Malignant tumours of the heart: a review of tumour type, diagnosis and therapy.

Primary cardiac neoplasms are rare and occur less commonly than metastatic disease of the heart. In this overview, current published studies concerning malignant neoplasms of the heart are reviewed, together with some insights into their aetiology, diagnosis and management. We searched medline using the subject 'cardiac neoplasms'. We selected about 110 articles from between 1973 and 2006, of which 76 sources were used to complete the review. Sarcomas are the most common cardiac tumours and include myxosarcoma, liposarcoma, angiosarcoma, fibrosarcoma, leiomyosarcoma, osteosarcoma, synovial sarcoma, rhabdomyosarcoma, neurofibrosarcoma, malignant fibrous histiocytoma and undifferentiated sarcoma. The classic symptoms of cardiac tumours are intracardiac obstruction, signs of systemic embolisation, and systemic or constitutional symptoms. However, serious complications including stroke, myocardial infarction and even sudden death from arrhythmia may be the first signs of a tumour. Echocardiography and angiography are essential diagnostic tools for evaluating cardiac neoplasms. Computed tomography and magnetic resonance imaging studies have improved the diagnostic approach in recent decades. Successful treatment for benign cardiac tumours is usually achieved by surgical resection. Unfortunately, resection of the tumour is not always feasible. The prognosis after surgery is usually excellent in the case of benign tumours, but the prognosis of malignant tumours remains dismal. In conclusion, there are limited published data concerning cardiac neoplasms. Therefore, a high level of suspicion is required for early diagnosis. Surgery is the cornerstone of therapy. However, a multi-treatment approach, including chemotherapy, radiation as well as evolving approaches such as gene therapy, might provide a better palliative and curative result.

Pathological effects of alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

BACKGROUND: The pathological effects and the mechanisms of action of intracoronary administration of ethanol for alcohol septal ablation (ASA) for the management of hypertrophic obstructive cardiomyopathy (HOCM) are unknown. METHODS: We examined surgical specimens and, in one case, autopsy specimens from four patients who underwent surgical septal myectomy 2 days to 14 months after unsuccessful ASA. RESULTS: Pathological examination early after ASA showed coagulative necrosis of both the myocardium and the septal perforator arteries. Affected arteries were distended and occluded by necrotic intraluminal debris, without platelet-fibrin thrombi. Late after unsuccessful ASA, excised septal tissue was heterogeneous, containing a region of dense scar, and adjacent tissue containing viable myocytes and interspersed scar. CONCLUSIONS: Intracoronary administration of ethanol in patients with HOCM causes acute myocardial infarction with vascular necrosis. The coagulative necrosis of the arteries, their distension by necrotic debris and the absence of platelet-fibrin thrombi distinguish ethanol-induced infarction from that caused by atherosclerotic coronary artery disease. The direct vascular toxicity of ethanol may be an important aspect of the mechanism of successful ASA.

Elevated troponin I level with hemoglobin based oxygen carrying solutions (HBOCs) as a priming solution despite improved left ventricular function.

Stroma free hemoglobin based oxygen-carrying solutions (HBOCs) have been shown to have the capability to transport oxygen, suggesting their use as a temporary blood substitute to maintain oxygenation of tissue. HBOCs might be the proper priming solution; however, elevated troponin associated with their application might be a major concern, particularly in patients with damaged myocardium. This study was performed in mongrel dogs (n=14). The animals underwent cardiac arrest with cardioplegic solution and aortic clamping using cardiopulmonary bypass (CPB). HBOC was used as a priming solution for CPB in the study group, and Lactated Ringer's in the control group. The extreme hemodilution in the study group was achieved by replacing more than 80% of the animal's blood with HBOC. A right heart bypass was performed to control the cardiac output. The hemodynamic parameters were measured with increasing cardiac output before and after CPB. At a cardiac output of 2500 ml/min, LAP (19+/-9 mmHg vs. 8.7+/-1.3 mmHg in the HBOCs group) and LVEDP (22+/-16 mmHg in the control group vs. 11+/-2.8 mmHg in the HBOC group) were significantly higher in control animals. The overall coronary sinus flow did not show any significant difference between both groups. The PO2 in the HBOCs group was slightly higher (534+/-10 mmHg vs. 494+/-71 mmHg) at 30 min after removal of aortic clamp compared to PO2 in control group. Post-ischemic troponin I level was increased in both groups, however, it was significantly higher in HBOCs group (49.64+/-48.58 ng/ml) compared to its level in control group (28.33+/-17.2 ng/ml). After the priming was completed and CPB was initiated, the hematocrit in the study group was 5.37+/-3.7% compared to 15+/-3.3% in the control group. However, the hemoglobin (Hb) in the study group remained higher throughout the experiment compared to control group, 8.34+/-1.55 g/dl vs. 5.37+/-1.04 g/dl, respectively. HBOC based priming permits cardiopulmonary bypass at a very low hematocrit with a better preservation of myocardium and adequate oxygen supply. However, elevated troponin I at the postischemic phase is a serious concern and its significance needs to be addressed before broad clinical application of HBOC.

