Dennis V. Cokkinos

Ascorbic Acid Prevents Contrast-Mediated Nephropathy in Patients With Renal Dysfunction Undergoing Coronary Angiography or Intervention

Background—Contrast agents can cause a reduction in renal function that may be due to the generation of reactive oxygen species. Conflicting evidence suggests that administration of the antioxidant acetylcysteine prevents this renal impairment. The action of other antioxidant agents has not been investigated. Methods and Results—We conducted a randomized, double-blind, placebo-controlled trial of ascorbic acid in 231 patients with a serum creatinine concentration ≥1.2 mg/dL who underwent coronary angiography and/or intervention. Ascorbic acid, 3 g at least 2 hours before the procedure and 2 g in the night and the morning after the procedure, or placebo was administered orally. Contrast-mediated nephropathy was defined by an absolute increase of serum creatinine ≥0.5 mg/dL or a relative increase of ≥25% measured 2 to 5 days after the procedure. Contrast-mediated nephropathy occurred in 11 of the 118 patients (9%) in the ascorbic acid group and in 23 of the 113 patients (20%) in the placebo group (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17 to 0.85; P=0.02). The mean serum creatinine concentration increased significantly in the placebo group (from 1.36±0.50 to 1.50±0.54 mg/dL, P<0.001) and nonsignificantly in the ascorbic acid group (from 1.46±0.52 to 1.52±0.64 mg/dL, P=0.07). The mean increase in serum creatinine concentration was greater in the placebo group than in the ascorbic acid group (difference of 0.09 mg/dL; 95% CI, 0.00 to 0.17; P=0.049). Conclusions—Prophylactic oral administration of ascorbic acid may protect against contrast-mediated nephropathy in high-risk patients undergoing a coronary procedure.

Acute coronary angiographic findings in survivors of out-of-hospital cardiac arrest.

BACKGROUND Diagnosis of acute coronary artery disease in survivors of out-of-hospital cardiac arrest (OHCA) is difficult. The role of emergency coronary angiography and percutaneous coronary intervention (PCI) in this setting is debated. The objective of this study was to assess the prevalence of coronary lesions on emergency angiography in survivors of OHCA. METHODS Seventy-two consecutive OHCA survivors underwent systematic emergency coronary angiography. Patients with critical stenoses or occlusion underwent ad hoc PCI. RESULTS Most (63.9%) OHCA survivors had angiographic coronary artery disease (> or =1 lesion >50%), but only a minority (37.5%) had clinical or angiographic evidence of an acute coronary syndrome due to either an acute occlusion (16.7%) or an irregular lesion suggestive of ruptured plaque or thrombus (25.0%). A final diagnosis of myocardial infarction was assigned in 27 patients (37.5%). Percutaneous coronary intervention was attempted and successful in 33.3% of the total cohort (n = 24). Hospital survival was 48.6%. By multivariable analysis, use of PCI was not an independent correlate of survival. ST-segment elevation on admission was an independent correlate of acute myocardial infarction (odds ratio 64.2, 95% CI 7.6-544.2, P = .0001), with high positive (82.6%) and negative (83.7%) predictive values. CONCLUSIONS A minority of OHCA patients has angiographic evidence of an acute coronary syndrome and one-third undergo PCI, but PCI is not an independent correlate of survival. The presence of ST elevation on admission was a strong independent correlate of acute myocardial infarction and may be used to triage OHCA patients to emergency angiography with a view to PCI.

Adherence to antihypertensive treatment: a critical factor for blood pressure control.

