Various Types Of Cardiac Diseases Research Articles

Occupational Exposure to Poorly Soluble Low Toxicity Particles and Cardiac Disease: A Look at Carbon Black and Titanium Dioxide.

Environmental particulate exposure and the potential risk to people with various types of cardiac diseases, most notably cardiovascular disease, have aroused scientific and regulatory interest worldwide. Epidemiological studies have shown associations between exposure to airborne environmental particulate matter (PM) and mortality from cardiovascular disease (CVD). The associations reported, however, are complex and may not involve a direct role for PM, since air pollutants are diverse and highly correlated. This study examines the potential role of occupational exposure to two types of particles, namely, manufactured carbon black (CB) and titanium dioxide (TiO2), on the risk of cardiovascular disease. To address the risk of cardiovascular disease from exposure to carbon black and titanium dioxide, as reflective of poorly soluble low toxicity particles, we reviewed the published cohort mortality studies of occupational exposure to carbon black and titanium dioxide. Mortality studies of carbon black have been conducted in the United States, Germany, and the United Kingdom. Five mortality studies related to workers involved in the manufacture of titanium dioxide in the United States and Europe have also been conducted. In addition, a meta-analysis of the three-carbon black mortality studies was performed. In the random-effects meta-analysis, full cohort meta-SMRs were 1.01 (95% confidence interval (CI): 0.79–1.29) for heart disease; 1.02 (95% CI: 0.80–1.30) for ischemic heart disease; and 1.08 (95% CI: 0.74–1.59) for acute myocardial infarction (AMI) mortality. A small but imprecise increased AMI mortality risk was suggested for cumulative exposure by a meta-HR = 1.10 per 100 mg/m3-years (95% CI: 0.92–1.31) but not for lugged exposures, that is, for recent exposures. Results of five cohort mortality studies of titanium dioxide workers in the United States and Europe showed no excess in all heart disease or cardiovascular disease. In the most recent study in the United States, an internal analysis, that is, within the cohort itself, with no lag time, showed that the exposure group 15–35 mg/m3-years yielded a significantly increased risk for heart disease; however, there was no evidence of increasing risk with increasing exposure for any of the exposure categories. In contrast to environmental studies, the results of cohort mortality studies do not demonstrate that airborne occupational exposure to carbon black and titanium dioxide particulates increases cardiovascular disease mortality. The lack of a relationship between carbon black and titanium dioxide and CVD mortality suggests that the associations reported in air pollution studies may not be driven by the particulate component.

Advances in Periprocedural Anticoagulation for Percutaneous Coronary Interventions

Percutaneous coronary intervention (PCI) is commonly used in the surgical treatment of patients with various types of cardiac diseases. Some patients require long-term anticoagulation in the presence of deep vein thrombosis, atrial fibrillation and mechanical heart valves, and inappropriate anticoagulation during the perioperative period may lead to bleeding events or thrombotic events. In this paper, the importance of anticoagulation in the practical application of percutaneous coronary intervention (PCI) is first introduced, and then the various drug regimens used in the perioperative anticoagulation of percutaneous coronary intervention are explored in detail in the light of current research advances, with a view to providing guidance for clinical practice.

Abstract 11466: Deficiency of Microrna-1 Induces Cardiac Electrical and Metabolic Remodeling of the Heart

