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At least 55 records · Page 3Linked to original sources
PubMed2026

Prediction of incident heart failure in established atherosclerotic cardiovascular disease: the SMART2-HF model.

BACKGROUND AND AIMS: Patients with established atherosclerotic cardiovascular disease (ASCVD) are at high risk of developing heart failure (HF). However, incident HF is not part of the risk assessment of current guideline-recommended models. The aim of this study was to develop and externally validate the SMART2-HF model for prediction of incident HF in patients with ASCVD. METHODS: SMART2-HF was developed in 7698 individuals with established ASCVD (coronary, cerebrovascular, or peripheral artery disease, or abdominal aortic aneurysm) but without prior HF from the UCC-SMART cohort. Cox proportional hazards models including sex-predictor interactions and with age as the time scale were derived to estimate the 10-year and lifetime risk of incident HF (hospitalization for HF or HF-related death), accounting for competing non-HF mortality. Predictors, limited to routinely available clinical characteristics, were aligned with the SMART2 risk model for recurrent cardiovascular (CV) risk in the same population. External validation was performed in 240 741 patients with ASCVD from six data sources: the Clinical Practice Research Datalink, the HUNT3 study, the SWEDEHEART Registry, the ASCVD-Particles cohort, the Estonian Biobank and the international REACH Registry. RESULTS: During a median follow-up of 11.2 years (interquartile range 6.1-16.4 years), 1031 incident HF events (13%) occurred in the UCC-SMART cohort. In the external validation data sources, a total of 24 885 incident HF events (10%) occurred. The pooled C-statistic was .696 (95% confidence interval .674-.717), with consistent performance in subgroups by sex and type of ASCVD. Predicted risks matched observed incidence in external validation. CONCLUSIONS: The SMART2-HF model enables the prediction of incident HF in patients with ASCVD. Aligned with the guideline-recommended SMART2 model for recurrent CV risk, SMART2-HF can be used as a complementary tool in this population.

Humans↗
PubMed1979

Cellular growth of cardiac muscle after birth.

Present concepts concerning DNA synthesis in the heart have been reviewed, and a speculative theory presented involving control of DNA synthesis in the developing heart. Research describing DNA synthesis in myocytes of the weanling rat heart undergoing hypertrophy has been presented. Its possible use for testing the control theory is suggested.

Aging↗
PubMed2025

Single-Cell Splicing Isoform Atlas of the Adult Human Heart and Heart Failure.

BACKGROUND: Alternative splicing plays crucial roles in normal heart development and cardiac disease by influencing protein-coding sequences, functional domains, and molecular networks. However, a detailed characterization of the human heart isoform landscape remains incomplete. METHODS: Leveraging long-read single-nucleus RNA sequencing and computational analysis, we dissected full-length isoform heterogeneities, expression patterns, and usage shifts across cell types, cell states, and cardiac conditions of the adult left ventricle. We applied in silico approaches to assess the functional relevance of identified isoforms; validated isoform compositions of representative cardiac genes using reverse transcription quantitative polymerase chain reaction and targeted amplicon sequencing; and developed a web server for interactive navigation of our results. RESULTS: The data revealed that isoform heterogeneity is widespread in the cardiac cellular system, serving as a posttranscriptional buffer mechanism that calibrates the molecule reservoirs in human hearts. In healthy left ventricles, ≈30% of cell type-specific genes were polyform, using multiple isoforms tailored to cell type-specific programs. Among ubiquitously expressed genes, >300 showed differential isoform usage with cell type specificity in normal hearts. Comparisons of cardiomyocytes across conditions uncovered 379 genes with marked isoform usage shifts, most of which are predicted to change protein coding outcomes through direct changes in protein coding sequences and switches between intron retention and non-protein-coding biotypes. In contrast, cell state-specific programs tend to operate on monoform genes associated with changes among cell states. In addition, our data revealed heart failure-associated differential isoform usage events in stromal and immune cell types in the cardiac microenvironment. CONCLUSIONS: We present a comprehensive atlas of splicing isoforms in the normal adult heart and heart failure through long-read single-nucleus RNA sequencing and computational analyses. The results suggest crucial roles of isoforms in buffering core cellular programs and contributing to disease-associated cell states. The full-length details of these cell-specific isoforms serve as an important reference for downstream translational and mechanistic studies and are available on our online data portal at https://github.com/gaolabtools/heart-isoform-atlas.

