Journal Of Clinical & Experimental Cardiology[JOURNAL]
Sun
200 papers
Uncovering atherosclerotic cardiovascular disease by PET imaging.
Maier A, Teunissen AJP, Nauta SA … +3 more , Lutgens E, Fayad ZA, van Leent MMT
Nat Rev Cardiol · 2024 Sep · PMID 38575752 · Full text
Assessing atherosclerosis severity is essential for precise patient stratification. Specifically, there is a need to identify patients with residual inflammation because these patients remain at high risk of cardiovascul...
Assessing atherosclerosis severity is essential for precise patient stratification. Specifically, there is a need to identify patients with residual inflammation because these patients remain at high risk of cardiovascular events despite optimal management of cardiovascular risk factors. Molecular imaging techniques, such as PET, can have an essential role in this context. PET imaging can indicate tissue-based disease status, detect early molecular changes and provide whole-body information. Advances in molecular biology and bioinformatics continue to help to decipher the complex pathogenesis of atherosclerosis and inform the development of imaging tracers. Concomitant advances in tracer synthesis methods and PET imaging technology provide future possibilities for atherosclerosis imaging. In this Review, we summarize the latest developments in PET imaging techniques and technologies for assessment of atherosclerotic cardiovascular disease and discuss the relationship between imaging readouts and transcriptomics-based plaque phenotyping.
Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation.
García-Lunar I, Jorge I, Sáiz J … +18 more , Solanes N, Dantas AP, Rodríguez-Arias JJ, Ascaso M, Galán-Arriola C, Jiménez FR, Sandoval E, Nuche J, Moran-Garrido M, Camafeita E, Rigol M, Sánchez-Gonzalez J, Fuster V, Vázquez J, Barbas C, Ibáñez B, Pereda D, García-Álvarez A
Basic Res Cardiol · 2024 Jun · PMID 38536505 · Full text
Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy...
Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magnetic resonance and blood sampling, and myocardial tissue was analyzed. Plasma unbiased proteomic and metabolomic data were compared among groups and integrated by an interaction network analysis. A total of 33 pigs completed follow-up (M1, n = 8; M2, n = 6; M3, n = 10; and M0, n = 9). M1 and M2 animals developed PH and reduced RV systolic function, whereas animals in M3 showed increased RV systolic pressure but maintained normal function. Significant plasma arginine and histidine deficiency and complement system activation were observed in both PH models (M1&M2), with additional alterations to taurine and purine pathways in M2. Changes in lipid metabolism were very remarkable, particularly the elevation of free fatty acids in M2. In the integrative analysis, arginine-histidine-purines deficiency, complement activation, and fatty acid accumulation were significantly associated with maladaptive RV hypertrophy. Our study integrating imaging and omics in large-animal experimental models demonstrates that, beyond pressure overload, metabolic alterations play a relevant role in RV dysfunction in PH.
Insulin and glycolysis dependency of cardioprotection by nicotinamide riboside.
Xiao Y, Wang Q, Zhang H … +10 more , Nederlof R, Bakker D, Siadari BA, Wesselink MW, Preckel B, Weber NC, Hollmann MW, Schomakers BV, van Weeghel M, Zuurbier CJ
Basic Res Cardiol · 2024 Jun · PMID 38528175 · Full text
Decreased nicotinamide adenine dinucleotide (NAD) levels contribute to various pathologies such as ageing, diabetes, heart failure and ischemia-reperfusion injury (IRI). Nicotinamide riboside (NR) has emerged as a promis...
