Importance of time to reperfusion for 30-day and late survival and recovery of left ventricular function after primary angioplasty for acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the importance of time to reperfusion for outcomes after primary angioplasty for acute myocardial infarction. BACKGROUND: Survival benefit of thrombolytic therapy for acute myocardial infarction is strongly dependent on time to treatment. Recent observations suggest that time to treatment may be less important for survival with primary angioplasty. METHODS: Consecutive patients (n=1,352) with acute myocardial infarction treated with primary angioplasty were followed for up to 13 years. Paired acute and follow-up ejection fraction data were obtained at cardiac catheterization in 606 patients. RESULTS: Reperfusion was achieved within 2 h in 164 patients (12%). Thirty-day mortality was lowest with early reperfusion (4.3% at <2 h vs. 9.2% at > or = 2 h, p=0.04) and was relatively independent of time to reperfusion after 2 h (9.0% at 2 to 4 h, 9.3% at 4 to 6 h, 9.5% at >6 h). Thirty-day-plus late cardiac mortality was also lowest with early reperfusion (9.1% at <2 h vs. 16.3% at > or = 2 h, p=0.02) and relatively independent at time to reperfusion after 2 h (16.4% at 2 to 4 h, 16.9% at 4 to 6 h, 15.6% at >6 h). Improvement in left ventricular ejection fraction was greatest in the early reperfusion group and relatively modest after 2 h (6.9% at <2 h vs. 3.1% at > or =2 h, p=0.007). CONCLUSIONS: Time to reperfusion, up to 2 h, is important for survival and recovery of left ventricular function. After 2 h, recovery of left ventricular function is modest and survival is relatively independent of time to reperfusion. These data suggest that factors other than myocardial salvage may be responsible for survival benefit in patients treated with primary angioplasty after 2 h.

Drug interactions with grapefruit juice.

Some drugs demonstrate a significantly greater (up to 3-fold) mean oral bioavailability on coadministration with grapefruit juice. With some calcium antagonists, the benzodiazepines midazolam and triazolam and the antihistamine terfenadine, changes in bioavailability are accompanied by altered drug action. Study design factors possibly contribute to the magnitude of changes in drug bioavailability; they include the source of the citrus, its intake schedule, drug formulations and individual metabolising capacity. The components of citrus juice that are responsible for clinical drug interactions have yet to be fully determined. Based on the flavonoid naringin's unique distribution in the plant kingdom, abundance in grapefruit and ability to inhibit metabolic enzymes, naringin is likely to be one of the grapefruit components influencing drug metabolism. Other components present in citrus fruit, such as furanocoumarins, may be more potent inhibitors than flavonoids and are under investigation. Conclusions drawn from clinical drug interaction studies should be considered specific to the citrus fruit products evaluated because of the variation in their natural product content. The predominant mechanism for enhanced bioavailability is presumably the inhibition of oxidative drug metabolism in the small intestine. The consistent findings across studies of diverse cytochrome P450 (CYP) 3A substrates support the mechanistic hypothesis that 1 or more grapefruit juice components inhibit CYP3A enzymes in the gastrointestinal tract. The evaluation of the need to avoid the concomitant intake of grapefruit products with drugs is best done on an individual drug basis rather than collectively by drug class. Based on the narrow therapeutic range of cyclosporin and research experience in organ transplant recipients, its interaction with grapefruit juice is likely to be clinically significant.

Timing and mechanism of death determined clinically after primary angioplasty for acute myocardial infarction.

We reviewed the timing and mechanism of death in 1,184 consecutive patients with acute myocardial infarction (AMI) treated with primary angioplasty from 1984 to 1995. Of 98 deaths, 48 (49%) occurred early on day 0 or 1. The mechanisms of death were pump failure in 60 patients (61%), reinfarction in 7 patients (7.1%), left ventricular rupture in 5 patients (5.1%), arrhythmia in 3 patients (3.1%), other cardiac causes in 5 patients (5.1%), stroke in 6 patients (6.1%), anoxic encephalopathy in 7 patients (7.1%), and procedure-related deaths in 5 patients (5.1%). The strongest predictors of mortality were cardiogenic shock and unsuccessful reperfusion. Our data indicate that mortality after primary angioplasty, like thrombolytic therapy, is highest in the early hours and is usually due to pump failure. In contrast to thrombolytic therapy, the incidence of death from myocardial rupture and bleeding complications is low. Future treatment strategies will need to focus on the large number of patients with early death due to pump failure, especially patients with cardiogenic shock.