Humans↗
PubMed1976

[Functional, morphologic and histochemical changes in the myocardium and their role in the development of cor pulmonale following pulmonary resection].

Functional, morphological and histochemical alterations were studied in 32 dogs within the period of 5 days--18 months after resection of 32-80% of the pulmonary tissue. According to the presence of hypertrophy of the heart right ventricle wall, morphological changes of the myocardium and disorders in the functional features of the cardiovascular activity all the animals were divided into 4 groups: 1--control animals; 2--experimental animals without hypertrophy of the right ventricle wall; 3--experimental animals with hypertrophy of the right ventricle wall in the stage of compensation; 4--experimental animals with hypertrophy of the right ventricle wall in the stage of decompensation. In the myocardium of the second group animals a decrease of aerobic processes and an increase of anaerobic ones were found to take place. The aerobic processes increased and the anaerobic processes decreased in the myocardium of dogs having hypertrophy of the right ventricle wall in the stage compensation. In the muscle of the decompensated pulmonary heart there occurred a pronounced decrease of aerobic and anaerobic processes, a disturbance of the protein and fat metabolism. All this resulted in a decreased contractive function of the myocardium with distrubed hemodynamics. The investigations have shown the interrelationships of morphological, histochemical and ECG alterations in the dynamics of the pulmonary heart development after resection of lungs.

Animals↗
PubMed1977

Intraoperative identification of the conduction system in repair of endocardial cushion defect.

Electrophysiological identification intraoperatively of the His-Purkinje system eliminates the complication of complete heart block consequent upon repair of endocardial cushion defect (ECD). Ten patients, 6 with complete ECD and 4 with incomplete ECD, underwent repair of the defect. None of the patients developed heart block. Slight variations were noted in the location of the His bundle in 9 patients, and a major deviation was found in 1 patient with incomplete ECD. The data support the use of intraoperative recordings as a necessary acconpaniment to the operative repair of ECD.

Bundle of His↗
PubMed1977

Direct effects of trypan blue on cardiac extracellular macromolecule synthesis.

The direct effects of the cardiac teratogen trypan blue on some parameters of embryonic chick heart metabolism were examined in vitro. Trypan blue inhibits chondroitin sulfate biosynthesis but stimulates incorporation of 3H-glucosamine into hyaluronate, heparin, and glycopeptides. 3H-fucose incorporation into glycoprotein is also stimulated. Total incorporation of 14C-labeled amino acids is elevated in the presence of trypan blue. Trypan blue does not cause qualitative changes in labeled end products; rather the metabolic alterations are quantitative. The possible exceptions are glucosamine-labeled glycoproteins since quantitative differences in glycopeptides could reflect qualitative differences in parent glycoproteins. These observations suggest that abnormal heart development, induced by trypan blue, may result from a multiplicity of metabolic alterations and not from any single chemical change.

Animals↗
PubMed1975

Combination of delta9-tetrahydrocannabinol with oxymorphone or pentobarbital: Effects on ventilatory control and cardiovascular dynamics.

