A novel flow-based parameter of collateral function assessed by intracoronary thermodilution.

BACKGROUND: Currently, many methods for quantitation of coronary collateral function are based on intracoronary pressure measurements distal of an occluded balloon, which do not fully account for the dynamic nature of collateral flow. Therefore, a flow-based parameter of coronary collateral function based upon principles of thermodilution was evaluated. METHODS: In 26 patients with a high-grade coronary artery stenosis, intracoronary hemodynamics were analyzed by the RadiAnalyzer system (St Jude Medical), including fractional flow reserve (FFR), index of microcirculatory resistance (IMR), and the pressure-based collateral flow index (CFI) during balloon occlusion and hyperemia (intravenous adenosine). Moreover, immediately after an intracoronary bolus of room-temperature saline, the balloon was occluded and the intracoronary temperature distal to the balloon was analyzed over time. The slope of the temperature-time curve was calculated after logarithmic transformation as an index of collateral blood flow (CBFI). RESULTS: The coefficient of variation between two measurements of CBFI amounted to 11 ± 2%. In patients with CFI ≥0.25, CBFI amounted to 0.55 ± 0.09, whereas in those with CFI <0.25, CBFI was 0.37 ± 0.03. CBFI correlated significantly with CFI (r = 0.65; P<.001). Interestingly, in the subgroup with IMR below the median (<14.2 mm Hg · s), the slope of the linear regression for CBFI vs CFI was steeper than in individuals with higher IMR, which indicates more effective collateral flow for any given intracoronary pressure distal to the occluded balloon in the group with lower microvascular resistance. CONCLUSIONS: This novel index might be useful as a flow-based index of collateral function, and should be evaluated in further studies.

Efficacy of a minicourse in radiation-reducing techniques in invasive cardiology: a multicenter field study.

OBJECTIVES: Our goal was to validate an educational 90-min minicourse in lower-irradiating cardiac invasive techniques. BACKGROUND: Despite comprehensive radiation safety programs, patient radiation exposure in invasive cardiology remains considerable. METHODS: Before and at a median period of 3.7 months after the minicourse at 32 German cardiac centers, 177 interventionalists consistently documented radiation parameters for 10 coronary angiographies: dose area product (DAP), radiographic and fluoroscopic fractions, fluoroscopy time, and number of radiographic frames and runs. RESULTS: A total of 154 cardiologists attended the minicourse and achieved significant (p < 0.001) decrease in patients' median overall DAP (-48.4%), from baseline 26.5 to 13.7 Gy × cm(2). They reduced fluoroscopy times (-20.8%), radiographic runs (-9.1%), frames/run (-18.6%) and frames (-29.6%), and both radiographic DAP/frame (-27.4%) and fluoroscopic DAP/s (-39.3%), which indicate improved collimation, reduced-irradiation angulations, or adequate image quality. Dose-related parameters for the remaining 23 invited cardiologists unable to attend the workshop did not change significantly in univariate comparison. Multilevel analysis (p < 0.001) confirmed the efficacy of the minicourse itself (-14.7 Gy × cm(2)) and revealed higher DAP for increasing body mass index (+1.5 Gy × cm(2) per kg/m(2)), male sex (+5.8 Gy × cm(2)), age (+1.5 Gy × cm(2)/decade), and-owing to different settings during image acquisition-for advanced flat-panel detector systems (+9.0 Gy × cm(2)) versus older, traditional image intensifier systems. CONCLUSIONS: Despite significant required training in radiation safety for all interventional cardiologists, the presented additional 90-min minicourse significantly reduced patient dose.

Do patients with type 1 and type 2 diabetes really have an impaired endothelial function? A population-based propensity score matching analysis.

BACKGROUND: Previous studies suggested an impaired endothelial function in patients with diabetes. However, the validity of this finding may be limited by the lack of adequate adjustment for further cardiovascular confounders. We assessed endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery in patients with either type 1 or type 2 diabetes in comparison with non-diabetic controls. METHODS: The study population comprised 1487 subjects including 122 subjects with type 2 diabetes, aged 25 to 85, from the population-based Study of Health in Pomerania, and 65 outpatients, aged 23 to 75, with type 1 diabetes. FMD measurements were performed using standardized ultrasound techniques. Subjects with type 1 and type 2 diabetes were matched 1:4 to healthy controls using propensity score matching. RESULTS: Neither type 1 diabetes (ß = 0.142; SE = 0.568, p = 0.803) nor type 2 diabetes (ß = 0.107; SE = 0.340, p = 0.752) were significantly associated with FMD in comparison with their non-diabetic controls after adjustment for major cardiovascular confounders like age, gender, body mass index, smoking status, hypertension, antihypertensive medication, LDL and HDL cholesterol levels. CONCLUSIONS: In this population-based study comparing adjusted FMD values of diabetic individuals with adequately matched controls, propensity score analyses revealed no association between diabetes and endothelial function. Since these findings are in discordance with the majority of previous reports, we suggest performing similar analyses using data from other population-based studies.

