RESUMO
Diagnosis of the ischemic power of epicardial stenosis with concomitant microvascular disease (MVD) is challenging during coronary interventions, especially under variable hemodynamic factors like heart rate (HR). The goal of this study is to assess the influence of variable HR and percent area stenosis (%AS) in the presence of MVD on pressure drop coefficient (CDP; ratio of transstenotic pressure drop to the distal dynamic pressure) and lesion flow coefficient (LFC; ratio of %AS to the CDP at the throat region). We hypothesize that CDP and LFC are independent of HR. %AS and MVD were created using angioplasty balloons and 90-µm microspheres, respectively. Simultaneous measurements of pressure drop (DP) and velocity were done in 11 Yorkshire pigs. Fractional flow reserve (FFR), CDP, and LFC were calculated for the groups HR < 120 and HR > 120 beats/min, %AS < 50 and %AS > 50, and additionally for DP < 14 and DP > 14 mmHg, and analyzed using regression and ANOVA analysis. Regression analysis showed independence between HR and the FFR, CDP, and LFC while it showed dependence between %AS and the FFR, CDP, and LFC. In the ANOVA analysis, for the HR < 120 beats/min and HR > 120 beats/min groups, the values of FFR (0.82 ± 0.02 and 0.82 ± 0.02), CDP (83.15 ± 26.19 and 98.62 ± 26.04), and LFC (0.16 ± 0.03 and 0.15 ± 0.03) were not significantly different (P > 0.05). However, for %AS < 50 and %AS > 50, the FFR (0.89 ± 0.02 and 0.75 ± 0.02), CDP (35.97 ± 25.79.10 and 143.80 ± 25.41), and LFC (0.09 ± 0.03 and 0.22 ± 0.03) were significantly different (P < 0.05). A similar trend was observed between the DP groups. Under MVD conditions, FFR, CDP, and LFC were not significantly influenced by changes in HR, while they can significantly distinguish %AS and DP groups.
Assuntos
Frequência Cardíaca/fisiologia , Hemodinâmica/fisiologia , Doenças Vasculares/fisiopatologia , Algoritmos , Análise de Variância , Animais , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Capilares/fisiopatologia , Cateterismo , Circulação Coronária/fisiologia , Interpretação Estatística de Dados , Determinação de Ponto Final , Microcirculação/fisiologia , Microesferas , Análise de Regressão , SuínosRESUMO
A limitation in the use of invasive coronary diagnostic indexes is that fluctuations in hemodynamic factors such as heart rate (HR), blood pressure, and contractility may alter resting or hyperemic flow measurements and may introduce uncertainties in the interpretation of these indexes. In this study, we focused on the effect of fluctuations in HR and area stenosis (AS) on diagnostic indexes. We hypothesized that the pressure drop coefficient (CDP(e), ratio of transstenotic pressure drop and distal dynamic pressure), lesion flow coefficient (LFC, square root of ratio of limiting value CDP and CDP at site of stenosis) derived from fluid dynamics principles, and fractional flow reserve (FFR, ratio of average distal and proximal pressures) are independent of HR and can significantly differentiate between the severity of stenosis. Cardiac catheterization was performed on 11 Yorkshire pigs. Simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual sensor-tipped guidewire for HR < 120 and HR > 120 beats/min, in the presence of epicardial coronary lesions of <50% AS and >50% AS. The mean values of FFR, CDP(e), and LFC were significantly different (P < 0.05) for lesions of <50% AS and >50% AS (0.88 ± 0.04, 0.76 ± 0.04; 62 ± 30, 151 ± 35, and 0.10 ± 0.02 and 0.16 ± 0.01, respectively). The mean values of FFR and CDP(e) were not significantly different (P > 0.05) for variable HR conditions of HR < 120 and HR > 120 beats/min (FFR, 0.81 ± 0.04 and 0.82 ± 0.04; and CDP(e), 95 ± 33 and 118 ± 36). The mean values of LFC do somewhat vary with HR (0.14 ± 0.01 and 0.12 ± 0.02). In conclusion, fluctuations in HR have no significant influence on the measured values of CDP(e) and FFR but have a marginal influence on the measured values of LFC. However, all three parameters can significantly differentiate between stenosis severities. These results suggest that the diagnostic parameters can be potentially used in a better assessment of coronary stenosis severity under a clinical setting.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Coronária/fisiologia , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Frequência Cardíaca/fisiologia , Análise de Variância , Animais , Pressão Sanguínea/fisiologia , Cateterismo Cardíaco , Angiografia Coronária , Modelos Animais de Doenças , Hemodinâmica , SuínosRESUMO