Marijuana is widely used, yet few data concerning its actions combined with other drugs exist. Psychologic, respiratory and cardiovascular effects of delta9-tetrahydrocannabinol (THC), the active component of marijuana, combined with oxymorphone (OXM) or with pentobarbital (PBL), were studies in 15 healthy volunteers. Oxymorphone, 1.0 mg/70 kg, iv, caused sedation and ventilatory depression (minute ventilation: 24.9 plus or minus 11.9 SD to 14.1 plus or minus 4.9 1/min with PETCO2 held at 50 torr) in eight volunteers. TCH (27, 40, 60, 90, and 134 mug/kg, iv) increased sedation and further decreased ventilation with each TCH dose to 6.6 plus or minus 3.7 1/min after 134 mug/kg. The combination of OXM and THC decreased the CO2-ventilation slope from 2.23 to 0.88 1/min/torr. When THC, 134 mug/kg, was added to OXM, which alone caused no significant cardiovascular change, cardiac index (4.1 plus or minus 1.3 to 5.0 plus or minus 2.2 1/min/m-2) and heart rate (66 plus or minus 12 to 107 plus or minus 31 beats/min) significantly increased and total peripheral resistance (1,030 plus or minus 260 to 660 plus or minus 200 dynes-sec/cm-5) decreased. Heart rates exceeded 150 beats/min in two subjects after 27 and 134 mug/kg THC. Pentobarbital alone, 100 mg/70 kg, iv, caused no significant ventilatory or cardiovascular change. THC, after PBL pretreatment, induced hallucinations and anxiety in five of seven volunteers; four failed to complete all five doses of THC becuase of the severe psychologic effects. The combination of PBL and 40 to 134 mug/kg THC did not affect ventilation significantly. After PBL pretreatment, THC significantly increased heart rate (76 plus or minus 17 to 130 plus or minus 32 beats/min). Cardiac index also increased (3.8 plus or minus 0.8 to 5.6 plus or minus 1.9 1/min/m-2) and total peripheral resistance decreased (1,070 plus or minus 240 to 720 plus or minus 300 dynes-sec/cm-5). Three subjects developed heart rates esceeding 150 beats/min after 27, 27, and 90 mug/kg THC; in all three, heart rates fell from maximal value with a further dose of THC.

Adult↗
PubMed1979

Two-years' study with a combination of pindolol and clopamide ('Viskaldix') in patients with moderate hypertension.

A study was carried out to evaluate the long-term effects and side-effects of a combination product containing the beta-blocker pindolol (10 mg) and the diuretic clopamide (5 mg) in 15 patients with moderate hypertension. All patients completed the 2-years' study. The dose of the combination was increased until blood pressure normalized or a maximum dose of 3 tablets (equivalent to 30 mg pindolol and 15 mg clopamide) daily was reached. Blood pressure and heart rate were recorded monthly and detailed medical examinations were done regularly throughout the study. A mean dose of 2 tablets of the combination product (20 mg pindolol and 10 mg clopamide) produced a significant reduction in blood pressure. In all but 1 patient, blood pressure control was achieved and maintained. No tolerance developed. Heart volume showed a marked decrease. No side-effects of clinical importance were noted.

Adult↗
PubMed1977

The effect of propranolol upon chick embryo cardiogenesis.

The teratogenic effects of propranolol HCl on cardiac development were studied in chick embryos of days 3 and 4 of incubation. Propranolol was injected into the yolk sac at doses ranging from 0.05 to 0.6 mg per egg. All the treated and control embryos were examined on day 7. The LD50 for the embryos treated on the 3rd and 4th day was 0.15 and 0.35 mg per embryo, respectively. Cardiac anomalies such as aortic stenosis ventricular septal defects and common truncus arteriosus were observed. Other malformations included atrial septal defects, thin atrial wall and defects of the pulmonic, aortic and atrioventricular valves. The incidence of cardiac anomalies in the controls was very low. Propranolol was observed to slow the heart rate in the experimental embryos. It is suggested that slowing of heart rate at the early stages of heart development caused aberrant bloodstream flow patterns which probably resulted in the genesis of cardiac anomalies. The results of this study indicate that propranolol has teratogenic effects on chick embryo cardiogenesis.

Abnormalities, Drug-Induced↗
PubMed1979

Heart adaptation to acute pressure overload: an involvement of endogenous prostaglandins.

