Hemodynamic tolerability and anti-ischemic efficacy of high dose intravenous diltiazem in patients with normal versus impaired ventricular function

AbstractObjectives. This study was designed to compare the acute systemic and coronary hemodynamic effects of high doses of intravenous diltiazem in patients with normal versus impaired left ventricular function, investigate the safety of this drug and compare its anti-ischemic potential in these two patient groups during pacing-induced stress.Background. Because coronary hemodynamic effects and negative inotropic properties of diltiazem are dose related, high dose intravenous diltiazem may improve anti-ischemic efficacy but may not be tolerated in patients with impaired cardiac function.Methods. High dose intravenous diltiazem, 0.4 mg/kg for 5 min followed by 0.4 mg/kg for 10 min, was administered to 23 normotensive patient's with coronary artery disease, 11 (group A) with normal and 12 (group B) with impaired ventricular function (ejection fraction <45%) during two identical atrial pacing stress tests performed 30 min before (pacing test I) and immediately after diltiazem (pacing test II).Results. Diltiazem was well tolerated despite high peak plasma levels, 869 ± 152 μ/liter (group A) and 926 ± 169 μgliter (group B). It resulted in immediate but similar reductions in systemic resistance from 1,321 ± 136 (control value) to 963 ± 113 dynes·s·cm−5(group A) and from 1,267 ± 106 to 865 ± 58 dynes ·s·cm−5(group B) and in mean arterial pressure from 107 ± 3 to 93 ± 4 mm Hg (group A) and from 103 ± 4 to 86 ± 4 mm Hg (group B), at 5 min after diltiazem (all p < 0.05 vs. control value). Diltiazem improved stroke output from 36 ± 3 (control value) to 46 ± 4 mi/beat per m2in group 6 and from 44 ± 4 (control value) to 49 ± 5 ml/beat per m2in group A, an effect that was significantly greater and more prolonged in group B than in group A. Although neither heart rate nor contractility was affected in either group, left ventricular end-diastolic pressure increased in group A (9 ± 2 mm Hg to 12 ± 1 mm Hg, p < 0.05) but not in group B. Despite similar reductions in coronary resistance and improvements in coronary flow, diltiazem consistently reduced myocardial oxygen extraction, but only in group B. Also, the anti-ischemic effects of diltiazem were more pronounced in group B. During pacing test II, myocardial lactate extraction normalized in group B (7 ± 5% vs. −6 ± 12% [pacing test I]) but not in group A, contractility indexes improved more and the increase in left ventricular filling pressure was reduced to a greater extent in group B. Moreover, the ischemia-induced increase in arterial pressures, observed in both groups during pacing test I, was prevented in group B but recurred in group A during pacing test II.Conclusions. High dose intravenous diltiazem is well tolerated, augments coronary flow and improves left ventricular pump function, particularly in patients with preexisting ventricular dysfunction. As its anti-ischemic effects also appear more pronounced in the latter group, high dose diltiazem may be particularly useful when ventricular function is depressed, for example, during prolonged ischemia at rest

Ischaemic heart disease in Turkish migrants with type 2 diabetes mellitus in The Netherlands: wait for the next generation?

OBJECTIVE: To study the prevalence of ischaemic heart disease in Turkish and Surinam-Asian migrants with type 2 diabetes mellitus in the Netherlands as compared with Europeans. METHODS: In a consecutive case-control study, 59 Turkish and 62 Surinam-Asian patients were compared with 185 Europeans referred to a diabetes clinic for treatment of type 2 diabetes in the period 1992 to 1998. Main outcome measures were ischaemic heart disease and its associated risk factors. RESULTS: The prevalence of ischaemic heart disease was lower (9%) in the Turks (p < 0.02), but higher (29%) in the Surinam-Asians compared with the Europeans (23%). The Turks (52 +/- 10 years) and Surinam-Asians (46 +/- 12 years) were younger than the Europeans (64 +/- 11 years, p < 0.001). Body mass index was 32 +/- 5 (p < 0.001) in the Turks, 27 +/- 5 in the Surinam-Asians (p < 0.05) and 29 +/- 5 in the Europeans. Turkish patients smoked less (23%, p < 0.05) and used less alcohol (4%, p < 0.05) than the Europeans. Proteinuria was found in 24% of the Turks (p < 0.05), 37% of the Surinam-Asians (NS) and 46% of the Europeans. In univariate analysis ischaemic heart disease was related to Turkish origin, OR 0.34 (0.14-0.83) p < 0.02, to Surinam-Asian origin, OR 1.84 (1.00-3.38) p = 0.05, and smoking, OR 1.78 (1.18-2.68) p < 0.01. Other variables were not related to ischaemic heart disease. Multivariate analysis in a model with ethnicity and smoking showed significant relations between ischaemic heart disease and Turkish ethnicity, OR 0.19 (0.06-0.65) p = 0.007, Surinam-Asian origin, OR 2.77 (1.45-5.28) p = 0.002, and smoking, OR 1.79 (1.20-2.66) p = 0.004. CONCLUSION: Type 2 diabetes mellitus in different ethnic groups results in a significant difference in incidence of ischaemic heart disease. The most remarkable finding is a low incidence of ischaemic heart disease in the Turkish patients with type 2 diabetes, independent of smoking. The high prevalence of ischaemic heart disease in young migrant Asians with diabetes is confirmed

