Noninvasive in vivo and in vitro study of the St. Jude mitral valve prosthesis: Evaluation using two dimensional and M mode echocardiography,phonocardiography and cinefluoroscopy

Fifteen patients with clinically normal function of a St. Jude mitral valve prosthesis were studied with two dimensional and M mode echocardiography, Cinefluoroscopy and phonocardiography 8 to 292 days after valve replacement. The valve was readily imaged from the left sternal edge and cardiac apex in all patients. On two dimensional echocardiography from the long axis and four chamber views, minimal end-diastolic and endsystolic distances between the interventricular septum and prosthetic valve were 18 ± 5 mm and 13 ± 3 mm, respectively (mean ± standard deviation). On M mode echocardiography both leaflets were imaged throughout the cardiac cycle from the left sternal edge and their motion relative to the valve ring and to one another was easily evaluated. The apical transducer position permits quantitative assessment of individual leaflet motion. Maximal individual diastolic leaflet excursion was 8.7 ± 1 mm and the velocity of leaflet opening and closure was 364 ±103 and 678 ±115 mm/s, respectively.Asynchronous early closure of the posterior leaflet was observed during long cardiac cycles in six of seven patients with atrial fibrillation; the seventh patient had a rapid ventricular response and no long cardiac cycles. Diastolic fluttering of one or both leaflets was also seen during atrial fibrillation after rotation of the patient from the supine to the left lateral decubitus position. Three of the six patients with asynchronous leaflet closure underwent Cinefluoroscopy, and similar leaflet behavior was documented in all. An atrial systolic wave was inscribed in the valve echogram in six of eight patients with sinus rhythm.Phonocardiography recorded prosthetic valve opening and closing sounds occurring 60 ± 20 ms after aortic closure and 61 ± 12 ms after the QRS complex, respectively. The prosthetic valve opening and closure sound amplitude ratio was 0.11 ± 0.06.A clear plexiglass water bath phantom was fitted to a pulse duplicator and constructed so as to permit in vitro simulation of valve echograms under a variety of conditions. With this method, it was possible to reproduce or approximate all images obtained in patients from both echocardiographic transducer positions.     

Derangements of myocardial metabolism preceding onset of ventricular fibrillation after coronary occlusion

To determine alterations in myocardial metabolism and and hemodynamics that occur within the first 30 minutes after coronary arterial occlusion, before the onset of ventricular fibrillation, measurements were compared in two series of dogs. Series A, 90 dogs that did not manifest ventricular fibrillation after coronary occlusion, were considered a control group. Series B consisted of 28 dogs that had ventricular fibrillation within 30 minutes after occlusion. All had similar comprehensive measurements completed preceding the onset of ventricular fibrillation. The animals in series B (subseuqnt fibrillation) had significantly higher heart rates before and after coronary occlusion. In this series cardiac metabolism of the occluded segment judged by transmyocardial lactate extraction, potassium balance, sodium/potassium ratio and blood pH because grossly more abnormal after coronary occlusion than in series A. In 5 animals whose measurements were obtained within 5 minutes of the onset of ventricular fibrillation, a sudden massive lactate production, potassium loss and increased acidosis of the occluded portion supervened minutes before the onset of the fatal arrhythmia. Animals with ventricular fibrillation had higher intracoronary S-T segment elevation that persisted until the onset of ventricular fibrillation. Measurements of abnormal hemodynamic function (left ventricular end-diastolic pressure, peak systolic pressure and first derivative of left ventricular pressure [DP/dt]) were not associated with an increased incidence of ventricular fibrillation. The study indicates that animals that manifest ventricular fibrillation within 30 minutes after coronary occlusion have higher preocclusion heart rates, a more severe metabolic disorder of the coronary occluded segment and more persistent intracoronary S-T segment elevation compared with animals that do not manifest ventricular fibrillation.     

