A heart within a heart

A 44‐year‐old man with a history of end‐stage dilated cardiomyopathy status‐post orthotopic cardiac transplant 14 years ago presented for coronary angiography in preparation for re‐operative tricuspid valve replacement. Coronary angiography revealed an anomalous origin of the left coronary artery, with a common coronary trunk arising from the right coronary cusp and bifurcating into right and left main coronary arteries. Interestingly, the right and left coronary arteries coursed to form the shape of a heart, hence, a heart within a heart! © 2017 Wiley Periodicals, Inc.     

Macromolecular transport within heart valves

The present study documents the permeability characteristics of heart valvular endothelium to low-density lipoprotein (LDL), albumin, and horseradish peroxidase (HRP). Using quantitative autoradiography, LDL and albumin concentrations were measured within aortic valves of squirrel monkeys and rabbits after 30 minutes of in vivo circulation. The valvular concentration profiles were analyzed using theoretical mathematical models based on fundamental transport principles. In vivo transvalvular concentration profiles of LDL and albumin displayed the highest tissue concentrations immediately beneath the endothelium and displayed the lowest concentrations near the midline of the valve. Tissue concentrations of LDL and albumin displayed large differences in magnitudes between different regions of individual valve leaflets suggesting marked spatial variation in the permeability properties of the valvular endothelium to LDL and albumin; this was also seen visually with HRP. The results of the theoretical analysis showed that 1) the aortic valvular endothelium limits the uptake of LDL and albumin into the valvular tissue, 2) the permeability of the valvular endothelium differs widely from one region of a valve to another and even from one side of the valve to the other within a single valvular region, and 3) intramural diffusion is the predominant mode of transport for LDL and albumin within the aortic valve, even in valvular regions exposed to large pressure differences across the valve.     

Mitochondrial oxygen tension within the heart

By using a newly developed optical technique which enables non-invasive measurement of mitochondrial oxygenation (mitoPO₂) in the intact heart, we addressed three long-standing oxygenation questions in cardiac physiology: 1) what is mitoPO₂ within the in vivo heart?, 2) is mitoPO₂ heterogeneously distributed?, and 3) how does mitoPO₂ of the isolated Langendorff-perfused heart compare with that in the in vivo working heart? Following calibration and validation studies of the optical technique in isolated cardiomyocytes, mitochondria and intact hearts, we show that in the in vivo condition mean mitoPO₂ was 35 ± 5 mm Hg. The mitoPO₂ was highly heterogeneous, with the largest fraction (26%) of mitochondria having a mitoPO₂ between 10 and 20 mm Hg, and 10% between 0 and 10 mm Hg. Hypoxic ventilation (10% oxygen) increased the fraction of mitochondria in the 0–10 mm Hg range to 45%, whereas hyperoxic ventilation (100% oxygen) had no major effect on mitoPO₂. For Langendorff-perfused rat hearts, mean mitoPO₂ was 29 ± 5 mm Hg with the largest fraction of mitochondria (30%) having a mitoPO₂ between 0 and 10 mm Hg. Only in the maximally vasodilated condition, did the isolated heart compare with the in vivo heart (11% of mitochondria between 0 and 10 mm Hg). These data indicate 1) that the mean oxygen tension at the level of the mitochondria within the heart in vivo is higher than generally considered, 2) that mitoPO₂ is considerably heterogeneous, and 3) that mitoPO₂ of the classic buffer-perfused Langendorff heart is shifted to lower values as compared to the in vivo heart.     

Hematologic diseases: from within the heart

The fundamental relationship between blood disorders and the cardiovascular system originates within multiple points of interface, ranging from the heart and its structural constituents to include heart chambers, valves, coronary arteries, coronary veins, and the cerebrovascular and peripheral vasculature. While the cellular components of circulating blood derive their primary origin from multipotent progenitor cells, plasma-based components, which include coagulation proteins, are mostly born of hepatic synthesis and endothelial cells. Here we provide a focused overview of nononcological blood disorders and their potential impact on the arterial circulatory system as common phenotypes, including myocardial infarction, ischemic stroke and peripheral arterial occlusive events. Venous thromboembolism is employed in our discussion as a clinical template. We also provide practical steps and guidance for diagnostic testing and management in routine clinical practice.Full English text available from: www.revespcardiol.org     

A model for predicting the future incidence of coronary heart disease within percentiles of coronary heart disease risk

