Costantino O. Costantini

Prospective, Multicenter Study of the Safety and Feasibility of Primary Stenting in Acute Myocardial Infarction: In-Hospital and 30-Day Results of the PAMI Stent Pilot Trial

Abstract Objectives. The goals of this study were to examine the safety and feasibility of a routine (primary) stent strategy in acute myocardial infarction (AMI). Background. Limitations of reperfusion by primary percutaneous transluminal coronary angioplasty (PTCA) in AMI include in-hospital recurrent ischemia or reinfarction in 10% to 15% of patients, restenosis in 37% to 49% and late infarct-related artery reocclusion in 9% to 14%. By lowering the residual stenosis and sealing dissection planes created by PTCA, primary stenting may further improve short- and long-term outcomes after mechanical reperfusion. Methods. Three hundred twelve consecutive patients treated with primary PTCA for AMI at nine international centers were prospectively enrolled. After PTCA, stenting was attempted in all eligible lesions (vessel size 3.0 to 4.0 mm; lesion length ≤2 stents; and the absence of giant thrombus burden after PTCA, major side branch jeopardy or excessive proximal tortuosity or calcification). Patients with stents were treated with aspirin, ticlopidine and a 60-h tapering heparin regimen. Results. Stenting was attempted in 240 (77%) of 312 patients, successfully in 236 (98%), with Thrombolysis in Myocardial Infarction grade 3 flow restored in 230 patients (96%). Patients with stents had low rates of in-hospital death (0.8%), reinfarction (1.7%), recurrent ischemia (3.8%) and predischarge target vessel revascularization for ischemia (1.3%). At 30-day follow-up, no additional deaths or reinfarctions occurred among patients with stents, and target vessel revascularization was required in only one additional patient (0.4%). Conclusions. Primary stenting is safe and feasible in the majority of patients with AMI and results in excellent short-term outcomes.

A prospective, randomized evaluation of prophylactic intraaortic balloon counterpulsation in high risk patients with acute myocardial infarction treated with primary angioplasty

OBJECTIVES A large, international, multicenter, prospective, randomized trial was performed to determine the role of prophylactic intraaortic balloon pump (IABP) counterpulsation after primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI). BACKGROUND Previous studies have suggested that routine IABP use after primary PTCA reduces infarct-related artery reocclusion, augments myocardial recovery and improves clinical outcomes. METHODS Cardiac catheterization was performed in 1,100 patients within 12 h of onset of AMI at 34 clinical centers. Clinical and angiographic variables were used to stratify patients undergoing primary PTCA into high and low risk groups. High risk patients were then randomized to 36 to 48 h of IABP (n = 211) or traditional care (n = 226). The study had 80% power to detect a reduction in the primary end point from 30% to 20%. RESULTS There was no significant difference in the predefined primary combined end point of death, reinfarction, infarct-related artery reocclusion, stroke or new-onset heart failure or sustained hypotension in patients treated with an IABP versus those treated conservatively (28.9% vs. 29.2%, p = 0.95). The IABP strategy conferred modest benefits in reduction of recurrent ischemia (13.3% vs. 19.6%, p = 0.08) and subsequent unscheduled repeat catheterization (7.6% vs. 13.3%, p = 0.05) but did not reduce the rate of infarct-related artery reocclusion (6.7% vs. 5.5%, p = 0.64), reinfarction (6.2% vs. 8.0%, p = 0.46) or mortality (4.3% vs. 3.1%) and was associated with a higher incidence of stroke (2.4% vs. 0%, p = 0.03). IABP use did not result in enhanced myocardial recovery as assessed by paired admission to predischarge and 6-week rest and exercise left ventricular ejection fraction. CONCLUSIONS In contrast to previous studies, a prophylactic IABP strategy after primary PTCA in hemodynamically stable high risk patients with AMI does not decrease the rates of infarct-related artery reocclusion or reinfarction, promote myocardial recovery or improve overall clinical outcome.

Impact of delay to angioplasty in patients with acute coronary syndromes undergoing invasive management: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial.