BACKGROUND: Experimental studies suggest that the cardioprotective effects of the late phase of ischemic preconditioning (PC) can be mimicked pharmacologically. However, to date, no drug has been tested with respect to its ability to elicit a late PC effect in humans. As a consequence, clinical exploitation of the powerful anti-stunning and anti-infarct actions of late PC has been elusive thus far. METHODS AND RESULTS: A total of 66 patients were randomized to receive a 4-hour intravenous infusion of nitroglycerin (NTG) or normal saline; on the following day, they underwent percutaneous transluminal coronary angioplasty (three 2-minute balloon inflations 5 minutes apart). Measurements of ST-segment shifts (intracoronary and surface ECGs), regional wall motion (quantitative 2D echocardiography), and chest pain score indicated that the infusion of NTG 24 hours before angioplasty rendered the myocardium relatively resistant to ischemia and that the degree of this cardioprotective effect was comparable to that afforded by the ischemia associated with the first balloon inflation in control subjects (early phase of ischemic PC). Collateral flow (estimated from a pressure-derived index) did not differ between control and NTG-pretreated patients, indicating that the enhanced tolerance to ischemia in NTG-pretreated patients cannot be accounted for by baseline differences in collateral function. CONCLUSIONS: NTG protects human myocardium against ischemia 24 hours after its administration. To the best of our knowledge, this is the first report that a late PC effect can be recruited pharmacologically in humans. The results suggest that prophylactic administration of nitrates could be a novel approach to the protection of the ischemic myocardium in patients.
Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/terapia , Precondicionamento Isquêmico Miocárdico/métodos , Nitroglicerina/administração & dosagem , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Dor no Peito/tratamento farmacológico , Circulação Colateral/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Doença das Coronárias/diagnóstico , Ecocardiografia , Eletrocardiografia/efeitos dos fármacos , Testes de Função Cardíaca/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Intravenosas , Infarto do Miocárdio/prevenção & controle , Miocárdio Atordoado/prevenção & controle , Método Simples-Cego , Resultado do Tratamento , Vasodilatadores/administração & dosagem , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
OBJECTIVES: The purpose of this study was to determine whether administration of bradykinin reproduces the cardioprotective effects of ischemic preconditioning (PC) in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Experimental studies suggest that activation of the bradykinin B2 receptor is an important trigger of ischemic PC. However, it is unknown whether bradykinin can precondition human myocardium against ischemia in vivo. Multicenter clinical trials have demonstrated an anti-ischemic effect of angiotensin-converting enzyme inhibitors, which has been postulated to result from potentiation of bradykinin; however, direct evidence for an anti-ischemic action of bradykinin in patients is lacking. METHODS: Thirty patients were randomized to receive a 10-min intracoronary infusion of bradykinin (2.5 microg/min) or normal saline. Ten minutes later they underwent PTCA (three 2-min balloon inflations 5 min apart). RESULTS: In control patients, the ST-segment shift on the intracoronary and surface electrocardiogram was significantly greater during the first inflation than during the second and third inflations, consistent with ischemic PC. In bradykinin-treated patients, the ST-segment shift during the first inflation was significantly smaller than in the control group, and there were no appreciable differences in ST-segment shift during the three inflations. Measurements of chest pain score and regional wall motion during inflation (quantitative two-dimensional echocardiography) paralleled those of ST-segment shift. Infusion of bradykinin had no hemodynamic effects and no significant adverse effects. Thus, intracoronary infusion of bradykinin before PTCA rendered the myocardium relatively resistant to subsequent ischemia, and the degree of this cardioprotective effect was comparable to that afforded by the ischemia associated with the first balloon inflation in control subjects. In a separate cohort of seven patients given the same dose of bradykinin, coronary hyperemia resolved completely within 10 min after the end of the infusion, indicating that bradykinin-induced vasodilation cannot account for the protective effects observed during the first balloon inflation. CONCLUSIONS: Bradykinin preconditions human myocardium against ischemia in vivo in the absence of systemic hemodynamic changes. Pretreatment with bradykinin appears to be just as effective as ischemic PC and could be used prophylactically to attenuate ischemia in selected patients undergoing PTCA.