BACKGROUND: We present a method (The CHD Prevention Model) for modelling the incidence of fatal and nonfatal coronary heart disease (CHD) within various CHD risk percentiles of an adult population. The model provides a relatively simple tool for lifetime risk prediction for subgroups within a population. It allows an estimation of the absolute primary CHD risk in different populations and will help identify subgroups of the adult population where primary CHD prevention is most appropriate and cost-effective. METHODS: The CHD risk distribution within the Australian population was modelled, based on the prevalence of CHD risk, individual estimates of integrated CHD risk, and current CHD mortality rates. Predicted incidence of first fatal and nonfatal myocardial infarction within CHD risk strata of the Australian population was determined. RESULTS: Approximately 25% of CHD deaths were predicted to occur amongst those in the top 10 percentiles of integrated CHD risk, regardless of age group or gender. It was found that while all causes survival did not differ markedly between percentiles of CHD risk before the ages of around 50-60, event-free survival began visibly to differ about 5 years earlier. CONCLUSIONS: The CHD Prevention Model provides a means of predicting future CHD incidence amongst various strata of integrated CHD risk within an adult population. It has significant application both in individual risk counselling and in the identification of subgroups of the population where drug therapy to reduce CHD risk is most cost-effective.     

康复运动对冠心病患者PTCA术后一周心功能的影响

目的:评价康复运动训练对冠心病患者PTCA术后1周心功能的影响。方法:将44例成功进行PTCA治疗的冠心病患者分为康复治疗组和常规治疗组。对康复治疗组实施康复运动训练方案,在患者术前1 d,术后第1、3、5、7 d每日定时测定血流动力学相关指标。结果:两组患者在PTCA术后第1、3 d无显著差异,术后第5 d及第7 d康复治疗组患者的心输出量(CO)、心肌收缩力(MCF)及左室总泵力(TPF)均有显著提高(P<0.05),平均动脉压(MAP)、心肌耗氧量(M VO)显著降低(P<0.05),其他指标无显著差异。结论:康复运动有助于提高患者术后心脏的泵血功能和心血管效率。     

Cell viability mapping within long-term heart valve organ cultures

BACKGROUND AND AIM OF THE STUDY: Organ cultures maintain cells within their native microstructural environment, and thus offer greater potential for studying tissue disease and remodeling than do monolayer cell cultures or pathological examinations of diseased tissue. To validate an in-vitro heart valve organ culture model, cell viability was examined within valve tissues over sustained culture periods. METHODS: Following culture of blocks of valve tissue for 1 to 49 days, cross-sections were cut with a vibratome, stained with a LIVE/DEAD kit, and imaged with confocal microscopy to quantify the number of live and dead cells present. RESULTS: In numerous organ cultures, valvular interstitial cells were found to be viable beyond 30 days. Live cells were abundant in the central region of the valve, but more sparse in the deepest central regions. Dead cells were found mainly on the surface of both fresh tissues and tissues after prolonged culture, with few dead cells occurring centrally. CONCLUSION: This is the first reported mapping of cell viability within heart valve organ cultures, and results suggest that extended organ culture of valve leaflets is indeed possible. The derived viability staining methods have wide applicability for organ cultures of other tissues as well as tissue-engineered matrices.     

Differential co-expression of alpha-actin genes within the human heart

Human cardiac muscle has been studied to determine whether the ratio of cardiac alpha-actin to skeletal alpha-actin varies between the different chambers of the human heart taken from a single individual. Using mRNA dot-blots, and DNA probes specific for the cardiac and skeletal alpha-actin isotypes, we have found that both cardiac and skeletal alpha-actin mRNAs are present and co-expressed throughout the human heart. The pattern of alpha-actin co-expression in the left and right ventricles and in the interventricular septum is approximately the same, with cardiac alpha-actin being the dominant isotype (approx. 80% of total). However, the left atrium has a different relative composition of the two actins, with an even higher level of cardiac alpha-actin expression (95% of total).     

Adaptation after treatment for heart disease: preliminary examination within a stress appraisal context.

OBJECTIVE: To examine, within a stress appraisal framework, intrapersonal psychosocial factors that may affect adaptation after treatment for heart disease. Hostility was examined as a variable that may affect cognitive appraisal of stress and, thus, adaptation. DESIGN: Quasi-experimental design with measures before and after treatment. SETTING: Large, Midwest hospital preadmitting department with follow-up by mail 1 month after treatment.Outcome Measure: Adaptation, operationalized as perceived quality of life. RESULTS: There was a significant, positive relation between hostility and cognitive appraisal of heart disease threat. Threat appraisal and state anxiety before treatment were significantly inversely related to posttreatment quality of life. Hostility was modestly, although nonsignificantly inversely related to posttreatment quality of life. Results provide tentative support for the theory-defined role of appraisal as a mediator between hostility and quality of life. CONCLUSIONS: Stress appraisal theory is tentatively supported as a useful framework for examining the adaptational outcome of quality of life in patients with heart disease.     