Decreased nicotinamide adenine dinucleotide (NAD) levels contribute to various pathologies such as ageing, diabetes, heart failure and ischemia-reperfusion injury (IRI). Nicotinamide riboside (NR) has emerged as a promising therapeutic NAD precursor due to efficient NAD elevation and was recently shown to be the only agent able to reduce cardiac IRI in models employing clinically relevant anesthesia. However, through which metabolic pathway(s) NR mediates IRI protection remains unknown. Furthermore, the influence of insulin, a known modulator of cardioprotective efficacy, on the protective effects of NR has not been investigated. Here, we used the isolated mouse heart allowing cardiac metabolic control to investigate: (1) whether NR can protect the isolated heart against IRI, (2) the metabolic pathways underlying NR-mediated protection, and (3) whether insulin abrogates NR protection. NR protection against cardiac IRI and effects on metabolic pathways employing metabolomics for determination of changes in metabolic intermediates, and C-glucose fluxomics for determination of metabolic pathway activities (glycolysis, pentose phosphate pathway (PPP) and mitochondrial/tricarboxylic acid cycle (TCA cycle) activities), were examined in isolated C57BL/6N mouse hearts perfused with either (a) glucose + fatty acids (FA) ("mild glycolysis group"), (b) lactate + pyruvate + FA ("no glycolysis group"), or (c) glucose + FA + insulin ("high glycolysis group"). NR increased cardiac NAD in all three metabolic groups. In glucose + FA perfused hearts, NR reduced IR injury, increased glycolytic intermediate phosphoenolpyruvate (PEP), TCA intermediate succinate and PPP intermediates ribose-5P (R5P) / sedoheptulose-7P (S7P), and was associated with activated glycolysis, without changes in TCA cycle or PPP activities. In the "no glycolysis" hearts, NR protection was lost, whereas NR still increased S7P. In the insulin hearts, glycolysis was largely accelerated, and NR protection abrogated. NR still increased PPP intermediates, with now high C-labeling of S7P, but NR was unable to increase metabolic pathway activities, including glycolysis. Protection by NR against IRI is only present in hearts with low glycolysis, and is associated with activation of glycolysis. When activation of glycolysis was prevented, through either examining "no glycolysis" hearts or "high glycolysis" hearts, NR protection was abolished. The data suggest that NR's acute cardioprotective effects are mediated through glycolysis activation and are lost in the presence of insulin because of already elevated glycolysis.
Early microvascular coronary endothelial dysfunction precedes pembrolizumab-induced cardiotoxicity. Preventive role of high dose of atorvastatin.
Efentakis P, Choustoulaki A, Kwiatkowski G … +16 more , Varela A, Kostopoulos IV, Tsekenis G, Ntanasis-Stathopoulos I, Georgoulis A, Vorgias CE, Gakiopoulou H, Briasoulis A, Davos CH, Kostomitsopoulos N, Tsitsilonis O, Dimopoulos MA, Terpos E, Chłopicki S, Gavriatopoulou M, Andreadou I
Basic Res Cardiol · 2025 Feb · PMID 38520533 · Full text
Immune checkpoint inhibitors (ICIs) exhibit remarkable antitumor activity and immune-related cardiotoxicity of unknown pathomechanism. The aim of the study was to investigate the ICI class-dependent cardiotoxicity in vit...
Immune checkpoint inhibitors (ICIs) exhibit remarkable antitumor activity and immune-related cardiotoxicity of unknown pathomechanism. The aim of the study was to investigate the ICI class-dependent cardiotoxicity in vitro and pembrolizumab's (Pem's) cardiotoxicity in vivo, seeking for translational prevention means. Cytotoxicity was investigated in primary cardiomyocytes and splenocytes, incubated with ipilimumab, Pem and avelumab. Pem's cross-reactivity was assessed by circular dichroism (CD) on biotechnologically produced human and murine PD-1 and in silico. C57BL6/J male mice received IgG4 or Pem for 2 and 5 weeks. Echocardiography, histology, and molecular analyses were performed. Coronary blood flow velocity mapping and cardiac magnetic resonance imaging were conducted at 2 weeks. Human EA.hy926 endothelial cells were incubated with Pem-conditioned media from human mononuclear cells, in presence and absence of statins and viability and molecular signaling were assessed. Atorvastatin (20 mg/kg, daily) was administered in vivo, as prophylaxis. Only Pem exerted immune-related cytotoxicity in vitro. Pem's cross-reactivity with the murine PD-1 was confirmed by CD and docking. In vivo, Pem initiated coronary endothelial and diastolic dysfunction at 2 weeks and systolic dysfunction at 5 weeks. At 2 weeks, Pem induced ICAM-1 and iNOS expression and intracardiac leukocyte infiltration. At 5 weeks, Pem exacerbated endothelial activation and triggered cardiac inflammation. Pem led to immune-related cytotoxicity in EA.hy926 cells, which was prevented by atorvastatin. Atorvastatin mitigated functional deficits, by inhibiting endothelial dysfunction in vivo. We established for the first time an in vivo model of Pem-induced cardiotoxicity. Coronary endothelial dysfunction precedes Pem-induced cardiotoxicity, whereas atorvastatin emerges as a novel prophylactic therapy.