Subclinical hyperthyroidism is not associated with progression of cardiac mass and development of left ventricular hypertrophy in middle-aged and older subjects: results from a 5-year follow-up.

BACKGROUND: Decreased serum TSH levels are associated with increased cardiovascular mortality in elderly, and subclinical hyperthyroidism (SCH) was associated with left ventricular hypertrophy (LVH) as a predictor of cardiovascular mortality in some cross-sectional and case-control studies. The aim was to assess whether SCH independently impacts development of LVH over time. METHODS: Of 3300 participants of the population-based Study of Health in Pomerania those with overt hyperthyroidism, hypothyroidism, possible thyroid disease or missing echocardiographic baseline data or follow-up were excluded, resulting in a study population of 1112 individuals (556 women) aged 45-81 years. Echocardiographic left ventricular mass divided by height(2·7) (LVMI(ht)), and LVH(ht) (LVMI(ht) > 44 g/m(2·7) in women and > 48 g/m(2·7) in men) was measured at baseline and after 5-year follow-up (median 5·00; range 4·92; 5·08). Comparison of subjects with (n = 107) and without (n = 1005) SCH were made by linear and logistic regression models adjusted for age, gender, smoking status, hypertension, and waist circumference. RESULTS: At follow-up, LVMI(ht) did not differ between subjects with and without SCH (50·2 g/m(2·7), interquartile range (IQR) 41·2; 59·5 vs 47·8 g/m(2·7), IQR 39·3; 56·9; P = 0·29). LVH(ht) was present in 66 (61·7%) subjects with and 543 (54·0%) persons without SCH (P = 0·13). Analyses revealed no association between SCH and progression of LVMI(ht) (ß = -0·18; 95%-confidence interval (CI) -2·34; -1·99; P = 0·873), and development of LVH(ht) (relative risk 0·86, 95%-CI 0·60; 1·26; P = 0·462), respectively. CONCLUSIONS: In this population-based sample, SCH had no impact on progression of LVMI and development of LVH during 5-year follow-up in subjects aged 45 years or older.

Mild renal dysfunction as a non-traditional cardiovascular risk factor?-Association of cystatin C-based glomerular filtration rate with flow-mediated vasodilation.

OBJECTIVE: Chronic kidney disease, at least in its advanced stages, can be regarded as a non-traditional cardiovascular risk factor. The purpose of this study was to evaluate whether early stages of renal dysfunction are associated with flow-mediated vasodilatation, as an early marker of the atherosclerotic disease process. METHODS: In 1515 subjects (753 females) from the population-based Study of Health in Pomerania, the relationship between flow-mediated vasodilatation of the brachial artery (cuff occlusion of the forearm for 5 min) and glomerular filtration rate, estimated on the basis of serum cystatin C levels, was analyzed under consideration of various cardiovascular risk factors. RESULTS: Flow-mediated vasodilatation was 5.75 + or - 0.16% in women and 4.29+/-0.12% in men (mean + or - SEM). Glomerular filtration rate amounted to 94.2 + or - 0.7 ml/min/1.73 m(2), with 8.1% subjects with glomerular filtration rate < or = 60 ml/min/1.73 m(2). Flow-mediated vasodilatation significantly correlated with glomerular filtration rate in the entire population (r=0.237, p<0.001), in women (r=0.224, p<0.001) and in men (r=0.168, p<0.001). Adjusting for age and multiple cardiovascular risk factors and also for high-sensitive C-reactive protein levels revealed a significant association of flow-mediated vasodilatation and glomerular filtration rate in women (p=0.01), but not in men, with similar results when the analyses were restricted to individuals with glomerular filtration rate >60 ml/min/1.73 m(2). CONCLUSION: Mild reduction in renal function is associated with alterations in endothelial function in females. Hence, very mild alterations in kidney function may also be regarded as a cardiovascular risk factor at least in women.

Heart valve sclerosis predicts all-cause and cardiovascular mortality.

