Joseph G. Murphy

Restenosis and the proportional neointimal response to coronary artery injury: Results in a porcine model☆

Restenosis is a reparative response to arterial injury occurring with percutaneous coronary revascularization. However, the quantitative characteristics of the relation between vessel injury and the magnitude of restenotic response remain unknown. This study was thus performed to determine the relation between severity of vessel wall injury and the thickness of resulting neointimal proliferation in a porcine model of coronary restenosis. Twenty-six porcine coronary artery segments in 24 pigs were subjected to deep arterial injury with use of overexpanded, percutaneously delivered tantalum wire coils. The vessels were studied microscopically 4 weeks after coil implantation to measure the relation between the extent of injury and the resulting neointimal thickness. For each wire site, a histopathologic score proportional to injury depth and the neointimal thicknesses at that site were determined. Mean injury scores were compared with both mean neointimal thickness and planimetry-derived area percent lumen stenosis. The severity of vessel injury strongly correlated with neointimal thickness and percent diameter stenosis (p less than 0.001). Neointimal proliferation resulting from a given wire was related to injury severity in adjacent wires, suggesting an interaction among effects at injured sites. If the results in this model apply to human coronary arteries, restenosis may depend on the degree of vessel injury sustained during angioplasty.

Long-Term Outcome in Patients Undergoing Surgical Repair of Tetralogy of Fallot

BACKGROUND Although corrective surgery for tetralogy of Fallot has been available for more than 30 years, the occurrence of late sudden death in patients in whom surgery was apparently successful remains worrisome. METHODS We studied long-term survival among 163 patients who survived 30 days after complete repair of tetralogy of Fallot, examining follow-up hospital records and death certificates when relevant. RESULTS The overall 32-year actuarial survival rate among all patients who survived surgery was 86 percent, as compared with an expected rate of 96 percent in a control population matched for age and sex (P < 0.01). Thirty-year actuarial survival rates were calculated for the patient subgroups. The survival rates among patients less than 5 years old, 5 to 7 years old, and 8 to 11 years old were 90, 93, and 91 percent, respectively--slightly less than the expected rates (P < 0.001, P = 0.06, and P = 0.02). Among patients 12 years old or older at the time of surgery, the survival rate was 76 percent, as compared with an expected rate of 93 percent (P < 0.001). The performance of a palliative Blalock-Taussig shunt procedure before repair, unlike the performance of a Waterston or Potts shunt procedure, was not associated with reduced long-term survival, nor was the need for a trans-annular patch at the time of surgery. Independent predictors of long-term survival were older age at operation (P = 0.02) and a higher ratio of right ventricular to left ventricular systolic pressure after surgery (P = 0.008). Late sudden death from cardiac causes occurred in 10 patients during the 32-year period. CONCLUSIONS Among patients with surgically repaired tetralogy of Fallot, the rate of long-term survival after the postoperative period is excellent but remains lower than that in the general population. The risk of late sudden death is small.

Long-term outcome after surgical repair of isolated atrial septal defect : follow-up at 27 to 32 years

BACKGROUND Atrial septal defects have been surgically correctable for more than 30 years. The long-term survival rates among patients treated in the early era of cardiac surgery are poorly documented, but such data are of critical importance to the future medical care, employability, and insurability of these patients. METHODS To determine the natural history of surgically corrected atrial septal defects, we studied all 123 patients who underwent repair of an isolated defect (ostium secundum or sinus venosus) at the Mayo Clinic between 1956 and 1960, 27 to 32 years after the procedure. The follow-up status of all patients was determined by written questionnaires and telephone interviews. Hospital records and death certificates were obtained if interim hospitalization or death had occurred. RESULTS The overall 30-year actuarial survival rate among survivors of the perioperative period was 74 percent, as compared with 85 percent among controls matched for age and sex. The perioperative mortality was 3.3 percent (four deaths). Actuarial 27-year survival rates among patients in the younger two quartiles according to age at operation (less than or equal to 11 years and 12 to 24 years) were no different from rates among controls--97 percent and 93 percent, respectively. In the two older quartiles (25 to 41 years and greater than 41 years), 27-year survival rates were significantly less (P less than 0.001)--84 percent and 40 percent, respectively--than in controls (91 and 59 percent). Independent predictors of long-term survival according to multivariate analysis were age at operation (P less than 0.0001) and systolic pressure in the main pulmonary artery before operation (P less than 0.0027). When repair was performed in older patients, late cardiac failure, stroke, and atrial fibrillation were significantly more frequent. CONCLUSIONS Among patients with surgically repaired atrial septal defects, those operated on before the age of 25 have an excellent prognosis, but older patients require careful, regular supervision.