Characterization of left ventricular mechanical function during arrhythmias with two dimensional echocardiography: I. premature ventricular contractions

Two dimensional echocardiography was applied experimentally in the closed chest dog to quantitate left ventricular function during and immediately after single premature ventricular contractions induced through threshold stimulation at the apex. Coupling intervals were varied over a range from 35 to 85 percent of the R-R interval during normal sinus rhythm (920 to 980 ms). The quality of tomographic echocardiographic images during premature as well as postextrasystolic beats was found to be satisfactory for quantitating short axis section areas at end-diastole and end-systole. A systolic fractional area change was computed from two dimensional echocardiographic measurements to characterize mid ventricular cardiac function, which correlated significantly with peak left ventricular pressure and maximal first derivative of left ventricular pressure (dP/dt). Marked shortening of coupling intervals reduced fractional shortening during premature systole and enhanced the degree of potentiation during the postextrasystolic beat. By contrast, premature beats with relatively long coupling intervals caused less reduction in contraction and only minor postextrasystolic potentiation.Systolic shortening of left ventricular length as well as transverse diameters were studied in a two dimensional echocardiographic long axis cross section. During long coupling intervals contraction was normal except for distinct regional systolic outward “bulging” in the apical region. In contrast, short coupling intervals were associated with a more significant generalized derangement of ventricular wall motion during systole. It is concluded that the two dimensional echocardiographic method can be used to portray and quantitate global as well as regional left ventricular function during disturbances of cardiac rhythm.     

Synchronized diastolic coronary venous retroperfusion: results of a preclinical safety and efficacy study

The safety and efficacy of a new clinical synchronized diastolic retroperfusion mechanical pump and autoinflatable balloon catheter was studied in 10 dogs during and after 6 hours of left anterior descending coronary artery occlusion. Eight other dogs served as the untreated control group. Infarct size measured by triphenyltetrazolium chloride, and expressed as a percent of area at risk, was significantly reduced by retroperfusion treatment (19 +/- 18 versus 58 +/- 36, p less than 0.01). Morphologic examination of the coronary sinus and cardiac veins did not demonstrate evidence of damage from synchronized retroperfusion. There was also no evidence of excess myocardial edema in either the jeopardized ischemic or normally perfused zones. There was no evidence of significant red cell hemolysis or platelet destruction from the treatment. Thus, it appears that synchronized diastolic retroperfusion is a safe and effective treatment of acute myocardial ischemia in experimental animals and warrants clinical testing.     

Medical and surgical management of myocardial infarction

The in-hospital and long-term mortality (18 to 56 months) of two groups of patients treated concurrently for acute transmural myocardial infarction are retrospectively compared. Group I (no. = 200) was given medical therapy, whereas Group II (no. = 187) underwent early coronary arterial bypass grafting. The groups were comparable in average age, incidence of previous myocardial infarctions, initial electrocardiographic findings (S-T segment elevation), area of electrocardiographic involvement, initial cardiac enzyme activity, coronary anatomy (when known) and Killip classes I to III on admission to the study. Significantly more patients in Group II were in Killip clinical class IV.

In-hospital mortality was lower in Group II than in Group I without (5.8 versus 11.5 percent) and with (1.2 versus 9.3 percent [P < 0.003]) exclusion of class IV patients from both groups. Long-term mortality during the observation period (18 to 56 months) was also lower in Group II without and with exclusion of class IV patients (11.7 versus 20.5 percent [P < 0.03] and 7.1 versus 18.1 percent [P < 0.005], respectively).

Group II was arbitrarily classified into two subgroups. Patients in subgroup IIA (no. 110) had abnormally elevated total creatine kinase (CK) activity (more than 90 IU) preoperatively and were placed on cardiopulmonary bypass 9.3 ± 2.6 hours (mean ± standard error of the mean) from the onset of symptoms. The in-hospital and long-term mortality rates were not significantly different from those in Group I (8.1 versus 11.5 percent and 17.2 versus 20.5 percent, respectively). Patients in subgroup IIB (no. = 77) had normal serum CK activity preoperatively and were placed on cardiopulmonary bypass 5.3 ± 1.4 hours from the onset of symptoms. The in-hospital and long-term mortality rates were significantly lower than those in Group I (2.6 versus 11.5 percent [P < 0.01] and 3.9 versus 20.5 percent [P < 0.001], respectively). In the 100 patients in Group II placed on cardiopulmonary bypass within 6 hours of symptoms regardless of CK activity, in-hospital and long-term mortality rates were significantly lower than in patients receiving medical therapy (2.0 versus 11.5 percent [P < 0.01] and 6.0 versus 20.5 percent [P < 0.001), respectively. Of the 100 patients, 46 were from subgroup IIA and 54 from subgroup IIB. The inhospital mortality rate was 2.1 percent (1 of 46) and 1.8 percent (1 of 54), respectively.

