Cardiovascular Disease Entities Research Articles

Cardio-hepatic syndrome in patients undergoing transcatheter aortic valve replacement

BackgroundCardiohepatic syndrome (CHS) has been identified as an important but underrecognized survival predictor in multiple cardiovascular disease entities. The objectives of this study were to evaluate the prevalence and prognostic value of CHS in patients undergoing TAVR for severe aortic stenosis (AS).MethodsThe study included patients with available laboratory parameters of hepatic function who underwent TAVR from July 2013 until December 2019 at our center. CHS was defined as an elevation of at least two of three laboratory cholestasis parameters above the upper limit of normal (bilirubin, alkaline phosphatase, and gamma glutamyl transferase). Study endpoints were three-year survival, technical and device failure (VARC 3), as well as New York Heart Association (NYHA) functional class at follow-up.ResultsAmong a total of 953 analyzed patients (47.6% females, median age 80.0 [76.0–85.0] years) CHS was present in 212 patients (22.4%). In patients with vs. without CHS, rates of technical (6.1% vs. 8.4%, p = 0.29) and device failure (18.9% vs. 17.3%, p = 0.59) were comparable. NYHA functional class at baseline and follow-up was more severe in patients with CHS. Nevertheless, heart failure symptoms improved from baseline to follow-up irrespective of hepatic function. Three-year survival rates were significantly lower in patients with CHS (49.4 vs. 65.4%, p < 0.001). The predictive value of CHS persisted after adjustment in a multivariable analysis (hazard ratio 1.58, p < 0.01).ConclusionIn patients undergoing TAVR, CHS is prevalent in 22% of patients and is associated with increased postinterventional mortality. Thus, CHS should be included in the decision-making process within the TAVR heart team.Graphical abstractCardiohepatic syndrome (CHS) as defined by an elevation of at least two of three laboratory cholestasis parameters above the upper limit of normal was prevalent in 22% of patients undergoing TAVR for severe AS. The presence of CHS was associated with more severe heart failure symptoms and worse three-year survival.

Recent Advances in Association Between Vitamin D Levels and Cardiovascular Disorders.

In this review, we discuss the evidence that vitamin D affects cardiovascular disease through interventional and observational studies and their corresponding association mechanisms. We also highlight the need for further research to definitively conclude clinical recommendations based on preliminary data and determine the extent to which vitamin D levels may impact the incidence and prognosis of major cardiovascular diseases in the future. Cardiovascular disease has long been recognized as the leading cause of morbidity and mortality worldwide, with many risk factors implicated in its pathogenesis. Vitamin D is a risk factor that, despite being known to be crucial for its role in maintaining bone health, also has several extra-skeletal effects due to vitamin D receptors in vascular smooth muscle and cardiomyocytes. Recent studies have documented a significant association between higher vitamin D levels and lower risk of each cardiovascular disease entity; 11 studies between serum vitamin D and heart failure, 7 studies between serum vitamin D and hypertension, 8 studies between serum vitamin D and coronary artery disease, and 5 studies between serum vitamin D and atrial fibrillation. More studies documenting a significant association between increased serum vitamin D and cardiovascular disease are in the context of heart failure compared to hypertension, coronary artery disease, and atrial fibrillation. Conversely, a significant association between increased serum vitamin D and a lower risk of atrial fibrillation is reported in fewer studies compared to the association of vitamin D with other cardiovascular disease entities. Although there is evidence documenting a clear significant association of vitamin D under each category, further research is still needed to definitively conclude the role of vitamin D in cardiovascular disease management.

Artificial intelligence in echocardiography: Review and limitations including epistemological concerns.

In this review we describe the use of artificial intelligence in the field of echocardiography. Various aspects and terminologies used in artificial intelligence are explained in an easy-to-understand manner and supplemented with illustrations related to echocardiography. Limitations of artificial intelligence, including epistemologic concerns from a philosophical standpoint, are also discussed. A narrative review of relevant papers was conducted. We provide an overview of the usefulness of artificial intelligence in echocardiography and focus on how it can supplement current day-to-day clinical practice in the assessment of various cardiovascular disease entities. On the other hand, there are significant limitations, including epistemological concerns, which need to be kept in perspective.

Heart Failure Relapses in Response to Acute Stresses - Role of Immunological and Inflammatory Pathways.