Assuntos
Angioplastia Coronária com Balão/métodos , Bradicinina/administração & dosagem , Precondicionamento Isquêmico Miocárdico/métodos , Adulto , Idoso , Análise de Variância , Angina Instável/diagnóstico , Angina Instável/fisiopatologia , Angina Instável/terapia , Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/estatística & dados numéricos , Circulação Colateral , Circulação Coronária , Eletrocardiografia/métodos , Eletrocardiografia/estatística & dados numéricos , Feminino , Humanos , Precondicionamento Isquêmico Miocárdico/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Fatores de TempoRESUMO
OBJECTIVES: The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. BACKGROUND: Reperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects. METHODS: The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6+/-1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke). RESULTS: In all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16%; odds ratio, 1.43; 95% confidence interval, 0.71 to 2.89). CONCLUSIONS: Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.
Assuntos
Adenosina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica , Vasodilatadores/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Estudos Prospectivos , Radiografia , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do TratamentoRESUMO
Intracoronary ultrasound is used to define plaque morphology and quantitative characteristics before and after coronary angioplasty. The cost of the technique was defined in 87 patients who underwent elective, noncomplex procedures: group A was composed of 37 patients without intracoronary ultrasound, who served as a control group; group B comprised 23 patients who had only postcoronary angioplasty ultrasound; and group C was 27 patients who had pre-and postangioplasty ultrasound. Economic analysis was done for the hospital ("bottom-up" methodology of equipment, supplies, support personnel, post-PTCA room) and physician costs (using resource-based relative value scale). The cost in the cardiac catheterization laboratory was: group A = $3,679 +/- $688; group B = $4,650 +/- $457; and group C = $5,301 +/- $835, p < 0.0001. The postprocedure cost for all groups was similar. The total cost was: group A = $5,326 +/- $1,135; group B = $6,815 +/- $1,276; and group C = $7,240 +/- $1,494, p < 0.0001. Intracoronary ultrasound modified the coronary angioplasty procedure in 36% of patients. Precoronary angioplasty intracoronary ultrasound defined the luminal diameter, precluding the use of additional balloons, and thus decreased the cost approximately $650. Use of ultrasound after the procedure increases the cost approximately $200 as a result of performing additional interventions. For intracoronary ultrasound to be economically viable, the change in angioplasty technique will need to be accompanied by improved clinical outcome.
Assuntos
Angioplastia Coronária com Balão/economia , Angioplastia Coronária com Balão/métodos , Doença das Coronárias/economia , Doença das Coronárias/terapia , Ultrassonografia de Intervenção/economia , Cateterismo Cardíaco/economia , Estudos de Casos e Controles , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Feminino , Custos Hospitalares , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Escalas de Valor RelativoRESUMO
Noncardiogenic pulmonary edema has not been (to our knowledge) previously reported associated with a verapamil overdose. We describe a 27-year-old woman who developed this complication after an overdose of 15, 120-mg verapamil tablets (total of 1,800 mg). This report illustrates the possibility of serious pulmonary embarrassment in the course of a verapamil overdose and the need to avoid excessive crystalloid administration during the hypotensive period.