Effects of antidepressant treatment on heart rate variability in major depression: A quantitative review

<p>Abstract</p> <p>Background</p> <p>The literature measuring effects of antidepressant and electroconvulsive therapy (ECT) for major depression on heart rate variability (HRV) in medically well individuals was reviewed.</p> <p>Methods</p> <p>Fourteen studies evaluating HRV were included. Twenty three pre-post or within group comparisons were available. Treatment impact on measures of HRV was pooled over studies. We examined different classes of antidepressants, and for short and long electrocardiogram (ECG) recordings separately.</p> <p>Results</p> <p>Tricyclic antidepressants (TCAs) were associated with declines in most measures of HRV and significant increase in heart rate (HR) in studies with short recording intervals. No significant changes were found for longer recording times.</p> <p>Treatment effects with selective serotonin reuptake inhibitors (SSRIs) were more variable. Short-recording studies revealed a significant decrease in HR and an increase in one HRV measure. In two 24-hour recording studies no significant changes were observed. No relationship between ECT and HRV has been established in the literature. The effects of other drugs are reported.</p> <p>Limitations</p> <p>Few studies measure the effects of treatment of depression on HRV. Existing studies have generally used very small samples, employing a variety of measurements and methodologies.</p> <p>Conclusion</p> <p>We confirm that TCAs are associated with a large decrease in HRV and increase HR. However, data for SSRIs is not clear. Although the effect of SSRIs on HRV is weaker than for TCAs, evidence shows that SSRIs are associated with a small decrease in HR, and an increase in one measure of HRV. The use of TCAs in depression leads to changes in HRV that are associated with increased risk of mortality.</p

Complex systems and the technology of variability analysis

Characteristic patterns of variation over time, namely rhythms, represent a defining feature of complex systems, one that is synonymous with life. Despite the intrinsic dynamic, interdependent and nonlinear relationships of their parts, complex biological systems exhibit robust systemic stability. Applied to critical care, it is the systemic properties of the host response to a physiological insult that manifest as health or illness and determine outcome in our patients. Variability analysis provides a novel technology with which to evaluate the overall properties of a complex system. This review highlights the means by which we scientifically measure variation, including analyses of overall variation (time domain analysis, frequency distribution, spectral power), frequency contribution (spectral analysis), scale invariant (fractal) behaviour (detrended fluctuation and power law analysis) and regularity (approximate and multiscale entropy). Each technique is presented with a definition, interpretation, clinical application, advantages, limitations and summary of its calculation. The ubiquitous association between altered variability and illness is highlighted, followed by an analysis of how variability analysis may significantly improve prognostication of severity of illness and guide therapeutic intervention in critically ill patients

Reduced costs with bisoprolol treatment for heart failure - An economic analysis of the second Cardiac Insufficiency Bisoprolol Study (CIBIS-II)

