Gus J. Vlahakes

Insights From Three-Dimensional Echocardiography Into the Mechanism of Functional Mitral Regurgitation Direct In Vivo Demonstration of Altered Leaflet Tethering Geometry

BACKGROUND Recent advances in three-dimensional (3D) echocardiography allow us to address uniquely 3D scientific questions, such as the mechanism of functional mitral regurgitation (MR) in patients with left ventricular (LV) dysfunction and its relation to the 3D geometry of mitral leaflet attachments. Competing hypotheses include global LV dysfunction with inadequate leaflet closing force versus geometric distortion of the mitral apparatus by LV dilatation, which increases leaflet tethering and restricts closure. Because geometric changes generally accompany dysfunction, these possibilities have been difficult to separate. METHODS AND RESULTS We created a model of global LV dysfunction by esmolol and phenylephrine infusion in six dogs. initially with LV expansion limited by increasing pericardial restraint and then with the pericardium opened. The mid-systolic 3D relations of the papillary muscle (PM) tips and mitral valve were reconstructed. Despite severe LV dysfunction (ejection fraction, 18+/-6%), only trace MR developed when pericardial restraint limited LV dilatation; with the pericardium opened, moderate MR accompanied LV dilatation (end-systolic volume, 44+/-5 mL versus 12+/-5 mL control, P<.001). Mitral regurgitant volume and orifice area did not correlate with LV ejection fraction and dP/dt (global function) but did correlate with changes in the tethering distance from the PMs to the anterior annulus derived from the 3D reconstructions, especially PM shifts in the posterior and mediolateral directions, as well as with annular area (P<.0005). By multiple regression, only changes in the PM-to-annulus distance independently predicted MR volume and orifice area (R2=.82 to .85, P=2x10(-7) to 6x10(-8)). CONCLUSIONS LV dysfunction without dilatation fails to produce important MR. Functional MR relates strongly to changes in the 3D geometry of the mitral valve attachments at the PM and annular levels, with practical implications for approaches that would restore a more favorable configuration.

The pathophysiology of failure in acute right ventricular hypertension: hemodynamic and biochemical correlations.

SUMMARY Acute right ventricular (RV) hypertension and failure occur clinically. In this study we examined the mechanism of RV failure. Adult dogs were studied acutely under anesthesia; dogs were instrumented for measurement of pressures and right coronary artery blood flow. Myocardial blood flow and cardiac output were determined with radionuclide-labeled microspheres, and the presence of ischemia was determined by biochemical analysis of ventricular biopsies. RV hypertension was produced by constricting the pulmonary artery and was increased until RV failure occurred, as evidenced by decreased aortic pressure and cardiac output and increased RV end-diastolic pressure. With increasing RV systolic pressure, RV myocardial blood flow failed to increase in proportion to demand. At the onset of RV failure, there was no reactive hyperemia of right coronary flow compared with control, indicating the absence of further coronary vascular reserve; biochemical analysis demonstrated that the RV free wall was ischemic; the LV free wall was not. Infusion of phenylephrine raised aortic pressure and hence, myocardial perfusion pressure; RV failure reversed as shown by decreased RV end-diastolic pressure and increased cardiac output and RV systolic pressure; reactive hyperemia of right coronary flow was restored and the biochemical indexes of ischemia were reversed, demonstrating that ischemia is the cause of failure in acute RV hypertension.

Inhaled nitric oxide in congenital heart disease.