Introduction: MicroRNA-1 (miR1) is an evolutionarily conserved, striated muscle-enriched microRNA and plays critical roles in regulation of the development and physiology of the heart. It has been found that miR1 was downregulated in various types of cardiac diseases. We observed that, compared to that in young mice (age 3-4 months), the expression of miR1 was significantly decreased to the level of 12.5±4.0% in the heart of aged animals (age 18 months). Hypothesis: We hypothesized that miR1 deficiency is a major etiology in diseased and/or aged hearts. In the mammalian genome, two distinct genes, miR1-1 and miR1-2 that are located on two chromosomes, generate identical mature miR1. Methods and Results: To study the hypothesis, we generated miR1-75% knockdown (75%KD) mice by crossbreeding miR1-1 knockout (KO) and miR1-2 KO animals and found that miR1-75%KD mice could survive to adult age with a relatively higher mortality, while miR1-100%-KO is postnatal lethal. The ejection fraction and fraction shortening of 75%KD hearts was significantly decreased than that of WT animals. Electrocardiogram showed that, compared to the WT group, 75%KD hearts had significantly slower heart rates with shorter PR interval and prolonged QRS interval with observed premature ventricular contractions. Optical mapping of ex vivo hearts revealed significantly slower ventricular conduction velocity in 75%KD hearts. Compared to WT cells, 75%KD ventricular cardiomyocytes had hyperpolarized RMPs with prolonged action potentials, and showed significantly decreased sarcomere shortening. Proteomic assays found that proteins of mitochondrial ATP synthesis and electron transport were significantly downregulated in 75%KD hearts. Conclusions: We conclude that the deficiency of miR1 is a major etiological factor of cardiac electrical and metabolic remodeling in the heart. Restoring the normal level of miR1 in the heart could be a critical and effective therapeutic strategy to prevent and/or treat heart diseases.

Tensor-Based ECG Anomaly Detection toward Cardiac Monitoring in the Internet of Health Things.

Advanced heart monitors, especially those enabled by the Internet of Health Things (IoHT), provide a great opportunity for continuous collection of the electrocardiogram (ECG), which contains rich information about underlying cardiac conditions. Realizing the full potential of IoHT-enabled cardiac monitoring hinges, to a great extent, on the detection of disease-induced anomalies from collected ECGs. However, challenges exist in the current literature for IoHT-based cardiac monitoring: (1) Most existing methods are based on supervised learning, which requires both normal and abnormal samples for training. This is impractical as it is generally unknown when and what kind of anomalies will occur during cardiac monitoring. (2) Furthermore, it is difficult to leverage advanced machine learning approaches for information processing of 1D ECG signals, as most of them are designed for 2D images and higher-dimensional data. To address these challenges, a new sensor-based unsupervised framework is developed for IoHT-based cardiac monitoring. First, a high-dimensional tensor is generated from the multi-channel ECG signals through the Gramian Angular Difference Field (GADF). Then, multi-linear principal component analysis (MPCA) is employed to unfold the ECG tensor and delineate the disease-altered patterns. Obtained principal components are used as features for anomaly detection using machine learning models (e.g., deep support vector data description (deep SVDD)) as well as statistical control charts (e.g., Hotelling chart). The developed framework is evaluated and validated using real-world ECG datasets. Comparing to the state-of-the-art approaches, the developed framework with deep SVDD achieves superior performances in detecting abnormal ECG patterns induced by various types of cardiac disease, e.g., an F-score of 0.9771 is achieved for detecting atrial fibrillation, 0.9986 for detecting right bundle branch block, and 0.9550 for detecting ST-depression. Additionally, the developed framework with the T2 control chart facilitates personalized cycle-to-cycle monitoring with timely detected abnormal ECG patterns. The developed framework has a great potential to be implemented in IoHT-enabled cardiac monitoring and smart management of cardiac health.

Relationship between oxidative stress and nuclear factor-erythroid-2-related factor 2 signaling in diabetic cardiomyopathy (Review).

Diabetic cardiomyopathy (DCM) is the leading cause of death worldwide, and oxidative stress was discovered to serve an important role in the pathophysiology of the condition. An imbalance between free radicals and antioxidant defenses is known to be associated with cellular dysfunction, leading to the development of various types of cardiac disease. Nuclear factor-erythroid-2-related factor 2 (NRF2) is a transcription factor that controls the basal and inducible expression levels of various antioxidant genes and other cytoprotective phase II detoxifying enzymes, which are ubiquitously expressed in the cardiac system. Kelch-like ECH-associated protein 1 (Keap1) serves as the main intracellular regulator of NRF2. Emerging evidence has revealed that NRF2 is a critical regulator of cardiac homeostasis via the suppression of oxidative stress. The activation of NRF2 was discovered to enhance specific endogenous antioxidant defense factors, one of which is antioxidant response element (ARE), which was subsequently illustrated to detoxify and counteract oxidative stress-associated DCM. The NRF2 signaling pathway is closely associated with the development of various types of cardiac disease, including ischemic heart disease, heart failure, myocardial infarction, atrial fibrillation and myocarditis. Therefore, it is hypothesized that drugs targeting this pathway may be developed to inhibit the activation of NRF2 signaling, thereby preventing the occurrence of DCM and effectively treating the disease.