Cardiovascular diseases continue to be the most imminent health care problems in the western world, accounting for numerous deaths per year. Heart failure (HF), namely the reduction of left ventricular function, is one of the major cardiovascular disease entities. It is chronically progressing with relapsing acute decompensations and an overall grave prognosis that is little different if not worse than most malignant diseases. Interestingly acute metabolically and/or immunologically challenging events like infections or major surgical procedures will cause relapses in the course of preexisting chronic heart failure, decrease the patients wellbeing and worsen myocardial function. HF itself and or its progression has been demonstrated to be driven at least in part by inflammatory pathways that are similarly turned on by infectious or non-infectious stress responses. These thus add to HF progression or relapse. TNF-α plasma levels are associated with disease severity and progression in HF. In addition, several cytokines (e.g., IL-1β, IL-6) are involved in deteriorating left ventricular function. Those observations are based on clinical studies using inhibitors of cytokines or their receptors or they stem from animal studies examining the effect of cytokine mediated inflammation on myocardial remodeling in models of heart failure. This short review summarizes the known underlying immunological processes that are shared by and drive all: chronic heart failure, select infectious diseases, and inflammatory stress responses. In conclusion the text provides a brief summary of the current development in immunomodulatory therapies for HF and their overlap with treatments of other disease entities.

A Comparative Analysis of Novel Biomarkers in Sepsis and Cardiovascular Disease

(1) Background: Sepsis still represents a major health care challenge, with mortality rates exceeding 25% in the western world. To further improve outcomes in this patient collective, new cardiovascular biomarkers present a promising opportunity as they target the paramount prognostic processes in sepsis: inflammation and ischemia. However, in contrast to cardiovascular diseases, a detailed analysis of novel biomarkers in sepsis is still lacking. (2) Objective: In this project, we aimed to perform a comparative analysis of biomarker levels in ischemic cardiovascular disease and sepsis. Analyzed markers comprised soluble suppression of tumorigenicity 2 (sST2; hemodynamics and inflammation), growth-differentiation factor 15 (GDF-15; injury, remodelling), soluble urokinase-type plasminogen activator receptor (suPAR; inflammation and remodeling) and heart-type fatty acid binding protein (H-FABP; myocardial ischemia). (3) Methods: In total, 311 patients were included in the study: 123 heart-failure (HF) patients, 60 patients with ST-segment elevation myocardial infarction (STEMI) and 53 sepsis patients. A total of 75 patients without coronary artery disease or signs of heart failure served as a control group. Plasma samples were analyzed by use of ELISA after informed consent. (4) Results: Patients with sepsis showed significantly increased plasma levels in all tested biomarkers compared to cardiovascular disease entities (sST2, suPAR, GDF-15: p &lt; 0.001; H-FABP: compared to HF p &lt; 0.001) and controls (sST2: 7.4-fold, suPAR: 3.4-fold, GDF-15: 6.5-fold and H-FABP: 15.3-fold increased plasma levels, p &lt; 0.001). Moreover, in patients with sepsis, serum concentrations of sST2 and suPAR were significantly elevated in patients with HF and patients with STEMI (sST2: HF: 1.6-fold increase and STEMI: 2.5-fold increase, p &lt; 0.001; suPAR: HF: 1.4-fold increase, p &lt; 0.001 and STEMI: 1.4-fold increase, p &lt; 0.01), whereas plasma levels of GDF-15 and H-FABP were markedly elevated in patients with STEMI only (GDF-15: 1.6-fold increase, H-FABP: 6.4-fold increase, p &lt; 0.001). (5) Conclusions: All tested novel cardiac biomarkers showed significantly elevated levels in sepsis patients. Interestingly, a secretion pattern similar to STEMI was observed with regards to sST2 and HFABP. Thus, by providing an assessment tool especially covering the cardiovascular component of the disease, novel biomarkers offer a promising tool in sepsis patients.