These preliminary data suggest that if the result of surgical reperfusion as treatment for acute evolving myocardial infarction is to be significantly different from that of medical management, reperfusion must be performed early in the course of infarction. A controlled randomized trial is suggested     

Characterization of left ventricular mechanical function during arrhythmias by two-dimensional echocardiography. II. Location of the site of onset of premature ventricular systoles

Two-dimensional echocardiography was applied experimentally in a closed chest dog model with intact pericardium to determine the location, magnitude and extent of contractile response during pacing from discrete ventricular sites. Midventricular short-axis tomographic images obtained during regular sinus rhythm and subsequent premature ventricular beats provided comparative measurements of global and segmental systolic changes of cross-sectional luminal areas and myocardial wall thickness. Computer-assisted standardized analysis of segmental systolic fractional area change and wall thickening was used to map left ventricular contraction during normal rhythm and premature beats of 70% coupling interval, induced alternately from anterior and lateral aspects of the mid-left ventricular short-axis cross-sectional plane. A characteristic pattern consisting of early systolic contraction and wall thickening was followed by paradoxical motion and wall thinning in late systole in segments corresponding to the region of direct electrical stimulation. Statistical analysis of segment by segment function indicated a maximal amount of premature beat contractile derangement at the site of the stimuli. Pacing from a right ventricular wall site in the midventricular plane caused a similar premature beat response at the anterior aspect of the interventricular septum. It is concluded that two-dimensional echographic analysis of segmental ventricular function can identify the location of electrical stimuli, and thus might noninvasively characterize regional patterns of contraction associated with ectopic foci during arrhythmias.     

Improvement in regional and global left ventricular function after intracoronary thrombolysis: assessment with two-dimensional echocardiography

After acute myocardial infarction, 23 patients undergoing intracoronary thrombolysis and 10 patients receiving conventional medical treatment were studied by 2-dimensional echocardiography to determine changes in regional and global left ventricular (LV) performance. Both quantitative and qualitative analysis of echocardiographic studies showed improvement in regional and global LV function in 18 patients with successful reperfusion immediately after thrombolysis to 10 days later (p less than 0.0005). Eleven patients who were studied before thrombolysis demonstrated no change in regional or global LV function immediately after thrombolysis. LV function did not improve in the conventionally treated group. These data indicate that in patients with acute coronary artery occlusion successfully reperfused by intracoronary thrombolysis, regional and global LV function improved by day 10 but not immediately after reperfusion.     

Relation between functional response to nitroglycerin and extent of myocardial necrosis in dogs: mapping of the left ventricle by 2-dimensional echocardiography

The relation between functional response to brief nitroglycerin infusions and extent of myocardial damage was studied sequentially in closed-chest dogs with acute occlusion of the left anterior descending coronary artery. Two-dimensional echocardiography was used to derive segmental left ventricular (LV) function (systolic fractional area change and systolic wall thickening), and this function was compared with the extent of necrosis measured 5 hours after occlusion in equivalent segments of corresponding pathologic slabs. Two-dimensional echocardiographic study before the dogs were killed indicated that remote nonnecrotic segments always responded to nitroglycerin by significant augmentation of segmental LV function. Segments in which necrosis was less than 40% showed a significant nitroglycerin-induced potentiation in segmental LV function. In contrast, segments in which necrosis was greater than 60% had no potentiation with nitroglycerin. In those segments in which eventual necrosis was 60 to 80%, significant nitroglycerin-induced augmentation in segmental LV function was observed only before and 30 minutes after the coronary occlusion. When the degree of necrosis was greater than 80%, no significant potentiation of segmental LV function was observed even as early as 30 minutes after occlusion. Thus, the degree of nitroglycerin-induced potentiation of segmental cardiac function is closely associated with the extent of myocardial necrosis in the particular ventricular segment. Two-dimensional echocardiography coupled with a nitroglycerin potentiation test might be useful for assessment of the viability of ischemic myocardium.     