Right ventricular performance during left ventricular unloading conditions: the contribution of the right ventricular free wall.

AIM: Right ventricular (RV) dysfunction is a significant complication following implantation of left ventricular assist device (LVAD). However, RV performance after LVAD implantation remains unclear. We have studied the effects of preload and afterload on RV performance under left ventricular (LV) unloading. METHODS: Six adult mongrel dogs were subjected to cardiopulmonary bypass. RV preload and afterload were independently regulated. Dynamic pressure-length analysis of RV free walls was performed using micromanometer catheter and sonomicrometric dimension transducers. Global RV systolic function was evaluated by the relationship between stroke volume vs. end-diastolic length (EDL) or end-diastolic pressure (EDP). We also examined the afterload dependency of RV performance at constant stroke volume. RESULTS: Stroke volume vs. EDP and stroke volume vs. EDL demonstrated a linear relationship (r(2) = 0.849 +/- 0.147 and 0.776 +/- 0.121, respectively). At constant stroke volume, RV systolic peak pressure vs. EDL or EDP were shown to have a linear relationship (r(2) = 0.906 +/- 0.050 vs. 0.909 +/- 0.047, respectively). CONCLUSION: The Frank-Starling relationship for RV performance was shown in this animal model. Without interventricular interaction, RV preload is dependent on RV afterload.

Long-term infection rates associated with the pectoral versus abdominal approach to cardioverter- defibrillator implants.

Infection is an uncommon (0% to 6.7%) but serious complication after implantable cardioverter-defibrillator (ICD) implantation. All ICD primary implants, replacements, or revisions performed at the Massachusetts General Hospital between April 1983 and May 1999 were reviewed. A total of 21 ICD-related infections (1.2%) were identified among 1,700 procedures affecting 1.8% of the 1,170 patients who underwent a primary implant, a generator change, or a revision of their systems. The mean follow-up time was 35 +/- 33 months. Of the 959 patients with long-term follow-up, 19 of the 584 patients (3.2%) with abdominal and 2 of the 375 patients (0.5%) with pectoral systems developed ICD-related infections (p = 0.03). There was no significant difference between the infection rate among the 959 primary ICD implants and the 447 replacements or system revisions. Only 5 of the patients (24%) had systemic signs of infection, including fever (T>100.5) and elevated white blood count >12,000. Cultures from the wound revealed staphylococcal species in 16 patients (76%). Nineteen patients were treated with removal of the entire ICD system in addition to intravenous antibiotics for 2 to 4 weeks. A decrease in the incidence of ICD-related infection has occurred since the advent of transvenous pectoral systems. The main organism responsible for ICD infection is Staphylococcus. The mainstay of ICD infection management consists of complete removal of the entire implanted system.

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.

Outcome following isolated tricuspid valve replacement.

