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At least 289 records · Page 16Linked to original sources
PubMed2026

Whole-genome sequencing implicates rare, low-frequency and structural non-coding variation at the SCN5A locus in Brugada syndrome.

Brugada syndrome (BrS) is an inherited cardiac condition characterized by a hallmark ECG pattern and an increased risk of sudden cardiac death. Central to the aetiology of BrS, the SCN5A region harbours both common non-coding risk variants and rare coding variants that are causative in approximately 20% of patients. However, rare non-coding genetic variation in this region remains largely unexplored. Here, we used whole-genome sequencing (WGS) of 752 European-ancestry BrS cases and 1,827 ancestry-matched controls to identify BrS-associated rare non-coding genetic variation at the SCN5A locus. Sliding-window and cis-regulatory element (CRE)-based rare-variant aggregate testing implicated three conserved CREs, including a dense aggregation of case singleton variants within a 178 bp enhancer in intron 17 of SCN5A which replicated in an independent BrS cohort. Prioritised BrS-associated rare and low-frequency non-coding variants within these elements were predicted to alter cardiac transcription factor motifs, and altered CRE activity in hiPSC-CM luciferase assays or were associated with BrS-relevant ECG endophenotypes in the UK Biobank. Single-variant analysis across the region identified a Bonferroni-significant five-fold case-enriched low-frequency variant within a known CRE in intron 1 of SCN5A, which replicated, was associated with slower cardiac conduction in the UK Biobank and accounted for part of the BrS GWAS signal at this locus. Structural variant analyses identified a 10.5 kb deletion upstream of SCN5A in a BrS case that encompassed a cardiac CRE and reduced sodium current density in a hiPSC-CM model, as well as a 6 kb BrS-enriched retrotransposon insertion in SCN5A that appeared to underlie part of the GWAS signal in this region. Together, these findings implicate rare and low-frequency non-coding variation at the SCN5A locus in BrS susceptibility and demonstrate the value of targeted WGS analysis of key disease loci.

Journal Article↗
PubMedDate not supplied

[Cardiac component of emotional stress in the elk, Alces alces, and the reindeer, Rangifer tarandus].

Using radiotelemetric technique, extraordinary changes have been found in cardiac activity of the elk and reindeer during spontaneous emotional stress under natural conditions. Cardiac reaction is characterized by rapid 2--3-fold increase in the heart rate and by 3--4-fold increase in the amplitude of T-wave. It was suggested that these changes are associated with abnormalities of metabolic processes in the heart.

Animals↗
PubMed2003

The influence of co-morbidity on health-related quality of life in asthma and COPD patients.

This study examines the association between somatic co-morbidity and both general and disease-specific health-related quality of life (HRQoL) in patients with asthma and chronic obstructive pulmonary disease (COPD). A cross-sectional analysis was done among 161 COPD patients and 395 asthma patients, aged 40-75 years, recruited from general practice. In the total study population, 47% had no, 32% had one, and 21% had two or more somatic co-morbid conditions, with no significant differences between asthma and COPD patients. Co-morbidity appeared to be associated with poor disease-specific HRQoL in asthma [odds ratio (OR) = 2.08 (1.37-3.18)] and with poor general HRQoL in asthma [OR = 2.96 (1.93-4.53)] and COPD [1.81 (0.91-3.60)] patients. Poorest HRQoL was found in patients with more than one co-morbid condition. Cardiac disease and hypertension were associated with poor disease-specific HRQoL in asthma. Of all co-morbid conditions, musculoskeletal disorders were most strongly associated with poor general HRQoL. Cardiac disease was found to be associated with general and disease-specific HRQoL in asthma but not in COPD. In studies on patients with asthma or COPD aged 40-75 years, co-morbidity should be treated as a determinant of HRQoL.

Adult↗
PubMed1998

Differential atrial and ventricular expression of myocardial BNP during evolution of heart failure.