Importance of infarct-related artery patency for recovery of left ventricular function and late survival after primary angioplasty for acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the importance of late infarct-related artery patency for recovery of left ventricular function and late survival after primary angio-plasty for acute myocardial infarction. BACKGROUND: Infarct-related artery patency is thought to improve late survival by its effect on preservation of left ventricular function. Patency may also enhance late survival by preventing left ventricular dilation and reducing arrhythmias, independent of myocardial salvage. However, most studies have not shown patency to be an independent predictor of survival when late left ventricular function is taken into account. METHODS: We followed up 576 hospital survivors of acute myocardial infarction treated with primary angioplasty for 5.3 years. Ejection fraction and infarct-related artery patency were determined at follow-up catheterization at 6 months. Predictors of late cardiac survival were determined using Cox regression models. RESULTS: Patients with patent arteries had more improvement and a better late ejection fraction than patients with occluded arteries (56.3% vs. 47.9%, p = 0.001). In patients with acute ejection fraction < 45%, late survival was better in those with patent versus occluded arteries (89% vs. 44%, p = 0.003), but patency was not a significant predictor after improvement in ejection fraction was taken into account. In patients with a large anterior infarction, patency was a significant independent predictor of late survival. CONCLUSIONS: Infarct-related artery patency is important for recovery of left ventricular function, and in patients with acute ejection fraction < 45%, patency is important for late survival. Our data are consistent with the hypothesis that the survival benefit is due primarily to the effect of patency on recovery of left ventricular function. In patients with a large anterior infarction, patency appears to provide an additional late survival benefit independent of myocardial salvage. These observations support the need for additional clinical trials of late reperfusion in patients with a large anterior infarction.

Flavanone absorption after naringin, hesperidin, and citrus administration.

Disposition of citrus flavonoids was evaluated after single oral doses of pure compounds (500 mg naringin and 500 mg hesperidin) and after multiple doses of combined grapefruit juice and orange juice and of once-daily grapefruit. Cumulative urinary recovery indicated low bioavailability ( < 25%) of naringin and hesperidin. The aglycones naringenin and hesperitin were detected in urine and plasma by positive chemical ionization-collisionally activated dissociation tandem mass spectrometry (PCI-CAD MS/MS). After juice administration, PCI-CAD MS/MS detected naringenin, hesperitin, and four related flavanones, tentatively identified as monomethoxy and dimethoxy derivatives. These methoxyflavanones appear to be absorbed from juice. Absorbed citrus flavanones may undergo glucuronidation before urinary excretion.

Benefit of late coronary reperfusion in patients with acute myocardial infarction and persistent ischemic chest pain.

The benefit of thrombolytic therapy given late after the onset of acute myocardial infarction (AMI) has been controversial because of low reperfusion rates and limited myocardial salvage. Persistent chest pain has been used as a criteria for late intervention, but there is little documentation to validate this practice. Clinical outcomes and myocardial salvage were evaluated in 74 patients with AMI and persistent chest pain who underwent late reperfusion (> 6 hours) with direct coronary angioplasty, and these were compared with outcomes in 460 patients with early reperfusion (< or = 6 hours). Patients with late reperfusion had a high infarct artery patency rate (96%), a low hospital mortality rate (5.4%), and a low incidence of reinfarction (1.4%) and recurrent ischemia that were similar to patients with early reperfusion. Patients with late reperfusion had surprisingly good recovery of left ventricular function with improvement in ejection fraction from 50% to 60% at follow-up angiography. Patients with late reperfusion had a greater incidence of collateral flow (45% vs 22%, p < 0.001) and a lower value of peak creatine kinase (1,357 vs 2,057 U/liter, p < 0.001) than patients with early reperfusion. This study emphasizes the importance of persistent chest pain as a marker of continued myocardial viability in patients who present late after AMI. These data suggest that the probable mechanism of continued viability is preserved flow to the infarct zone. Patients with AMI and persistent chest pain may benefit from reperfusion therapy beyond 6 to 12 hours.

Six-month clinical and angiographic follow-up after direct angioplasty for acute myocardial infarction. Final results from the Primary Angioplasty Registry.