BackgroundCongenital heart lesions may be complicated by pulmonary arterial smooth muscle hyperplasia, hypertrophy, and hypertension. We assessed whether inhaling low levels of nitric oxide (NO), an endothelium-derived relaxing factor, would produce selective pulmonary vasodilation in pediatric patients with congenital heart disease and pulmonary hypertension. We also compared the pulmonary vasodilator potencies of inhaled NO and oxygen in these patients. Methods and ResultsIn 10 sequentially presenting, spontaneously breathing patients, we determined whether inhaling 20-80 ppm by volume of NO at inspired oxygen concentrations (FIO2) of 0.21-0.3 and 0.9 would reduce the pulmonary vascular resistance index (Rp). We then compared breathing oxygen with inhaling NO. Inhaling 80 ppm NO at F102 0.21-0.3 reduced mean pulmonary artery pressure from 48 ± 19 to 40+14 mm Hg and Rp from 658±421 to 491±417 dyne sec cm-5 m-2 (mean±SD, both p<0.05). Increasing the F102 to 0.9 without adding NO did not reduce mean pulmonary artery pressure but reduced Rp and increased the ratio of pulmonary to systemic blood flow (Qp/Qs), primarily by increasing Qp (p<0.05). Breathing 80 ppm NO at F1O2 0.9 reduced mean pulmonary artery pressure and Rp to the lowest levels and increased Qp and Qp/Qs (all p<0.05). While breathing at F102 0.9, inhalation of 40 ppm NO reduced Rp (p<0.05); the maximum reduction of Rp occurred while breathing 80 ppm NO. Inhaling 80 ppm NO at F102 0.21-0.9 did not alter mean aortic pressure or systemic vascular resistance. Methemoglobin levels were unchanged by breathing up to 80 ppm NO for 30 minutes. ConclusionInhaled NO is a potent and selective pulmonary vasodilator in pediatric patients with congenital heart disease complicated by pulmonary artery hypertension. Inhaling low levels of NO may provide an important and safe means for evaluating the pulmonary vasodilatory capacity of patients with congenital heart disease without producing systemic vasodilation.

The automatic implantable cardioverter defibrillator: Efficacy, complications and survival in patients with malignant ventricular arrhythmias

Ninety-four patients underwent surgery for automatic implantable cardioverter-defibrillator implantation. Ninety patients were discharged from the hospital with the device and were followed up for a mean period of 17 +/- 10 months. Forty-six patients experienced at least one discharge of the device under circumstances consistent with a malignant ventricular arrhythmia. One sudden death occurred. Complications included perioperative death (3 patients), post-operative ventricular tachycardia (12 patients) and atrial fibrillation (8 patients), perioperative myocardial infarction (1 patient) and device discharges for sinus tachycardia and supraventricular arrhythmias (17 patients). Six and 12 month survival rates by life table analysis were 98.7 and 95.4%, respectively. Thus, the automatic implantable cardioverter-defibrillator is a highly effective and relatively low risk treatment modality for patients with refractory life-threatening ventricular arrhythmias.

Mechanism of ischemic mitral regurgitation with segmental left ventricular dysfunction: three-dimensional echocardiographic studies in models of acute and chronic progressive regurgitation

OBJECTIVES This study aimed to separate proposed mechanisms for segmental ischemic mitral regurgitation (MR), including left ventricular (LV) dysfunction versus geometric distortion by LV dilation, using models of acute and chronic segmental ischemic LV dysfunction evaluated by three-dimensional (3D) echocardiography. BACKGROUND Dysfunction and dilation-both mechanisms with practical therapeutic implications-are difficult to separate in patients. METHODS In seven dogs with acute left circumflex (LCX) coronary ligation, LV expansion was initially restricted and then permitted to occur. In seven sheep with LCX branch ligation, LV expansion was also initially limited but became prominent with remodeling over eight weeks. Three-dimensional echo reconstruction quantified mitral apparatus geometry and MR volume. RESULTS In the acute model, despite LV dysfunction with ejection fraction = 23 +/- 8%, MR was initially trace with limited LV dilation, but it became moderate with subsequent prominent dilation. In the chronic model, MR was also initially trace, but it became moderate over eight weeks as the LV dilated and changed shape. In both models, the only independent predictor of MR volume was increased tethering distance from the papillary muscles (PMs) to the anterior annulus, especially medial and posterior shift of the ischemic medial PM, measured by 3D reconstruction (r2 = 0.75 and 0.86, respectively). Mitral regurgitation volume did not correlate with LV ejection fraction or dP/dt. CONCLUSIONS Segmental ischemic LV contractile dysfunction without dilation, even in the PM territory, fails to produce important MR. The development of MR relates strongly to changes in the 3D geometry of the mitral apparatus, with implications for approaches to restore a more favorable configuration.

