Raymond G. McKay

Left ventricular remodeling after myocardial infarction: a corollary to infarct expansion.

Dilatation of infarcted segments (infarct expansion) may occur during recovery from myocardial infarction, but the fate of noninfarcted segments is uncertain. Accordingly, left ventricular geometric changes were assessed by left ventricular angiography and M mode echocardiography on admission and 2 weeks later in 30 patients with their first acute transmural myocardial infarction. All patients demonstrated chest pain, ST segment elevation with subsequent development of Q waves (15 anterior, 15 inferior), and elevation of cardiac enzymes. Sequential left ventricular angiographic and hemodynamic findings were available in these patients by virtue of their participation in a study of thrombolysis in acute myocardial infarction. By that study design, all patients treated successfully with thrombolytic therapy and demonstrating improvement of flow in an occluded coronary artery underwent repeat cardiac catheterization. At 2 weeks there was a significant decrease in left ventricular and pulmonary capillary wedge pressures (p less than .01), whereas both left ventricular end-diastolic (LVEDV) and end-systolic (LVESV) volume indexes increased (p less than .01). The increase in LVEDV correlated directly with the percentage of the ventriculographic silhouette that was akinetic or dyskinetic at the initial catheterization (r = .71, p less than .001). To assess regional changes in both infarcted and noninfarcted segments, serial endocardial perimeter lengths of both the akinetic-dyskinetic segments (infarction zone) and of the remainder of the cardiac silhouette (noninfarction zone) were measured in all patients who demonstrated at least a 20% increase in their LVEDV at 2 weeks after myocardial infarction. Notably, there was a mean increase of 13% in the endocardial perimeter length of infarcted segments and a 19% increase in the endocardial perimeter length of noninfarcted segments. Serial M mode echocardiographic studies showed no significant change in the wall thickness of noninfarcted myocardial segments. Hemodynamic changes that occurred in this subgroup of patients included significant decreases in left ventricular end-diastolic and pulmonary capillary wedge pressures (p less than .05) and significant increases in angiographic cardiac index (p less than .01) and LVESV index (p less than .01). We conclude that in patients who manifest cardiac dilatation in the early convalescent period after myocardial infarction, there is remodeling of the entire left ventricle including infarct expansion of akinetic-dyskinetic segments and volume-overload hypertrophy of noninfarcted segments.(ABSTRACT TRUNCATED AT 400 WORDS)

Randomized Comparison of Prasugrel (CS-747, LY640315), a Novel Thienopyridine P2Y12 Antagonist, With Clopidogrel in Percutaneous Coronary Intervention Results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)–TIMI 26 Trial

Background—Despite the current standard antiplatelet regimen of aspirin and clopidogrel (with or without glycoprotein IIb/IIIa inhibitors) in percutaneous coronary intervention patients, periprocedural and postprocedural ischemic events continue to occur. Prasugrel (CS-747, LY640315), a novel potent thienopyridine P2Y12 receptor antagonist, has the potential to achieve higher levels of inhibition of ADP-induced platelet aggregation than currently approved doses of clopidogrel. Methods and Results—Joint Utilization of Medications to Block Platelets Optimally–Thrombolysis In Myocardial Infarction 26 (JUMBO-TIMI 26) was a phase 2, randomized, dose-ranging, double-blind safety trial of prasugrel versus clopidogrel in 904 patients undergoing elective or urgent percutaneous coronary intervention. Patients were randomized to either standard dosing with clopidogrel or 1 of 3 prasugrel regimens. Subjects were monitored for 30 days for bleeding and clinical events. The primary end point of the trial was clinically significant (TIMI major plus minor) non–CABG-related bleeding events in prasugrel- versus clopidogrel-treated patients. Hemorrhagic complications were infrequent, with no significant difference between patients treated with prasugrel or clopidogrel in the rate of significant bleeding (1.7% versus 1.2%; hazard ratio, 1.42; 95% CI, 0.40, 5.08). In prasugrel-treated patients, there were numerically lower incidences of the primary efficacy composite end point (30-day major adverse cardiac events) and of the secondary end points myocardial infarction, recurrent ischemia, and clinical target vessel thrombosis. Conclusions—In this phase 2 study, which was designed to assess safety when administered at the time of percutaneous coronary intervention, prasugrel and clopidogrel both resulted in low rates of bleeding. The results of this trial serve as a foundation for the large phase 3 clinical trial designed to assess both efficacy and safety.