OBJECTIVES The aim of this study was to determine the impact of delay to angioplasty in patients with acute coronary syndromes (ACS). BACKGROUND There is a paucity of data on the impact of delays to percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) undergoing an invasive management strategy. METHODS Patients undergoing PCI in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial were stratified according to timing of PCI after clinical presentation for outcome analysis. RESULTS Percutaneous coronary intervention was performed in 7,749 patients (median age 63 years; 73% male) with NSTE-ACS at a median of 19.5 h after presentation (<8 h [n=2,197], 8 to 24 h [n=2,740], and >24 h [n=2,812]). Delay to PCI>24 h after clinical presentation was significantly associated with increased 30-day mortality, myocardial infarction (MI), and composite ischemia (death, MI, and unplanned revascularization). By multivariable analysis, delay to PCI of >24 h was a significant independent predictor of 30-day and 1-year mortality. The incremental risk of death attributable to PCI delay>24 h was greatest in those patients presenting with high-risk features. CONCLUSIONS In this large-scale study, delaying revascularization with PCI>24 h in patients with NSTE-ACS was an independent predictor of early and late mortality and adverse ischemic outcomes. These findings suggest that urgent angiography and triage to revascularization should be a priority in NSTE-ACS patients.

Coronary venous retroperfusion support during high risk angioplasty in patients with unstable angina: Preliminary experience

Synchronized coronary venous retroperfusion was used during coronary balloon angioplasty to support the ischemic myocardium of 20 patients with unstable angina and anatomy at high risk of a coronary event. Hemodynamics and left ventricular function were the major end points of the study. Coronary venous catheterization and retroperfusion were successfully performed in 15 patients. The target vessel was an unprotected left main artery in 2, left anterior descending artery in 10, left circumflex coronary artery in 1 and right coronary artery in 2 patients. A nonsupported balloon inflation (mean 44 +/- 13 s) was compared with a later retroperfusion-supported inflation (mean 145 +/- 21 s). Right anterior oblique left ventriculograms, aortic blood pressure, pulmonary artery pressure and thermodilution cardiac output were obtained before and during peak untreated and treated balloon inflations and on completion of angioplasty. All patients had either a baseline left ventricular ejection fraction less than 0.40 or greater than 40% of contracting myocardium estimated to be at risk for severe ischemia during angioplasty. The cardiac (liters/min per m2) and stroke work (g.m/m2) indexes decreased from mean baseline values of 2.5 +/- 0.52 and 52 +/- 15 to 1.7 +/- 0.47 and 27 +/- 12 (mean +/- SD), respectively, during nonsupported balloon inflations but decreased only to 2.1 +/- 0.52 (p less than 0.01 vs. nonsupported) and to 36 +/- 14 (p = 0.01 vs. nonsupported), respectively, during retroperfusion-supported inflations. Ejection fraction (n = 8) decreased from a baseline value of 55 +/- 13% to 27 +/- 7.3% during nonsupported inflations but only to 39 +/- 10% during retroperfusion-supported inflations (p = 0.01 vs. nonsupported). Regional wall motion (area change) in the ischemic (target) region was reduced from a baseline value of 49 +/- 17% to 11 +/- 16% during nonsupported inflations but only to 27 +/- 15% during retroperfusion-supported inflations (p less than 0.01 vs. nonsupported). All but two patients had a favorable hemodynamic response to retroperfusion. There were no serious adverse effects related to the procedures and no hospital deaths. It is concluded from this preliminary study that coronary venous retroperfusion appears to be safe, to provide hemodynamic support and to improve left ventricular function during angioplasty in patients with unstable angina and anatomy at high risk of a coronary event.

Prevalence and prognostic impact of diastolic dysfunction in patients with chronic kidney disease on hemodialysis