Risk Factors for Pancreatic Cellular Injury after Cardiopulmonary Bypass

BACKGROUND Pancreatitis is a known complication of cardiac surgery with cardiopulmonary bypass. Although ischemia is believed to be a factor, the cause of pancreatitis after cardiopulmonary bypass remains unknown. METHODS We prospectively studied 300 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass. Serum amylase, pancreatic isoamylase, and serum lipase were measured on postoperative days 1,2,3,7, and 10. Pancreatic cellular injury was defined as the presence of hyperamylasemia (greater than 123 U per liter) with an increase in either the serum level of lipase (greater than 24 U per liter) or the peak level of pancreatic isoamylase. Trypsinogen-activation peptides, which indicate intrapancreatic enzyme activation, were measured in the urine of the last 101 patients studied. RESULTS Evidence of pancreatic cellular injury was detected in 80 patients (27 percent), of whom 23 had associated abdominal signs or symptoms and 3 had severe pancreatitis (2 with pancreatic abscess and 1 with necrotizing hemorrhagic pancreatitis). Two of 19 postoperative deaths were secondary to pancreatitis. In multivariate analyses, the development of pancreatic cellular injury was significantly associated with preoperative renal insufficiency, valve surgery, postoperative hypotension, and perioperative administration of calcium chloride. The administration of more than 800 mg of calcium chloride per square meter of body-surface area was an independent predictor of pancreatic cellular injury, and the increase in risk was dose-related. No differences were found in the level of trypsinogen-activation peptides between patients who had pancreatic cellular injury and those who did not. CONCLUSIONS Pancreatic cellular injury, as indicated by hyperamylasemia of pancreatic origin, is common after cardiac surgery. The administration of large doses of calcium chloride is an independent predictor of pancreatic cellular injury and may be a cause of it.

Cardiac operations in patients 80 years old and older.

BACKGROUND Because the elderly are increasingly referred for operation, we reviewed results with cardiac surgical patients 80 years old or older. METHODS Records of 600 consecutive patients 80 years old or older having cardiac operations between 1985 and 1995 were reviewed. Follow-up was 99% complete. RESULTS Two hundred ninety-two patients had coronary grafting (CABG), 105 aortic valve replacement (AVR), 111 AVR + CABG, 42 mitral valve repair/ replacement (MVR) +/- CABG, and 50 other operations. Rates of hospital death, stroke, and prolonged stay (> 14 days) were as follows: CABG: 17 (5.8%), 23 (7.9%) and 91 (31.2%); AVR: 8 (7.6%), 1 (1.0%), and 31 (29.5%); AVR + CABG: 7 (6.3%), 12 (10.8%), and 57 (51.4%); MVR +/- CABG: 4 (9.5%), 3 (7.1%), and 16 (38.1%); other: 9 (18.0%), 3 (6.0%), and 23 (46.0%). Multivariate predictors (p < 0.05) of hospital death were chronic lung disease, postoperative stroke, preoperative intraaortic balloon, and congestive heart failure; predictors of stroke were CABG and carotid disease; and predictors of prolonged stay were postoperative stroke and New York Heart Association class. Actuarial 5-year survival was as follows: CABG, 66%; AVR, 67%; AVR + CABG, 59%; MVR +/- CABG, 57%; other, 48%; and total, 63%. Multivariate predictors of late death were renal insufficiency, postoperative stroke, chronic lung disease, and congestive heart failure. Eighty-seven percent of patients believed having a heart operation after age 80 years was a good choice. CONCLUSIONS Cardiac operations are successful in most octogenarians with increased hospital mortality, postoperative stroke, and longer hospital stay. Long-term survival is largely determined by concurrent medical diseases.

Surgical coronary revascularization in survivors of prehospital cardiac arrest: its effect on inducible ventricular arrhythmias and long-term survival.

In a selected subgroup of 50 survivors of cardiac arrest, the impact of surgical myocardial revascularization on inducible arrhythmias, arrhythmia recurrence and long-term survival was examined. The effects of several clinical, angiographic and electrophysiologic variables on arrhythmia recurrence and survival were also analyzed. All patients had a prehospital cardiac arrest and severe operable coronary artery disease and underwent myocardial revascularization. Preoperative electrophysiologic study was performed in 41 patients; 33 (80%) had inducible ventricular arrhythmias. Of 42 patients studied off antiarrhythmic drugs postoperatively, 19 (45%) had inducible ventricular arrhythmias. Thirty patients with inducible arrhythmias preoperatively underwent postoperative testing off antiarrhythmic drugs; arrhythmia induction was suppressed in 14 (47%). By multivariate analysis, the induction of ventricular fibrillation at the preoperative electrophysiologic study was the only significant predictor of induced ventricular arrhythmia suppression by coronary surgery (p less than 0.001). Inducible ventricular fibrillation was not present postoperatively in any of the 11 patients who manifested this arrhythmia preoperatively. In contrast, inducible ventricular tachycardia persisted in 80% of patients in whom preoperative testing induced this arrhythmia. Patients were followed up for 39 +/- 29 months. There were four arrhythmia recurrences; one was fatal. There were three nonsudden cardiac deaths and three noncardiac deaths. By life-table analysis, 5 year survival, cardiac survival and arrhythmia-free survival rates were 88%, 98%, and 88%, respectively. Depressed left ventricular ejection fraction and advanced age were predictive of death (p = 0.015 and 0.026, respectively) and cardiac death (p = 0.037 and 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of implantable cardioverter-defibrillators on the long-term prognosis of survivors of out-of-hospital cardiac arrest.