Cardiac Rehabilitation and Endothelial Function.

Endothelial dysfunction is an early abnormality in the process of atherosclerosis and cardiovascular disease and has been associated with worse clinical outcome. Cardiac rehabilitation (CR) has been reported to be helpful to reduce cardiovascular events in various types of cardiac disease, but the mechanisms of its beneficial effects remain only partially known. In this article, we review the studies that assessed the effect of CR on endothelial function in patients with various cardiac conditions. Available data show that CR significantly improves impaired endothelial function in these patients, which may contribute to the beneficial effects of CR on clinical outcome.

A NOVEL METHOD TO ISCHEMIC HEART DISEASE DETECTION BASED ON NON-INVASIVE ECG IMAGING

Electrocardiogram (ECG) signals containing very important information about the cardiac are one of the most common tools for physicians in the diagnosis of various types of cardiac diseases. Low accuracy in positioning, limitation of time accuracy, the similarity of signals between some diseases and normal signals and probability of missing some aspect of data are the defect aspects of this method. Importance of cardiac signals and defects of current methods in diagnosis show the need of substituting a new method to show the activity of cardiac. One of the most dangerous defections is ischemia, which corrects and on time diagnose could avoid the latter effect of it. Each of common methods for diagnosis of this illness has their own advantages and disadvantages. In this paper, we consider describing a non-invasive method for ischemic episode detection based on mapping of ECG signals. With this method, we can present the signals with virtual colors and facilitate the diagnosis of ischemic disease. So, a new method of 12-lead cardiac presentation is described that in fact present the 12-lead signals in two images. The result of this paper will present the indicators of sensitivity, specificity and accuracy in the context of disease diagnosis. This paper proposed a novel ECG imaging algorithm for classifying the normal and ischemic signals and 95.35% specificity, 96.79% sensitivity and 95.76% accuracy were achieved which are very much promising compared to the other methods and doctor’s accuracy.

Homeobox Genes and Homeodomain Proteins: New Insights into Cardiac Development, Degeneration and Regeneration.

Cardiovascular diseases are the most common cause of human death in the developing world. Extensive evidence indicates that various toxic environmental factors and unhealthy lifestyle choices contribute to the risk, incidence and severity of cardiovascular diseases. Alterations in the genetic level of myocardium affects normal heart development and initiates pathological processes leading to various types of cardiac diseases. Homeobox genes are a large and highly specialized family of closely related genes that direct the formation of body structure, including cardiac development. Homeobox genes encode homeodomain proteins that function as transcription factors with characteristic structures that allow them to bind to DNA, regulate gene expression and subsequently control the proper physiological function of cells, tissues and organs. Mutations in homeobox genes are rare and usually lethal with evident alterations in cardiac function at or soon after the birth. Our understanding of homeobox gene family expression and function has expanded significantly during the recent years. However, the involvement of homeobox genes in the development of human and animal cardiac tissue requires further investigation. The phenotype of human congenital heart defects unveils only some aspects of human heart development. Therefore, mouse models are often used to gain a better understanding of human heart function, pathology and regeneration. In this review, we have focused on the role of homeobox genes in the development and pathology of human heart as potential tools for the future development of targeted regenerative strategies for various heart malfunctions.