OBJECTIVES: The clinical outcome of isolated tricuspid valve replacement is not well defined because this procedure is usually performed concomitantly with other valve surgery. METHODS: We retrospectively studied the short and long-term outcome of 15 consecutive patients (six men and nine women, aged 61+/-3 years) undergoing isolated tricuspid valve replacement from 1984 to 1996. The cause of valve dysfunction was rheumatic heart disease in 12 patients, healed endocarditis in two patients, and sarcoidosis in one patient. The tricuspid valve was stenotic in one patient, regurgitant in eight patients, and both stenotic and regurgitant in six patients. A St. Jude Medical prosthesis was placed in eight patients, Carpentier-Edwards in five patients, and Björk-Shiley and Starr-Edwards in one patient each. RESULTS: The median survival was only 1.2 years. Three patients (20%) died < or =30 days after the surgery or before discharge, and six other patients (40%) died within 3 years of surgery. Anasarca was the only predictor of short-term mortality (P=0.03), while the predictors of long-term mortality were anemia (P=0.01), rheumatic heart disease (P=0.04), previous stroke (P=0.04), and previous mitral valve surgery (P=0.04). CONCLUSIONS: Isolated tricuspid valve replacement is characterized by a poor short and long-term outcome.

Long-term results and determinants of mortality after surgery for native and prosthetic valve endocarditis.

BACKGROUND AND AIM OF THE STUDY: The study aim was to describe the long-term results and determinants of mortality after operative treatment of native and prosthetic valve endocarditis at a single institution. METHODS: Between March 1985 and October 1999, 171 patients underwent surgery for native (NVE) or prosthetic valve endocarditis (PVE). NVE was present in 98 patients (57%), and PVE in 73 patients (43%). Mean follow up was 5.6+/-3.9 years (range: 0 to 15 years). RESULTS: Overall hospital mortality was 9.9% (n = 17). Hospital mortality was higher among patients with PVE (15.1%) than those with NVE (6.1%; p = 0.05). Overall survival at 10 years was 46+/-5%. Patients with NVE had a higher 10-year survival rate (53+/-7%) than those with PVE (37+/-7%; p = 0.02). At 10 years, overall freedom from any late complication was 47+/-6% and from residual or recurrent endocarditis was 78+/-5%. Predictors of hospital death were emergency surgery (p <0.003) and preoperative renal insufficiency (p <0.008). Predictors of late death were age >70 years (p <0.002), renal failure (p <0.03) and fungal endocarditis (p <0.04). CONCLUSION: These findings demonstrate the increased perioperative, as well as postoperative, risks associated with PVE versus NVE. Cardiac and extracardiac manifestations of the disease, as well as fungal organisms, but not the activity of the endocarditis, were significant adverse determinants of late outcome.

Myocardial perfusion and right ventricular function.

OBJECTIVE: Maximal right ventricular (RV) performance is influenced by left heart hemodynamics and hence coronary perfusion. We examined the role of myocardial perfusion of the right ventricle as potential determinant of maximal RV function. MATERIALS AND METHODS: In 6 canine isovolumic right heart preparations, incremental volumes were introduced into a high compliance RV balloon until RV failure occurred. Maximal RV developed pressure (RVDP) and maximal positive RV dP/dt were determined at a constant controlled left ventricular (LV) output of 2 l/min and at controlled mean arterial pressures of 50, 80 and 120 mmHg. Right coronary artery (RCA) flow was measured. RESULTS: Maximal RVDP increased significantly with increasing mean arterial pressures (44.8+/-11.2 vs 57.2+/-15.5 vs 75.4+/-2.5 mmHg for systemic pressures of 50, 80 and 120 mmHg respectively, p < 0. 05). With increasing mean arterial pressures RCA flow increased significantly (33.1+/-11.0 vs 46.1+/-20.4 vs 79.6+/-35.3 ml/min). At the onset of RV failure, RCA blood flow significantly decreased in all preparations compared to the maximal flow in the RCA (1.9+/-1.0 vs 33.1+/-11.0 ml/min at 50 mmHg; 13.6+/-10.2 vs 46.1+/-20.4 ml at 80 mmHg and 18.7+/-8.0 vs 79.6+/-35.3 ml/min at 120 mmHg; p < 0.05). CONCLUSIONS: These results suggest that coronary perfusion is a major determinant of maximal RV function. The coronary artery driving pressure must be sufficient to avoid the onset of RV failure. Maintaining systemic pressure and hence RV myocardial blood flow may thus extend RV function.

Effect of cardiopulmonary bypass and calcium administration on the splanchnic circulation.