BACKGROUND: After direct angioplasty in the setting of acute myocardial infarction, patients were followed clinically and angiographically for 6 months at six experienced centers to evaluate outcomes. METHODS AND RESULTS: Of 258 patients with 6-month follow-up after surviving initial hospitalization, 5 (2%) died, 8 (3%) had nonfatal infarctions, 56 (22%) had chest pain, of whom 25 (10%) required hospitalization, and 42 (16%) patients needed repeat angioplasty. Of 203 eligible patients, 154 (76%) had angiographic follow-up. The infarct-related artery remained patent (defined as TIMI 2 or 3 flow) in 87%, while 13% developed reocclusion (TIMI 0 or 1 flow) by 6 months after discharge. Patients with reocclusion were more likely to have adverse events, including 35% with clinically evident reinfarction and 59% requiring repeat angioplasty. The median ejection fraction improvement from acute to follow-up study was 6%, with no improvement in patients with a reoccluded infarct-related artery and an 8% improvement in patients with a patent infarct-related artery. CONCLUSIONS: The positive clinical outcomes recorded immediately after direct angioplasty persisted through 6 months of follow-up. Although the incidence of clinical end points was equivalent to or lower than thrombolytic therapy trials, restenosis is a substantial problem. These findings provide evidence beyond the initial hospitalization that direct angioplasty is a reasonable choice for the treatment of acute myocardial infarction.

Importance of a patent infarct-related artery for hospital and late survival after direct coronary angioplasty for acute myocardial infarction.

The importance of a patent infarct-related artery (IRA) for hospital and late survival was examined in 383 patients with acute myocardial infarction treated with direct coronary angioplasty. At hospital discharge, 317 of 348 patients (91%) had a patent IRA and mean follow-up left ventricular (LV) ejection fraction (EF) was 58%. Cardiac survival after hospital discharge at 1, 3 and 6 years was 99, 95 and 90%. Patency of the IRA was the most important determinant of hospital mortality: patent versus occluded IRA, 5 vs 39% mortality, p less than 0.001. Follow-up LVEF was the most important determinant of late cardiac mortality: follow-up LVEF greater than or equal to 45 versus less than 45%, 2 versus 24% mortality, p less than 0.001. Patency of the IRA was not a significant predictor of late cardiac mortality in the group as a whole: patent versus occluded IRA, 4.7 versus 6.5% mortality, p = 0.67. In the subgroup of patients with depressed initial LVEF less than 45%, patency was a significant predictor of late cardiac mortality: patent versus occluded IRA, 9.2 versus 40% mortality, p = 0.03. Patients with a patent IRA had better recovery of LV function than patients with an occluded IRA (follow-up LVEF 58.5 versus 47.6%, p less than 0.001). When late cardiac mortality was adjusted for differences in follow-up LVEF, patency was no longer a significant predictor of late mortality. Our results indicate patency of the IRA is the most important determinant of hospital survival, and LV function (measured after recovery) is the most important determinant of late cardiac survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcomes of direct coronary angioplasty for acute myocardial infarction in candidates and non-candidates for thrombolytic therapy.

Coronary angioplasty without prior thrombolytic therapy was performed in 383 patients with acute myocardial infarction (AMI). Patients were divided into 2 groups depending on whether they were candidates or non-candidates for thrombolytic therapy. Patients were not considered thrombolytic candidates if they: (1) presented in cardiogenic shock, (2) were greater than or equal to 75 years of age, (3) had had coronary artery bypass surgery or, (4) had a reperfusion time of greater than 6 hours. Thrombolytic and nonthrombolytic candidates had similar rates of reperfusion (92 vs 88%), nonfatal reinfarction (6.0 vs 5.9%) and recurrent myocardial ischemia (1.8 vs 0%). Thrombolytic candidates had a lower mortality rate (3.9 vs 24%, p less than 0.0001) and a lower incidence of bleeding (4.6 vs 10.9%, p less than 0.05). Improvement in left ventricular ejection fraction at follow-up angiography was 4.4% in thrombolytic and 10.5% in nonthrombolytic candidates (p less than 0.002). Ejection fraction improved most in patients with anterior wall AMI (7.7% in thrombolytic candidates, 15.1% in nonthrombolytic candidates) and in patients with reperfusion times greater than 6 hours (14.2%). These outcomes suggest that direct coronary angioplasty is a viable alternative method of reperfusion in patients with AMI who are candidates for thrombolytic therapy. Nonthrombolytic candidates are a high-risk group of patients. Direct coronary angioplasty may be beneficial in certain subgroups, especially for patients in cardiogenic shock and for patients presenting greater than 6 hours after the onset of chest pain with evidence of ongoing ischemia.