Prevention of ischemic injury and early reperfusion derangements by hypothermic retroperfusion

Hypothermic synchronized retroperfusion was applied during coronary artery occlusion to determine its ability to alleviate junctional derangements of reperfusion and to reduce infarct size. The proximal left anterior descending coronary artery was occluded in 25 closed chest dogs for 3 hours and then reperfused for 7 days. Thirteen dogs with no reperfusion pretreatment served as a control group (Group A). In 12 dogs, hypothermic retroperfusion was applied from 30 minutes up to 3 hours of the occlusion period (Group B). Sequential two-dimensional echocardiographic and hemodynamic as well as metabolic measurements were performed. Compared with untreated control dogs, dogs with hypothermic synchronized retroperfusion had significantly reduced heart rate and rate-pressure product, decreased left ventricular volumes and improved ejection fraction during the occlusion period. Two-dimensional echocardiographically-derived ischemic zone systolic fractional area change and systolic wall thickening indicated significantly improved function as a result of retroperfusion. During the reperfusion period, untreated control dogs (group A) had more severe derangements in hemodynamics and wall motion than dogs treated by hypothermic retroperfusion (group B). Mortality was 30.7% in group A, 16.7% in group B and 7th day infarct size as percent of the left ventricle was 12.0 +/- 6.5 (mean +/- standard deviation) and 4.2 +/- 5.9, respectively (p less than 0.02). It is concluded that hypothermic synchronized retroperfusion applied after coronary occlusion and before reperfusion significantly improves cardiac function during occlusion, minimizes complications of reperfusion and reduces the ultimate infarct size. Because this form of circulatory assistance helps maintain cardiac function and delays the evolution of myocardial necrosis, its application may be beneficial during an evolving acute myocardial infarction before achievement of surgical or nonsurgical reperfusion.     

Regional differences in left ventricular response to atrial pacing in the dog: mapping of segmental function by two-dimensional echocardiography

Two-dimensional echocardiography was applied in 10 closed-chest dogs to evaluate, in several left ventricular (LV) short-axis cross sections and subsegments, the regional contractile response to right atrial pacing. Compared with sinus rhythm (81 +/- 10 beats/min), which exhibited a moderate 7.2 +/- 12.0% (mean +/- standard deviation) base-to-apex increment in function, this gradient was significantly augmented to 34 +/- 12% by pacing at a heart rate of 180 beats/min. Measurements of wall thickening and perimeter shortening exhibited similar trends. Differences also were observed in subsegments of individual cross sections: in sinus rhythm the base-to-apex difference in function was relatively minor in the anterior and lateral aspects of the left ventricle (-9.1 +/- 18% and -1.9 +/- 19%), whereas a significant increase was noted in posterior and midseptal zones (18 +/- 17% and 22 +/- 30%). In response to pacing, the anterior and lateral wall base-to-apex gradients were significantly augmented (25 +/- 8% and 35 +/- 34%), but there was no further change in the posterior or septal regions. In conclusion, apical regions of the canine left ventricle responded to right atrial pacing with significant augmentation of contractile function, whereas more basal levels showed little response. Circumferentially, response to atrial pacing was most pronounced in the anterior and lateral segments.     

Regional distribution of pulmonary blood volume: An index of pulmonary capillary wedge pressure determined from blood pool scintigraphy

Progressive redistribution of pulmonary blood flow to the lung apices occurs with increasing degrees of left ventricular failure, and correlates with increasing pulmonary capillary wedge pressure (PCWP). If similar changes in pulmonary blood volume (PBV) occur, then technetium-99m equilibrium blood pool scintigraphy, by assessing relative distribution of PBV, may allow prediction of PCWP. Therefore 30 patients being monitored with pulmonary artery balloon flotation catheters underwent imaging. PCWP was compared with the average radioactive count density arising from apical (A) and basal (B) regions of interest within the right lung, expressed as an $\text{A}\text{B}$ ratio. Correlation was strong for patients imaged erect, either posteriorly (r = 0.864, p = 0.001) or in the 45 ° left anterior oblique position (r = 0.842, p = 0.001), and only slightly less impressive for patients imaged supine (r = 0.678, p = 0.001). Especially when imaging was performed with patients erect, an $\text{A}\text{B}$ ratio greater than unity identified with high sensitivity (100%) and specificity (83 to 88%) an abnormally elevated PCWP (> 12 mm Hg). Moreover, directional changes in the $\text{A}\text{B}$ ratio reflected concomitant changes in PCWP after intervention. Thus, analysis of lung $\text{A}\text{B}$ radioactive count ratios obtained by equilibrium blood pool scintigraphy may be used to evaluate PCWP.     