Gastrointestinal complications following cardiopulmonary bypass (CPB) are associated with high mortality rates. The identification of prolonged CPB time and calcium administration as independent predictors of gastrointestinal complications suggests decreased splanchnic perfusion as a possible mechanism. To test this hypothesis, we evaluated splanchnic organ perfusion during CPB and after calcium chloride administration. Mongrel dogs were studied under anesthesia and were cannulated for bypass. CPB was begun at 37 degrees C, and the heart was fibrillated and vented. After 30 min, CPB temperature was reduced to 25 degrees C for 1 h with the heart arrested through cold crystalloid cardioplegia. After rewarming to 37 degrees C for 30 min, the heart was cardioverted, and CPB was weaned off. Calcium chloride (10 mg/kg) or saline was administered. Organ blood flow was determined with radiolabeled microspheres at baseline, during CPB, and after weaning from CPB. Splanchnic organ blood flow did not decrease during any phase of CPB. Calcium chloride administration after CPB had no effect on splanchnic organ blood flow. While gastrointestinal injury may result from CPB, this study suggests that the mechanism of injury is not decreased by splanchnic organ perfusion during bypass. While calcium chloride can cause pancreatic injury, the responsible mechanism is not calcium-induced hypoperfusion.

Contribution of the interventricular septum to maximal right ventricular function.

OBJECTIVE: Maximal right ventricular (RV) function is influenced by left heart hemodynamics, possibly mediated by the interventricular scpturn (IVS). We examined the potential contribution of the IVS function to right heart function. METHODS: In 12 canine isovolumic right heart preparations, incremental volumes were introduced into a high compliance RV balloon until RV failure occurred. Maximal RV developed pressure (RVDP) and maximal positive RV dP/dt were determined with a working IVS at a constant left ventricular (LV) output of 2 l/min and at a constant mean arterial pressure of 80 mmHg. Thereafter the IVS was thermally inactivated, and measurements were repeated using the same protocol. RESULTS: At constant arterial pressure and constant LV output, thermal inactivation of the IVS led to a significant decrease in maximal RVDP (inactivated vs. working IVS: 36.1+/-9.8 vs. 56.8+/-16.2 mmHg, respectively, P < 0.001), and RV dP/dt (inactivated vs. working IVS: 720+/-220 vs. 1350+/-190 mmHg/s, respectively, P < 0.001). CONCLUSIONS: These results suggest that the functional status of the IVS is a major determinant of maximal RV function. At constant LV conditions and arterial pressure, an inactivated IVS leads to a significant decrease in maximal RVDP and RV dP/dt under the conditions of this study.

Repeat aortic root replacement.

BACKGROUND: Aortic root replacement in patients who have undergone previous aortic root replacement presents a formidable technical challenge, which may lead to increased surgical mortality. METHODS: We reviewed our experience from January 1989 through November 1995. Seven consecutive patients (6 men and 1 woman) underwent eight repeat aortic root replacements. Mean follow-up was 19 months. Previous root replacement had been performed with homograft in 1 patient, with a bioprosthetic valve composite graft in 1 patient, and with a mechanical valve composite graft in 6 patients. The techniques used at the previous procedures were the Cabrol technique (2 patients), Bentall technique (3 patients), and the coronary button technique (3 patients). Reoperation was indicated for pseudoaneurysm formation in 4 patients and for endocarditis in the others. RESULTS: Aortic homografts were implanted in all patients with endocarditis and mechanical valve composite grafts were used in the others. In all reoperations, the coronary button technique was used. No procedures were done emergently. Concomitant procedures were performed in 2 patients, including mitral valve replacement and aortic arch aneurysm repair. One patient had recurrence of his endocarditis 36 months after operation because of continued intravenous drug use requiring a second successful homograft root replacement. There were no early deaths and one late death at 16 months after operation. CONCLUSIONS: Repeat aortic root replacement, even in the setting of endocarditis, can be done with low mortality.

Risk of reoperative valve replacement for failed mitral and aortic bioprostheses.