Role of neprilysin inhibitors in cardiovascular Disease-A short review

Cardiovascular diseases (CVD) continue to represent the major cause of death, morbidity and healthcare expenditure worldwide. Hypertension and heart failure, the most important cardiovascular disease entities, are associated with imbalance in neurohormonal systems activity such as the renin-angiotensin-aldosterone system, the sympathetic nervous system and the endothelin system. Neprilysin is an enzyme that contributes to the breakdown of the biologically active natriuretic peptides and several other vasoactive compounds. Inhibiting neprilysin has been a therapeutic target for several compounds that have been tested in cardiovascular disease, including ecadotril, candoxatril, omapatrilat. Its ability to inhibit the renin-angiotensin-aldosterone axis and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular diseases. The role of neprilysin inhibitors in cardiovascular disease has been discussed in this article.

MicroRNAs in cardiovascular disease - clinical application.

microRNAs (miRNAs) are well-known, powerful regulators of gene expression, and their potential to serve as circulating biomarkers is widely accepted. In cardiovascular disease (CVD), numerous studies have suggested miRNAs as strong circulating biomarkers with high diagnostic as well as prognostic power. In coronary artery disease (CAD) and heart failure (HF), miRNAs have been suggested as reliable biomarkers matching up to established protein-based such as cardiac troponins (cT) or natriuretic peptides. Also, in other CVD entities, miRNAs were identified as surprisingly specific biomarkers - with great potential for clinical applicability, especially in those entities that lack specific protein-based biomarkers such as atrial fibrillation (AF) and acute pulmonary embolism (APE). In this regard, miRNA signatures, comprising a set of miRNAs, yield high sensitivity and specificity. Attempts to utilize miRNAs as therapeutic agents have led to promising results. In this article, we review the clinical applicability of circulating miRNAs in CVD. We are giving an overview of miRNAs as biomarkers in numerous CVD entities to depict the variety of their potential clinical deployment. We illustrate the function of miRNAs by means of single miRNA examples in CVD.

Cardiovascular Disease in Women: Clinical Perspectives.

Cardiovascular disease continues to be the leading cause of death among women in the United States, accounting for ≈1 of every 3 female deaths. Sex-specific data focused on cardiovascular disease have been increasing steadily, yet is not routinely collected nor translated into practice. This comprehensive review focuses on novel and unique aspects of cardiovascular health in women and sex differences as they relate to clinical practice in the prevention, diagnosis, and treatment of cardiovascular disease. This review also provides current approaches to the evaluation and treatment of acute coronary syndromes that are more prevalent in women, including myocardial infarction associated with nonobstructive coronary arteries, spontaneous coronary artery dissection, and stress-induced cardiomyopathy (Takotsubo Syndrome). Other cardiovascular disease entities with higher prevalence or unique considerations in women, such as heart failure with preserved ejection fraction, peripheral arterial disease, and abdominal aortic aneurysms, are also briefly reviewed. Finally, recommendations for cardiac rehabilitation are addressed.

Association of relative telomere length with cardiovascular disease in a large chronic kidney disease cohort: The GCKD study

BackgroundChronic kidney disease (CKD) affects 10–15% of the general population and affected individuals are at an increased risk for cardiovascular disease (CVD). Since telomere length is considered to be involved in biological aging, we tested whether relative telomere length (RTL) might be a marker for these two diseases. MethodsThe German Chronic Kidney Disease (GCKD) study is an ongoing prospective cohort study including patients with CKD of moderate severity. RTL was measured by qPCR in 4955 out of 5217 GCKD patients at baseline. ResultsRTL was distributed in the cohort with a mean ± SD of 0.95 ± 0.19. CVD was present in 1266 patients. Each decrease of RTL by 0.1 unit was associated with a higher probability for prevalent CVD: OR = 1.06, 95% CI 1.02–1.11, p = 0.007 (adjusted for age, sex, eGFR, BMI, ln-CRP, smoking, hypertension, diabetes, and lipids). Similar findings were observed for history of specific CVD entities, such as coronary artery disease (OR = 1.05, p = 0.025), myocardial infarction (OR = 1.08, p = 0.013) and percutaneous transluminal coronary angioplasty (OR = 1.06, p = 0.032). The strongest associations were found for interventions at the carotid arteries (OR = 1.25, p = 0.001) as well as aortic aneurysms (OR = 1.22, p = 0.001). ConclusionsIn the presence of CKD there is a significant association between shorter RTL and CVD manifestations. RTL appears to be a marker reflecting changes in homeostasis associated with CKD that may contribute to the excess CVD risk.