Background To compare rates of blood pressure (BP) control with the level of adherence to antihypertensive treatment and factors influencing compliance in Greek patients. Design An observational cross-sectional study on 1000 consecutively treated hypertensive patients, admitted to a University department of general surgery in a Greek hospital. Methods Patients were interviewed by the same doctor using pre-coded questionnaires with questions on demographic data, health and treatment status. Blood pressure was measured using a standard mercury sphygmomanometer. Treatment of hypertension was defined as current use of antihypertensive medication. Compliance was defined as an affirmative reply to a number of questions regarding regular use of antihypertensive medication according to the physicians instructions. Results Satisfactory BP control (levels <140/90 mmHg) was documented in only 20% of the treated hypertensives. Compliance to antihypertensive treatment was found in only 15% of the patients. Control of BP was positively associated with compliance. Compliance was more common among patients aged <60, city dwellers, the better educated, those more adequately counselled by their physicians and those followed by a private doctor. As regards treatment, compliance was better among those taking one antihypertensive tablet per day, those who had never changed their antihypertensive regimen and those who had never changed their doctor. Conclusions Compliance is associated with more effective BP control. Physicians can enhance patient compliance and hypertension control by devoting more time to counselling, avoiding unnecessary changes in drug regimens and restricting the tablet numbers.

Prognostic significance of echocardiographically estimated right ventricular shortening in advanced heart failure

Little is known about the association of echocardiographic estimates of right ventricular (RV) function with survival, in relation to hemodynamic and exercise-derived predictors of outcome in congestive heart failure. We prospectively studied 40 patients (age 55+/-10 years, in New York Heart Association functional class III [70%] and IV [30%]), with left ventricular (LV) ejection fraction <30%. At enrollment, all patients underwent echocardiographic evaluation of LV dimensions and function. RV shortening was measured as the difference of the end-diastolic distance - the end-systolic distance between the tricuspid annulus and the RV apex. Thirty-five patients (88%) were able to perform a maximal symptom-limited exercise test. Peak oxygen consumption (peak VO2) and percent peak age- and gender-adjusted predicted oxygen consumption (%peak VO2) were calculated. Of 40 patients, 10 died during a mean follow-up period of 14+/-10 months. On univariate analysis, nonsurvivors had lower RV shortening (p=0.0001), higher pulmonary artery wedge pressure (p=0.009), higher pulmonary vascular resistance (p=0.02), and lower mean aortic pressure (p=0.05). Cox proportional-hazards model revealed that the only independent associate of survival was RV shortening (p=0.0005), with a trend toward significance for mean aortic pressure (p=0.08). The best cutoff point of RV shortening identified by the receiver-operating curve was 1.25 cm. This value had a sensitivity of 90%, specificity of 80%, and overall predictive accuracy of 83% to distinguish survivors from nonsurvivors. In patients with advanced heart failure, preserved RV function as indicated by an echocardiographically derived RV shortening > 1.25 cm is a strong predictor of survival.

Estimation of coronary flow reserve using the Thrombolysis In Myocardial Infarction (TIMI) frame count method

A simple and readily available method of estimating coronary flow velocity reserve may have significant clinical value. With use of intracoronary adenosine we documented a very good correlation between coronary flow reserve values obtained with the Thrombolysis In Myocardial Infarction trial frame count method and the invasive Doppler wire (Flowire) technique.

Early Percutaneous Coronary Intervention, Platelet Inhibition With Eptifibatide, and Clinical Outcomes in Patients With Acute Coronary Syndromes

BACKGROUND Platelet glycoprotein (GP) IIb/IIIa antagonists prevent the composite end point of death or myocardial infarction (MI) in patients with acute coronary syndromes. There is uncertainty about whether this effect is confined to patients who have percutaneous coronary interventions (PCIs) and whether PCIs further prevent death or MI in patients already treated with GP IIb/IIIa antagonists. METHODS AND RESULTS PURSUIT patients were treated with the GP IIb/IIIa antagonist eptifibatide or placebo; PCIs were performed according to physician practices. In 2253 of 9641 patients (23.4%), PCI was performed by 30 days. Early (<72 hours) PCI was performed in 1228 (12.7%). In 34 placebo patients (5.5%) and 10 treated with eptifibatide (1.7%) (P=0.001), MI preceded early PCI. In patients censored for PCI across the 30-day period, there was a significant reduction in the primary composite end point in eptifibatide patients (P=0.035). Eptifibatide reduced 30-day events in patients who had early PCI (11.6% versus 16.7%, P=0.01) and in patients who did not (14.6% versus 15.6%, P=0.23). After adjustment for PCI propensity, there was no evidence that eptifibatide treatment effect differed between patients with or without early PCI (P for interaction=0.634). PCI was not associated with a reduction of the primary composite end point but was associated with a reduced (nonspecified) composite of death or Q-wave MI. This association disappeared after adjustment for propensity for early PCI. CONCLUSIONS Eptifibatide reduced the composite rates of death or MI in PCI patients and those managed conservatively.