Restenosis after balloon angioplasty. A practical proliferative model in porcine coronary arteries.

A model of proliferative human restenosis was developed in domestic pigs by using deep injury to the coronary arterial media. Metal wire coils were delivered percutaneously to the coronary arteries of 11 pigs with an oversized, high-pressure (14 atm) balloon and were left in place for times ranging from 28 to 70 days. During placement, the balloon expanded the coils and delivered them securely within the arterial lumen. Light microscopic examination of the vessels confirmed fracture of the internal elastic lamina by the coil. An extensive proliferative response occurred in 10 of the 11 pigs and was associated with a luminal area narrowing of at least 50% in all but one pig. The histopathologic features of the proliferative response were identical to those observed in human cases of restenosis after angioplasty. Immunohistochemical studies confirmed the prominence of smooth muscle cells in the proliferative tissue. A similar response was obtained in two of five porcine coronary arteries in which balloon inflation only was performed, without coil implant. This model is practical and inexpensive and closely mimics the proliferative portion of human restenosis both grossly and microscopically. Thus, it may be useful for understanding human restenosis and for testing therapies aimed at preventing restenosis after balloon angioplasty or other coronary interventional procedures.

Emboli in Infective Endocarditis: The Prognostic Value of Echocardiography

OBJECTIVE To determine whether vegetations visualized on two-dimensional echocardiography are an independent risk factor for the development of subsequent emboli in patients with infective endocarditis and to assess the timing of emboli relative to the initiation of antimicrobial therapy. DESIGN Investigator-blinded, retrospective incidence cohort study. SETTING Tertiary referral center. PATIENTS Patients with left-sided native valve infective endocarditis who had two-dimensional echocardiography within 72 hours of beginning antimicrobial therapy. MEASUREMENTS AND MAIN RESULTS The crude incidence rate of first embolic events in patients receiving antimicrobial therapy was 6.2 per 1000 patient-days (95% CI, 4.2 to 9.2). The rates in patients with and without vegetations were 7.1 and 4.9 per 1000 patient-days, respectively (incidence rate ratio, 1.4; 95% CI, 0.6 to 3.3). The relation between vegetations and risk for emboli was microorganism-dependent: Stratified incidence rate ratios were 6.9 (95% CI, 1.1 to 42.5; P less than 0.05) and 1.0 (95% CI, 0.2 to 3.9) for viridans streptococcal and Staphylococcus aureus endocarditis, respectively. The rate of first embolic events diminished over time (P less than 0.001), falling from 13 per 1000 patient-days during the first week of therapy to less than 1.2 per 1000 patient-days after completion of the second week of therapy. CONCLUSIONS Overall, the presence of vegetations on echocardiography was not associated with a significantly higher risk for embolus in patients with left-sided native valve infective endocarditis. The relative risk for embolic events associated with echocardiographically visualized vegetations may be microorganism-dependent, with a significantly increased risk seen only in patients with viridans streptococcal infection. The rate of embolic events declines with time after initiation of antimicrobial treatment.

Five-year prospective study of the incidence and prognosis of peripartum cardiomyopathy at a single institution.