FUNDAMENTO: Disfuncao diastolica e frequente em pacientes de hemodialise, mas seu impacto na evolucao clinica e incerto. OBJETIVO: Avaliar a prevalencia e o impacto prognostico da disfuncao diastolica (DD) avancada (DDA) do ventriculo esquerdo (VE) em pacientes de hemodialise. METODOS: Ecocardiogramas foram realizados em pacientes no primeiro ano de hemodialise, em ritmo sinusal, sem doenca cardiovascular manifestada, excluindo-se aqueles com valvopatia significativa ou derrame pericardico. Pela avaliacao integrada dos dados ecodopplercardiograficos, a funcao diastolica foi classificada como: 1) normal, 2) DD discreta (alteracao do relaxamento) e 3) DDA (pseudonormalizacao e fluxo restritivo). Os desfechos pesquisados foram mortalidade geral e eventos cardiovasculares. RESULTADOS: Foram incluidos 129 pacientes (78 homens), com idade 52 ± 16 anos e prevalencia de DD de 73% (50% com DD discreta e 23% com DDA). No grupo com DDA, demonstrou-se maior idade (p < 0,01), pressao arterial sistolica (p < 0,01) e diastolica (p = 0,043), massa do VE (p < 0,01), indice do volume do atrio esquerdo (p < 0,01) e proporcao de diabeticos (p = 0,019), alem de menor fracao de ejecao (p < 0,01). Apos 17 ± 7 meses, a mortalidade geral foi significativamente maior naqueles com DDA, em comparacao aos normais e com DD discreta (p = 0,012, log rank test). Na analise multivariada de Cox, a DDA foi preditiva de eventos cardiovasculares (hazard ratio 2,2, intervalo de confianca 1,1-4,3, p = 0,021) apos ajuste para idade, genero, diabete, massa do VE e fracao de ejecao. CONCLUSAO: A DDA subclinica foi encontrada em aproximadamente um quarto dos pacientes de hemodialise e acarretou impacto prognostico, independente de outros dados clinicos e ecocardiograficos.BACKGROUND Diastolic dysfunction (DD) is frequent in patients on hemodialysis (HD), but its impact on the clinical evolution is yet to be established. OBJECTIVE To evaluate the prevalence and prognostic impact of left ventricular (LV) advanced diastolic dysfunction (ADD) in patients on hemodialysis. METHODS The echocardiograms were performed during the first year of HD therapy, in patients with sinus rhythm, with no evidence of cardiovascular disease, excluding those with significant valvopathy or pericardial effusion. The combined assessment of the Doppler echocardiographic data classified the diastolic dysfunction as: 1) normal diastolic function; 2) mild DD (relaxation alteration) and 3) ADD (pseudonormalization and restrictive flow pattern). The assessed outcomes were general mortality and cardiovascular events. RESULTS A total of 129 patients (78 males), aged 52 +/- 16 years, with a DD prevalence of 73% (50% with mild DD and 23% with ADD) were included in the study. The group with ADD was older (p < 0.01) and presented higher systolic (p < 0.01) and diastolic BP (p = 0.043), LV mass (p < 0.01), left atrial volume index (p < 0.01) and number of diabetic patients (p = 0.019), as well as lower ejection fraction (EF) (p < 0.01). After 17 +/- 7 months, the general mortality was significantly higher in individuals with ADD, when compared to those with normal function and mild DD (p = 0.012, log rank test). At Cox multivariate analysis, ADD was predictive of cardiovascular events (hazard ratio 2.2; confidence interval: 1.1-4.3; p = 0.021) after adjusted for age, gender, diabetes, LV mass and EF. CONCLUSION The subclinical ADD was identified in approximately 25% of the patients undergoing hemodialysis and had a prognostic impact, regardless of other clinical and echocardiographic data.

Prevalência e impacto prognóstico da disfunção diastólica na doença renal crônica em hemodiálise