Although brain natriuretic peptide (BNP) of myocardial origin is important in cardiovascular and renal function and as a marker of cardiac dysfunction, the expression of BNP in atrial and ventricular myocardium remains controversial both under normal conditions and in heart failure. We therefore determined left atrial and left ventricular (LV) gene expression and tissue concentration as well as circulating BNP during the evolution of rapid ventricular pacing-induced congestive heart failure (CHF) in the dog. Early LV dysfunction after 10 days of pacing was characterized by impaired LV function but maintained arterial pressure, and overt CHF after 38 days of pacing was characterized by further impaired LV function and decreased systemic arterial pressure. Under normal conditions, cardiac BNP mRNA and cardiac tissue BNP were of atrial origin. In early LV dysfunction, BNP mRNA and tissue BNP were markedly increased in the left atrium in association with an increase in circulating BNP but remained below or at the limit of detection in the LV. In overt CHF, BNP mRNA was further increased in the left atrium and first increased in the LV, together with an increase in LV tissue BNP and a further increase in circulating BNP. In the progression of CHF, early LV dysfunction is characterized by a selective increase in atrial BNP expression in association with increased circulating BNP. Overt CHF is characterized by an additional recruitment of ventricular BNP expression and a further increase in circulating BNP. These studies provide important new insight into the local and temporal regulation of cardiac BNP gene expression during the progression of heart failure and underscore the predominant endocrine role of atrial myocardium under normal conditions and in early LV dysfunction.

Animals↗
PubMed1990

[Alternative closure of the sternum after heart surgery].

We report on 27 patients who, between November 1986 and December 1988, had a delayed sternal closure after cardiac surgery out of the following reasons: post-ECC low output syndrome: 17 patients (15 with IABP, 11 transfemoral, 4 transaortic), haemodynamic breakdown with sternal approximation: 9 patients, diffuse bleeding: one patient. In 13 patients perioperative infarction was diagnosed (4 right heart infarctions) as a cause for the poor cardiac condition. The surgery performed had been: 26 coronary artery bypass operations (18 combined with other procedures), and one double valve replacement. The temporary closure of the wound generally is now performed by a sterile zipper (Ethizip). Sternal closure was possible one to nineteen days postoperatively, most often (19 patients) on the 2nd postoperative day. We did not note any serious complications or wound infection due to the management with delayed sternal closure. Three patients died from cardiac failure with chest open, 4 patients died six days to eight weeks postoperatively with closed chest. Among the 20 patients discharged from hospital, 17 are at present in satisfactory clinical condition, one patient suffers from recurrent angina, one from cardiac insufficiency and one is in poor general condition. As a conclusion we think that delayed sternal closure after cardiac surgery is a helpful tool in patients with 1) haemodynamic breakdown with sternal approximation, 2) diffuse bleeding.

Coronary Artery Bypass↗
PubMed2004

Atypical echocardiographic findings of endocarditis in an immunocompromised patient.

Cardiovascular manifestations in patients infected with human immunodeficiency virus (HIV) have been altered by the introduction of highly active antiretroviral therapy regimens that allow more effective prophylactic treatment and an increased time of survival. Because of this, noninfectious cardiac conditions associated with HIV disease are being recognized with increasing frequency in these patients. Cardiac involvement in HIV-infected patients varies from clinically silent to overtly symptomatic disease. By some estimates a direct cardiac cause of mortality is between 1% and 6% of all cases. Pericardial effusion, pericarditis, myocarditis, cardiomyopathy, endocarditis, and pulmonary hypertension are well-recognized cardiac illnesses associated with HIV infection. Echocardiography has been crucial in evaluating HIV-infected patients to assess the extent of cardiac involvement. This case report illustrates atypical echocardiographic manifestations of endocarditis and paravalvular abscess in an immunocompromised patient.

AIDS-Related Opportunistic Infections↗
PubMed2004

Targeted expression of cyclin D2 results in cardiomyocyte DNA synthesis and infarct regression in transgenic mice.