Randomized Controlled Trial of a Multipronged Intervention to Improve Blood Pressure Control among Stroke Survivors in Nigeria

Stroke is the second-leading cause of death in low- and middle-income countries, but use of evidence-based therapies for stroke prevention in such countries, especially those in Africa, is extremely poor. This study is designed to enhance the implementation and sustainability of secondary stroke-preventive services following hospital discharge. The primary study aim is to test whether a Chronic Care Model-based initiative entitled the Tailored Hospital-based Risk reduction to Impede Vascular Events after Stroke (THRIVES) significantly improves blood pressure control after stroke. This prospective triple-blind randomized controlled trial will include a cohort of 400 patients with a recent stroke discharged from four medical care facilities in Nigeria. The culturally sensitive, system-appropriate intervention comprises patient report cards, phone text messaging, an educational video, and coordination of posthospitalization care. The primary outcome is improvement of blood pressure control. Secondary endpoints include control of other stroke risk factors, medication adherence, functional status, and quality of life. We will also perform a cost analysis of THRIVES from the viewpoint of government policy-makers. We anticipate that a successful intervention will serve as a scalable model of effective postdischarge chronic blood pressure management for stroke in sub-Saharan Africa and possibly for other symptomatic cardiovascular disease entities in the region.

Estrogen status and the renin angiotensin aldosterone system.

The renin-angiotensin-aldosterone system (RAAS) is integrally involved in multiple cardiovascular physiological processes including arterial blood pressure (BP) regulation. Over activity of the RAAS has been implicated in the pathogenesis of a number of cardiovascular disease entities, including hypertension. Several lines of evidence suggest estrogen favorably modulates the RAAS. Conversely, estrogen deficiency due to menopause may contribute to over activity of the RAAS. Of importance, estrogen deficiency in women is not exclusive to the postmenopausal period. Functional hypothalamic amenorrhea is a reversible cause of premenopausal hypoestrogenemia. In contrast to postmenopausal women (PMW), premenopausal women with exercise-associated functional hypothalamic amenorrhea demonstrate decreased, not increased, resting BP compared with their estrogen-replete eumenorrheic counterpart. In this review we briefly examine the effects of estrogen status on the RAAS and present the hypothesis that the RAAS is altered in physically active women with functional hypothalamic amenorrhea.

Sympathetic Overactivity in Hypertension and Cardiovascular Disease

From the first description of its anatomy by T. Willis to the novel therapeutic manipulations, it is unanimously recognized that the sympathetic nervous system (SNS) holds a crucial role in cardiovascular homeostasis. The introduction of sophisticated techniques, as microneurography and regional norepinephrine spillover provided the evidence for the role of sympathetic overactivity in various cardiovascular disease entities. Sympathetic activation is common in patients with essential hypertension and contributes to initiation, maintenance and progression of the disease and it contributes to the manifestation of its major complications. A considerable body of evidence relates SNS overactivity with high sodium intake in experimental animals and humans and the underlying mechanisms have nowadays been elucidated. SNS activity is more pronounced in patients with resistant hypertension and there are several conditions that lead to this phenomenon, as older age, kidney disease, obesity and metabolic syndrome, mental stress and sleep apnea. SNS overactivity holds also a key physiopathological role in heart failure, acute coronary syndromes and arrhythmias. Moreover, inhibition of sympathetic overactivity by various means, including central SNS suppressing drugs, peripheral alpha- and beta- adrenergic receptor blockers, or novel approaches as renal sympathetic denervation have been used successfully in the treatment of all these disorders.

Extra cardiac findings in cardiovascular MR: Why cardiologists and radiologists should read together