FUNDAMENTO: Disfuncao diastolica e frequente em pacientes de hemodialise, mas seu impacto na evolucao clinica e incerto. OBJETIVO: Avaliar a prevalencia e o impacto prognostico da disfuncao diastolica (DD) avancada (DDA) do ventriculo esquerdo (VE) em pacientes de hemodialise. METODOS: Ecocardiogramas foram realizados em pacientes no primeiro ano de hemodialise, em ritmo sinusal, sem doenca cardiovascular manifestada, excluindo-se aqueles com valvopatia significativa ou derrame pericardico. Pela avaliacao integrada dos dados ecodopplercardiograficos, a funcao diastolica foi classificada como: 1) normal, 2) DD discreta (alteracao do relaxamento) e 3) DDA (pseudonormalizacao e fluxo restritivo). Os desfechos pesquisados foram mortalidade geral e eventos cardiovasculares. RESULTADOS: Foram incluidos 129 pacientes (78 homens), com idade 52 ± 16 anos e prevalencia de DD de 73% (50% com DD discreta e 23% com DDA). No grupo com DDA, demonstrou-se maior idade (p < 0,01), pressao arterial sistolica (p < 0,01) e diastolica (p = 0,043), massa do VE (p < 0,01), indice do volume do atrio esquerdo (p < 0,01) e proporcao de diabeticos (p = 0,019), alem de menor fracao de ejecao (p < 0,01). Apos 17 ± 7 meses, a mortalidade geral foi significativamente maior naqueles com DDA, em comparacao aos normais e com DD discreta (p = 0,012, log rank test). Na analise multivariada de Cox, a DDA foi preditiva de eventos cardiovasculares (hazard ratio 2,2, intervalo de confianca 1,1-4,3, p = 0,021) apos ajuste para idade, genero, diabete, massa do VE e fracao de ejecao. CONCLUSAO: A DDA subclinica foi encontrada em aproximadamente um quarto dos pacientes de hemodialise e acarretou impacto prognostico, independente de outros dados clinicos e ecocardiograficos.BACKGROUND Diastolic dysfunction (DD) is frequent in patients on hemodialysis (HD), but its impact on the clinical evolution is yet to be established. OBJECTIVE To evaluate the prevalence and prognostic impact of left ventricular (LV) advanced diastolic dysfunction (ADD) in patients on hemodialysis. METHODS The echocardiograms were performed during the first year of HD therapy, in patients with sinus rhythm, with no evidence of cardiovascular disease, excluding those with significant valvopathy or pericardial effusion. The combined assessment of the Doppler echocardiographic data classified the diastolic dysfunction as: 1) normal diastolic function; 2) mild DD (relaxation alteration) and 3) ADD (pseudonormalization and restrictive flow pattern). The assessed outcomes were general mortality and cardiovascular events. RESULTS A total of 129 patients (78 males), aged 52 +/- 16 years, with a DD prevalence of 73% (50% with mild DD and 23% with ADD) were included in the study. The group with ADD was older (p < 0.01) and presented higher systolic (p < 0.01) and diastolic BP (p = 0.043), LV mass (p < 0.01), left atrial volume index (p < 0.01) and number of diabetic patients (p = 0.019), as well as lower ejection fraction (EF) (p < 0.01). After 17 +/- 7 months, the general mortality was significantly higher in individuals with ADD, when compared to those with normal function and mild DD (p = 0.012, log rank test). At Cox multivariate analysis, ADD was predictive of cardiovascular events (hazard ratio 2.2; confidence interval: 1.1-4.3; p = 0.021) after adjusted for age, gender, diabetes, LV mass and EF. CONCLUSION The subclinical ADD was identified in approximately 25% of the patients undergoing hemodialysis and had a prognostic impact, regardless of other clinical and echocardiographic data.

901-1 A Prospective, Randomized Trial Evaluating Early Discharge (Day 3) without Non-invasive Risk Stratification in Low Risk Patients with Acute Myocardial Infarction: PAMI-2

Few data exist regarding the need for noninvasive testing after reperfusion therapy in myocardial patients at low clinical risk. Moreover, after thrombolysis, recurrent ischemia occurs frequently and unpredictably and has resulted in physician reluctance to shorten the length of hospitalization in these patients. Alternatively, emergency catheterization with primary PTCA may provide acute determination of risk status, a stable method of reperfusion and the potential for early discharge. The objective of this multicenter study was to prospectively test the hypothesis that early discharge (day 3) without noninvasive risk stratification in low risk MI patients treated with primary angioplasty is safe, feasible, and cost effective. Patients with acute myocardial infarction 0–12 hrs who had an emergency catheterization and immediate PTCA of the infarct related artery were stratified into a low risk group if age ≤70 yrs, 1 or 2 vessel disease, EF g 45%, successful infarct vessel PTCA and no malignant arrhythmias persisted after the PTCA. Low risk patients were randomized to admission to either the intensive care unit (with hospitalization a minimum of 5 days and predischarge exercise testing) or admission to a non-intensive care PTCA unit with no non-invasive testing and discharge on day 3. To date, 340 of the anticipated 400 patients have been enrolled. The mean age was 56 ± 9, estimated ejection fraction 56 ± 9 and 74% had single vessel disease. As expected, in-hospital complications occurred infrequently; death 1.1%, recurrent MI 1.7%; stroke 0.6%; heart failure 4.6%. At 1 week follow-up, no complications attributed to early discharge have occurred. Thus, acute catheterization does allow identification of low risk MI patients who can be safely admitted to an elective PTCA unit and discharged in 3 days without additional testing. Complete data on the 400 patient cohort including cost and 6 week follow-up will be available by March 1995.

Intravascular brachytherapy for native coronary ostial in-stent restenotic lesions.