The purpose of this investigation was to study the relationships between the contractile behavior of the heart and myocardial prostaglandins. Using an open-chest model in rabbits, we assayed the left ventricular tissue content to prostaglandins (PG) E and F2 alpha at various intervals following acute pressure overload created by graduated aortic stenosis. The results suggest that the rabbits could be divided into two distinct groups based on specific hemodynamic changes following coarctation (systolic and diastolic pressure, dP/dt, and contractility index). The first group included rabbits whose adaptation to pressure overload was expressed as a gradual increase in the contractility index. The second group was comprised of rabbits that developed heart failure following coarctation. The increase in contractility in response to overload in the first group was paralleled by an increase in the content of PGE and PGF 2 alpha in the left ventricle, whereas, in rabbits with heart failure, the prostaglandin level did not rise above that of the control hearts. It is suggested that an increased endogenous prostaglandin content may be an important factor in adaptation to acute overload.

Animals↗
PubMed2025

New Genetic Loci Implicated in Cardiac Morphology and Function Using Three-Dimensional Population Phenotyping.

BACKGROUND: Cardiac remodeling occurs in the mature heart and is a cascade of adaptations in response to stress, which are primed in early life. A key question remains as to the processes that regulate the geometry and motion of the heart and how it adapts to stress. METHODS: We performed spatially resolved phenotyping using machine learning-based analysis of cardiac magnetic resonance imaging in 47 549 UK Biobank participants. We analyzed 16 left ventricular spatial phenotypes, including regional myocardial wall thickness and systolic strain in both circumferential and radial directions. In up to 40 058 participants, genetic associations across the allele frequency spectrum were assessed using genome-wide association studies with imputed genotype participants, and exome-wide association studies and gene-based burden tests using whole-exome sequencing data. We integrated transcriptomic data from the GTEx project and used pathway enrichment analyses to further interpret the biological relevance of identified loci. To investigate causal relationships, we conducted Mendelian randomization analyses to evaluate the effects of blood pressure on regional cardiac traits and the effects of these traits on cardiomyopathy risk. RESULTS: We found 42 loci associated with cardiac structure and contractility, many of which reveal patterns of spatial organization in the heart. Whole-exome sequencing revealed 3 additional variants not captured by the genome-wide association study, including a missense variant in CSRP3 (minor allele frequency 0.5%). The majority of newly discovered loci are found in cardiomyopathy-associated genes, suggesting that they regulate spatially distinct patterns of remodeling in the left ventricle in an adult population. Our causal analysis also found regional modulation of blood pressure on cardiac wall thickness and strain. CONCLUSIONS: These findings provide a comprehensive description of the pathways that orchestrate heart development and cardiac remodeling. These data highlight the role that cardiomyopathy-associated genes have on the regulation of spatial adaptations in those without known disease.

Humans↗
PubMed1976

Responsiveness to glucagon in fetal hearts. Species variability and apparent disparities between changes in beating, adenylate cyclase activation, and cyclic AMP concentration.

Previous studies of the ability of the immature heart to respond to glucagon have yielded conflicting results. To test the possibility that the apparent discrepancies might be explained in part by species variability, isolated hearts of fetal mice and rats (13-22 days' gestational age) were studied under identical conditions in vitro. Changes in atrial rate and ventricular contractility were measured in spontaneously beating hearts exposed to glucagon, and activation of adenylate cyclase was assayed in cardiac homogenates. In mice of 16 days' gestational age or less, there was no change in heart rate in response to glucagon; at 17-18 days, minimal responsiveness was present; and after 19 days, 10muM glucagon caused an increase in spontaneous atrial rate of 30 +/- 4% (SEM) (P less than 0.001). Measurement of the extent and speed of volume displacement of the isotonically contracting hearts with a specially constructed capacitance transducer revealed that ventricular inotropic responsiveness also appeared after 17-19 days. Cardiac stores of glycogen were reduced in older hearts exposed to glucagon, but not in those aged less than 16 days. In contrast, glucagon failed to activate adenylate cyclase in homogenates of hearts of fetal mice at any age. Furthermore, glucagon failed to elicit an increase in the concentration of cyclic AMP in spontaneously beating hearts that developed tachycardia. Responses in hearts of fetal rats were distinctly different from those in mouse hearts: at no age was there any change in heart rate, strength of contraction, glycogen content, or adenylate cyclase activation. Thus, there are major species differences in cardiac pharmacological maturation. Although the mouse heart develops the ability to increase its rate and strength of contraction and to undergo glycogenolysis in response to glucagon well before birth, the rat heart does not. In addition, there is an apparent disparity in late fetal mouse hearts between the ability of glucagon to induce functional responses and its ability to stimulate adenylate cyclase and increase cyclic AMP levels. It is impossible, of course, to rule out absolutely the possibility that localized increases in a critical cyclic AMP pool were present but too small to measure in the entire tissue. Nevertheless, the most obvious interpretation of our results is that they are compatible with the hypothesis that glucagon may exert some of its hemodynamic effects independently from the adenylate cyclase-cyclic AMP system in the late-fetal mouse heart.