Non-coding RNAs as therapeutic targets and biomarkers in ischaemic heart disease.
Caporali A, Anwar M, Devaux Y … +5 more , Katare R, Martelli F, Srivastava PK, Pedrazzini T, Emanueli C
Nat Rev Cardiol · 2024 Aug · PMID 38499868 · Publisher ↗
The adult heart is a complex, multicellular organ that is subjected to a series of regulatory stimuli and circuits and has poor reparative potential. Despite progress in our understanding of disease mechanisms and in the...
The adult heart is a complex, multicellular organ that is subjected to a series of regulatory stimuli and circuits and has poor reparative potential. Despite progress in our understanding of disease mechanisms and in the quality of health care, ischaemic heart disease remains the leading cause of death globally, owing to adverse cardiac remodelling, leading to ischaemic cardiomyopathy and heart failure. Therapeutic targets are urgently required for the protection and repair of the ischaemic heart. Moreover, personalized clinical biomarkers are necessary for clinical diagnosis, medical management and to inform the individual response to treatment. Non-coding RNAs (ncRNAs) deeply influence cardiovascular functions and contribute to communication between cells in the cardiac microenvironment and between the heart and other organs. As such, ncRNAs are candidates for translation into clinical practice. However, ncRNA biology has not yet been completely deciphered, given that classes and modes of action have emerged only in the past 5 years. In this Review, we discuss the latest discoveries from basic research on ncRNAs and highlight both the clinical value and the challenges underscoring the translation of these molecules as biomarkers and therapeutic regulators of the processes contributing to the initiation, progression and potentially the prevention or resolution of ischaemic heart disease and heart failure.
Oxidation-reduction imaging of myoglobin reveals two-phase oxidation in the reperfused myocardium.
Badawi S, Leboullenger C, Chourrout M … +14 more , Gouriou Y, Paccalet A, Pillot B, Augeul L, Bolbos R, Bongiovani A, Mewton N, Bochaton T, Ovize M, Tardivel M, Kurdi M, Canet-Soulas E, Da Silva CC, Bidaux G
Basic Res Cardiol · 2024 Jun · PMID 38499702 · Full text
Myocardial infarction (MI) is a serious acute cardiovascular syndrome that causes myocardial injury due to blood flow obstruction to a specific myocardial area. Under ischemic-reperfusion settings, a burst of reactive ox...
Myocardial infarction (MI) is a serious acute cardiovascular syndrome that causes myocardial injury due to blood flow obstruction to a specific myocardial area. Under ischemic-reperfusion settings, a burst of reactive oxygen species is generated, leading to redox imbalance that could be attributed to several molecules, including myoglobin. Myoglobin is dynamic and exhibits various oxidation-reduction states that have been an early subject of attention in the food industry, specifically for meat consumers. However, rarely if ever have the myoglobin optical properties been used to measure the severity of MI. In the current study, we develop a novel imaging pipeline that integrates tissue clearing, confocal and light sheet fluorescence microscopy, combined with imaging analysis, and processing tools to investigate and characterize the oxidation-reduction states of myoglobin in the ischemic area of the cleared myocardium post-MI. Using spectral imaging, we have characterized the endogenous fluorescence of the myocardium and demonstrated that it is partly composed by fluorescence of myoglobin. Under ischemia-reperfusion experimental settings, we report that the infarcted myocardium spectral signature is similar to that of oxidized myoglobin signal that peaks 3 h post-reperfusion and decreases with cardioprotection. The infarct size assessed by oxidation-reduction imaging at 3 h post-reperfusion was correlated to the one estimated with late gadolinium enhancement MRI at 24 h post-reperfusion. In conclusion, this original work suggests that the redox state of myoglobin can be used as a promising imaging biomarker for characterizing and estimating the size of the MI during early phases of reperfusion.