Factors that predict improvement in left ventricular ejection fraction after coronary angioplasty for acute myocardial infarction.

Acute and follow-up angiograms were analyzed in 75 patients with acute myocardial infarction treated with emergency coronary angioplasty to determine factors that might predict improvement in left ventricular ejection fraction. Ejection fraction improved 8.4 +/- 8.2% in 60 patients who maintained patent infarct vessels at follow-up angiography, compared with -4.1 +/- 6.0% in 15 patients who developed reocclusion (p less than .001). In patients with patent infarct vessels, univariate analysis revealed the following significant predictors of improvement in ejection fraction: initial ejection fraction (r = -.38, p less than .003) subtotal vs total stenosis (12.9 +/- 9.3% vs 6.9 +/- 7.3%, p less than .02), infarct vessel (left anterior descending 11.0 +/- 8.4%, right 6.8 +/- 6.4%, circumflex 2.6 +/- 7.5%, p less than .02), and time to follow-up study (less than or equal to 15 days vs greater than 15 days) (4.8 +/- 5.8% vs 9.8 +/- 8.6%, p less than .03). Reperfusion time (less than or equal to 2 hr vs greater than 2 hr) predicted improvement when subtotal stenoses and stuttering infarctions were excluded (10.6 +/- 7.0% vs 4.9 +/- 6.9, p less than .03). Multivariate analysis showed initial ejection fraction and subtotal vs total stenosis to be independent predictors. Patients with anterior infarctions, low initial ejection fractions, and subtotal stenoses or reperfusion times less than or equal to 2 hr are likely to benefit most from coronary angioplasty for acute myocardial infarction.

Emergency coronary angioplasty for acute myocardial infarction. Results from a community hospital.

Emergency coronary angioplasty was performed in 127 patients presenting to a community hospital with acute myocardial infarction. Reperfusion and successful dilatation were performed in 117 patients (92%) at 3.3 +/- 1.8 hours from the onset of pain. Eleven patients (8.6%) died, ten patients (7.9%) developed reocclusion, and ten patients (7.9%) required coronary bypass surgery during the initial hospitalization. Late restenosis occurred in 36% (27/76) of patients restudied or 27% (27/100) of patients at risk for restenosis. Ejection fraction improved in patients with patent vs occluded vessels (8.4% +/- 8.2% vs -4.1% +/- 6.0%) and improved most in anterior vs inferior vs posterolateral infarcts (11.0% +/- 8.4% vs 6.8% +/- 6.4% vs 2.6% +/- 7.5%). Posthospitalization follow-up in all patients (mean, 13.4 months) revealed only one late death. Of the patients followed up, 83% had no angina, and 17% of patients had mild angina. Our experience demonstrates that coronary angioplasty for acute myocardial infarction can be performed in the community hospital by an experienced cardiovascular laboratory team with a high success rate, a low reocclusion rate, an improvement in ejection fraction, and an excellent long-term prognosis. The community hospital setting allows early access to patients and creates the potential for early reperfusion and myocardial salvage.

Successful medical therapy for endocarditis due to Candida parapsilosis. A clinical and epidemiologic study.

A heroin addict with asymmetric septal hypertrophy and persistent fungemia with Candida parapsilosis was treated with amphotericin B and flucytosine (5-fluorocytosine). The diagnosis of endocarditis was based on the subsequent development of a murmur of mitral regurgitation and echocardiographic evidence of prolapse of the posterior leaflet of the mitral valve. Cure was effected with antifungal therapy alone. Thus, when the diagnosis of fungal endocarditis is made early in its course, open-heart surgery may not be needed. To investigate the relative frequency of isolation of C parapsilosis from particular sites, a mycologic survey was conducted in our hospital. Among the isolates of yeasts, C parapsilosis represented 8.0, 17.1, and 26.7 percent of those from all cultured sites, from contaminated intravenous catheters, and from cultures of blood, respectively. Since this trend to cluster in cases of fungemia was not seen with other yeasts, C parapsilosis appears to be more invasive than other species of Candida.