Restriction point transit and commitment to a new round of cell division is regulated by the activity of cyclin-dependent kinase 4 and its obligate activating partners, the D-type cyclins. In this study, we examined the ability of D-type cyclins to promote cardiomyocyte cell cycle activity. Adult transgenic mice expressing cyclin D1, D2, or D3 under the regulation of the alpha cardiac myosin heavy chain promoter exhibited high rates of cardiomyocyte DNA synthesis under baseline conditions. Cardiac injury in mice expressing cyclin D1 or D3 resulted in cytoplasmic cyclin D accumulation, with a concomitant reduction in the level of cardiomyocyte DNA synthesis. In contrast, cardiac injury in mice expressing cyclin D2 did not alter subcellular cyclin localization. Consequently, cardiomyocyte cell cycle activity persisted in injured hearts expressing cyclin D2, ultimately resulting in infarct regression. These data suggested that modulation of D-type cyclins could be exploited to promote regenerative growth in injured hearts.

Age Factors↗
PubMed1995

Syncope in athletes.

Syncope is a brief sudden loss of consciousness and muscle tone secondary to cerebral ischaemia, inadequate oxygen or glucose delivery to the brain. The causes of syncope may be benign and require very little in the way of evaluation or treatment. However, syncope may be the harbinger of sudden death, and extensive evaluation, monitoring and detailed recommendations regarding advisability of participating in sports should be reviewed with the patient. The history is the most important clue when attempting to identify which patient with syncope is at risk for sudden death. A careful cardiac and neurological examination should be performed in any patient presenting with syncope. Selective use of laboratory testing and cardiac monitoring may assist the practitioner in making the diagnosis. Most often patients with syncope will have a benign cause such as vaso-vagal events, hyperventilation or orthostatic hypotension. Patients with a cardiac condition causing their syncope are at increased risk for sudden death. The ominous, cardiac-related causes of syncope in the younger population include hypertrophic cardiomyopathy, aberrant coronary arteries and aortic dissection secondary to Marfan's syndrome. In the older athletic population, coronary atherosclerosis may present with syncope. Dysrhythmias may be the cause of syncope in both populations.

Adolescent↗
PubMed2001

[Physiological cardiovascular adaptation in pregnancy--its significance for cardiac diseases].

Stroke volume and heart rate rise at the very beginning of a pregnancy and decline after birth, over the course of months. Arterial blood pressure is lowered, plasma volume is increased while central venous pressure stays constant during pregnancy. The rise in cardiac output in early pregnancy can be induced quantitatively by oestrogen. The pregnancy-induced rise in cardiac output is based on the fairly general remodelling of the cardiovascular system. In a process of development, many portions of the cardiovascular system undergo programmed dilation (expansion): There is a programmed dilation of the heart, of the aorta, of the resistance vessels of the kidney and the resistance vessels of the placenta, and a programmed dilation of the venous system. All the changes favour the perfusion of the pregnant body. Cardiac dilation increases directly stroke volume, aortic dilation increases the susceptance (Windkessel function) of the aorta, the peripheral dilation increases the vascular conductance, and the venous dilation raises blood volume. Since the vascular conductance increase by peripheral dilation is higher than the increase in stroke volume, arterial pressure drops and evokes, via the baroreceptor reflex, an increase in heart rate; the increase in cardiac output occurs to an equal extent by an increase in stroke volume and an increase in heart rate. Compression of the caval vein by the pregnant uterus increases peripheral venous pressure and possibly slows down blood flow in the limbs. Increase in cardiac output means a burden for the heart, especially when associated with increase in heart rate. In this condition, cardiac energy expenditure is increased while oxygen supply is decreased. The rise in energy expenditure by an increase in flow rate is especially high for turbulent flow conditions at stenotic valves. In addition, there is an increased risk of arterial rupture by arterial remodelling and an increased risk of thrombosis by deceleration of venous blood flow velocity. Thus, the cardiovascular adaptation to pregnancy means an increased cardiovascular risk which may, on the basis of a basic cardiac disease, lead to cardiac failure.