OBJECTIVES: Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) might predict future adverse events. We undertook the present study to investigate the association of AVS and MAC with all-cause and cardiovascular mortality. We further studied whether a combined presence of AVS and MAC is more strongly associated with mortality than the single items and sought to disclose possible gender differences in the investigated associations. METHODS: We used data from 2081 participants aged > or =45 years (1063 women) of the Study of Health in Pomerania (SHIP). AVS and MAC were determined echocardiographically, and a heart valve sclerosis score was calculated by summing up the AVS and MAC variables. The median duration of mortality follow-up was 8.6 years (17,162 person-years). RESULTS: There were 528 subjects (25.4%) with isolated AVS, 35 with isolated MAC (1.7%) and 89 with both AVS and MAC (4.3%). A total number of 228 deaths (11.0%) occurred during follow-up, including 133 (21.6%) with AVS and 95 subjects (6.5%) without AVS (incidence rate ratio 3.49, 95% CI 2.77; 4.40, p<0.001). Likewise, mortality rates were higher for subjects with MAC than subjects without MAC (incidence rate ratio 3.79, 95% CI 2.82; 5.02, p<0.001). Multivariable analyses revealed that the associations of AVS and MAC with all-cause and cardiovascular mortality were independent of major confounders and strongest for highest values of the heart valve sclerosis score. AVS-related mortality was more pronounced in women than in men. CONCLUSION: AVS and MAC are associated with all-cause and cardiovascular mortality. The association between AVS and mortality is gender-specific with women with AVS being at a higher mortality risk than men with AVS. The summation of AVS and MAC to a heart valve sclerosis score improves the predictability with respect to mortality.

Intracoronary blood- or bone marrow-derived cell transplantation in patients with ischemic heart disease.

Soon after the first experimental scientific investigations of cell transplantation in various animal models of myocardial infarction and left ventricular dysfunction, a growing number of clinical trials evaluated the effects of intracoronary injection of peripheral blood- or bone marrow-derived cells in patients with myocardial infarction or chronic ischemic heart disease. In most of these trials, changes in parameters of left ventricular remodeling over time, such as left ventricular volumes, ejection fraction or infarct size, were used as trial end points, whereas information on mortality and morbidity after cell transplantation is sparse. Several meta-analyses, each including various sets of studies, estimated that intracoronary cell therapy was associated with small reductions in left ventricular end-systolic volumes and a moderate increase in left ventricular ejection fraction of 2.9-6.1% over time compared with control patients. As most of the clinical trials included a limited number of patients, results vary substantially between different studies. When evaluating whether effects of intracoronary cell transplantation on parameters of left ventricular remodeling may be transferable to meaningful consequences in terms of clinical outcome, the following aspects appear to be imperative. Robust data on mortality and clinical events based on a sufficient number of patients are required. Furthermore, effects of cell therapy must be compared with established therapeutic concepts for the treatment of myocardial infarction, such as reperfusion therapy or pharmacological interventions aiming at favorably influencing the remodeling process. Moreover, the potential effects of cell therapy must be evaluated as treatment options additive to established therapeutic strategies.

Quinaprilat: a review of its pharmacokinetics, pharmacodynamics, toxicological data and clinical application.

BACKGROUND: Quinaprilat is an ACE inhibitor for intravenous use especially in patients with arterial hypertension or chronic heart failure. In contrast to the oral prodrug quinapril, it has not been approved for clinical application. OBJECTIVE: In this review, the pharmacokinetic and pharmacodynamic profile of quinaprilat as well as toxicological data and results of preclinical and clinical studies are summarized. METHODS: In a PubMed search for the terms "quinaprilat" and "quinapril", literature relevant for this review was selected. RESULTS: Quinaprilat is a potent nonsulfhydryl selective ACE inhibitor with a short elimination half-life of 2 - 3 h, but due to slow dissociation from tissue ACE, once daily dosing is sufficient for effective ACE inhibition. Quinaprilat is excreted mainly in urine. In long-term animal studies, quinaprilat was not teratogenic, mutagenic or carcinogenic. However, due to the risk of fetal and neonatal morbidity and death, it should not be administrated in pregnancy. Quinaprilat is characterized by an excellent safety profile; adverse events occur infrequently and are rarely serious. CONCLUSION: Quinaprilat is an attractive ACE inhibitor, which potently inhibits tissue ACE.

Promise of blood- and bone marrow-derived stem cell transplantation for functional cardiac repair: putting it in perspective with existing therapy.

Intracoronary transplantation of peripheral blood- or bone marrow-derived cells, as tested in several recent trials, is associated with moderate increases in left ventricular (LV) ejection fraction (EF) and a small reduction of LV end-systolic volumes. Substantial variability exists between trials, and most of them are based on a small number of patients. Meta-analyses estimated an increase in EF of 3% to 4% more in comparison with control patients. In this review, the effects are put into perspective with established treatment options for acute myocardial infarction (AMI), such as thrombolysis and acute percutaneous interventions or pharmacotherapy aimed at favorably influencing the cardiac remodeling process. Changes in functional and morphometric parameters of LV performance after cell therapy appear to be in the range of effects observed with reperfusion therapy, pharmacotherapeutic interventions influencing the renin-angiotensin-aldosterone pathway, and beta-blockers after AMI.

