The Impact of Advanced Age on Major Cardiovascular Events and Mortality in Patients with ST-Elevation Myocardial Infarction Undergoing a Pharmaco-Invasive Strategy.

BACKGROUND: There is little research in the efficacy and safety of a pharmaco-invasive strategy (PIS) in patients ≥75 years versus <75 years of age. We aimed to evaluate and compare the influence of advanced age on the risk of death and major adverse cardiac events (MACE) in patients undergoing PIS. METHODS: Between January 2010 and November 2016, 14 municipal emergency rooms in São Paulo, Brazil, used full-dose tenecteplase to treat patients with STEMI as part of a pharmaco-invasive strategy for a local network implementation. RESULTS: A total of 1852 patients undergoing PIS were evaluated, of which 160 (9%) were ≥75 years of age. Compared to patients <75 years, those ≥75 years were more often female, had lower body mass index, higher rates of hypertension; higher incidence of hypothyroidism, chronic renal failure, prior stroke, and diabetes. Compared to patients <75 years of age, in-hospital MACE and mortality were higher in patients with ≥75 years (6.5% versus 19.4%; p<0.001; and 4.0% versus 18.2%; p<0.001, respectively). Patients ≥75 years had higher rates of in-hospital major bleeding (2.7% versus 5.6%; p=0.04) and higher incidence of cardiogenic shock (7.0% versus 19.6%; p<0.001). By multivariable analysis, age ≥75 years was independent predictor of MACE (OR 3.57, 95% CI 1.72 to 7.42, p=0.001) and death (OR 2.07, 95% CI 1.12-3.82, p=0.020). CONCLUSION: In patients with ST-segment elevation myocardial infarction undergoing PIS, age ≥75 years was an independent factor that entailed a 3.5-fold higher MACE and 2-fold higher mortality rate compared to patients <75 years of age.

Relation between the ankle-brachial index and the complexity of coronary artery disease in older patients.

BACKGROUND: In the elderly, the ankle-brachial index (ABI) has greater than 90% sensitivity and specificity for peripheral artery disease identification. A well-known relation exists between peripheral artery disease and the number of diseased coronary vessels. Yet, other anatomical characteristics have important impacts on the type of treatment and prognosis. PURPOSE: To determine the relation between ABI and the complexity of coronary artery disease, by different anatomical classifications. METHODS: This study was a prospective analysis of patients ≥65 years old who were undergoing elective coronary angiography for ischemic coronary disease. The ABI was calculated for each leg, as the ratio between the lowest ankle pressure and the highest brachial pressure. The analysis of coronary anatomy was performed by three interventional cardiologists; it included classification of each lesion with >50% diameter stenosis, according to the American Heart Association criteria, and calculation of the SYNTAX score. RESULTS: The study recruited 204 consecutive patients (median age: 72.5 years). Stable angina was present in 51% of patients. Although only 1% of patients reported peripheral artery disease, 45% exhibited an abnormal ABI. The number of lesions per patient, the number of patients with complex lesions, and the median SYNTAX scores were greater in the group with abnormal ABI. However, among 144 patients with obstructive coronary artery disease, despite abnormal ABI being able to identify a higher rate of patients with B2 or C type lesions (70.9% versus 53.8%; P=0.039), the mean SYNTAX scores (13 versus 9; P=0.14), and the proportion of patients with SYNTAX score >16 (34.2% versus 27.7%; P=0.47), were similar, irrespective of ABI. CONCLUSION: In patients ≥65 years old the presence of peripheral artery disease could discriminate a group of patients with greater occurrence of B2 and C type lesions, but similar median SYNTAX score.

Ankle-brachial index as a predictor of coronary disease events in elderly patients submitted to coronary angiography

OBJECTIVES: To correlate the importance of the ankle-brachial index in terms of cardiovascular morbimortality and the extent of coronary arterial disease amongst elderly patients without clinical manifestations of lower limb peripheral arterial disease. METHODS: We analyzed prospective data from 100 patients over 65 years of age with coronary arterial disease, as confirmed by coronary angiography, and with over 70% stenosis of at least one sub-epicardial coronary artery. We measured the ankle-brachial index immediately after coronary angiography, and a value of <0.9 was used to diagnose peripheral arterial disease. RESULTS: The patients' average age was 77.4 years. The most prevalent risk factor was hypertension (96%), and the median late follow-up appointment was 28.9 months. The ankle-brachial index was <0.9 in 47% of the patients, and a low index was more prevalent in patients with multiarterial coronary disease compared to patients with uniarterial disease in the same group. Using a bivariate analysis, only an ankle-brachial index of <0.9 was a strong predictive factor for cardiovascular events, thereby increasing all-cause deaths and fatal and non-fatal acute myocardial infarctions two- to three-fold. CONCLUSION: In elderly patients with documented coronary disease, a low ankle-brachial index (<0.9) was associated with the severity and extent of coronary arterial disease, and in late follow-up appointments, a low index was correlated with an increase in the occurrence of major cardiovascular events. .