Long‐term oral bosentan treatment in patients with pulmonary arterial hypertension related to congenital heart disease: a 2‐year study

Objective: To evaluate the long-term clinical and exercise effect of chronic oral administration of the non-selective endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD). Design: Extension of a preceding prospective non-randomised open clinical study on bosentan treatment in PAH related to CHD. Setting: A tertiary referral centre for cardiology. Patients: 19 of the original 21 patients of mean (standard deviation (SD)) age 22 (3) years (13 with Eisenmenger syndrome) in World Health Organization (WHO) class II–IV and having a mean (SD) oxygen saturation of 87 (2) %. Intervention: Patients received bosentan treatment for 2.4 (0.1) years and underwent clinical and exercise evaluation at baseline, 16 weeks and 2 years of treatment, with haemodynamic assessment at baseline and 16 weeks. Results: All patients remained stable with sustained subjective clinical and WHO class improvement (p<0.01) at 16 weeks and 2 years of treatment without significant side effects or changes in oxygen saturation. After the initial 16-week improvement (p<0.05) in peak oxygen consumption and exercise duration at treadmill test, and walking distance and Borg dyspnoea index at 6-min walk test, all exercise parameters appeared to return to their baseline values at 2 years of follow-up. Conclusions: Long-term bosentan treatment in patients with PAH related to CHD is safe and induces clinical stability and improvement, but the objective exercise values appear to slowly return to baseline. Larger studies on long-term endothelin receptor antagonism including quality of life assessment are needed to evaluate the therapeutic role of bosentan in this population.

Intracoronary Infusion of CD133+ and CD133−CD34+ Selected Autologous Bone Marrow Progenitor Cells in Patients with Chronic Ischemic Cardiomyopathy: Cell Isolation, Adherence to the Infarcted Area, and Body Distribution

Central issues in intracoronary infusion (ICI) of bone marrow (BM)‐cells to damaged myocardium for improving cardiac function are the cell number that is feasible and safe to be administrated as well as the retention of cells in the target area. Our study addressed these issues in eight patients with chronic ischemic cardiomyopathy undergoing ICI of selected BM‐progenitors. We could immunomagnetically isolate 0.8 ± 0.32 × 107 CD133+ cells and 0.75 ± 0.24 × 107 CD133−CD34+ cells from 310 ± 40 ml BM. After labeling these cells with 99mTc‐hexamethylpropylenamineoxime, they were infused into the infarct‐related artery without any complication. Scintigraphic images 1 (eight patients) and 24 hours (four patients) after ICI revealed an uptake of 9.2% ± 3.6 and 6.8% ± 2.4 of the total infused radioactivity in the infarcted area of the heart, respectively; the remaining activity was distributed mainly to liver and spleen. We conclude that through ICI of CD133+ and CD133−CD34+ BM‐progenitors a significant number of them are preferentially attracted to and retained in the chronic ischemic myocardium.

Inspiratory muscle training using an incremental endurance test alleviates dyspnea and improves functional status in patients with chronic heart failure.