Comparative study of cardiac size by chest X-ray and echocardiography

Introduction: The study of cardiac size is important for the diagnosis of various types of cardiac diseases such as left ventricular enlargement due to aortic stenosis and right ventricular enlargement due to pulmonary stenosis. Although echocardiography is considered as gold standard for the diagnosis of cardiomegaly, it is costly and needs trained personnel for performing and interpreting the results of this diagnostic procedure. Chest X-ray is used as an alternative. Materials and methods: The present comparative study was carried on 35 males aged 25–60 years. On the basis of provisional clinical diagnosis, the patients were divided into three groups: (i) group A - 15 patients in whom clinical history did not suspect any cardiac enlargement; (ii) group B - 15 patients whose clinical history predisposed to left ventricular enlargement; and (iii) group C - 5 patients whose clinical history predisposed to right ventricular enlargement. All patients underwent chest X-ray (postero-anterior view) and 2D-echocardiography examinations. The findings of the two modalities were compared. Observations: The observations were very informative and showed that chest X-ray is useful for the diagnosis of cardiomegaly due to various types of cardiac diseases. On chest X-ray, the cardiothoracic ratio and transverse diameter showed a strong positive correlation with total ventricular dimension on echocardiography. Other parameters such as transverse diameter and transverse left diameter on chest X-ray also showed a positive correlation with right ventricular dimension on echocardiography. Conclusion: Chest X-ray is a reliable alternative for the diagnosis of cardiomegaly in the absence of echocardiography.

Plasma B-Type Natriuretic Peptide Is Useful for Cardiovascular Risk Assessment in Community-Based Diabetes Subjects

Diabetes mellitus (DM) is a strong risk factor for cardiovascular (CV) disease. Plasma B-type natriuretic peptide (BNP) levels are elevated in various types of cardiac diseases. Increased plasma BNP levels have been reported to be associated with CV risk in apparently healthy individuals. However, no studies have yet examined the specific value of plasma BNP for predicting CV incidence in unselected DM subjects in a community-based population.In a community-based DM cohort (n = 1,059, mean = 66 years), baseline BNP levels were determined, and CV events were followed and captured prospectively. The cohort was divided by plasma BNP quintiles. The Cox proportional hazard model was used to determine the relative hazard ratios (HR) among the quintiles. In addition, the effects of adding the plasma BNP or urine albumin-to-creatinine ratio (UACR) to an established CV risk scoring model was examined by calculating the area under the receiver operating characteristic (ROC) curve (AUC).During the 5.7 year follow-up period, CV events were identified in 65 of the DM cohort. There was a significant association between plasma BNP levels and CV event rate (P < 0.001). HR was significantly increased in the highest quintile compared to the lowest (HR = 4.38; 95%CI 1.69 -11.84). The AUC generated from ROC analysis of the Framingham risk score for predicting general CV events was improved by adding BNP testing (from 0.66 to 0.74; P = 0.05), but not by adding UACR (from 0.66 to 0.67; P = 0.49).In a community sample of people with DM, plasma BNP levels above the 80 percentile are directly associated with CV risk, and measurement of plasma BNP alone or in conjunction with an established CV risk score is of value in predicting CV events in these subjects.

Cardiac Disease in Pregnancy

After completing this article, readers should be able to: 1. Describe how the cardiovascular changes of pregnancy can affect the woman who has cardiac disease. 2. Review the importance of preconception counseling. 3. Discuss the purpose of a multidisciplinary team approach to the management of the woman who has cardiac disease during pregnancy. 4. Review delivery management of women who have cardiac disease. Pregnancy causes considerable physiologic change in women, particularly in their cardiovascular systems. Circulating blood volume increases dramatically, and cardiac output increases up to 50% by the end of pregnancy. Pregnant women who have cardiac disease must be able to accommodate these normal changes to have a successful pregnancy. Inability to do so can result in increased morbidity and mortality. Cardiac disease is an important cause of nonobstetric mortality during pregnancy and can result in significant morbidity. (1)(2) Approximately 10% of all maternal deaths in the United States can be attributed to cardiac disease, a number that has remained consistent for the last half century. (1) In one study of 1,000 pregnant women who had various types of cardiac disease and were followed by the same health-care team over a 10-year period, more than 75% of the women had no complications during pregnancy. (2) Among the remaining 25%, the following complications were seen most often: The overall maternal mortality rate in this group was 2.7%, and the stillbirth and spontaneous abortion rate was 7.7%. Cardiac disease covers a wide range of conditions, including congenital heart disease, acquired disease such as rheumatic valvular disease, and coronary disease. It is estimated that 1% to 3% of women either have cardiac disease entering pregnancy or are diagnosed with cardiac disease while they are pregnant. …

Causes of sudden cardiac death in young Australians.