Retrograde coronary venous contrast echocardiography: assessment of shunting and delineation of regional myocardium in the normal and ischemic canine heart

Coronary venous injections of sonicated Renografin-76 were performed in seven closed chest dogs during two-dimensional echocardiography to study the ability of this new technique to opacify regional myocardium before and after occlusion of the left anterior descending coronary artery. The balloon of a 4F double lumen catheter was inflated in the great cardiac vein for each contrast injection to prevent backflow through the coronary sinus into the right atrium. Retrograde injections before coronary artery occlusion generally resulted in patchy myocardial contrast uptake. Injections after coronary occlusion always resulted in confluent and transmural myocardial opacification which occupied 42.8 +/- 8.6% (range 26 to 54) (mean +/- standard deviation) of the myocardial circumference. Retrograde opacification always extended into adjacent myocardium beyond the ischemic zone, which was assessed in echocardiograms with antegrade contrast injections into the left main coronary artery and which measured 30 +/- 6.3% of the ventricular circumference. Shunting from the coronary venous system to cardiac chambers was evaluated in a parasternal four chamber view and was graded on a scale of 0 to 4+. Contrast appearance was equally intense in the right atrium and right ventricle (3.5 +/- 0.6+, range 2+ to 4+), less intense in the left ventricular cavity (1.5 +/- 0.6+, range 1+ to 3+) and absent in the left atrium. Postmortem anatomic validation with retrograde great cardiac vein injections of indocyanine green corroborated and in vivo contrast appearance in chambers. Retrograde coronary venous contrast echocardiography appears capable of providing in vivo information about the extent and location of myocardial zones that can be reached by retrograde infusions of therapeutic agents and about the ability of these agents to reach ischemic myocardium. In addition, this new method allows for in vivo evaluation of shunts between coronary veins and cardiac chambers, which may influence the efficacy of retrograde interventions.     

Enhanced detection of proximal right coronary artery stenosis with the additional analysis of right ventricular thallium-201 uptake in stress scintigrams

The value of right ventricular thallium-201 analysis in detecting proximal right coronary artery stenosis in exercise myocardial scintigraphy was analyzed in 52 patients, 27 with and 25 without proximal right coronary artery stenosis. For the detection of proximal right coronary artery stenosis, the sensitivity and specificity of thallium scintigraphic analysis were 59 and 88% for a right ventricular abnormality, 67 and 68% for a left ventricular inferior wall abnormality, and 93 and 56% for an abnormality of either. When both right and left ventricular thallium images were abnormal, all 9 patients had proximal right coronary artery stenoses, and when both were normal, 26 of 28 patients had a normal proximal right coronary artery. The sensitivity and specificity of blood pool scintigraphic variables during exercise (right ventricular ejection fraction and left ventricular inferior wall motion) were not significantly different for detection of proximal right coronary artery stenosis.Thus, the additional analysis of the right ventricle on thallium-201 stress scintigrams can improve the detection of proximal right coronary artery stenosis. When both right ventricular and left ventricular thallium scintigrams are abnormal (or normal), the ability to predict the presence (or absence) of proximal right coronary artery stenosis is very high.     

Synchronized retroperfusion of coronary veins for circulatory support of jeopardized ischemic myocardium