OBJECTIVES We analyzed the effects of vascular brachytherapy (VBT) on ostial in-stent restenosis (ISR). BACKGROUND In-stent restenosis has a high recurrence rate after percutaneous reintervention. The recurrence rate of ostial ISR lesions and the impact of VBT remain unknown. METHODS We evaluated 133 patients with native coronary ostial ISR from a pooled database of 990 patients enrolled in randomized VBT trials. Independent quantitative angiography was performed at baseline and follow-up in 45 gamma, 27 beta, and 61 placebo patients. RESULTS Binary restenosis was significantly higher in placebo than radiated patients (75.4% vs. 17.8% in gamma vs. 22.2% in beta, p < 0.0001). The treatment effect of both gamma (odds ratio [OR] 0.06; 95% confidence interval [CI] 0.02 to 0.17) and beta VBT (OR 0.10; 95% CI 0.03 to 0.31) was maintained after controlling for differences in baseline lesion length. Proximal and distal radiation edge restenosis rates were similar among the groups. Vascular brachytherapy of true aorto-ostial lesions (n = 34) was similarly beneficial: restenosis rates of placebo versus gamma or beta patients of 83.3% versus 6.7% versus 28.6%, p = 0.0002. CONCLUSIONS Conventional treatment of ostial ISR is associated with a recurrence rate of over 75%. Vascular brachytherapy with either gamma or beta sources results in significant and similar reductions in restenosis compared with placebo. Similar benefits after VBT prevail in true aorto-ostial lesions.

A comparative analysis of primary stenting and optimal balloon coronary angioplasty in acute myocardial infarction. Six month results from the STENT PAMI trial

OBJECTIVE To compare the outcome of balloon PTCA with final coronary stenosis diameter (SD) < or =30 %, with elective coronary stenting. METHODS We performed a comparative analysis of the 6 month outcomes in patients treated with primary stenting and those who obtained an optimal balloon PTCA result treated during the first 12 hours of AMI onset included in the STENT PAMI randomized trial. RESULTS The results were analysed into 3 groups: primary stenting (441 patients, SD=22+/-6 %), optimal PTCA (245 patients), and non-optimal PTCA (182 patients, SD= 37+/-5 %). At the end of the 6 months primary stent group presented with the lowest restenosis(23 vs. 31 vs. 45 %, p=0.001, respectively). Ischemia-driven target vessel revascularization rate (TVR) (7 vs. 15.5 vs. 19 %, p=0.001, respectively). CONCLUSION At the 6 month follow-up, primary stenting offered the lowest restenosis and ischemia-driven TVR rates. Compared to optimal balloon PTCA. Non-optimal primary balloon PTCA pts (SD=31-50 %), had the worst late angiographic outcomes and should be treated more actively with coronary stent implantation.

Associação entre marcadores de inflamação e aumento do átrio esquerdo em pacientes de hemodiálise

BACKGROUND In individuals with concurrent chronic kidney disease (CKD) and cardiovascular disease (CVD), the association between left atrial volume (LAV) and serum levels of C-reactive protein (CRP) is shown. OBJECTIVE Verify the presence of associations between systemic inflammation and LA dilation in patients on hemodialysis (HD) without clinically evident CVD. METHODS This was an observational cross-sectional study of a population on HD (> 3 months), which excluded patients with acute or chronic inflammatory diseases (infections, malignancies, autoimmune diseases) hemodynamic instability, use of anti-inflammatory drugs, hyperparathyroidism, arrhythmias, mitral valve disease and prior cardiovascular (CV) events. CRP and interleukin-6 (IL-6) measurements as well as Doppler echocardiography were obtained. Correlation coefficients were determined to evaluate the associations between variables. RESULTS A total of 58 patients were included (28 men, aged 55 ± 15 years), on HD for 24 ± 16 months, 45% were hypertensive, 26% diabetic, with median CRP of 5.1 mg/dL and IL-6 of 6.1 pg/dL. CRP significantly correlated with LAV (p = 0.040), LAV index (LAVi, p = 0.02) and mitral inflow E wave (p = 0.014). IL-6, despite the strong association with CRP levels (r = 0.75, p < 0.001), did not correlate with echocardiographic indices. Individuals in the top quartile of CRP had significantly higher LAVi than the others (42 ± 17 versus 32 ± 11 mL/m², p = 0.015). CONCLUSIONS In subjects on HD with no prior CV event, there was an association between elevated CRP levels and LA enlargement. The findings suggest an association between physiopathological processes related to left atrial dilation and systemic inflammatory state of patients on HD.