To determine the causes of sudden cardiac death in people aged 35 years or younger. A review of all autopsies performed between 1 January 1994 and 31 December 2002 at a major Sydney forensic medicine department serving an area with over 2 million people. Incidence of various types of cardiac disease causing sudden death in those aged <or= 35 years; proportion of deaths in which no cause was found at autopsy. There were 10 199 autopsies performed during the study period. Of these, 2986 (29.2%) deaths occurred in people aged <or= 35 years; 193 were classified as sudden cardiac deaths. The cause of sudden death in this group was not established in 60 (31%), and was presumed to be due to primary arrhythmogenic disorders. Coronary artery disease occurred in 46 (24%), hypertrophic cardiomyopathy/unexplained left ventricular hypertrophy in 29 (15%), and myocarditis in 23 (12%). Unexplained deaths, presumed to result from sudden primary arrhythmogenic causes, occur in young Australians with structurally normal hearts. That underlying disease-causing genetic defects may be involved has clinical implications for family members.

Diagnostic performance of a computerized algorithm for augmenting the ECG with acoustical data

Introduction: Various types of cardiac disease can have characteristic electrical and hemodynamic manifestations. For example, acute myocardial ischemia is typically associated both with displacement of the ST segments of the ECG and with alterations of the mechanical properties of the left ventricle. The latter changes may produce pathological heart sounds, i.e. an S3 and/or an S4. Since ECG and acoustical parameters are orthogonal, their concordance in a given patient would constitute strong corroborative evidence of the presence or the absence, respectively, of the disease of interest. To facilitate the acquisition of these types of diagnostic information, we have developed a highly efficient system to record and interpret simultaneous 12-lead ECG and cardiac acoustical data. Methods: An expert phonocardiographer visually reviewed the acoustical recordings of each patient to determine whether an S3 or an S4 was present. Results: The following data show the ability of our computerized acoustical algorithm to detect an S3 or an S4 in patients in a variety of clinical settings. The performance of the algorithm is compared to a consensus of 2 experienced cardiologists concerning the audibility of the recorded S3 or the S4 in the each of the same patients.

The relationship between somatic mtDNA rearrangements, human heart disease and aging.

The lifetime accumulation of low-abundance, somatic mtDNA re-arrangements (sublimons) has been proposed as a potential contributor to aging, and also to diseases such as cardiomyopathy or coronary heart disease. Tissue-specific sublimons, varying in abundance by three orders of magnitude between individuals, have recently been observed in myocardium of control subjects. To study the relationship between myocardial sublimon levels and various types of cardiac disease and aging, we applied a semi-quantitative fluorescent PCR assay on cellular DNA extracted from left ventricle in a series of 300 well characterized male victims of sudden death up to age 70 (Helsinki Sudden Death Study). The most prevalent classes of sublimons were present at <0.1 to 91 copies per cell, but their abundance did not correlate with any cardiac disease phenotype. In multiple regression analyses age (beta = 0.43, P < 0.0001) and smoking (bet = 0.25, P = 0.012) were the only independent factors found to correlate with sublimon levels. Thus, sublimons are inferred to accumulate with age in myocardium of a subset of individuals, but to levels where they do not appear to have any phenotypic effects during a typical life span. We propose that, instead of being a causal factor in cardiac aging, sublimons co-exist with wild-type mtDNA in an equilibrium which is regulated by as yet unknown mechanisms.

PET and SPET tracers for mapping the cardiac nervous system.