Characterization of anthracycline-induced cardiotoxicity by diffusion tensor magnetic resonance imaging.
Lohr D, Thiele A, Stahnke M … +9 more , Braun VM, Klopfleisch R, Klein O, Dresen S, Landmesser U, Foryst-Ludwig A, Kintscher U, Schreiber LM, Beyhoff N
Basic Res Cardiol · 2025 Feb · PMID 38483601 · Full text
Anthracyclines are highly potent anti-cancer drugs, but their clinical use is limited by severe cardiotoxic side effects. The impact of anthracycline-induced cardiotoxicity (AIC) on left ventricular (LV) microarchitectur...
Anthracyclines are highly potent anti-cancer drugs, but their clinical use is limited by severe cardiotoxic side effects. The impact of anthracycline-induced cardiotoxicity (AIC) on left ventricular (LV) microarchitecture and diffusion properties remains unknown. This study sought to characterize AIC by cardiovascular magnetic resonance diffusion tensor imaging (DTI). Mice were treated with Doxorubicin (DOX; n = 16) for induction of AIC or saline as corresponding control (n = 15). Cardiac function was assessed via echocardiography at the end of the study period. Whole hearts (n = 8 per group) were scanned ex vivo by high-resolution DTI at 7 T. Results were correlated with histopathology and mass spectrometry imaging. Mice with AIC demonstrated systolic dysfunction (LVEF 52 ± 3% vs. 43 ± 6%, P < 0.001), impaired global longitudinal strain (-19.6 ± 2.0% vs. -16.6 ± 3.0%, P < 0.01), and cardiac atrophy (LV mass index [mg/mm], 4.3 ± 0.1 vs. 3.6 ± 0.2, P < 0.01). Regional sheetlet angles were significantly lower in AIC, whereas helix angle and relative helicity remained unchanged. In AIC, fractional anisotropy was increased (0.12 ± 0.01 vs. 0.14 ± 0.02, P < 0.05). DOX-treated mice displayed higher planar and less spherical anisotropy (C 0.07 ± 0.01 vs. 0.09 ± 0.01, P < 0.01; C 0.89 ± 0.01 vs. 0.87 ± 0.02, P < 0.05). C and C yielded good discriminatory power to distinguish between mice with and without AIC (c-index 0.91 and 0.84, respectively, P for both < 0.05). AIC is associated with regional changes in sheetlet angle but no major abnormalities of global LV microarchitecture. The geometric shape of the diffusion tensor is altered in AIC. DTI may provide a new tool for myocardial characterization in patients with AIC, which warrants future clinical studies to evaluate its diagnostic utility.
Role of CD4 T-cells for regulating splenic myelopoiesis and monocyte differentiation after experimental myocardial infarction.
Gladow N, Hollmann C, Weirather J … +10 more , Ding X, Burkard M, Uehlein S, Bharti R, Förstner K, Kerkau T, Beyersdorf N, Frantz S, Ramos G, Hofmann U
Basic Res Cardiol · 2024 Apr · PMID 38436707 · Full text
Myocardial infarction (MI) induces the generation of proinflammatory Ly6C monocytes in the spleen and the recruitment of these cells to the myocardium. CD4 Foxp3 CD25 T-cells (Tregs) promote the healing process after myo...