Assuntos
Edema Pulmonar/induzido quimicamente , Verapamil/intoxicação , Adulto , Overdose de Drogas , Dispneia/induzido quimicamente , Feminino , Humanos , Hipotensão/induzido quimicamente , Hipóxia/induzido quimicamenteRESUMO
The assessment of functional coronary lesion severity using intracoronary hemodynamic parameters like the pressure-derived fractional flow reserve and the flow-derived coronary flow reserve are known to rely critically on the establishment of maximal hyperemia. We evaluated a hyperemia-free index, basal pressure drop coefficient (bCDP), that combines pressure and velocity for simultaneous assessment of the status of both epicardial and microvascular circulations. In 23 pigs, simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual-sensor tipped guidewire in the settings of both normal and abnormal microcirculation with the presence of epicardial lesions of area stenosis (AS) < 50% and AS > 50%. The bCDP, a parameter based on fundamental fluid dynamics principles, was calculated as the transtenotic pressure-drop divided by the dynamic pressure in the distal vessel, measured under baseline (without hyperemia) conditions. The group mean values of bCDP for normal (84 ± 18) and abnormal (124.5 ± 15.6) microcirculation were significantly different. Similarly, the mean values of bCDP from AS < 50% (72.5 ± 16.1) and AS > 50% (136 ± 17.2) were also significantly different (p < 0.05). The bCDP could significantly distinguish between lesions of AS < 50% to AS > 50% under normal microcirculation (52.1 vs. 85.8; p < 0.05) and abnormal microcirculation (84.9 vs. 172; p < 0.05). Further, the bCDP correlated linearly and significantly with the hyperemic parameters FFR (r = 0.42, p < 0.05) and CDP (r = 0.50, p < 0.05). The bCDP is a promising clinical diagnostic parameter that can independently assess the severity of epicardial stenosis and microvascular impairment. We believe that it has an immediate appeal for detection of coronary artery disease if validated clinically.
Assuntos
Pressão Arterial/fisiologia , Circulação Coronária/fisiologia , Microcirculação/fisiologia , Animais , Velocidade do Fluxo Sanguíneo , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiologia , Coração/fisiologia , Hiperemia/fisiopatologia , SuínosRESUMO
OBJECTIVES AND BACKGROUND: Decisions based on invasive functional diagnostic measurements are often made in the setting of fluctuating hemodynamic variables that may alter resting or hyperemic measurements. The purpose of this investigation is to analyze the effect of myocardial contractility (CY) on invasive functional parameters. We hypothesize that the pressure drop coefficient (CDPe; ratio of pressure drop to distal dynamic pressure) and fractional flow reserve (FFR; ratio of average pressures distal and proximal to a stenosis) are not affected by fluctuations in CY and can distinguish between different severities of epicardial stenosis. METHODS: Simultaneous measurements of distal coronary-arterial pressure and velocity were performed in 10 pigs using a dual-sensor tipped guidewire for heart rate (HR) <110 bpm and HR >110 bpm, in the presence of coronary lesions of <50% area stenosis (AS) and >50% AS. Variations in myocardial function and vascular resistance were induced by atrial pacing, papaverine and balloon obstruction, respectively. The maximum rate of rise of left ventricular pressure ([dp/dt]max) was the index of contractility. The contractile function of the heart was empirically defined as CY >900 mm Hg/sec (higher) and CY <900 mm Hg/sec (normal). RESULTS: For CY >900 mm Hg/sec, under AS <50% and AS >50%, the mean values of FFR (0.91 ± 0.02 and 0.78 ± 0.02), and CDPe (15.6 ± 5.3 and 70.7 ± 24.7) were significantly different (P<.05). Similarly, for CY <900 mm Hg/sec, under AS <50% and AS >50%, the mean values of FFR (0.83 ± 0.04 and 0.63 ± 0.04), and CDPe (43.8 ± 14.9 and 191.8 ± 61.4) were also significantly different (P<.05). CONCLUSIONS: Both FFR and CDPe could effectively distinguish between stenosis severity at normal and higher levels of myocardial contractility.
