Does treatment guided by vitamin K in the diet alter the quality of life of anticoagulated patients?

PURPOSE: To compare whether health-related quality of life (HRQoL) is altered in patients undergoing a treatment strategy guided by changes in dietary vitamin K. METHODS: This study is a randomized clinical trial carried out with chronic oral anticoagulation outpatients randomized into a control group (conventional dose adjustment of oral anticoagulants) (n = 66) and an intervention group (strategy based on changes in dietary vitamin K intake) (n = 66). HRQoL was measured using the Duke Anticoagulation Satisfaction Scale (DASS) at baseline and 90 days of follow-up. RESULTS: Patients with worse HRQoL were younger (p = 0.005) and were using a higher dose of baseline oral anticoagulants (p = 0.008), while those with better HRQoL scores had a higher level of education (p = 0.01). Both groups had significant improvements in HRQoL from baseline to 90 days in the global DASS score (p < 0.001), as well as in the negative and positive psychological impact (p < 0.001) domains. We did not observe differences in the variations of HRQoL scores in any of the DASS domains (p values > 0.05) between groups of interventions. Patients who achieved oral anticoagulation stability (n = 23) had significantly better HRQoL scores than patients who did not achieve stability (p = 0.003). CONCLUSION: Patients receiving the treatment strategy based on changes in dietary vitamin K intake did not have better HRQoL scores; however, both treatment approaches to manage oral anticoagulation improved HRQoL. Patients with greater oral anticoagulation stability had better HRQoL scores.

Dietary vitamin K intake and stability of anticoagulation with coumarins: evidence derived from a clinical trial.

BACKGROUND: Dietary vitamin K intake has been considered a major factor that influences stability of oral anticoagulation (OA) with coumarins. Few studies have evaluated the relationship between amounts of dietary vitamin K intake and stability of anticoagulation. OBJECTIVE: To assess whether high dietary vitamin K intake is associated to stability of International Normalized Ratio (INR) of the prothrombin time. METHODS: We performed a sub-analysis of a randomized clinical trial involving outpatients from the anticoagulation clinic of a university hospital. INR and vitamin K intake were prospectively collected at baseline, 15, 30, 60 and 90 days after randomization. Patients were considered with a stable anticoagulation when their INR coefficient of variation was less than 10%. Dietary vitamin K intake was assessed by a food frequency questionnair and a score of intake was derived. RESULTS: We studied 132 patients on chronic OA (57 ± 13 years; 55% males); 23 patients (17%) were achieved stable anticoagulation. Stable and unstable patients had no significant differences in baseline characteristics. The dietary vitamin K score over the entire follow-up for stable patients was significantly lower than that for unstable patients (p = 0.012). DISCUSSION: Our findings suggest that INR stability could be achieved with relatively low amounts of dietary vitamin K.

Impact of beta-2 Thr164Ile and combined beta-adrenergic receptor polymorphisms on prognosis in a cohort of heart failure outpatients.

Genetic polymorphisms of adrenergic receptors (ARs) have been associated with the development, progression, and prognosis of patients with heart failure (HF), with few data for the Brazilian population. We evaluated the role of the beta2-AR Thr164Ile polymorphism at codon 164 on prognosis in a prospective study on 315 adult Brazilian HF patients, predominantly middle-aged Caucasian men in functional class I-II, with severe left ventricular systolic dysfunction. Genomic DNA was extracted from peripheral blood and beta2-AR164 genotypes were detected by PCR followed by restriction fragment length analysis. During a median follow-up of 3 years, 95 deaths occurred and 57 (60%) were HF-related. Unexpectedly, Ile164 carriers (N = 12) had no HF-related events (log-rank P value = 0.13). Analysis using genotype combination with beta1-AR polymorphisms at codons 49 and 389 identified patients with favorable genotypes (Thr164Ile of beta2-AR, Gly49Gly of beta1-AR and/or Gly389Gly of beta1-AR), who had lower HF-related mortality (P = 0.01). In a Cox proportional hazard model adjusted for other clinical characteristics, having any of the favorable genotypes remained as independent predictor of all-cause (hazard ratio (HR): 0.41, 95%CI: 0.17-0.95) and HF-related mortality (HR: 0.12, 95%CI: 0.02-0.90). These data show that the beta2-AR Thr164Ile polymorphism had an impact on prognosis in a Brazilian cohort of HF patients. When combined with common beta1-AR polymorphisms, a group of patients with a combination of favorable genotypes could be identified.