Myocardial infarction (MI) induces the generation of proinflammatory Ly6C monocytes in the spleen and the recruitment of these cells to the myocardium. CD4 Foxp3 CD25 T-cells (Tregs) promote the healing process after myocardial infarction by engendering a pro-healing differentiation state in myocardial monocyte-derived macrophages. We aimed to study the effects of CD4 T-cells on splenic myelopoiesis and monocyte differentiation. We instigated MI in mice and found that MI-induced splenic myelopoiesis is abrogated in CD4 T-cell deficient animals. Conventional CD4 T-cells promoted myelopoiesis in vitro by cell-cell-contact and paracrine mechanisms, including interferon-gamma (IFN-γ) signalling. Depletion of regulatory T-cells enhanced myelopoiesis in vivo, as evidenced by increases in progenitor cell numbers and proliferative activity in the spleen 5 days after MI. The frequency of CD4 T-cells-producing factors that promote myelopoiesis increased within the spleen of Treg-depleted mice. Moreover, depletion of Tregs caused a proinflammatory bias in splenic Ly6C monocytes, which showed predominantly upregulated expression of IFN-γ responsive genes after MI. Our results indicate that conventional CD4 T-cells promote and Tregs attenuate splenic myelopoiesis and proinflammatory differentiation of monocytes.
Risks and Benefits of Intermittent Fasting for the Aging Cardiovascular System.
Ozcan M, Abdellatif M, Javaheri A … +1 more , Sedej S
Can J Cardiol · 2024 Aug · PMID 38354947 · Publisher ↗
Population aging and the associated increase in cardiovascular disease rates pose serious threats to global public health. Different forms of fasting have become an increasingly attractive strategy to directly address ag...
Population aging and the associated increase in cardiovascular disease rates pose serious threats to global public health. Different forms of fasting have become an increasingly attractive strategy to directly address aging and potentially limit or delay the onset of cardiovascular diseases. A growing number of experimental studies and clinical trials indicate that the amount and timing of food intake as well as the daily time window during which food is consumed, are crucial determinants of cardiovascular health. Indeed, intermittent fasting counteracts the molecular hallmarks of cardiovascular aging and promotes different aspects of cardiometabolic health, including blood pressure and glycemic control, as well as body weight reduction. In this report, we summarize current evidence from randomized clinical trials of intermittent fasting on body weight and composition as well as cardiovascular and metabolic risk factors. Moreover, we critically discuss the preventive and therapeutic potential of intermittent fasting, but also possible detrimental effects in the context of cardiovascular aging and related disease. We delve into the physiological mechanisms through which intermittent fasting might improve cardiovascular health, and raise important factors to consider in the design of clinical trials on the efficacy of intermittent fasting to reduce major adverse cardiovascular events among aged individuals at high risk of cardiovascular disease. We conclude that despite growing evidence and interest among the lay and scientific communities in the cardiovascular health-improving effects of intermittent fasting, further research efforts and appropriate caution are warranted before broadly implementing intermittent fasting regimens, especially in elderly persons.
Statins affect human iPSC-derived cardiomyocytes by interfering with mitochondrial function and intracellular acidification.
Somers T, Siddiqi S, Maas RGC … +7 more , Sluijter JPG, Buikema JW, van den Broek PHH, Meuwissen TJ, Morshuis WJ, Russel FGM, Schirris TJJ
Basic Res Cardiol · 2024 Apr · PMID 38305903 · Publisher ↗
Statins are effective drugs in reducing cardiovascular morbidity and mortality by inhibiting cholesterol synthesis. These effects are primarily beneficial for the patient's vascular system. A significant number of statin...
Statins are effective drugs in reducing cardiovascular morbidity and mortality by inhibiting cholesterol synthesis. These effects are primarily beneficial for the patient's vascular system. A significant number of statin users suffer from muscle complaints probably due to mitochondrial dysfunction, a mechanism that has recently been elucidated. This has raised our interest in exploring the effects of statins on cardiac muscle cells in an era where the elderly and patients with poorer functioning hearts and less metabolic spare capacity start dominating our patient population. Here, we investigated the effects of statins on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-derived CMs). hiPSC-derived CMs were exposed to simvastatin, atorvastatin, rosuvastatin, and cerivastatin at increasing concentrations. Metabolic assays and fluorescent microscopy were employed to evaluate cellular viability, metabolic capacity, respiration, intracellular acidity, and mitochondrial membrane potential and morphology. Over a concentration range of 0.3-100 µM, simvastatin lactone and atorvastatin acid showed a significant reduction in cellular viability by 42-64%. Simvastatin lactone was the most potent inhibitor of basal and maximal respiration by 56% and 73%, respectively, whereas simvastatin acid and cerivastatin acid only reduced maximal respiration by 50% and 42%, respectively. Simvastatin acid and lactone and atorvastatin acid significantly decreased mitochondrial membrane potential by 20%, 6% and 3%, respectively. The more hydrophilic atorvastatin acid did not seem to affect cardiomyocyte metabolism. This calls for further research on the translatability to the clinical setting, in which a more conscientious approach to statin prescribing might be considered, especially regarding the current shift in population toward older patients with poor cardiac function.