Adenylyl Cyclases↗
PubMed1979

Influence of a phosphodiesterase inhibitor on the chronotropic effects of glucagon and norepinephrine in fetal mouse hearts.

Fetal mouse hearts develop tachycardia in response both to norepinephrine and to glucagon, but although adenylate cyclase is stimulated and adenosine 3':5'-monophosphate (cyclic AMP) elevated by norepinephrine, no measurable changes are produced by glucagon. To test further the possible independence of glucagon chronotropy from the cyclic AMP system, the effects of a phosphodiesterase inhibitor were evaluated. The dose-response curve to norepinephrine was shifted to the left by the phosphodiesterase inhibitor 4-(3,4-dimethoxybenzyl)-2-imidazolidinone (Ro7-2956), but the dose-response curve to glucagon was unaltered. Thus, 10(-6) M norepinephrine produced an increase of 40 +/- 5 beats/min in hearts pretreated with Ro7-2956, as compared to an increase of 22 +/- 3 in control hearts (P less than .01). In contrast, 10(-6) M glucagon produced a rate increase of 25 +/- 4 beats/min in treated hearts vs. 26 +/- 4 beats/min in controls. These data are compatible with the hypothesis that adenylate cyclase and cyclic AMP are involved in the chronotropic response of the fetal mouse heart to norepinephrine but not to glucagon.

Animals↗
PubMed1975

Inherited susceptibility of cattle to high-altitude pulmonary hypertension.

This study examines the hypothesis that susceptibility of cattle to high-altitude pulmonary hypertension and heart failure (high mountain disease) is genetically transmitted. Eight offspring of cattle recovered from high mountain disease were considered "susceptible." Eleven offspring of healthy cattle residing at high altitude were considered "resistant." At the resident altitude of 1,524 m, 10-day-old susceptible calves had higher pulmonary arterial pressures than did resistant calves (34 vs.21 mmHg), but at 90 days of age the pressures for the two groups were similar (26 vs. 24 mmHg). After 64 days of exposure to an altitude of 3,048 m, the susceptible calves (87 +/- 7 (SE) vs. 40 +/- 3 mmHg). By 124 days at 3,048 m, all susceptible but none of the resistant calves had developed heart failure. The results indicated that susceptibility to pulmonary hypertension at high altitude was inherited. Susceptible cattle may provide a useful model of human hypoxic pulmonary hypertension.

Age Factors↗
PubMed2025

Transcription factor 4 maintains endothelial cell identity by inhibiting endothelial to mesenchymal transition.