BACKGROUND Survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction are at high risk for recurrent cardiac arrest and sudden cardiac death. The impact of the implantable cardioverter-defibrillator on long-term prognosis in these patients is uncertain. METHODS AND RESULTS Three hundred thirty-one survivors of out-of-hospital cardiac arrest (age, 56 +/- 13.7 years) underwent electrophysiologically guided therapy. Implantable defibrillators were placed in 150 patients (45.3%), and 181 patients (54.7%) received pharmacological and/or surgical therapy alone. Left ventricular ejection fraction was 35.2 +/- 16.6% in defibrillator recipients and 45.3 +/- 18.2% in nondefibrillator patients. Median patient follow-up was 24 months in the defibrillator group and 46 months in the nondefibrillator group. In a proportional hazards model, the independent predictors of total cardiac mortality were left ventricular ejection fraction of less than 0.40 (relative risk, 4.55; 95% confidence interval, 2.44 to 8.33; P = .0001), absence of an implantable defibrillator (relative risk, 2.70; confidence interval, 1.41 to 5.00; P = .017), and persistence of inducible sustained ventricular tachycardia (relative risk, 1.84; 95% confidence interval, 0.97 to 3.49; P = .045). The 1- and 5-year probabilities of survival free of cardiac mortality in patients with left ventricular ejection fraction of less than 0.40 were 94.3% and 69.6% with a defibrillator and 82.1% and 45.3% without a defibrillator, respectively. For patients with left ventricular ejection fraction of 0.40 or more, the 1- and 5-year probabilities of survival free of cardiac mortality were 97.7% and 94.6% with a defibrillator and 95.4% and 86.9% without a defibrillator, respectively. CONCLUSIONS In survivors of out-of-hospital cardiac arrest, the implantable defibrillator is associated with a reduction in cardiac mortality, particularly in patients with impaired left ventricular function.

Papillary Muscle Displacement Causes Systolic Anterior Motion of the Mitral Valve Experimental Validation and Insights Into the Mechanism of Subaortic Obstruction

BACKGROUND Systolic anterior motion (SAM) of the mitral valve in hypertrophic cardiomyopathy (HCM) has generally been explained by a Venturi effect related to septal hypertrophy, causing outflow tract narrowing and high velocities. Patients with HCM, however, also have primary abnormalities of the mitral apparatus, including anterior and inward or central displacement of the papillary muscles, and leaflet elongation. These findings have led to the hypothesis that changes in the mitral apparatus can be a primary cause of SAM by altering the forces acting on the mitral valve and its ability to move in response to them. Despite suggestive observations, however, it has never been prospectively demonstrated that such changes can actually cause SAM. METHODS AND RESULTS To test this hypothesis in vivo, anterior papillary muscle displacement was created in 7 dogs studied by echocardiography, with controlled cardiac output and heart rate. In all 7 dogs, papillary muscle displacement caused SAM, with an outflow tract gradient (33 +/- 19 mm Hg) and mitral regurgitation in 6. As in patients with HCM, the mitral valve was displaced anteriorly and the coaptation point shifted toward the insertion of the leaflets, creating longer distal residual leaflets that moved anteriorly. CONCLUSIONS Primary changes in the mitral apparatus can cause SAM without septal hypertrophy. In this model, SAM appears to be determined by the ability of the leaflets to move anteriorly (papillary muscle displacement causing slack and increased residual leaflet length) and their interposition into the outflow stream by anterior displacement, determining the direction of this motion. Geometric factors observed in HCM and in patients with SAM without HCM can therefore play a primary role in causing SAM.