Current complications of diagnostic and therapeutic cardiac catheterization

Data from 2,883 cardiac catheterizations performed during an 18 month period (from July 1986 through December 1987) were analyzed to assess the current complication profile of diagnostic and therapeutic procedures. Procedures performed during the study period included 1,609 diagnostic catheterizations, 933 percutaneous transluminal coronary angioplasties and 199 percutaneous balloon valvuloplasties. Overall, the mortality rate was 0.28% but ranged from 0.12% for diagnostic catheterizations to 0.3% for coronary angioplasty and 1.5% for balloon valvuloplasty. Emergency cardiac surgery was required in 12 angioplasty patients (1.2%). Cardiac perforation occurred in seven patients (0.2%), of whom six were undergoing valvuloplasty, and five (2.5% of valvuloplasty attempts) required emergency surgery for correction. Local vascular complications requiring operative repair occurred in 1.9% of patients overall, ranging from 1.6% for diagnostic catheterization to 1.5% for angioplasty and 7.5% for valvuloplasty. Although the complication rates for diagnostic catheterization compare favorably with those of previous multicenter registries, current overall complication rates are significantly higher because of the performance of therapeutic procedures with greater intrinsic risk and the inclusion of increasingly aged and acutely ill or unstable patients.

Simultaneous assessment of left ventricular systolic and diastolic dysfunction during pacing-induced ischemia.

Both systolic and diastolic dysfunction have been described during pacing-induced ischemia, but the temporal sequence of systolic and diastolic impairment has not been established. Accordingly, 22 patients with coronary artery disease were paced at increasing heart rates and studied with simultaneous hemodynamic monitoring, electrocardiographic recording, and radionuclide ventriculography. In addition, with synchronized left ventricular pressure tracings and radionuclide volume curves, three sequential pressure-volume diagrams were constructed for each patient corresponding to baseline, intermediate, and maximum pacing levels. Eleven patients (group I) demonstrated a nonischemic response to pacing tachycardia without chest pain, significant electrocardiographic changes, or significant rise in left ventricular end-diastolic pressure (LVEDP) in the immediate postpacing period. These patients demonstrated a progressive decrease in LVEDP, end-diastolic volume, and end-systolic volume, no change in cardiac output or left ventricular ejection fraction, and a progressive increase in left ventricular diastolic peak filling rate and the end-systolic pressure-volume ratio. Pressure-volume diagrams shifted progressively leftward and slightly downward, suggesting both an increase in contractility and a mild increase in left ventricular distensibility. The remaining 11 patients (group II) exhibited an ischemic response to pacing tachycardia, with each patient experiencing angina pectoris, demonstrating greater than 1 mm ST segment depression on the electrocardiogram, and exhibiting greater than 5 mm Hg rise in LVEDP immediately after pacing. LVEDP, end-diastolic volume, and end-systolic volume in these patients initially decreased and then subsequently increased during angina, with no change in cardiac output but a decrease in ejection fraction. Left ventricular peak diastolic filling rate and the left ventricular end-systolic pressure-volume ratio both increased at the intermediate pacing rate but fell at maximum pacing. Pressure-volume diagrams for these patients shifted leftward initially, then back to the right, during intermediate and peak pacing levels, often with an upward shift in the diastolic pressure-volume relationship. LVEDP in group II was significantly higher than that in group I at the intermediate pacing level with no difference in end-diastolic or end-systolic volumes, suggesting decreased left ventricular distensibility in these patients before the onset of systolic dysfunction at the maximum pacing level.(ABSTRACT TRUNCATED AT 400 WORDS)

Balloon dilatation of calcific aortic stenosis in elderly patients: postmortem, intraoperative, and percutaneous valvuloplasty studies.

To assess the safety and efficacy of percutaneous balloon valvuloplasty in calcific aortic stenosis, balloon dilatation of critically stenosed, calcified aortic valves was performed in five postmortem hearts, in five patients intraoperatively before aortic valve replacement, and in two elderly patients percutaneously at the time of diagnostic catheterization. The etiology of aortic stenosis in the 12 cases was rheumatic in two, congenital bicuspid calcific stenosis in one, and senile calcific degenerative stenosis in the remaining nine. Prevalvuloplasty examination in the 10 postmortem and intraoperative cases revealed rigid valve leaflets with commissural fusion in three valves and extensive nodular calcification in seven. Subsequent balloon dilatation with 15 to 18 mm valvuloplasty balloons resulted in decreased cusp rigidity and increased mobility of valve leaflets in all cases, without evidence of tearing of valve leaflets, disruption of the valvular ring, or liberation of calcific or valvular debris. In the three valve specimens with commissural fusion, balloon dilatation resulted in partial or complete separation of leaflets along fused commissures. In two cases with extensive nodular calcification, balloon dilatation resulted in a fracture of a calcified leaflet that was evident on both gross and radiologic examination. After postmortem and intraoperative studies, percutaneous catheter valvuloplasty was performed at the time of diagnostic catheterization in two elderly patients (93- and 85-year-old women) with long-standing calcific aortic stenosis. Balloon dilatation with 12 to 18 mm balloons resulted in significant decreases in aortic gradients and significant increases in cardiac index and aortic valve area in both patients. Percutaneous valvuloplasty in both patients resulted in a mild increase in aortic insufficiency and no evidence of embolic phenomena.