Endothelial to mesenchymal transition (EndoMT) is essential for embryonic heart development and contributes to many pathological processes. It is unclear how the balance between endothelial cell (EC) identity and EndoMT mediators is regulated to drive this transition. This study identifies transcription factor 4 (TCF4; also known as ITF2) as a critical EC identity gene. TCF4 knockdown impairs EC phenotype and function, and induces a transition towards a mesenchymal-like state. This discovery suggests that TCF4 safeguards EC identity against EndoMT. Mechanistically, TCF4 directly binds to the promoter of multiple key genes in the transforming growth factor-β (TGFβ) signaling pathway, thereby repressing their expression. TCF4 expression is consistently down-regulated in three EndoMT models. TCF4 down-regulation diminishes its inhibitory effect on the TGFβ signaling pathway, leading to pathway activation and subsequently enhancing EndoMT. This, in turn, further suppresses TCF4 expression. Consequently, the TCF4-TGFβ feedback loop is formed to intensify the EndoMT process. We demonstrate that introducing exogenous TCF4 disrupts this TCF4-TGFβ feedback loop of EndoMT, rescuing the EC phenotype and function under TGFβ stimulation, as well as ECs from human patients with heart failure. Our results reveal a key role for TCF4 in safeguarding EC identity and preventing EndoMT, suggesting a therapeutic potential of targeting TCF4 for EndoMT-related cardiovascular diseases.

Humans↗
PubMed1977

Primary amyloidosis with cardiac involvement diagnosed by left ventricular endomyocardial biopsy.

A case of primary amyloidosis is described. The patient presented with the nephrotic syndrome and later developed heart failure. Left ventricular endomyocardial biopsy was performed and haemodynamic data were recorded. The findings were those of a 'restrictive' cardiomyopathy. Histology of the biopsy was pathognomonic of amyloid involvement of the heart. The patient was started on chemotherapy consisting of prednisone, penicillamine, melphalan and fluoxymesterone. This case demonstrates the ability of endomyocardial biopsy in arriving at a definitive diagnosis in this patient.

Amyloidosis↗
PubMed1979

Augmented aftercontractions in papillary muscles from rats with cardiac hypertrophy.

Paired-pulse stimulation induced larger aftercontractions in papillary muscles from spontaneously hypertensive rats (SHR) than from normotensive Wistar-Kyoto rats (WKY). To determine whether aftercontraction exaggeration is a general characteristic of hypertrophied cardiac muscle, three models were examined: SHRs, deoxycorticosterone acetate (DOCA)-treated rats, and aorta-constricted rats. Responses of pipillary muscles from hypertrophied hearts tested under conditions conducive to aftercontraction generation were compared to pipillary muscles from WKY or sham-treated controls, respectively. Field-stimulated papillary muscles mounted in an oxygenated temperature-controlled physiologic salt solution were exposed to calcium concentrations of 2.5 and 5.0 mM, and temperatures of 27 degrees C and 17 degrees C. Although testing conditions influenced the contractile responses to single stimuli, there was no difference in active tension, time to peak tension, or one-half relaxation time between the three experimental groups and their respective controls. Paired-pulse stimulation induced aftercontractions that were enhanced in high-calcium and low-temperature solutions. Under these conditions, papillary muscles from hypertrophied hearts developed larger aftercontractions than did their respective controls.

Animals↗
PubMed1977

Pericarditis and perimyocarditis associated with active Mycoplasma pneumoniae infection.

In 13 patients an association existed from 1970-73 between Mycoplasma pneumoniae infection and acute pericarditis (in eight) or perimyocarditis (in five). In 12 patients the association was moderately probable, with a fourfold rise in complement-fixing antibody titers between acute and convalescent phase sera being noted. In the last patient, a lesser-order association was found using only convalsecent phase serum. The presence of influenza, herpes simplex, Coxsackie B, or adenovirus was excluded by serologic testing. Acute illness was variable, with four patients developing heart failure. Long-term evaluation (mean, 47 months) found eight patients asymptomatic and three symptomatic. Two patients died. Residual effects of the Mycoplasma infection seemed at least partially responsible in one compromised patient and in one who died. Mycoplasma infection should be considered in the presence of acute cardiovascular decompensation, especially when preceded by upper respiratory infection, and added to the possible causes of idiopathic cardiomyopathy.

Acute Disease↗