BACKGROUND: One factor influencing the choice of mechanical versus bioprosthetic valves is reoperation for bioprosthetic valve failure. To define its operative risk, we reviewed our results with valve reoperation for bioprosthetic valve failure. METHODS: Records of 400 consecutive patients having reoperative mitral, aortic, or mitral and aortic bioprosthetic valve replacement from January 1985 to March 1997 were reviewed. RESULTS: Reoperations were for failed bioprosthetic mitral valves in 219 patients, failed aortic valves in 153 patients, and failed aortic and mitral valves in 28 patients. Including 26 operations (6%) for acute endocarditis, 153 operations (38%) were nonelective. One hundred nine patients (27%) had other valves repaired or replaced, and 72 (18%) had coronary bypass grafting. The incidence of death in the mitral, aortic, and double-valve groups was respectively, 15 (6.8%), 12 (7.8%), and 4 (14.3%); and the incidence of prolonged postoperative hospital stay (>14 days) was, respectively, 57 (26.0%), 41 (26.8%), and 8 (28.6%). Only 7 of 147 patients (4.8%) having elective, isolated, first-time valve reoperation died. Multivariable predictors (p < 0.05) of hospital death were age greater than 65 years, male sex, renal insufficiency, and nonelective operation; and predictors of prolonged stay were acute endocarditis, renal insufficiency, any concurrent cardiac operation, and elevated pulmonary artery systolic pressure. CONCLUSIONS: Reoperative bioprosthetic valve replacement can be performed with acceptable mortality and hospital stay. The best results are achieved with elective valve replacement, without concurrent cardiac procedures.

Hemoglobin based oxygen carrying solution stability in extracorporeal circulation: an in vitro evaluation and implications for clinical use.

This study evaluated the stability of a hemoglobin based oxygen carrying (HBOC) solution during extracorporeal circulation. HBOC solution was diluted 1:1 with normal saline, 2 L of the resulting solution was oxygenated in either a bubble oxygenator (n=5) or membrane oxygenator (n=5), and it was placed in extracorporeal circulation at a rate of 2 L/min for 5 hr at 37 degrees C. To assess the effect of added human blood, 500 ml of fresh human whole blood was added to 1.5 L of diluted HBOC solution, and circulated as described. Methemoglobin level, hemoglobin integrity (percent of HBOC solution tetramer), and oxygen affinity (PO2 at 50% hemoglobin saturation) were measured. Extracorporeal circulation using the bubble oxygenator slightly altered (<1%) hemoglobin integrity compared with controls. Oxygen affinity decreased during extracorporeal circulation with both the membrane and bubble oxygenators; there was no significant difference between the oxygenators. Methemoglobin formation in controls and in extracorporeal circulation with either oxygenator was significant, with a slight advantage of the membrane compared with the bubble oxygenator; however, the presence of blood significantly decreased the rate of methemoglobin formation. In the presence of blood, HBOC solution remains structurally stable and efficacious for oxygen delivery during extracorporeal circulation.

Slide tracheoplasty for long-segment tracheal stenosis.

OBJECTIVE: To introduce a novel surgical technique for the repair of congenital long-segment tracheal stenosis. DESIGN: Retrospective case series. SETTING: Tertiary-care hospital. PATIENTS: Three children ranging in age from 3 months to 3 years, all with complete tracheal rings, the stenotic segments representing between 36% and 49% of the total tracheal length. One patient had an anomalous right upper lobe bronchus and an associated pulmonary artery sling. INTERVENTION: Slide tracheoplasty reconstruction. MAIN OUTCOME MEASURE(S): Postoperative clinical status as evidenced by day and site of extubation, duration of hospitalization, number of bronchoscopic examinations performed before discharge, and subsequent need for urgent bronchoscopic examinations, which reflects the adequacy of the reconstructed airway. RESULTS: Two patients were extubated on the day of surgery, 1 intraoperatively; the child with the pulmonary artery sling required 3 days of elective intubation for postoperative ventilatory support. The duration of hospitalization ranged from 8 to 10 days. All patients underwent elective bronchoscopy once before discharge; none had granuloma formation. Follow-up ranged from 1 to 4 1/2 years. One patient required a single urgent bronchoscopic examination in addition to planned surveillance endoscopy. Growth of the reconstructed hemitracheal rings is demonstrable. CONCLUSIONS: Slide tracheoplasty achieves successful tracheal reconstruction using the patient's own tracheal tissues. Advantages of this method include the potential avoidance of cardiopulmonary bypass, immediate or early postoperative extubation, and the near-complete absence of granulation tissue formation. The latter obviates the need for multiple postoperative bronchoscopic examinations, as has been reported in tracheoplasty procedures using either costal cartilage or pericardium.

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.

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.