone and 4 of 15 (27%) with conventional antiarrhythmic therapy died suddenly. The remaining 4 patients died of nonarrhythmic causes in the postoperative period. Of 47 patients without inducible sustained ventricular arrhythmias, 15 (32%) died suddenly at a mean follow-up of 20 months, 10 (34%) with and 15 (28%) without empiric therapy. It is concluded that sustained ventricular arrhythmias can be initiated in most patients resuscitated from cardiac arrest. Patients with inducible arrhythmias have greater left ventricular dysfunction than those without inducible arrhythmias. Medical or surgical therapy that prevented the induction of sustained ventricular arrhythmias was predictive of a successful outcome in 85% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Incidence and clinical significance of induced ventricular tachycardia

Five hundred twenty-nine patients were studied with programmed ventricular stimulation for evaluation of supraventricular and ventricular tachyarrhythmias. Eighty-six patients had clinical ventricular tachycardia. Sustained ventricular tachycardia was induced in 52 (91 percent) of the 57 patients with a sustained form of the arrhythmia clinically. Nonsustained ventricular tachycardia was induced in 18 (62 percent) of 29 patients with a symptomatic nonsustained form clinically, in 2 (4 percent) of 57 patients with a sustained form and in 3 (0.7 percent) of the 443 patients with no documented spontaneous ventricular tachycardia. Ventricular tachycardia (sustained or nonsustained) was induced by double right or left ventricular extrastimuli in 47 patients (63 percent) and by single right ventricular extrastimuli in 23 (31 percent); in 5 (7 percent), it was inducible only by rapid ventricular pacing and in 9 (12 percent) only by left ventricular stimulation.All 52 patients with induced sustained ventricular tachycardia had the sustained form clinically. Of the 23 patients with induced nonsustained ventricular tachycardia, 18 (78 percent) had the nonsustained form clinically. Four hundred fifty-four patients had no induced ventricular tachycardia; only 14 (3 percent) of these had the arrhythmia spontaneously. The morphologic features, axis and cycle length of 54 of 62 episodes of induced ventricular tachycardia in 43 patients were similar to those of the clinically observed arrhythmia. It is concluded that ventricular tachycardia resembling the clinical variety can be induced in the laboratory in almost all patients with sustained ventricular tachycardia clinically, in the majority of those with symptomatic nonsustained ventricular tachycardia clinically, and only rarely in patients with no previously documented ventricular tachycardia. Conversely, induction of ventricular tachycardia implies the likelihood of spontaneous episodes of this arrhythmia.     

Large dose procainamide therapy for ventricular tachyarrhythmia

The efficacy and toxicity of large dose procainamide therapy (500 to 1,500 mg given orally every 4 hours) for recurrent ventricular tachyarrhythmla were examined in 35 patients referred for electrophysiologic evaluation. In 16 patients procainamide was determined by programmed ventricular stimulation and serial drug testing to be the most effective agent. A long-term oral regimen was begun followed by periodic clinical evaluation and 24 hour ambulatory electrocardlographic monitoring for recurrence of symptomatic arrhythmia. In all 16 patients drug efficacy, acutely, correlated with specific plasma drug levels, which averaged 13.6 ± 8.6 μg/ml (mean ± standard deviation). Dose-dependent effects of procainamide at lower than the acute effective level were observed in six patients and included progressive slowing of the tachycardia and increasing ease of arrhythmia induction. In 14 of 16 patients, efficacy of the long-term oral regimen correlated with the acute effective plasma level. All 11 patients with plasma concentrations maintained at or above the acute effective plasma level have been free of symptomatic arrhythmia for up to 48 months, whereas all five patients with concentrations below the acute effective plasma level have had early symptomatic recurrences. Manifestations of acute toxicity, including hypotension, excessive Q-T prolongation or progression of infranodal conduction disturbances, were not observed. Chronic toxicity was limited to gastrointestinal disturbances in two patients (12.5 percent) and drug-induced lupus erythematosus in four (25 percent). It is concluded that large dose procainamide therapy is quite effective in the treatment of recurrent inducible ventricular tachyarrhythmia, and that the improved efficacy over small dose therapy may be achieved without an increased incidence of toxic side effects.     

Ventricular fibrillation during programmed ventricular stimulation: Incidence and clinical implications

Ventricular fibrillation occurred in 10 (3.3 percent) of 300 patients consecutively studied with programmed ventricular stimulation. One hundred twenty-five of these patients were studied with double ventricular extrastimuli including 68 patients with and 57 patients without documented or suspected ventricular tachycardia or fibrillation, or both. Ventricular fibrillation did not develop in response to a single ventricular extrastimulus delivered during sinus rhythm, ventricular pacing or ventricular tachycardia or in response to ventricular pacing at cycle lengths of 300 msec or greater and occurred only in response to double ventricular extrastimuli. All 10 patients who manifested ventricular fibrillation during programmed stimulation were in the group of patients with suspected or documented ventricular tachycardia or fibrillation. Ventricular fibrillation was initiated in seven patients with double ventricular extrastimuli delivered during sinus rhythm or ventricular pacing and in three patients with double ventricular extrastimuli delivered during ventricular tachycardia. Four patients had spontaneous conversion to sinus rhythm and the remainder underwent defibrillation without sequelae. Recurrent ventricular fibrillation occurred clinically in 7 of the 10 patients. This study suggests that ventricular fibrillation occurs uncommonly during programmed ventricular stimulation and only in response to double ventricular extrastimuli in patients in whom spontaneous episodes are likely to occur.     

Mechanism of ventricular fibrillation in man. Observations based on electrode catheter recordings.

Observations are reported on the initiation and spontaneous termination of ventricular fibrillation in man using endocardial electrode catheter recordings. The report is based on 16 patients in whom ventricular fibrillation developed during electrophysiologic study. In 11 patients ventricular fibrillation was initiated by programmed ventricular stimulation and in 5 patients ventricular fibrillation occurred spontaneously. In each patient two to five simultaneous ventricular electrograms were recorded at the onset or termination, or both, of ventricular fibrillation. In most patients ventricular fibrillation began as a rapid and accelerating ventricular rhythm in which local electrograms remained discrete and with progressively shortening coupling intervals. Degeneration of local electrograms into fibrillatory activity occurred at random and at varying times. In four patients ventricular fibrillation developed spontaneously during sustained ventricular tachycardia. In these cases there was acceleration of the ventricular tachycardia before degeneration to ventricular fibrillation. Fragmentation and disorganization in local ventricular electrograms did not appear to spread between contiguous areas, but occurred randomly in widely separated areas. In six patients ventricular fibrillation spontaneously converted to sinus rhythm. In four of these cases spontaneous conversion was preceded by sequential reorganization of the electrograms and a tendency toward increasing interelectrographic intervals. These observations are compatible with the multiple wavelet (reentrant) theory of ventricular fibrillation.