Time course of left ventricular dilation after myocardial infarction: Influence of infarct-related artery and success of coronary thrombolysis

Dilation of the left ventricle after myocardial infarction is common, occurs rapidly (within 2 weeks of infarction) and may be self-limited. To evaluate the time course of postinfarction left ventricular dilation and to assess the impact of successful coronary thrombolysis, serial radionuclide left ventricular volume analyses were performed in 36 patients undergoing attempted thrombolysis for acute transmural myocardial infarction. All patients underwent cardiac catheterization, coronary angiography and attempted thrombolysis within 7 h of the onset of symptoms. The site of coronary occlusion was the left anterior descending coronary artery in 17 patients, the right coronary artery in 18 and, in 1 patient, occluded bypass grafts to the right and left circumflex coronary arteries. Attempted reperfusion using a thrombolytic agent was successful in 22 individuals, occurring 5 +/- 1 h after the onset of symptoms. Gated radionuclide ventriculography was performed early (mean time 1 day after admission, n = 36), subacutely (mean time 11 days postinfarction, n = 36) and late after infarction (mean time 10.5 months, n = 25), and a geometric technique was used to measure serial left ventricular end-diastolic volume. Left ventricular end-diastolic volume for the entire group increased significantly (p less than 0.01) from 153 +/- 30 ml at baseline to 172 +/- 45 ml (at 11 days) to 220 +/- 63 ml (at 10.5 months). Twenty of 36 patients showed greater than 20% increase in left ventricular end-diastolic volume (dilation) with time. This appeared early in seven patients, occurred remote from infarction in seven others and showed a progressive pattern in six.(ABSTRACT TRUNCATED AT 250 WORDS)

Balloon aortic valvuloplasty in 170 consecutive patients

Between October 1, 1985, and April 1, 1988, we performed balloon aortic valvuloplasty in 170 patients (mean age [+/- SD], 77 +/- 5 years) who had symptomatic aortic stenosis. The procedure was completed successfully in 168 patients and resulted in significant increases in the mean (+/- SD) aortic-valve area (from 0.6 +/- 0.2 to 0.9 +/- 0.3 cm2) and cardiac output (from 4.6 +/- 3.4 to 4.8 +/- 1.4 liters per minute) and decreases in the peak aortic-valve pressure gradient (from 71 +/- 20 to 36 +/- 14 mm Hg) (P less than 0.01 for all three comparisons). There were six in-hospital deaths, and five patients required early aortic-valve replacement. Follow-up data were available for all patients, for a period averaging 9.1 months. In addition to the 6 patients who died in the hospital, 25 patients died an average of 6.4 +/- 5.3 months after discharge. Symptoms recurred in 44 patients; they were managed by repeat valvuloplasty in 16 patients, by aortic-valve replacement in 17, and by medical therapy in 11. At the most recent follow-up examination, the symptoms of 103 patients had improved after valvuloplasty; this number includes 15 patients with restenosis who successfully underwent redilation. Life-table analysis indicates that the probability of survival 12 months after the procedure was 74 percent. We conclude that balloon aortic valvuloplasty is an effective palliative therapy for some elderly patients with symptomatic aortic stenosis. Symptoms improve in the majority of patients; although restenosis is common, it can be managed in some patients by repeat balloon dilation.

Improvement in indexes of diastolic performance in patients with congestive heart failure treated with milrinone.