OBJECTIVE To determine the incidence and prognosis of peripartum cardiomyopathy (PPCM) in rural Haiti. PATIENTS AND METHODS Prospectively identified patients with PPCM treated at the Hospital Albert Schweitzer (HAS), Deschapelles, Haiti, were included in this study. Patients who presented to HAS from February 1, 2000, to January 31, 2005, were identified through a search of the HAS PPCM Registry. Clinical and serial echocardiographic data were collected on these patients. RESULTS The 5-year experience confirms the high incidence of PPCM in this area, approximately 1 case per 300 live births, which is severalfold the estimated incidence in the United States (estimated 1 case per 3000 to 4000 live births). In this population, the ratio of PPCM deaths for the 5-year period was 47.1 per 100,000 births compared with the US ratio of 0.62 per 100,000 births. The mortality rate was 15.3% (15 deaths of 98 patients), and the mean follow-up was 2.2 years (range, 1 month to 5 years). Five years after the initiation of the HAS PPCM Registry search, 26 (28%) of 92 patients with PPCM observed for at least 6 months had regained normal left ventricular function. The difference in left ventricular echocardiographic features at diagnosis between deceased patients and survivors was not statistically significant: mean end-diastolic dimension (6.2 vs 5.8 cm; P=.08), ejection fraction (22% vs 25%; P=.12), and fractional shortening (16% vs 15%; P=.46). Left ventricular echocardiographic features at diagnosis were unable to predict individually who would eventually recover, although a statistically significant difference occurred at diagnosis between the recovered group and nonrecovered group for mean ejection fraction (28% vs 23%; P<.001) and fractional shortening (17% vs 14%; P=.004). CONCLUSION Peripartum cardiomyopathy occurs significantly more commonly in rural Haiti on a per capita basis than in the United States. Patients with PPCM have a higher mortality rate and a poorer return of normal ventricular function.

Percutaneous polymeric stents in porcine coronary arteries. Initial experience with polyethylene terephthalate stents.

BackgroundTo test the feasibility of percutaneous deployment of intracoronary polymeric stents, a prototype polyethylene terephthalate (PET) stent and a catheter-based delivery system were developed. Methods and ResultsPolymeric stents were deployed in the coronary arteries of 11 Yucatan swine: six stents were placed in the left anterior descending coronary artery, four stents were placed in the circumflex artery, and one stent was placed in the right coronary artery. Stent deployment was achieved by withdrawal of an outer delivery sheath, thus allowing the PET stent to self-expand to a preformed configuration. Two animals died during surgery, one during stent placement and the other several hours after implantation due to intracoronary thrombus formation. Two animals were electively sacrificed within 24 hours of stent implant to examine the adequacy of stent deployment within the coronary vessel. The remaining seven animals survived until the termination of the study 4–6 weeks later. Light microscopic examination of the stented vessels showed an extensive neointimal proliferative response with vessel occlusion in all animals who survived initial stent placement. There were two distinct types of histological responses to the PET stent–a chronic foreign body inflammatory response around the stent tines and a neointimal proliferative response in the center of the occluded vessel lumen. The histological response seen in the central area of the vessel was morphologically similar to that seen in patients with restenosis after successful percutaneous transluminal coronary angioplasty, whereas the morphological response seen at the periphery of the stent tine was similar to that exhibited by a chronic foreign body reaction and was not typical of that seen in a restenosis lesion. A ventricular aneurysm also developed in the area of myocardium that was previously supplied by the occluded vessel. ConclusionsThis study demonstrates that percutaneous deployment of polymeric stents in the coronary arteries is technically feasible. The use of PET polymer was associated with an intense proliferative neointimal response that resulted in complete vessel occlusion. Histological examination of the stented segments of the vessel revealed no evidence that dissection of the vessel wall had occurred at the time of initial stent deployment. Although the PET polymer was of similar quality to that used in the manufacture of balloon angioplasty catheters, a toxic chemical or contaminant effect cannot be completely excluded as the stimulus to intimal proliferation. This finding may have relevance to the selection of materials for use as intravascular devices.