Adaptation, Physiological↗
PubMed2001

Clinical importance of stunned and hibernating myocardium.

Myocardial stunning and hibernation are states of potentially reversible myocardial dysfunction, which were first described more than 20 years ago (c.1980). Important advances have now been made in the ability to detect stunned and hibernating myocardium, as well as in the understanding of the impact of these conditions on patient outcomes. We discuss here the clinical importance of stunned and hibernating myocardium for patients with several common cardiac conditions.

Angina Pectoris↗
PubMed1980

The ultrasound cardioscope: a hand-held scanner for real-time cardiac imaging.

A miniaturized hand-held ultrasound scanner that permits two-dimensional echocardiography is described. The device has been routinely used in our emergency department, coronary care unit, wards, and outpatient department. The device has advantages in situations where rapid decisions are demanded of the expert echocardiographer. It permits improved bedside analysis of patients with puzzling cardiac conditions. An important feature is that the instrument can be used as a substitute for cardiac fluoroscopy in office practice. Tests performed in 100 consecutive patients have demonstrated that reasonable semiquantitative estimation of the sizes of left-side heart structures is possible. This new-generation instrument can make diagnostic ultrasound more readily available in emergency situations and should have considerable influence on the use of cardiac ultrasound for bedside diagnosis. It will undoubtedly affect future developments in automatic, portable, and special dedicated ultrasound equipment.

Adult↗
PubMed1993

Tidal variation of pulmonary blood flow and blood volume in piglets during mechanical ventilation during hyper-, normo- and hypovolaemia.

Effects of changes in blood volume on changes in pulmonary blood flow and pulmonary blood volume during the ventilatory cycle during mechanical ventilation with a positive end-expiratory pressure of 2 cm H2O were determined in six pentobarbital anaesthetized, curarized pigs weighing about 10 kg. Haemodynamic variables were analysed for each cardiac cycle in eight ventilatory cycles in four consecutive series under hyper-, normo- and hypovolaemic conditions. Cardiac output was highest in hypervolaemia. Compared with normo- and hypovolaemia, it decreased less during inflation, due to a smaller rise in central venous pressure and presumably a larger filling state of the venous system. The smaller decrease in right ventricular output in hypervolaemia coincided with a larger fall in transmural central venous pressure (right ventricular filling pressure), due to right ventricular action at a higher, less steep part of its function curve. The difference between right ventricular-output (electromagnetic flow measurement) and left ventricular-output (pulse contour) indicated changes in pulmonary blood volume. In hypervolaemia less blood shifted from the pulmonary circulation into the systemic system during inflation than in normo- and hypovolaemia. This difference can be explained by two mechanisms namely, the smaller fall in input into the pulmonary vascular beds and a smaller pulmonary vascular volume decrease as a result of transmural pressure fall at a steeper part of the pressure-volume curve.

Animals↗
PubMed1989

Influence of intracellular pH on mitochondrial calcium during ischaemia of the isolated rat heart.

Under physiological conditions cardiac mitochondria seem to play a minor role in maintaining intracellular Ca2+ homoeostasis. However, under conditions of cellular Ca2+ overload, mitochondria may accumulate large amounts of Ca2+. Using transmission and analytical electron microscopy, we investigated, in globally ischaemic rat heart preparations, the influence of intracellular pH on the development of Ca2+-containing intramitochondrial inclusions. We confirmed that under these experimental conditions Ca2+ was a major element of mitochondrial inclusions. The size of these inclusions increased with external Ca2+ concentration. An intracellular alkalinization, produced by addition of 20 mM NH4Cl to the perfusate prior to ischaemia, inhibited the formation of such inclusions. On the other hand, a pre-ischaemic intracellular acidification, produced by the addition and subsequent withdrawal of the 20 mM NH4Cl, increased the number of inclusions present at the end of an ischaemic episode. The presence of amiloride (10(-3) M), prior to and during ischaemia, increased the number of inclusions. These data suggest that cytoplasmic pH may be an important factor in mitochondrial Ca2+ accumulation in pathological conditions.