The human cardiac nervous system consists of a sympathetic and a parasympathetic branch with (-)-norepinephrine and acetylcholine as the respective endogenous neurotransmitters. Dysfunction of the cardiac nervous system is implicated in various types of cardiac disease, such as heart failure, myocardial infarction and diabetic autonomic neuropathy. In vivo assessment of the distribution and function of cardiac sympathetic and parasympathetic neurones with positron emission tomography (PET) and single-photon emission tomography (SPET) can be achieved by means of a number of carbon-11-, fluorine-18-, bromine-76- and iodine-123-labelled tracer molecules. Available tracers for mapping sympathetic neurones can be divided into radiolabelled catecholamines, such as 6-[18F]fluorodopamine, (-)-6-[18F]fluoronorepinephrine and (-)-[11C]epinephrine, and radiolabelled catecholamine analogues, such as [123I]meta-iodobenzylguanidine, [11C]meta-hydroxyephedrine, [18F]fluorometaraminol, [11C]phenylephrine and meta-[76Br]bromobenzylguanidine. Resistance to metabolism by monoamine oxidase and catechol-O-methyl transferase simplifies the myocardial kinetics of the second group. Both groups of compounds are excellent agents for an overall assessment of sympathetic innervation. Biomathematical modelling of tracer kinetics is complicated by the complexity of the steps governing neuronal uptake, retention and release of these agents as well as by their high neuronal affinity, which leads to partial flow dependence of uptake. Mapping of cardiac parasympathetic neurones is limited by a low density and focal distribution pattern of these neurones in myocardium. Available tracers are derivatives of vesamicol, a molecule that binds to a receptor associated with the vesicular acetylcholine transporter. Compounds like (-)-[18F]fluoroethoxybenzovesamicol display a high degree of non-specific binding in myocardium which restricts their utility for cardiac neuronal imaging.

Lubeluzole Treatment of Acute Ischemic Stroke

To the Editor: The final conclusion of the recently published article1 on lubeluzole treatment of acute ischemic stroke, that “treatment with lubeluzole within 6 hours of the onset of ischemic stroke resulted in improved clinical outcome at three months with no safety concerns,” may not result from the data presented and the way they were analyzed. The primary aim of this trial was to test the null hypothesis that treatment with lubeluzole results in outcome similar in terms of death at 3 months to placebo treatment. As the primary end points “all deaths” showed no statistically significant difference between groups, the null hypothesis cannot be rejected. The fact that the number of deaths were (not statistically significant) lower in the lubeluzole group may well be due to chance because of small numbers or to differences in baseline characteristics; fewer males and fewer patients with various types of cardiac disease in the lubeluzole-treated group may have favored better outcome in the treatment group. From the analysis description, adjustments for these differences cannot be inferred. Secondly, fewer patients …

Decreased 123I-MIBG uptake and increased clearance in various cardiac diseases

123I-metaiodobenzylguanidine (MIBG), a tracer for sympathetic neuron integrity and function, was applied to 155 patients with various types of cardiac disease. The methods for quantification of MIBG and washout were studied as well as normal ranges. Heart-to-mediastinum average count ratio (H/M) correlated well with total heart count divided by injected activity (r = 0.60, P < 0.0001 and r = 0.72, P < 0.0001 for early and delayed images, respectively). Although as a whole left ventricular ejection fraction (LVEF) positively correlated with H/M ratio, decreased H/M ratio could be associated with normal LVEF, which may indicate that the MIBG activity was an independent variable compared with cardiac contractility. High washout rate was seen in various cardiac diseases, such as dilated cardiomyopathy, hypertrophic cardiomyopathy, ischaemic heart disease, hypertension, hypothyroidism and arrhythmia. The increased washout seems to be nonspecific to disease type, but is a common feature of damaged or failing myocardium.