Assuntos
Pressão Sanguínea/fisiologia , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Modelos Animais , Contração Miocárdica/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Animais , Velocidade do Fluxo Sanguíneo/fisiologia , Angiografia Coronária , Estenose Coronária/diagnóstico , Frequência Cardíaca/fisiologia , Hemodinâmica/fisiologia , Índice de Gravidade de Doença , Suínos , Resistência Vascular/fisiologiaRESUMO
BACKGROUND: It is unknown whether adenosine can precondition human myocardium against ischemia in vivo. METHODS AND RESULTS: Thirty patients were randomized to receive a 10-minute intracoronary infusion of adenosine (2 mg/min) or normal saline; 10 minutes later, they underwent percutaneous transluminal coronary angioplasty (PTCA; three 2-minute balloon inflations 5 minutes apart). In control patients, the ST-segment shift on the intracoronary ECG was significantly greater during the first inflation than during the second and third inflations, consistent with ischemic preconditioning. In contrast, in adenosine-treated patients, there were no differences in ST-segment shift during the three inflations. The ST-segment shift was significantly smaller in the adenosine-treated group compared with the control group during all three inflations. The reduction in ST-segment shift afforded by adenosine during the first inflation (-72% versus first inflation in control subjects) was greater than that afforded by ischemic preconditioning in control subjects (-52% during the third versus first inflation). Measurements of chest pain score paralleled those of ST-segment shift. Adenosine had no effect on baseline regional wall motion as determined by quantitative two-dimensional echocardiography. Thus, intracoronary infusion of adenosine before PTCA rendered the myocardium remarkably resistant to subsequent ischemia. Judging from the intracoronary ECG, the protection provided by adenosine was even superior to that provided in control subjects by the ischemia associated with the first two balloon inflations. Infusion of adenosine had no major adverse effects in patients undergoing PTCA of the left anterior descending or circumflex arteries. CONCLUSIONS: Adenosine preconditions human myocardium against ischemia in vivo. Pretreatment with adenosine is remarkably effective (even more effective than ischemic preconditioning) and could be used prophylactically to attenuate ischemia in selected patients undergoing PTCA of the left anterior descending coronary artery. Whether adenosine can be safely infused into the right or the circumflex coronary artery in the presence of a temporary pacemaker remains to be established.
Assuntos
Adenosina/administração & dosagem , Angioplastia Coronária com Balão/métodos , Precondicionamento Isquêmico Miocárdico/métodos , Ecocardiografia , Eletrocardiografia , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The cost of performing percutaneous transluminal coronary angioplasty (PTCA) is accelerating. The angiographic, clinical, technical, and procedural variables associated with PTCA cost are largely unknown. METHODS: To determine an interrelationship between equipment size, operator experience, and PTCA cost, 50 patients were randomized to have PTCA performed with large (0.014") or small (0.010") balloon systems. A secondary randomization determined the primary operator of the procedure; either experienced attending physician or inexperienced fellow in interventional cardiology. END POINTS: Primary: PTCA cost (equipment, supplies, support personal, post-PTCA room, and physician (utilizing resource-based relative value scale); Secondary: measures of technical procedural and clinical outcome. RESULTS: The total cost of the PTCA was $4,047 +/- $2,133 for 0.010" systems versus $3,451 +/- $1,004 for the 0.014" systems, P = NS. Independent variables associated with increased cost included: age, diabetes, and duration of procedure in the cardiac catheterization laboratory. There was no significant difference in procedural duration, complications, or outcome between the smaller or larger PTCA catheter systems, and, the less experienced PTCA operator required additional fluoroscopic time to cross the lesion, as well as procedure time compared with the attending physician. CONCLUSIONS: Neither miniaturization of equipment size nor primary operator experience led to PTCA cost savings. Clinical and procedural characteristics are independently correlated with increased PTCA cost. Additional study is needed to determine the exact determinants of PTCA cost, in order to stabilize the cost of this procedure.