Impact of β-2 Thr164Ile and combined β-adrenergic receptor polymorphisms on prognosis in a cohort of heart failure outpatients

Genetic polymorphisms of adrenergic receptors (ARs) have been associated with the development, progression, and prognosis of patients with heart failure (HF), with few data for the Brazilian population. We evaluated the role of the β2-AR Thr164Ile polymorphism at codon 164 on prognosis in a prospective study on 315 adult Brazilian HF patients, predominantly middle-aged Caucasian men in functional class I-II, with severe left ventricular systolic dysfunction. Genomic DNA was extracted from peripheral blood and β2-AR164 genotypes were detected by PCR followed by restriction fragment length analysis. During a median follow-up of 3 years, 95 deaths occurred and 57 (60 percent) were HF-related. Unexpectedly, Ile164 carriers (N = 12) had no HF-related events (log-rank P value = 0.13). Analysis using genotype combination with β1-AR polymorphisms at codons 49 and 389 identified patients with favorable genotypes (Thr164Ile of β2-AR, Gly49Gly of β1-AR and/or Gly389Gly of β1-AR), who had lower HF-related mortality (P = 0.01). In a Cox proportional hazard model adjusted for other clinical characteristics, having any of the favorable genotypes remained as independent predictor of all-cause (hazard ratio (HR): 0.41, 95 percentCI: 0.17-0.95) and HF-related mortality (HR: 0.12, 95 percentCI: 0.02-0.90). These data show that the β2-AR Thr164Ile polymorphism had an impact on prognosis in a Brazilian cohort of HF patients. When combined with common β1-AR polymorphisms, a group of patients with a combination of favorable genotypes could be identified.

Health-related quality of life and right ventricular function in the midterm follow-up assessment after tetralogy of fallot repair.

BACKGROUND: Few data are available on quality of life after surgical repair of tetralogy of Fallot (ToF), and on its relationship to right ventricle function. METHODS: Patients with at least 1 year of follow-up evaluation after surgery were studied. Right ventricle function was evaluated by the Doppler-derived myocardial performance index (MPI), and health-related quality of life (HRQL) was assessed by the Child Health Questionnaire, Parent Form-50. Findings were compared with those for an age- and sex-matched group of healthy children. RESULTS: The study enrolled 35 successfully repaired ToF patients with 4.9 years (range, 3-7 years) of follow-up evaluation after surgery and 36 healthy children. The MPI demonstrated right ventricle dysfunction in patients compared with controls (0.34; range, 0.26-0.49 vs 0.2; range, 0.13-0.27; p < 0.01), although HRQL for the psychosocial domain was similar between patients and healthy children (summary score, 47.9; range, 45-52 vs 47.5; range, 44.5-50; p = 0.17). A trend for poorer physical area results was observed in patients (summary score, 44; range, 31-52 vs 48.5; range, 45.7-51.7; p = 0.06). Neither physical nor psychosocial summary scores for HRQL had any correlation with right ventricle MPI. CONCLUSIONS: Right ventricle dysfunction is present in postoperative ToF patients. The psychosocial domain of HRQL is preserved after surgery. A trend for worse results was observed in the physical domain. The right ventricle function is not related to quality of life after surgical repair of ToF.

The role of adrenergic receptor polymorphisms in heart failure.

The main function of the cardiac adrenergic system is to regulate cardiac work both in physiologic and pathologic states. A better understanding of this system has permitted the elucidation of its role in the development and progression of heart failure. Regardless of the initial insult, depressed cardiac output results in sympathetic activation. Adrenergic receptors provide a limiting step to this activation and their sustained recruitment in chronic heart failure has proven to be deleterious to the failing heart. This concept has been confirmed by examining the effect of beta-blockers on the progression of heart failure. Studies of adrenergic receptor polymorphisms have recently focused on their impact on the adrenergic system regarding its adaptive mechanisms, susceptibilities and pharmacological responses. In this article, we review the function of the adrenergic system and its maladaptive responses in heart failure. Next, we discuss major adrenergic receptor polymorphisms and their consequences for heart failure risk, progression and prognosis. Finally, we discuss possible therapeutic implications resulting from the understanding of polymorphisms and the identification of individual genetic characteristics.