Diastolic dysfunction as a cause of heart failure

Diastolic dysfunction is an important cause of symptoms in patiente with various types of cardiac disease. Increased left ventricular diastolic pressure may lead to pulmonary congestion, even in the setting of normal left ventricular systolic function. Although the physiology of diastolic function is complex, left ventricular diastolic pressure may become elevated through one of three broad mechanisms. Abnormalities intrinsic to the left ventricle may include 1) impaired left ventricular relaxation, a finding that is common in most cardiac diseases and may be particularly important during ischemia; 2) increased left ventricular wall thickness relative to cavity volume, which will shift the diastolic pressure-volume relation such that the same volume is associated with a higher pressure; and 3) increased myocardial stiffness, which is thought to be associated with interstitial fibrosis or scar tissue formation. In addition, diastolic pressures may become elevated because of factors extrinsic to the left ventricle. These may include 1) increased central blood volume, which will increase left ventricular pressure without altering the left ventricular pressure-volume relation; and 2) ventricular interaction mediated by pericardial restraint, which may cause a parallel upward shift of the diastolic pressure-volume relation. Treatment of the factors extrinsic to the left ventricle tends to be much more successful man treating abnormalities that are intrinsic to the ventricle. Improved understanding of myocardial relaxation at the cellular level and delineation of the molecular regulation of myocyte hypertrophy and fibroblast proliferation may lead to new and innovative approaches to the treatment of heart failure.

Severity of cardiac failure from the standpoint of pulmonary circulation: studies centered on distribution of pulmonary perfusion.

In a normal man sitting upright, pulmonary perfusion is several times greater in the lower lung zone than in the upper zone. This pattern may sometimes be reversed in patients with cardiac disease. Tc99m-macro-aggregated albumin pulmonary perfusion images were computerized to isocounts area images (digital perfusion images; DPI). DPI were applied to various types of cardiac disease and patterns of DPI were divided into 4 classes according to amount of nonperfused pulmonary vascular bed. C-0; normal perfusion. C-1; decrease of nonperfused pulmonary vascular bed. C-2; disappearance of nonperfused pulmonary vascular bed. C-3; decrease of pulmonary vascular bed. In 71 patients with mitral stenosis relationships between pulmonary hemodynamics during exercise and distribution of pulmonary perfusion were studied, i.e. at rest (n = 71, mean pulmonary arterial pressure; 23 mmHg-cardiac index; 2.4 L/m) and during exercise C-0 (n = 13, 41 mmHg-5.4 L/m), C-1 (n = 17, 52 mmHg-5.2 L/m), C-2 (n = 27, 52 mmHg-4.5 L/m) and C-3 (n = 14, 65 mmHg-3.6 L/m) respectively. In patients with congestive heart failure cardiac status was classified to 4 classes according to ejection fraction and DPI. Patients with EF less than 30% and DPI more than C-2 showed high morbidity and mortality (two years mortality 47%; 27/40). Pulmonary venous pressure increases to maintain the cardiac index (Starling's law) in cases of decline in cardiac function or mitral stenosis. It was shown that increases in pulmonary venous pressure cause changes in distribution of pulmonary perfusion, which in turn works to depress the cardiac index. A decline in cardiac function and changes in the distribution of pulmonary perfusion coexist, mediated by pulmonary venous pressure and cardiac index. The distribution of pulmonary perfusion reflects the severity of cardiac failure itself, so by using DPI the severity of cardiac failure can be easily evaluated.

Characterization of the circulatory response to maximal upright exercise in normal subjects and patients with heart disease.

The circulatory responses to mild and maximal upright exercise were studied in six normal subjects and 21 patients with various types of cardiac disease. It was found that the usual hemodynamic indices employed to evaluate cardiac performance during exertion were unreliable in separating patients from normal persons. In contrast, the cardiac index achieved at a pulmonary arterial (PA) O 2 saturation of 30% was found to be highly reliable and sensitive for distinguishing the normal from the abnormal response to exercise. At a level of exercise that lowers PA O 2 saturation to 30%, all normal subjects achieved a cardiac index greater than 7.0 L/minm 2 while no patient exceeded 4.8 L/min/m. 2 In addition, the maximal capacity to extract O 2 was greater in patients than in normal subjects; thus, during maximal exercise it was not unusual for patients to achieve PA O 2 saturations of 15% or less, while the lowest value achieved in normal subjects was 23%.