A retroperfusion system was developed that augments retrograde delivery of arterial blood into an acutely ischemic myocardial region during diastole and facilitates coronary venous drainage in systole. An electrocardiogram-synchronized, gas-actuated bladder pump propels retroperfusate through an autoinflatable balloon catheter whose tip is placed within the regional coronary vein that drains the ischemic myocardium. Experiments were performed in 26 closed chest dogs with 4 hour intracoronary balloon occlusion of the proximal left anterior descending coronary artery. An untreated control series consisted of 13 dogs; the remaining 13 dogs were treated with retroperfusion, which was initiated after the first hour of acute coronary occlusion. Synchronized retroperfusion resulted in a significant 37 ± 10 percent (mean ± standard error of the mean) decrease in left ventricular end-diastolic pressure from 11 ± 2 to 5 ± 21 mm Hg, a 20 ± 4 percent decrease in peak systolic pressure (140 ± 7 to 110 ± 6 mm Hg) and a 25 ± 6 percent reduction in systemic vascular resistance (3,880 ± 340 to 2,380 ± 300 dynes sec cm⁻⁵). Ischemic region intracoronary S-T segment elevation decreased 40 ± 15 percent, and potassium loss was reduced 92 ± 22 percent. Partial pressure of oxygen measured distal to the coronary occlusion decreased 36 ± 2 percent, suggesting oxygen delivery to and extraction by the jeopardized ischemic myocardium. Ventriculography in four dogs revealed an increase in left ventricular ejection fraction and reversal of ischemic segment dyskinesia by synchronized retroperfusion. A nitro-blue tetrazollum study of 10 excised hearts indicated that 3 hours of synchronized retroperfusion significantly reduced the size of Ischemic Injury to 3.3 ± 2 percent of the left ventricle (versus 16.2 ± 5 percent in the untreated control group). In addition, retroperfusion appeared to correct ischemic arrhythmias.

The experimental data suggest that this treatment is capable of improving cardiac function and salvaging jeopardized myocardium. Clinical application is envisioned as a prompt temporary emergency support for acute and profound ischemic dysfunction not readily treatable by other interventions.     

Advances in clinical management of acute myocardial infarction in the past 25 years

The management of acute myocardial infarction in the past 25 years has emerged from a state of masterful inactivity to one of intensive care based on a new discipline of aggressive management. This has increased the chances of survival of the victim of infarction and cquld well be one of the major reasons for the decline in mortality due to coronary heart disease in the United States since 1968. Because resuscitative techniques must be instituted within 4 minutes after the onset of cardiac arrest, the attendant nurse had to learn (he new emergency lifesaving techniques and assume a crucial role as a physician's assistant. The various stages in the evolution of coronary care discipline began with cardiopulmonary resuscitation and were followed by pacemaker application, arrhythmia prophylaxis and insertion of pulmonary venous flow-directed catheters and arterial lines that permit monitoring and control of ventricular filling pressures. Other developments in better management of the failing heart have included methods to salvage jeopardized myocardium, strategies for the prevention of sudden death, the application of revascularization techniques after acute coronary occlusion and new noninvasive computerized technology to provide enhanced contrast images of cardiac perfusion that can be directly integrated with measurement of function.     

Differential effects of nitroprusside on ischemic and nonischemic myocardial segments demonstrated by computer-assisted two dimensional echocardiography

Two dimensional echocardiographic analysis of global and regional left ventricular function was applied in seven closed chest dogs to study the effects of nitroprusslde In ischemic heart failure. Simultaneous hemodynamic and two dimensional echocardiographic measurements were obtained sequentially: (1) in the control period, (2) after proximal occlusion of the left anterior descending coronary artery, (3) after volume loading, which increased left ventricular end-diastollc pressure to 30.3 ± 9.1 mm Hg (mean ± siandard deviation), (4) during nltroprusside infusion at 33.8 ± 29.4 jug/min and (5) after discontinuation of infusion of nitroprusside. A Simpson reconstruction using five echocardiographic short axis cross sections was used for assessment of left ventricular volumes. Regional function in short axis cross sections at different levels of the left ventricle was expressed as sectional systolic fractional area of change. Furthermore, each short axis section was subdivided into eight 45 ° segments and segmental fractional area change was automatically calculated by computer.Nitroprusside reduced global end-diastolic and end-systolic volumes (p <0.05) and increased ejection fraction (p <0.05). Differential responses to nitroprusside were observed with two dimensional echocardiography in various zones of the left ventricle. Thus, in the mitral valve level cross section above the site of coronary occlusion, normal contraction prevailed in all segments. In the mid papillary muscle level section, nitroprusside significantly enhanced function of segments that were within the left anterior descending arterial supply zone. In contrast, segments in the severely ischemic dysfunctioning zone at the low papillary muscle level did not respond to the vasodilator. These differential responses to nitroprusside in profoundly ischemic, marginally ischémie and nonlschemic myocardium were readily demonstrated with two dimensional echocardiography standardized for quantitative assessment of ventricular sequence.