Severity of the cardiac impairment determines whether digitalis prolongs or reduces survival of rats with heart failure due to myocardial infarction.

BACKGROUND: The aim of the present study was to evaluate if the influence of digitalis on survival depends on the severity of cardiac dysfunction in heart failure (HF). METHODS AND RESULTS: Doppler echocardiogram (DE) parameters were analyzed in 84 Wistar control (C) and 80 Wistar rats treated with 0.1mg/100g/day of digitoxin (D) five days after coronary occlusion. The DE variables correlated with the survival of the animals were: myocardial infarction size, left chamber dimensions, fractional area change and E/A ratio. The animals were observed for up to 280 days. Mortality was worsened in rats in the D group with a myocardial infarction (MI)<37% and with better DE predictors of survival. Digitoxin was found to prolong survival in rats with an MI ≥ 37% and worse DE predictors. CONCLUSION: For the first time our study has shown experimentally that the action of digitalis glycosides can positively or negatively influence survival during treatment of HF. It prolongs survival of those in advanced state and compromises survival when there is less severity of the disease. In fact, the greater benefits occur when digitoxin was used in heightened ventricular dilatations and worse ventricular performance.

Ankle-brachial index as a predictor of coronary disease events in elderly patients submitted to coronary angiography.

OBJECTIVES: To correlate the importance of the ankle-brachial index in terms of cardiovascular morbimortality and the extent of coronary arterial disease amongst elderly patients without clinical manifestations of lower limb peripheral arterial disease. METHODS: We analyzed prospective data from 100 patients over 65 years of age with coronary arterial disease, as confirmed by coronary angiography, and with over 70% stenosis of at least one sub-epicardial coronary artery. We measured the ankle-brachial index immediately after coronary angiography, and a value of <0.9 was used to diagnose peripheral arterial disease. RESULTS: The patients' average age was 77.4 years. The most prevalent risk factor was hypertension (96%), and the median late follow-up appointment was 28.9 months. The ankle-brachial index was <0.9 in 47% of the patients, and a low index was more prevalent in patients with multiarterial coronary disease compared to patients with uniarterial disease in the same group. Using a bivariate analysis, only an ankle-brachial index of <0.9 was a strong predictive factor for cardiovascular events, thereby increasing all-cause deaths and fatal and non-fatal acute myocardial infarctions two- to three-fold. CONCLUSION: In elderly patients with documented coronary disease, a low ankle-brachial index (<0.9) was associated with the severity and extent of coronary arterial disease, and in late follow-up appointments, a low index was correlated with an increase in the occurrence of major cardiovascular events.

[Digoxin: the results of the DIG study in the XXI century]. / Digitálicos: os resultados do DIG no século XXI.

After the report that there was no statistical significance in the general mortality of the DIG study, the indication of digoxin in the treatment regimens for congestive heart failure (CHF) drastically decreased. Post hoc studies that reassessed the DIG study data, indicated that an aspect that was not considered in this multicenter study has a critical influence on the prognosis of patients: the serum levels of digoxin. Regarding those that received a placebo, the general mortality and hospitalization were decreased in patients with a digoxin level < 0.9 ng/ml. At the first study that assessed the influence of digitalis in an experimental model of CHF, we verified in our lab that female rats with congestive syndrome secondary to myocardial infarction have a prolonged survival when undergoing treatment with digitoxin. The current information recommends that the merits of digoxin continue to be analyzed in order to adequately establish its importance in the treatment of CHF.

Digitálicos: os resultados do DIG no século XXI / Digoxin: the results of the DIG study in the XXI century / Digitálicos: los resultados del DIG en el siglo XXI

Depois da divulgação de que não houve significância estatística na mortalidade geral do estudo DIG, a indicação dos digitálicos nos esquemas de tratamento da insuficiência cardíaca congestiva (ICC) reduziu drasticamente. Estudos post hoc, que reavaliaram os dados do DIG, indicaram que um aspecto não considerado neste ensaio multicêntrico exerce influência decisiva no prognóstico dos pacientes: a concentração sérica da digoxina. Em relação àqueles que receberam placebo, a mortalidade geral e a hospitalização foram reduzidas em pacientes com concentração de digoxina inferior a 0,9 ng/ml. No primeiro trabalho que avaliou a influência dos digitálicos em modelo experimental de ICC, verificamos em nosso laboratório que ratas com síndrome congestiva secundária a infarto do miocárdio têm a sobrevida prolongada sob tratamento com digitoxina. As informações atuais recomendam que os méritos dos digitálicos continuem a ser analisados para estabelecer adequadamente sua importância no tratamento da ICC.