To assess prevalence and significance of extra cardiac findings (ECF) in clinical routine cardiovascular magnetic resonance (CMR) studies reported by cardiologists alone versus cardiologist and radiologist working together. One-thousand-seventy-four consecutive patients presenting at our institution for CMR work-up of multiple cardiovascular disease entities were enrolled retrospectively in two groups (cardiologists reading alone vs. cardiologists and radiologist reading together). In 1,074 routine CMR studies a total of 357 ECF's were identified in 235 patients yielding a prevalence of 21.9 %. Of these 357 ECF's more than one-third were previously known. In the remaining 223 previously unknown findings 118 (52.9 %) were considered as major ECF's (92 patients), and 105 (47.1 %) were considered as minor ECF's (69 patients). Cardiologists reading alone reported 23 previously unknown ECF's in 23 patients, versus 200 previously unknown ECF in 138 patients by cardiologists and radiologists working together, p < 0.0001. Nevertheless, highly significant ECF's with major prognostic implications, such as the initial diagnosis of malignancy in an individual with no history of cancer, are extremely rare (n = 3, 0.3 %). Cardiologists alone, as well as cardiologists and radiologists working together seem to do well with reporting of such extremely important ECF's. The prevalence of all ECF's was 21.9 %, and 14.9 % of previously unknown ECF's, respectively. However, the prevalence of highly significant ECF's was low. Joint reading with cardiologists and radiologists may increase the number of ECF's detected in CMR studies, but it remains unclear if this could result in an improved long-term outcome of patients undergoing routine CMR.

Pigs in space

Despite the common knowledge that experimental data from animal models cannot readily be translated into human disease, clinical trials are often based on translational research performed on species evolutionarily distant from humans. The troublesome task of extrapolating the findings from one species to another has haunted physiological experimentation since its early dawn, and the issue is still relevant in cardiovascular science with the common use of genetically modified mice. For instance, diabetic and ischemic changes in the myocardium are often pursued using in-vivo and in-vitro models mainly based on rodent cardiovascular physiology and cellular biology 1. The concern does not stop with only speculative reservation. Modern pharmacological studies most often test new drugs on small animals, resulting in a series of disappointments in human phase-3 trials 2,3, which has certainly cost us astronomical sums and may have even led to disease and death. The cardiac response to myocardial hypoxia should ideally be pursued in models that mimic human anatomy, biochemistry, and function in both health and disease. In this context, we suggest the porcine heart as the best model of choice in experimental cardiovascular research because of the following hallmarks: first and foremost, the coronary blood supply to the myocardium equals that of the normal human anatomy 4. In contrast, the functional end arteries do not supply the heart muscle in other mammalian species. Second, the cardiac production of natriuretic peptides, the gold standard endocrine markers of heart failure, differs markedly among mammalian hearts, wherein normal hormonal expression resides in the human and porcine atria 5,6 but is most dominant in the ventricular chambers in, for instance, rodents 7. Such intrinsic differences are likely to affect the endocrine cardiac response during the disease. Finally, porcine and human cardiac functions are similar, which facilitates direct interpretation to human medicine 8. Elucidation of several cardiovascular disease entities can be achieved using porcine models. For instance, we compared the neonate cardiovascular response of pigs in terms of cardiac natriuretic peptide gene expression and found patterns similar to those of neonate children. This opens up for the possibility of studying, for instance, the effects of gestational diabetes on neonate physiology. Moreover, cardiac congenital anomalies present in humans can easily be induced in pigs, and the devices for treating these conditions can even be tested on pigs 9. Another major disease entity for cardiovascular endocrinology is heart failure, in which natriuretic peptides have a central role in both pathobiological and clinical diagnosis. Accurate biochemical tools have been developed for this peptide system in pigs 10, which is not the case for other species, including mice. With an increasing appreciation and understanding of the porcine transcriptome 11,12, as well as genetically modified pigs already over the doorstep 13,14, cardiovascular endocrinology should consider the best choice of animal models for the studies on human cardiovascular pathophysiology. In this respect, a completely new pig model for human atherosclerosis has just been developed at our university by inducing overexpression of the gene for liver-specific proprotein convertase subtilisin/kexin type 9 (PCSK9), which causes severe hypercholesterolemia and human-like atherosclerosis 15. This model may easily prove valuable for several types of translational research on atherosclerosis and also in diabetes complications. For now, we would like to advocate that the use of pigs should be pursued more eagerly in elucidating human cardiovascular endocrinology (as pigs are only found in space in the Muppet Show) 16,17. Acknowledgements Conflicts of interest There are no conflicts of interest.

Urotensin II

Urotensin II was first identified over 30 years ago as a potent vasoconstrictor, and the identification of its receptor in the heart, lungs, blood vessels, and brain have made it a potential target for human pharmacotherapy. Current research would suggest that urotensin II plays a major role in the pathophysiology of various cardiovascular disease entities. This article discusses the biologic effects of urotensin under normal and pathophysiologic conditions, and reviews the research experiences with synthetic urotensin blockers in the treatment of various cardiovascular illnesses.