A novel minimal-invasive model of chronic myocardial infarction in swine.

BACKGROUND: Most animal studies on myocardial infarction (MI) have used open-chest models with direct surgical coronary artery ligation, which imply local as well as generalized side effects of major surgery. Some closed-chest models of MI have been established, mainly using catheterization techniques with coronary artery embolization, balloon occlusion, and intracoronary injection of thrombogenic agents. The aim of this study was to develop a closed-chest technique of chronic coronary artery occlusion at a selected location with subsequent thrombus formation without use of balloon inflation or thrombotic chemical agents. METHODS AND RESULTS: A coronary angiography via the carotid artery was performed using a 7 F guiding catheter in 21 pigs. After insertion of a percutaneous transluminal coronary angioplasty (PTCA) guide wire into the distal coronary artery, a vessel-size adapted flexible foreign body comprising an open-cell sponge was advanced into the coronary artery via the guide wire by a non-inflated PTCA balloon. Five min after removal of the guide wire and the balloon catheter, total coronary artery occlusion was documented by angiography. Retrograde thrombosis of the coronary artery occurred in three animals. After one week, total vessel occlusion at the previously selected location was visualized by coronary angiography in animals that had survived. Macroscopic analysis demonstrated the foreign body with subsequent thrombus formation in the coronary artery and distal MI. Post-mortem histological analysis revealed myocardial necrosis and granulocyte infiltration at the margin of the infarction, without damage to remote myocardium. CONCLUSIONS: This new easy-to-perform closed-chest technique provides reproducible chronic coronary artery occlusion at a selected location with subsequent MI. It avoids major surgery and thoracotomy and does not require balloon inflation or intracoronary injection of thrombotic or chemical agents.

Effects of adenosine and verapamil on anatomic no-reflow in a rabbit model of coronary artery occlusion and reperfusion.

Adenosine and verapamil have successfully been used in the treatment of clinical no-reflow after direct angioplasty for acute myocardial infarction. However, their effects on anatomic perfusion defects in experimental myocardial ischemia/reperfusion are unknown. Thus the area of no-reflow (ANR), visualized after in-vivo staining of perfused tissue by thioflavin S (% of the risk area, RA, blue dye), and regional myocardial blood flow (radioactive microspheres) were determined in anesthetized open-chest rabbits after 30 minutes of occlusion and 120 minutes of reperfusion. Adenosine, administered intravenously during the entire reperfusion period, reduced vascular resistance in the RA at 120 minutes of reperfusion by 39% compared with controls (P < 0.053). However, in every animal, sizable perfusion defects developed and the ANR with adenosine treatment (29 +/- 3%) was not significantly different from saline controls (35 +/- 6%). Intravenous verapamil, given during the entire reperfusion period, reduced vascular resistance in the RA by 54% at 120 minutes of reperfusion (P < 0.03). But perfusion defects, visible in every animal, were similar in size between verapamil (38 +/- 5%) and saline (35 +/- 6%) groups. Therefore, neither treatment prevented or attenuated perfusion defects after ischemia/reperfusion despite reducing vascular resistance in the RA; hence vasospasm is not a major contributor to microvascular perfusion defects in this model.

Cardiomyocyte transplantation into the failing heart-new therapeutic approach for heart failure?

Heart failure, frequently the consequence of irreversible myocardial damage with subsequent formation of akinetic scar tissue, is a highly prevalent disease, and in its advanced stages associated with high mortality. The transplantation of exogenous cells with the inherent ability to contract has been put forward as one potential treatment strategy to increase contractility and cardiac performance. Besides skeletal myoblasts or stem cells from various sources, immature cardiomyocytes, such as fetal or neonatal cardiomyocytes, have been transplanted into normal, cryoinjured, infarcted myocardium, as well as into models of global heart failure. Survival of transplanted immature cardiomyocytes has been demonstrated up to 6-7 months, accompanied by vascularization of the grafted tissue. Transplants developed sarcomeric structures and other morphological features of differentiation. The principal possibility of cell-to-cell coupling between graft and host cells was demonstrated after cardiomyocyte transplantation into normal hearts and in some studies in damaged myocardium. But most long-term follow-up investigations in models of myocardial infarction reported that optimal integration of the engrafted cells appeared to be hindered by scar tissue, separating the transplant from the host. Nonetheless, in several studies, improved parameters of cardiac performance were demonstrated ex-vivo and in vivo. Potential mechanisms might involve beneficial effects on the remodeling process. In this review, we critically evaluate the potential value of cardiomyocyte transplantation as a new approach in the treatment of the syndrome of "heart failure".