After the report that there was no statistical significance in the general mortality of the DIG study, the indication of digoxin in the treatment regimens for congestive heart failure (CHF) drastically decreased. Post hoc studies that reassessed the DIG study data, indicated that an aspect that was not considered in this multicenter study has a critical influence on the prognosis of patients: the serum levels of digoxin. Regarding those that received a placebo, the general mortality and hospitalization were decreased in patients with a digoxin level < 0.9 ng/ml. At the first study that assessed the influence of digitalis in an experimental model of CHF, we verified in our lab that female rats with congestive syndrome secondary to myocardial infarction have a prolonged survival when undergoing treatment with digitoxin. The current information recommends that the merits of digoxin continue to be analyzed in order to adequately establish its importance in the treatment of CHF.

Después de la divulgación de que no hubo significancia estadística en la mortalidad general del estudio DIG, la indicación de los digitálicos en los esquemas de tratamiento de la insuficiencia cardíaca congestiva (ICC) se redujo drásticamente. Estudios post hoc, que reevaluaron los datos del DIG, indicaron que un aspecto no considerado en este ensayo multicéntrico ejerce influencia decisiva en el pronóstico de los pacientes: la concentración sérica de la digoxina. En relación a aquellos que recibieron placebo, la mortalidad general y la hospitalización fueron reducidas en pacientes con concentración de digoxina inferior a 0,9 ng/ml. En el primer trabajo que evaluó la influencia de los digitálicos en modelo experimental de ICC, verificamos en nuestro laboratorio que ratas con síndrome congestivo secundario a infarto de miocardio tienen la sobrevida prolongada bajo tratamiento con digitoxina. Las informaciones actuales recomiendan que los méritos de los digitálicos continúen a ser analizados para establecer adecuadamente su importancia en el tratamiento de la ICC.

Digitoxin prolongs survival of female rats with heart failure due to large myocardial infarction.

BACKGROUND: We analyzed whether digitoxin affects the survival of rats with congestive heart failure. METHODS AND RESULTS: The influence of digitoxin (0.1 mg.100 g.day, orally) on the survival of infarcted female rats (n=170) randomized as Control Infarcted (CI, n=85) or Digitoxin (D, n=85) was evaluated for 280 days. Mean survival was 235+/-7 days for CI and 255+/-5 days for D (log-rank test: P=.0602). Digitoxin did not affect survival in rats with congestive heart failure from myocardial infarction <40% of the left ventricle, but did prolong survival in rats with infarction >or=40%. The log-rank test defined higher mortality (P=.0161) in CI >40% (56%) than in D >40% (34%), with a hazard ratio of 2.03. Pulmonary water content and papillary muscle mechanics were analyzed in CI (n=7) and D (n=14) survivors. Significant differences were observed regarding pulmonary water content (CI: 82+/-0.3; D: 80+/-0.3%; P=.0014), developed tension (CI: 2.7+/-0.3; D: 3.8+/-0.3g/mm(2); P=.0286) and +dT/dt (CI: 24+/-3; D: 39+/-4 mg mm(2).s; P=.0109). CONCLUSION: In conclusion, long-term digitoxin administration reduced cardiac impairment after myocardium infarction, attenuated myocardial dysfunction, reduced pulmonary congestion, and provided the first evidence regarding the efficiency of digitoxin in prolonging survival in experimental cardiac failure.

A novel inexpensive murine model of oral chronic digitalization.

A novel inexpensive murine model of oral administration of digitoxin (100 micro g/kg per day) added to routine chow is described. Serum digitoxin levels achieved after oral (n = 5; 116 +/- 14 ng/mL) and subcutaneous (n = 5; 124 +/- 11 ng/mL) administration were similar. A significant increase in the maximal left ventricular pressure rise of treated (n = 9) compared with control (n = 6) rats (dP/dt: 8956 +/- 233 vs 7980 +/- 234 mmHg/s, respectively; P = 0.01) characterized the positive inotropic action of digitoxin. In addition, no differences were observed in treated compared with control rats with regard to the electrocardiogram and systolic and diastolic left ventricular pressures.