Amino-Terminal Pro-B-Type Natriuretic Peptide and B-Type Natriuretic Peptide

Recent studies report that, in the absence of heart failure and renal failure, plasma B-type natriuretic peptide (BNP) has prognostic value for mortality. We sought to confirm and extend these previous studies to assess BNP, measured by 3 distinct assays, as a biomarker for mortality in a strategy to enhance efforts at primary prevention and to better understand the clinical phenotype of such subjects at risk. We used a community-based cohort of 2042 subjects from Olmsted County, Minn, and individuals with heart or renal failure were excluded. BNP was assessed using 3 assays including Biosite and Shionogi for mature, biologically active BNP and the Roche assay for apparently nonbiologically active amino-terminal pro-BNP (NT-proBNP). Thorough echocardiographic and clinical data were recorded for all of the participants. Median follow-up for mortality was 5.6 years. BNP by all 3 of the assays was predictive of mortality. NT-proBNP and Biosite assays remained significant even after adjustment for traditional clinical risk factors and echocardiographic abnormalities including left ventricular hypertrophy and diastolic dysfunction. Echocardiography documented widespread structural changes in those with increasing BNP levels yet below levels observed in heart failure. We report in a large, well-characterized community-based cohort, free of heart failure, the first study to compare 3 distinct BNP assays as biomarkers for mortality in the same cohort. Our findings confirm the potential use of NT-proBNP and BNP biomarkers for future events and underscore that these peptides may also serve as biomarkers for underlying cardiac remodeling secondary to diverse cardiovascular disease entities.

Heart failure

Heart failure

Matrix metalloproteinases: a therapeutic target in cardiovascular disease.

Cardiovascular disease is the leading cause of death in Western society. Extracellular matrix turnover is important in many cardiovascular pathologies, such as arterial remodeling, plaque rupture, restenosis, aneurysm formation and heart failure. Matrix metalloproteinases (MMPs) belong to a group of zinc and calcium dependent proteases and cause breakdown of the extracellular matrix. MMP inhibitors have been developed and tested for their effect on the outcome of oncological disease [1]. Recent preclinical research revealed that these MMP inhibitors could also have great potential in the field of cardiovascular disease. This preclinical research has encouraged investigators to design and start the first clinical studies with cardiovascular endpoints. In the present paper, the various aspects of MMP participation in cardiovascular disease will be summarized. Preclinical animal studies that demonstrated the effect and potential of applicable MMP inhibitors on different cardiovascular disease entities will be discussed. We will specifically focus on the role of MMPs and the potential of their inhibitors in de novo atherosclerotic plaque destabilization, arterial remodeling, restenosis after ballon angioplasty and stenting, aneurysm formation and heart failure. We conclude that MMP inhibitors are likely to be useful in the development of pharmacological approaches to reduce cardiovascular death, considering the positive outcomes after usage of MMP inhibitors in restenosis and arterial remodeling.

Calcium antagonists in patients with cardiovascular disease. Current perspectives.

Since their introduction in the United States about 4 years ago, the calcium antagonists have achieved an important place in the medical therapy of several cardiovascular disease entities. These pharmacologic agents differ markedly in their clinical utility. Verapamil is extremely effective in patients with supraventricular tachyarrhythmias, hypertrophic cardiomyopathy, and the various anginal syndromes, but it appears to be ineffective or possibly even deleterious in those with pulmonary hypertension, congestive heart failure of any cause, and Raynaud's phenomenon or disease. Nifedipine exerts a powerful vasodilatory effect and, as a result, is efficacious in individuals with systemic or pulmonary hypertension, congestive heart failure, and Raynaud's phenomenon or disease. It is also beneficial in patients with various kinds of angina, especially when it is administered concomitantly with a beta-adrenergic blocker. It is totally ineffective as an antiarrhythmic agent. Diltiazem is an effective antianginal agent and may be beneficial as an antiarrhythmic agent, but it is largely untested in patients with systemic or pulmonary hypertension, Raynaud's disease, and hypertrophic cardiomyopathy. A thorough understanding of each drug's hemodynamic and electrophysiologic effects allows the practicing physician to prescribe them skillfully and safely.