Background Beta-blockers, used as an adjunctive to diuretics, digoxin and angiotensin converting enzyme inhibitors, improve survival in chronic heart failure. We report a prospectively planned economic analysis of the cost of adjunctive beta-blocker therapy in the second Cardiac Insufficiency BIsoprolol Study (CIBIS II). Methods Resource utilization data (drug therapy, number of hospital admissions, length of hospital stay, ward type) were collected prospectively in all patients in CIBIS . These data were used to determine the additional direct costs incurred, and savings made, with bisoprolol therapy. As well as the cost of the drug, additional costs related to bisoprolol therapy were added to cover the supervision of treatment initiation and titration (four outpatient clinic/office visits). Per them (hospital bed day) costings were carried out for France, Germany and the U.K. Diagnosis related group costings were performed for France and the U.K. Our analyses took the perspective of a third party payer in France and Germany and the National Health Service in the U.K. Results Overall, fewer patients were hospitalized in the bisoprolol group, there were fewer hospital admissions perpatient hospitalized, fewer hospital admissions overall, fewer days spent in hospital and fewer days spent in the most expensive type of ward. As a consequence the cost of care in the bisoprolol group was 5-10% less in all three countries, in the per them analysis, even taking into account the cost of bisoprolol and the extra initiation/up-titration visits. The cost per patient treated in the placebo and bisoprolol groups was FF35 009 vs FF31 762 in France, DM11 563 vs DM10 784 in Germany and pound 4987 vs pound 4722 in the U.K. The diagnosis related group analysis gave similar results. Interpretation Not only did bisoprolol increase survival and reduce hospital admissions in CIBIS II, it also cut the cost of care in so doing. This `win-win' situation of positive health benefits associated with cost savings is Favourable from the point of view of both the patient and health care systems. These findings add further support for the use of beta-blockers in chronic heart failure

Effect of Systemic Hypertension With Versus Without Left Ventricular Hypertrophy on the Progression of Atrial Fibrillation (from the Euro Heart Survey).

Hypertension is a risk factor for both progression of atrial fibrillation (AF) and development of AF-related complications, that is major adverse cardiac and cerebrovascular events (MACCE). It is unknown whether left ventricular hypertrophy (LVH) as a consequence of hypertension is also a risk factor for both these end points. We aimed to assess this in low-risk AF patients, also assessing gender-related differences. We included 799 patients from the Euro Heart Survey with nonvalvular AF and a baseline echocardiogram. Patients with and without hypertension were included. End points after 1 year were occurrence of AF progression, that is paroxysmal AF becoming persistent and/or permanent AF, and MACCE. Echocardiographic LVH was present in 33% of 379 hypertensive patients. AF progression after 1 year occurred in 10.2% of 373 patients with rhythm follow-up. In hypertensive patients with LVH, AF progression occurred more frequently as compared with hypertensive patients without LVH (23.3% vs 8.8%, p = 0.011). In hypertensive AF patients, LVH was the most important multivariably adjusted determinant of AF progression on multivariable logistic regression (odds ratio 4.84, 95% confidence interval 1.70 to 13.78, p = 0.003). This effect was only seen in male patients (27.5% vs 5.8%, p = 0.002), while in female hypertensive patients, no differences were found in AF progression rates regarding the presence or absence of LVH (15.2% vs 15.0%, p = 0.999). No differences were seen in MACCE for hypertensive patients with and without LVH. In conclusion, in men with hypertension, LVH is associated with AF progression. This association seems to be absent in hypertensive women

Progression From Paroxysmal to Persistent Atrial Fibrillation. Clinical Correlates and Prognosis

Objectives: We investigated clinical correlates of atrial fibrillation (AF) progression and evaluated the prognosis of patients demonstrating AF progression in a large population. Background: Progression of paroxysmal AF to more sustained forms is frequently seen. However, not all patients will progress to persistent AF. Methods: We included 1,219 patients with paroxysmal AF who participated in the Euro Heart Survey on AF and had a known rhythm status at follow-up. Patients who experienced AF progression after 1 year of follow-up were identified. Results: Progression of AF occurred in 178 (15%) patients. Multivariate analysis showed that heart failure, age, previous transient ischemic attack or stroke, chronic obstructive pulmonary disease, and hypertension were the only independent predictors of AF progression. Using the regression coefficient as a benchmark, we calculated the HATCH score. Nearly 50% of the patients with a HATCH score &gt;5 progressed to persistent AF compared with only 6% of the patients with a HATCH score of 0. During follow-up, patients with AF progression were more often admitted to the hospital and had more major adverse cardiovascular events. Conclusions: A substantial number of patients progress to sustained AF within 1 year. The clinical outcome of these patients regarding hospital admissions and major adverse cardiovascular events was worse compared with patients demonstrating no AF progression. Factors known to cause atrial structural remodeling (age and underlying heart disease) were independent predictors of AF progression. The HATCH score may help to identify patients who are likely to progress to sustained forms of AF in the near future. \ua9 2010 American College of Cardiology Foundation