Restenosis, reocclusion and adverse cardiovascular events after successful balloon angioplasty of occluded versus nonoccluded coronary arteries: Results from the multicenter american research trial with cilazapril after angioplasty to prevent transluminal coronary obstruction and restenosis (MARCATOR)

OBJECTIVES This study sought to compare the frequency of restenosis, reocclusion and adverse cardiovascular events after angioplasty of occluded versus nonoccluded coronary arteries. BACKGROUND Angioplasty of chronically occluded coronary arteries is believed to be associated with a higher frequency of restenosis and reocclusion than angioplasty of subtotal stenoses. Whether this leads to adverse cardiovascular events is unknown. METHODS The Multicenter American Research Trial With Cilazapril After Angioplasty to Prevent Restenosis (MARCATOR) was a placebo-controlled trial with angiographic follow-up to determine the effect of the angiotensin-converting enzyme inhibitor cilazapril on the frequency of restenosis. In this trial, restenosis was defined as 1) angiographic reduction of minimal lumen diameter > or = 0.72 mm between angioplasty and the follow-up visit; and 2) > 50% diameter stenosis on the follow-up angiogram. We identified 139 patients with successful angioplasty of a coronary occlusion (Group 1) and compared the frequency of restenosis, reocclusion and adverse cardiovascular events with that in 1,295 patients with successful angioplasty of a subtotal stenosis (Group 2). RESULTS Restenosis occurred in 36 patients with occluded arteries (29%) versus 264 with nonoccluded arteries (23%, p = 0.177) by definition 1 and in 62 patients with occluded arteries (49%) versus 478 with nonoccluded arteries (42%, p = 0.119) by definition 2. Occlusion was present in 24 Group 1 patients (19%) compared with 74 Group 2 patients (7%) (p < 0.001). During the 6 month follow-up period, two Group 1 patients (1.4%) and six Group 2 patients (0.5%) died; no Group 1 patients and 10 Group 2 patients (0.8%) developed severe congestive heart failure; nonfatal myocardial infarction occurred in 4 Group 1 patients (2.9%) and 31 Group 2 patients (2.4%); repeat coronary angioplasty or bypass surgery was performed in 29 Group 1 patients (21%) and 232 Group 2 patients (18%); and angina was present in 18 Group 1 and 163 Group 2 patients (13% for both). Eighty-six Group 1 patients (62%) and 853 Group 2 patients (66%) remained free of these adverse events during the 6-month follow-up period (p = 0.513). CONCLUSIONS The frequency of restenosis was slightly but not significantly greater after successful angioplasty of an occluded artery than after angioplasty of a subtotal stenosis. Although reocclusion was more frequent, occurring in 19% of patients, the net clinical benefit of angioplasty in such patients was similar to that in patients with subtotal stenoses over the 6-month follow-up period.

Acute impairment of regional myocardial glucose uptake in the apical ballooning (takotsubo) syndrome

BACKGROUND Apical ballooning syndrome (ABS) is a poorly understood clinical entity characterized by acute, transient systolic dysfunction of the left ventricular (LV) apex in the absence of epicardial coronary artery disease and commonly associated with acute emotional stress. We report abnormal regional myocardial perfusion and glucose uptake in 4 consecutive ABS patients studied using positron emission tomography with 13N-ammonia and 18F-fluorodeoxyglucose within 72 hours of presentation with ABS. METHODS All patients were postmenopausal females, 3 of whom had a major recent life stress event. Coronary angiography revealed no or minimal obstructive epicardial coronary artery disease. All patients exhibited reduced glucose uptake in the mid-LV and apical myocardial segments, which was out of proportion to perfusion abnormalities in half of the cases. CONCLUSION In all 4 patients, affected regions subsequently recovered regional LV systolic function within 6 weeks.

Effect of concomitant or very early statin administration on in-hospital mortality and reinfarction in patients with acute myocardial infarction.

In a retrospective analysis, 66 patients identified as having received a statin drug within 24 hours of admission for acute myocardial infarction were matched 3:1 with a control group of 198 patients not treated with a statin agent. End points of in-hospital mortality and in-hospital reinfarction were significantly lower in the statin-treated group, pointing to a benefit from very early statin treatment in acute myocardial infarction.