To elucidate the mechanisms by which the new bipyridine inotropic agent milrinone improves cardiac function, we examined multiple indexes of left ventricular diastolic function before and after administration of milrinone to patients with advanced (NYHA class III or IV) congestive heart failure. In 13 patients left ventricular pressure measurements were made with a micromanometer to permit assessment of peak negative dP/dt and the time constant of left ventricular isovolumic relaxation, T, before and after milrinone. In nine patients radionuclide ventriculographic studies were performed during left heart catheterization, allowing calculation of left ventricular peak filling rate, volumes, and the diastolic pressure-volume relationship before and after milrinone. After intravenous administration of milrinone, peak negative dP/dt increased (+ 18%; p less than .01) and T decreased (-30%; p less than .01), while heart rate increased by only 8% (87 +/- 12 to 94 +/- 15 beats/min; p less than .01), left ventricular systolic pressure did not change, and mean aortic pressure fell by 11% (p less than .01). Left ventricular peak filling rate increased (1.2 +/- 0.6 to 1.7 +/- 0.7 end-diastolic volumes/sec; p less than or equal to .02) despite a decrease in left ventricular filling pressure (mean pulmonary wedge pressure 27 +/- 7 to 18 +/- 9 mm Hg; p less than .01). There was a fall in left ventricular end-diastolic pressure (28.6 +/- 6 to 19 +/- 7 mm Hg; p less than or equal to .01), with no significant change in left ventricular end-diastolic volume. This was associated with a downward shift in the left ventricular diastolic pressure-volume relationship in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Balloon dilation of mitral stenosis in adult patients: postmortem and percutaneous mitral valvuloplasty studies.

Preliminary reports have documented the utility of percutaneous balloon valvuloplasty of the mitral valve in adult patients with mitral stenosis, but the mechanism of successful valve dilation and the effect of mitral valvuloplasty on cardiac performance have not been studied in detail. Accordingly, mitral valvuloplasty was performed in five postmortem specimens and in 18 adult patients with rheumatic mitral stenosis, using either one (25 mm) or two (18 and 20 mm) dilation balloons. Postmortem balloon dilation resulted in increased valve orifice area in all five postmortem specimens, secondary to separation of fused commissures and fracture of nodular calcium within the mitral leaflets. In no case did balloon dilation result in tearing of valve leaflets, disruption of the mitral ring or liberation of potentially embolic debris. Percutaneous mitral valvuloplasty in 18 patients with severe mitral stenosis (including 9 with a heavily calcified valve) resulted in an increase in cardiac output (4.3 +/- 1.1 to 5.1 +/- 1.5 liters/min, p less than 0.01) and mitral valve area (0.9 +/- 0.2 to 1.6 +/- 0.4 cm2, p less than 0.0001), and a decrease in mean mitral pressure gradient (15 +/- 5 to 9 +/- 4 mm Hg, p less than 0.0001), pulmonary capillary wedge pressure (23 +/- 7 to 18 +/- 7 mm Hg, p less than 0.0001) and mean pulmonary artery pressure (36 +/- 12 to 33 +/- 12 mm Hg, p less than 0.01). Left ventriculography before and after valvuloplasty in 14 of the 18 patients showed a mild (less than or equal to 1+) increase in mitral regurgitation in five patients and no change in the remainder.(ABSTRACT TRUNCATED AT 250 WORDS)

Initial success and long-term follow-up of percutaneous transluminal coronary angioplasty in chronic total occlusions versus conventional stenoses.

Coronary angioplasty was attempted in 1,074 consecutive patients, including 169 patients with total (100%) occlusion (group 1), 102 patients with functional total (99%) occlusion (group 2) and 711 patients with conventional (70 to 95%) stenoses (group 3). After exclusion of 92 patients with acute myocardial infarction, the mean age of the patients was 57 +/- 12 years, including 727 men (74%) and 255 women (26%). Although there were no differences between groups with respect to anginal symptoms or extent of coronary artery disease, the primary success rate (by lesion) varied according to lesion severity, and was 63%, 78% and 90% for groups 1, 2 and 3, respectively (p less than 0.001). Only 3 patients (1%) with chronic coronary artery occlusion (groups 1 and 2) required emergency surgery because of side-branch occlusion in 2 patients and guidewire fracture in 1 patient, whereas emergency surgery was required in 14 patients (2%) in group 3. Long-term follow-up averaging 19 +/- 11 months was available for 95% of patients. Although the combined likelihood of death or nonfatal myocardial infarction was below 6% for each group at 2 years (difference not significant), the likelihood of death, nonfatal infarction, coronary bypass surgery or repeat percutaneous transluminal coronary angioplasty was higher (41%) in group 1 than in groups 2 (28%) or 3 (28%) (p less than 0.001). Thus, coronary angioplasty can be performed safely and effectively in patients with chronic total occlusion, although neither the primary success rate nor the long-term follow-up are as favorable as in patients with conventional stenoses.