From Atrial Fibrillation Management to Atrial Myopathy Assessment: The Evolving Concept of Left Atrium Disease in Hypertrophic Cardiomyopathy.
Fumagalli C, Zocchi C, Ciabatti M … +5 more , Milazzo A, Cappelli F, Fumagalli S, Pieroni M, Olivotto I
Can J Cardiol · 2024 May · PMID 38286174 · Publisher ↗
Hypertrophic cardiomyopathy (HCM) is the most prevalent genetically inherited cardiovascular disorder in adults and a significant cause of heart failure and sudden cardiac death. Historically, atrial fibrillation (AF) ha...
Hypertrophic cardiomyopathy (HCM) is the most prevalent genetically inherited cardiovascular disorder in adults and a significant cause of heart failure and sudden cardiac death. Historically, atrial fibrillation (AF) has been considered as a critical aspect in HCM patients as it is considered to be a marker of disease progression, escalates the frequency of heart failure hospitalisations, increases the risk of thromboembolic events, and worsens quality of life and outcome. Increasing evidence suggests that AF is the result of a subtle long-standing process that starts early in the history of HCM. The process of left atrial dilation accompanied by morphologic and functional remodelling is the quintessential prerequisite for the onset of AF. This review aims to describe the current understanding of AF pathophysiology in HCM, emphasising the role of left atrial myopathy in its development. In addition, we discuss risk factors and management strategies specific to AF in the context of HCM, providing insights into the complexities and challenges of treating this specific patient population.
Association between BMI and Efficacy of SGLT2 Inhibitors in Patients with Heart Failure or at Risk of Heart Failure: A Meta-Analysis Based on Randomized Controlled Trials.
Zhou Y, Dai M, Huang T … +5 more , Chen B, Xiang Z, Tang J, Zheng M, Guo L
Cardiology · 2024 · PMID 38008068 · Publisher ↗
INTRODUCTION: This meta-analysis aimed to investigate the effect of SGLT2 inhibitors on the prognosis of patients with heart failure (HF) or at risk of HF across different body mass index (BMI). METHODS: We searched PubM...
INTRODUCTION: This meta-analysis aimed to investigate the effect of SGLT2 inhibitors on the prognosis of patients with heart failure (HF) or at risk of HF across different body mass index (BMI). METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library for all randomized controlled trials comparing SGLT2 inhibitors with placebo in patients with HF or at risk of HF and extracted relevant data up to April 2023 for meta-analysis. RESULTS: A total of 29,500 patients were enrolled in the selected five studies. The results showed that patients treated with SGLT2 inhibitors had lower HF hospitalization (HHF) or cardiovascular (CV) mortality compared to those taking placebo (hazard ratio [HR] = 0.73, p < 0.001). Patients taking SGLT2 inhibitors also had a lower all-cause mortality rate than those taking placebo (HR = 0.85, p = 0.017). In BMI subgroup analysis, the HHF rate in the experimental group was lower than that in the control group at BMI ≤24.9 kg/m2, 25.0-29.9 kg/m2, and ≥30.0 kg/m2. There was no significant difference in CV mortality between the two groups at BMI ≤24.9 kg/m2 (HR = 0.91, p = 0.331) and 25.0-29.9 kg/m2 (HR = 0.92, p = 0.307). However, when the BMI was ≥30.0 kg/m2, CV mortality with SGLT2 inhibitors was lower than in the control group (HR = 0.79, p = 0.002). When patients had a BMI ≤24.9 kg/m2 (HR = 0.85, p = 0.033) and 25.0-29.9 kg/m2 (HR = 0.83, p = 0.046), the all-cause mortality was lower in the experimental group than in the control group. However, there was no significant difference between the 2 groups in patients with a BMI ≥30.0 kg/m2 (HR = 0.87, p = 0.094). CONCLUSION: SGLT2 inhibitors improve the prognosis in patients with HF or at risk of HF. This effect is affected by BMI.