The role of adrenergic receptor polymorphisms in heart failure

The main function of the cardiac adrenergic system is to regulate cardiac work both in physiologic and pathologic states. A better understanding of this system has permitted the elucidation of its role in the development and progression of heart failure. Regardless of the initial insult, depressed cardiac output results in sympathetic activation. Adrenergic receptors provide a limiting step to this activation and their sustained recruitment in chronic heart failure has proven to be deleterious to the failing heart. This concept has been confirmed by examining the effect of ß-blockers on the progression of heart failure. Studies of adrenergic receptor polymorphisms have recently focused on their impact on the adrenergic system regarding its adaptive mechanisms, susceptibilities and pharmacological responses. In this article, we review the function of the adrenergic system and its maladaptive responses in heart failure. Next, we discuss major adrenergic receptor polymorphisms and their consequences for heart failure risk, progression and prognosis. Finally, we discuss possible therapeutic implications resulting from the understanding of polymorphisms and the identification of individual genetic characteristics.

The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis.

End-stage renal disease (ESRD) patients frequently develop structural cardiac abnormalities, particularly left ventricular hypertrophy (LVH). The mechanisms involved in these processes are not completely understood. In the present study, we evaluated a possible association between parathyroid hormone (PTH) levels and left ventricular mass (LVM) in patients with ESRD. Stable uremic patients on intermittent hemodialysis treatment were evaluated by standard two-dimensional echocardiography and their sera were analyzed for intact PTH. Forty-one patients (mean age 45 years, range 18 to 61 years), 61% males, who had been on hemodialysis for 3 to 186 months, were evaluated. Patients were stratified into 3 groups according to serum PTH: low levels (< 100 pg/ml; group I = 10 patients), intermediate levels (100 to 280 pg/ml; group II = 10 patients) and high levels (> 280 pg/ml; group III = 21 patients). A positive statistically significant association between LVM index and PTH was identified (r = 0.34; P = 0.03, Pearson's correlation coefficient) in the sample as a whole. In subgroup analyses, we did not observe significant associations in the low and intermediate PTH groups; nevertheless, PTH and LVM index were correlated in patients with high PTH levels (r = 0.62; P = 0.003). LVM index was also inversely associated with hemoglobin (r = -0.34; P = 0.03). In multivariate analysis, after adjustment for age, hemoglobin, body mass index, and blood pressure, the only independent predictor of LVM index was PTH level. Therefore, PTH is an independent predictor of LVH in patients undergoing chronic hemodialysis. Secondary hyperparathyroidism may contribute to the elevated cardiovascular morbidity associated with LVH in ESRD.

The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis

End-stage renal disease (ESRD) patients frequently develop structural cardiac abnormalities, particularly left ventricular hypertrophy (LVH). The mechanisms involved in these processes are not completely understood. In the present study, we evaluated a possible association between parathyroid hormone (PTH) levels and left ventricular mass (LVM) in patients with ESRD. Stable uremic patients on intermittent hemodialysis treatment were evaluated by standard two-dimensional echocardiography and their sera were analyzed for intact PTH. Forty-one patients (mean age 45 years, range 18 to 61 years), 61 percent males, who had been on hemodialysis for 3 to 186 months, were evaluated. Patients were stratified into 3 groups according to serum PTH: low levels (<100 pg/ml; group I = 10 patients), intermediate levels (100 to 280 pg/ml; group II = 10 patients) and high levels (>280 pg/ml; group III = 21 patients). A positive statistically significant association between LVM index and PTH was identified (r = 0.34; P = 0.03, Pearson's correlation coefficient) in the sample as a whole. In subgroup analyses, we did not observe significant associations in the low and intermediate PTH groups; nevertheless, PTH and LVM index were correlated in patients with high PTH levels (r = 0.62; P = 0.003). LVM index was also inversely associated with hemoglobin (r = -0.34; P = 0.03). In multivariate analysis, after adjustment for age, hemoglobin, body mass index, and blood pressure, the only independent predictor of LVM index was PTH level. Therefore, PTH is an independent predictor of LVH in patients undergoing chronic hemodialysis. Secondary hyperparathyroidism may contribute to the elevated cardiovascular morbidity associated with LVH in ESRD.

Impact of age on perioperative complications and length of stay in patients undergoing noncardiac surgery.