Gut dysbiosis and heart failure: navigating the universe within

Alternations in gut microbial composition (i.e. loss of microbial diversity or ‘gut dysbiosis’) have been associated with heart failure with reduced ejection fraction (HFrEF). It has also been suggested that increased chronic low‐level inflammation and immune system dysregulation seen in patients with HFrEF could be related to gut dysbiosis and increased intestinal permeability. Hence, the concept of modulating gut microbial composition with the goal of reducing systemic inflammation and controlling HFrEF progression has generated a substantial interest in the scientific community. However, several challenges to the gut dysbiosis theory remain as the exact gut microbial composition in HFrEF patients in these studies is not the same and a common microbiome linked to HFrEF is not yet established. With the advances in culture independent sequencing techniques it has also become evident that the gut microbiome may be much more diverse than previously believed. Further, various ‘omic’ technologies have enabled us to appreciate the potential role of gut microbial metabolites in various physiological processes in the host. Hence, identification of specific gut microbial metabolites may offer an alternative approach at solving this gut microbiome‐HFrEF puzzle. In the current review, we evaluate the concept of gut symbiosis, the potential role of gut dysbiosis in systemic inflammation and HFrEF, and finally highlight the challenges faced by the gut dysbiosis theory in HFrEF and provide a framework for the possible solutions.     

A polymorphism within a conserved beta(1)-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure

Heterogeneity of heart failure (HF) phenotypes indicates contributions from underlying common polymorphisms. We considered polymorphisms in the beta(1)-adrenergic receptor (beta(1)AR), a beta-blocker target, as candidate pharmacogenomic loci. Transfected cells, genotyped human nonfailing and failing ventricles, and a clinical trial were used to ascertain phenotype and mechanism. In nonfailing and failing isolated ventricles, beta(1)-Arg-389 had respective 2.8 +/- 0.3- and 4.3 +/- 2.1-fold greater agonist-promoted contractility vs. beta(1)-Gly-389, defining enhanced physiologic coupling under relevant conditions of endogenous expression and HF. The beta-blocker bucindolol was an inverse agonist in failing Arg, but not Gly, ventricles, without partial agonist activity at either receptor; carvedilol was a genotype-independent neutral antagonist. In transfected cells, bucindolol antagonized agonist-stimulated cAMP, with a greater absolute decrease observed for Arg-389 (435 +/- 80 vs. 115 +/- 23 fmol per well). Potential pathophysiologic correlates were assessed in a placebo-controlled trial of bucindolol in 1,040 HF patients. No outcome was associated with genotype in the placebo group, indicating little impact on the natural course of HF. However, the Arg-389 homozygotes treated with bucindolol had an age-, sex-, and race-adjusted 38% reduction in mortality (P = 0.03) and 34% reduction in mortality or hospitalization (P = 0.004) vs. placebo. In contrast, Gly-389 carriers had no clinical response to bucindolol compared with placebo. Those with Arg-389 and high baseline norepinephrine levels trended toward improved survival, but no advantage with this allele and exaggerated sympatholysis was identified. We conclude that beta(1)AR-389 variation alters signaling in multiple models and affects the beta-blocker therapeutic response in HF and, thus, might be used to individualize treatment of the syndrome.     

Validation of a risk score for dying within 1 year of an admission for heart failure

BackgroundDevelopment of heart failure greatly reduces life expectancy. Accurate estimates of the risk of dying are needed in clinical practice and for risk adjustment in observational studies. A relatively simple risk score has been developed to determine the risk of dying within 1-year of an admission for heart failure. We wanted to evaluate the risk score's predictive validity.Methods and ResultsData were abstracted from the electronic medical records of 769 patients admitted to the Minneapolis Veterans Administration medical center with a primary diagnosis of heart failure. Mortality within 1 year of admission was 25%. The c-index for the risk score was 0.71 (95% confidence interval 0.67–0.76). Similar to the original derivation cohort, mortality in risk score groups was 7% for a score lower than 60 (n = 44), 14% for 61 to 90 (n = 246), 26% for 91 to 120 (n = 222), 51% for 121 to 150 (n = 106), and 50% for scores greater than 150 (n = 8).ConclusionA previously developed risk score for 1-year mortality after an admission for heart failure provided a moderate degree of discrimination in a validation cohort from a different setting. Mortality in risk score groups was consistent with the original patient cohort. These results support the validity of the risk score and its application to a different patient population.