Amiloride↗
PubMed1978

Apex sector echocardiography in evaluation of the right atrium in patients with mitral stenosis and atrial septal defect.

Cross-sectional echocardiography utilizing the four chamber apical view was used to evaluate right atrial dimensions as a means of detecting abnormal right heart hemodynamics in 20 patients with mitral stenosis, 5 patients with an atrial septal defect and 10 patients without heart disease. Right and left atrial dimensions on apex echocardiography were 40 mm or less in control subjects. There was a good correlation (r = 0.81) between left atrial size assessed with apex sector and M mode echocardiography. In patients with an atrial septal defect, the left atrium was of normal size on apex sector echocardiography; in patients with mitral stenosis, it was larger on apex echocardiography (59 +/- 9 mm) than on M mode echocardiography (51 +/- 8 mm). The right atrium was enlarged (54 +/- 5 mm) on apex echocardiography in all five patients with an atrial septal defect, but the right ventricle was enlarged in only four. Seventeen of 20 patients with mitral stenosis had an enlarged right atrium (53 +/- 7 mm) on apex echocardiography, whereas 15 had normal right ventricular dimensions (21 +/- 9 mm) on M mode echocardiography. Right atrial size on apex echocardiography was enlarged (54 +/- 6 mm) in 10 of 11 patients with mitral stenosis and pulmonary arterial hypertension. Thus, evaluation of the right atrial dimension with apex echocardiography may be more sensitive than M mode echocardiography in detecting early right heart involvement in specific cardiac conditions.

Adult↗
PubMed2001

Windows of opportunity to improve diabetes care when patients with diabetes are hospitalized for other conditions.

OBJECTIVE: The overwhelming majority of hospitalizations for patients with diabetes occur for treatment of comorbid conditions. This study assessed broad-based interventions to improve diabetes care for patients hospitalized with cardiac conditions. RESEARCH DESIGN AND METHODS: A pre-post quasi-experimental study design was used to evaluate the implementation of two quality improvement interventions: 1) revision of the hospital's capillary blood glucose monitoring form into a color-coded process control chart and 2) a clinical path for type 2 diabetes as a secondary diagnosis. Interventions were implemented on the medical and surgical cardiac care units (not including the intensive care units on these services) of a tertiary academic medical center. A chart abstraction sample included 328 subjects with no exposure to the interventions and 336 subjects hospitalized after both interventions were implemented. Telephone surveys were conducted after discharge on 446 patients. RESULTS: The frequency of patients with severe hyperglycemia (at least one glucose level >400 mg/dl) and prolonged hyperglycemia (at least three consecutive glucose levels >250 mg/dl) decreased from 12 and 17% preintervention to 6.6 and 10% postintervention (P = 0.017 and P = 0.013, respectively). We found that 9% of the patients preintervention and 5% of the patients postintervention (P = 0.05) had nosocomial infections. Patient-reported receipt of self-care instruction varied from 44 to 69% on nine survey items preintervention. Postintervention linear regression slopes for receipt of self-care instruction were all greater than preintervention slopes, but the differences did not achieve statistical significance. We found that 40% of the patients had important diabetes knowledge deficits. CONCLUSIONS: Our broad-based interventions were associated with a decreased frequency of prolonged and severe hyperglycemia and a decreased frequency of nosocomial infections. We also identified opportunities to improve diabetes self-care instruction before discharge and to address important knowledge deficits of patients.

Aged↗
PubMed1991

Morphologic comparison of patients with mitral valve prolapse who died suddenly with patients who died from severe valvular dysfunction or other conditions.