BACKGROUND: Major surgical procedures are performed with increasing frequency in elderly persons, but the impact of age on resource use and outcomes is uncertain. OBJECTIVE: To evaluate the influence of age on perioperative cardiac and noncardiac complications and length of stay in patients undergoing noncardiac surgery. DESIGN: Prospective cohort study. SETTING: Urban academic medical center. PATIENTS: Consecutive sample of 4315 patients 50 years of age or older who underwent nonemergent major noncardiac procedures. MEASUREMENTS: Major perioperative complications (cardiac and noncardiac), in-hospital mortality, and length of stay. RESULTS: Major perioperative complications occurred in 4.3% (44 of 1015) of patients 59 years of age or younger, 5.7% (93 of 1646) of patients 60 to 69 years of age, 9.6% (129 of 1341) of patients 70 to 79 years of age, and 12.5% (39 of 313) of patients 80 years of age or older (P < 0.001). In-hospital mortality was significantly higher in patients 80 years of age or older than in those younger than 80 years of age (0.7% vs. 2.6%, respectively). Multivariate analyses indicated an increased odds ratio for perioperative complications or in-hospital mortality in patients 70 to 79 years of age (1.8 [95% CI, 1.2 to 2.7]) and those 80 years of age or older (OR, 2.1 [CI, 1.2 to 3.6]) compared with patients 50 to 59 years of age. Patients 80 years of age or older stayed an average of 1 day more in the hospital, after adjustment for other clinical data (P = 0.001). CONCLUSIONS: Elderly patients had a higher rate of major perioperative complications and mortality after noncardiac surgery and a longer length of stay, but even in patients 80 years of age or older, mortality was low.

Three-dimensional return map: a new tool for quantification of heart rate variability.

BACKGROUND: Several methods are used to study heart rate variability, but they have limitations, which might be overcome by the use of a three-dimensional return map. OBJECTIVES: To evaluate the performance of three-dimensional return map-derived indices to detect (1) sympathetic and parasympathetic modulation to the sinus node and (2) autonomic dysfunction in diabetic patients. METHODS: Six healthy subjects underwent partial and total pharmacological autonomic blockade in a protocol that incorporated vagal and sympathetic predominance. Twenty-two patients with type 2 diabetes mellitus and 12 normal controls participated in the subsequent validation experiment. Three-dimensional return maps were constructed by plotting RRn intervals versus the difference between adjacent RR intervals [(RRn+1)-(RRn)] versus the number of counts, and four derived indices (P1, P2, P3, MN) were created for quantification. RESULTS: Both indices P1 and MN were significantly increased after sympathetic blockade with propranolol, while all indices except P1 were modified after parasympathetic blockade (P < 0.05). During the validation experiments, P1 and MN detected differences between normal controls, and diabetic patients with and without autonomic neuropathy. The overall accuracy of most three-dimensional indices to detect autonomic dysfunction, estimated by the area under the ROC curve, was significantly better than traditional time domain indices. Three-dimensional return map-derived indices also showed adequate reproducibility on two different recording days (intra-class correlation coefficients of 0.69 to 0.82; P < 0.001). CONCLUSIONS: Three-dimensional return map-derived indices are reproducible, quantify parasympathetic as well as sympathetic modulation to the sinus node, and are capable of detecting autonomic dysfunction in diabetic patients.

Circulating endothelin-1 and tumor necrosis factor-alpha: early predictors of mortality in patients with septic shock.

OBJECTIVES: To determine the predictive value of early determination of tumor necrosis factor (TNF)-alpha, TNF-alpha 1 and 2 soluble receptors (sTNFR1 and sTNFR2) and endothelin-1 (ET-1) for mortality in patients with septic shock. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS: Twenty-one patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients with septic shock had a pulmonary artery catheter inserted and blood samples drawn at time zero, 6, 12 and 24 h, simultaneously with hemodynamic assessments. Plasma levels of all markers were measured by ELISA. All patients were followed up to hospital discharge or death. Age and APACHE II scores were significantly higher in nonsurvivors (n = 11) than in survivors (n = 10). Hemodynamic assessments did not aid in the discrimination between the two groups of patients (P > 0.05). Levels of TNF-alpha were higher in nonsurvivors than in survivors at all time-points. sTNFR1 and sTNFR2 were also significantly elevated in nonsurvivors, but not in all measurements. Endothelin-1, however, was significantly higher in nonsurvivors than in survivors only at 6 h (P = 0.02). When both TNF-alpha and ET-1 were increased at early time-points, the best predictive values for mortality were obtained [positive and negative predictive values of 72 and 100% at 6 h, odds ratio 3.0, 95% CI (1.2-7.6)]. CONCLUSIONS: Increased levels of TNF-alpha were consistently higher at all time-points in nonsurvivors with septic shock. ET-1 levels, however, appeared also to be an early and sensitive predictor of mortality. Very early determination of TNF-alpha and ET-1 in septic shock may help to identify patients at higher risk for adverse outcome.

Effect of partial arrhythmia suppression with amiodarone on heart rate variability of patients with congestive heart failure.