Background The benefits of inspiratory muscle training (IMT) in patients with chronic heart failure (CHF) have been inadequately studied. Design and methods Using a prospective, age and sex-matched controlled study, we investigated 35 patients with moderate to severe CHF (NYHA class II–III and left ventricular ejection fraction 24.4 ± 1.3% [mean ± SEM]). An incremental respiratory endurance test using a fixed respiratory workload was provided by software with an electronic mouth pressure manometer interfaced with a computer. The training group (n = 20) exercised at 60% of individual sustained maximal inspiratory pressure (SMIP) and the control group (n = 15) at 15% of SMIP. All patients exercised three times weekly for 10 weeks. Pulmonary function, exercise capacity, dyspnea and quality of life were assessed, pre- and post-training. Results The training group significantly increased both maximum inspiratory pressure (Pimax), (111 ± 6.8 versus 83 ± 5.7cmH2O, P<0.001), and SMIP (527822 ± 51358 versus 367360 ± 41111 cmH2O/sec × 10-1, P < 0.001). Peak VO2 increased after training (17.8 ± 1.2 versus 15.4 ± 0.9 ml/kg/min, P< 0.005), as did the six-minute walking distance (433 ± 16 versus 367 ± 22 meters, P < 0.001). Perceived dyspnea assessed using the Borg scale was reduced for both the treadmill (12.7 ± 0.57 versus 14.2 ± 0.48, P < 0.005) and the walking (9 ± 0.48 versus 10.5 ± 0.67, P< 0.005) exercise tests and the quality of life score was also improved (21.1 ± 3.5 versus 25.2 ± 4, P < 0.01). Resting heart rate was significantly reduced with training (77 ± 3.3 versus 80 ± 3beats/min, P < 0.05). The control group significantly increased Pimax (86.6 ± 6.3 versus 78.4 ± 6.9cmH2O, P < 0.05), but decreased SMIP (274972 ± 32399 versus 204661 ± 37184cmH2O/sec × 101, P < 0.005). No other significant effect on exercise capacity, heart rate, dyspnea, or quality of life was observed in this group. Conclusion Inspiratory muscle training using an incremental endurance test, successfully increases both inspiratory strength and endurance, alleviates dyspnea and improves functional status in CHF.

A comparison of magnetic resonance imaging and cardiac biopsy in the evaluation of heart iron overload in patients with β‐thalassemia major

Abstract:  Objectives: To apply magnetic resonance imaging (MRI) for the assessment of myocardial iron deposition in patients with β‐thalassemia and compare the results with cardiac biopsy data. Background: Myocardial iron accumulation is the main cause for cardiac complications in β‐thalassemia. Methods: Twenty‐five consecutive thalassemic patients were studied using a 0.5‐T (Tesla) system, ECG‐gated, with echo time (TE) = 17–68 ms. T2 relaxation time of the interventricular septum was calculated assuming simple monoexponential decay. A heart T2 relaxation time value of 32 ms was used for the discrimination between high and low iron deposition. Heart biopsy was performed within a week after the MRI study. Patients with stainable iron in more than 50% of the myofibrils were graded as having severe iron deposition. A serum ferritin level below 2000 ng/mL was considered as an indication of successful chelation. Results: Seven of the 25 patients had heart biopsy indicative of low iron deposition (Group L) and the remaining 18 patients had heart biopsy indicative of high iron deposition (Group H). T2 relaxation time of the heart (T2H) was lower in Group H compared to Group L (31.5 ± 3.9 (range: 28–40) ms vs. 35.7 ± 3.7 (range: 29–40) ms, P = 0.026). The T2H was in agreement with heart biopsy in 86% of the patients in Group L and in 78% of the patients in Group H (overall agreement 80%). Similarly, serum ferritin levels were in agreement with heart biopsy in 28% and 88%, respectively (overall agreement 72%). In Group L, MRI was in better agreement with biopsy compared to serum ferritin (86% vs. 28%, P < 0.05). A receiver operating characteristic curve (ROC) analysis confirmed that a T2 relaxation time of 32 ms had the highest discriminating ability for the corresponding biopsy outcome. Conclusions: Heart T2 relaxation time appears in agreement with cardiac biopsy, both in high and low iron deposition, and may become a useful non‐invasive index in β‐thalassemia.