Clinical and necropsy findings are described in 56 patients with mitral valve prolapse: 15 patients, aged 16 to 69 years (mean 39), died suddenly and mitral valve prolapse was the only cardiac condition found at necropsy (hereafter called isolated mitral valve prolapse); the remaining 41 patients had other conditions that were capable of being fatal. Of the latter 41 patients, 7, aged 17 to 59 years (mean 45), had associated congenital heart disease, and 34 patients, aged 17 to 70 years (mean 52), had no associated congenital cardiac abnormalities. Compared with the 34 patients without associated congenital heart disease and with nonmitral valve prolapse conditions capable in themselves of being fatal, the 15 patients who died suddenly with isolated mitral valve prolapse were younger (mean age 39 +/- 17 versus 52 +/- 15 years; p = 0.01), more often women (67% versus 26%; p = 0.008) and had a lower frequency of mitral regurgitation (7% versus 38%; p = 0.02). The 15 patients dying suddenly with isolated mitral valve prolapse also were less likely to have evidence of ruptured chordae tendineae (29% versus 67%; p = 0.04). The frequency of increased heart weight (67% versus 59%), a dilated mitral valve anulus (80% versus 81%), a dilated tricuspid valve anulus (17% versus 17%), an elongated anterior mitral leaflet (86% versus 54%), an elongated posterior mitral leaflet (79% versus 77%) and fibrous endocardial plaque under the posterior mitral leaflet (73% versus 63%) was similar between the two groups. The severity of the prolapse (mild 20% versus 11%; moderate 27% versus 58%; severe 53% versus 32%) also was similar between the two groups. Thus, persons with mitral valve prolapse dying suddenly without another recognized condition tend to be relatively young women without mitral regurgitation.

Adolescent↗
PubMed2001

[Dilated cardiomyopathy and panuveitis as presenting symptoms of Lyme disease. General review of one case].

INTRODUCTION: The clinical expression of Lyme disease is highly variable. If a patient presents clinical findings consistent with a systemic Lyme borreliosis, this disease must be considered in an endemic area because of its favorable outcome with adequate treatment. EXEGESIS: The authors report and discuss the case of a patient with an unusual history of dilated cardiomyopathy and supraventricular fibrillation followed by bilateral panuveitis. Enzyme-linked immunosorbent assay and Western blot were positive for Borrelia burgdorferi antigens. The diagnosis of Lyme disease was made after other infectious, inflammatory and autoimmune disorders were excluded by clinical, instrumental and biological investigations. The treatment by ceftriaxone and amoxicillin resolved the ophthalmologic manifestations and improved the cardiac condition. CONCLUSION: This report underlines the possibility of an unusual presentation of Lyme disease. Ophthalmologic and cardiac involvement should be known by clinicians.

Adult↗
PubMed2002

Investigating six-month health outcomes of patients with angina discharged from a chest pain service.

Hospital admissions for patients with suspected cardiac chest pain are increasing. The development of a chest pain service allows rapid diagnosis, investigation and treatment. Since the in-patient stay is often short, there is limited time for education and risk factor management. Little is known about the patients' recovery post discharge. This study was completed to investigate the 6-month health outcomes of 57 patients discharged from the chest pain service by measuring cardiovascular symptoms and risk profiles, mood and quality of life, adherence to secondary prevention, morbidity and mortality. The results of this study showed that 58% of the sample still suffered angina, 72% reported breathlessness, and 79% reported lethargy. Assessment of mood showed that 76% suffered from anxiety and 78% depression. Quality of life was impaired. A reduction of cholesterol level was the only significant change in risk factors. Secondary prevention measures showed that there was still room for improvement. Twenty-five percent of the sample was readmitted to hospital due to their cardiac condition. Patients had an average of eight contacts with their general practitioner, four of which were cardiac related. The ongoing symptoms, anxiety and depression and uncorrected risk factors can impact on their recovery. Currently, however, no programme of rehabilitation is available for angina patients, despite the potential for up to 30% of patients suffering a subsequent cardiac event (Ghandi et al., British Heart Journal 73 (1995) 193-198). This study suggests the need to develop, implement and evaluate a CR programme in this client group.

Adult↗