BACKGROUND: Some antiarrythmic agents that may increase mortality rates have been shown to reduce heart rate variability in patients with heart failure. Amiodarone is a potent antiarrhythmic agent that may reduce mortality rates in heart failure, but little is known about its effects on heart rate variability. METHODS AND RESULTS: The purpose of this study was to evaluate the effect of partial arrhythmia suppression by amiodarone on indexes of heart rate variability in patients with heart failure. Ten clinically stable patients in New York Heart Association class II-III received amiodarone during a 4-week period (600 mg every day for 14 days and 300 mg every day for 16 days), and 24-hour Holter recordings were performed before and after treatment. Heart rate variability indexes were calculated by a semiautomatic method that applies a 20% filter to the temporal series, excluding ectopy and compensatory pauses. After amiodarone administration, there was a significant reduction in pNN50 from 8% +/- 7% to 3% +/- 2% (p < 0.05) and there was a trend toward reduction in rMSSD (p = 0.06). Other time domain indexes did not change significantly. Spectral analysis demonstrated a significant reduction of low-frequency components (421 +/- 122 to 151 +/- 25 msec2; p < 0.05) and total power (1503 +/- 314 to 609 +/- 144 msec2, p < 0.05). Multivariate analysis showed that the observed reduction in pNN50 was strongly associated with the number and the reduction of ventricular premature contractions before and after amiodarone administration (r2 = 0.94; p < 0.01). CONCLUSIONS: These findings indicate that despite the use of software corrections for arrhythmia, short-term time domain indexes of heart rate variability may be affected by partial suppression of ectopy.

[Problems and solutions in the interpretation of diagnostic tests]. / Problemas y soluciones en la interpretación de pruebas diagnósticas.

The interpretation of diagnostic tests has had a remarkable progress in recent years with a tendency towards a more clinical and patient-oriented perspective. Here we emphasize the limitations of using the dichotomy positive/negative testing or cut-off points for normality in many of our medical decisions. We also introduce alternative methods to interpret diagnostic tests, specially in unusual circumstances, i.e., in the development of new diagnostic tests that may be better than the accepted gold standard or when there is no gold standard. Finally we analyze the different interpretations of false negative results that may modify the interpretation of subsequent testing in a patient.

Sympathetic nervous system representation in time and frequency domain indices of heart rate variability.

This study evaluated the contributions of sympathetic and parasympathetic modulation to heart rate variability during situations in which vagal and sympathetic tone predominated. In a placebo-controlled, randomized, double blind blockade study, six young healthy male individuals received propranolol (0.2 mg x kg(-1)), atropine (0.04 mg x kg(-1)), propranolol plus atropine, or placebo infusions over 4 days. Time-domain indices were calculated during 40 min of rest and 20 min of exercise at 70% of maximal exercise intensity. Spectrum analysis, using fast Fourier transformation, was also performed at rest and during the exercise. The time-domain indices standard deviation of R-R intervals, mean of the standard deviations of all R-R intervals for all 5-min segments, percentage of number of pairs of adjacent R-R intervals differing by more than 50 ms, and square root of the mean of the sum of squares of differences between adjacent R-R intervals were reduced after atropine and propranolol plus atropine. Propranolol alone caused no appreciable change in any of the time-domain indices. At rest, all spectrum components were similar after placebo and propranolol infusions, but following parasympathetic and double autonomic blockade there was a reduction in all components of the spectrum analysis, except for the low:high ratio. During exercise, partial and double blockade did not change significantly any of the spectrum components. Thus, time and frequency-domain indices of heart rate variability were able to detect vagal activity, but could not detect sympathetic activity. During exercise, spectrum analysis is not capable of evaluating autonomic modulation of heart rate.

[Measuring the impact of medical interventions at the individual level]. / Medición del impacto de intervenciones médicas a nivel individual.

Medical interventions have a variable response among individuals. It is desirable to detect patients who are getting a therapeutic benefit. Any medical intervention has to show a favorable effect in survival and/or control of symptoms in order to be considered useful. In many clinical scenarios, laboratory test results are not enough to be confident of the effectiveness of a treatment. In order to do a clinical evaluation focused on patients' interests, we suggest the use of instruments to measure quality of life. Currently there are quality of life scales that have undergone a rigorous process of validation and reliability. Sub-group analysis is frequently used to predict an individual benefit of medical interventions. In the interpretation of sub-group analysis, it is important to be aware of the risk of misinterpretation, making false positive or false negative conclusions about the effect of the treatment. The N-of-1 trial is a valid scientific alternative to define individual effectiveness of therapy. Defining the degree of therapeutic benefit timely we avoid useless therapies, unnecessary side effects, and sequelae secondary to the lack of opportune treatment.