Abbreviated or Standard Dual Antiplatelet Therapy by Sex in Patients at High Bleeding Risk: A Prespecified Secondary Analysis of a Randomized Clinical Trial.
Landi A, Alasnag M, Heg D … +19 more , Frigoli E, Malik FTN, Gomez-Blazquez I, Pourbaix S, Chieffo A, Spaulding C, Sainz F, Routledge H, Andò G, Testa L, Sciahbasi A, Contractor H, Jepson N, Mieres J, Imran SS, Noor H, Smits PC, Valgimigli M, MASTER DAPT Investigators
JAMA Cardiol · 2024 Jan · PMID 37991745 · Full text
IMPORTANCE: Abbreviated dual antiplatelet therapy (DAPT) reduces bleeding with no increase in ischemic events in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI). OBJECTIVES: To ev...
IMPORTANCE: Abbreviated dual antiplatelet therapy (DAPT) reduces bleeding with no increase in ischemic events in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI). OBJECTIVES: To evaluate the association of sex with the comparative effectiveness of abbreviated vs standard DAPT in patients with HBR. DESIGN, SETTING, AND PATIENTS: This prespecified subgroup comparative effectiveness analysis followed the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated vs Standard DAPT Regimen (MASTER DAPT) trial, a multicenter, randomized, open-label clinical trial conducted at 140 sites in 30 countries and performed from February 28, 2017, to December 5, 2019. A total of 4579 patients with HBR were randomized at 1 month after PCI to abbreviated or standard DAPT. Data were analyzed from July 1 to October 31, 2022. INTERVENTIONS: Abbreviated (immediate DAPT discontinuation, followed by single APT for ≥6 months) or standard (DAPT for ≥2 additional months, followed by single APT for 11 months) treatment groups. MAIN OUTCOMES AND MEASURES: One-year net adverse clinical events (NACEs) (a composite of death due to any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (MACCEs) (a composite of death due to any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding (MCB). RESULTS: Of the 4579 patients included in the analysis, 1408 (30.7%) were women and 3171 (69.3%) were men (mean [SD] age, 76.0 [8.7] years). Ischemic and bleeding events were similar between sexes. Abbreviated DAPT was associated with comparable NACE rates in men (hazard ratio [HR], 0.97 [95% CI, 0.75-1.24]) and women (HR, 0.87 [95% CI, 0.60-1.26]; P = .65 for interaction). There was evidence of heterogeneity of treatment effect by sex for MACCEs, with a trend toward benefit in women (HR, 0.68 [95% CI, 0.44-1.05]) but not in men (HR, 1.17 [95% CI, 0.88-1.55]; P = .04 for interaction). There was no significant interaction for MCB across sex, although the benefit with abbreviated DAPT was relatively greater in men (HR, 0.65 [95% CI, 0.50-0.84]) than in women (HR, 0.77 [95% CI, 0.53-1.12]; P = .46 for interaction). Results remained consistent in patients with acute coronary syndrome and/or complex PCI. CONCLUSIONS AND RELEVANCE: These findings suggest that women with HBR did not experience higher rates of ischemic or bleeding events compared with men and may derive particular benefit from abbreviated compared with standard DAPT owing to these numerically lower rates of events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03023020.
Activation of the integrated stress response rewires cardiac metabolism in Barth syndrome.
Kutschka I, Bertero E, Wasmus C … +22 more , Xiao K, Yang L, Chen X, Oshima Y, Fischer M, Erk M, Arslan B, Alhasan L, Grosser D, Ermer KJ, Nickel A, Kohlhaas M, Eberl H, Rebs S, Streckfuss-Bömeke K, Schmitz W, Rehling P, Thum T, Higuchi T, Rabinowitz J, Maack C, Dudek J
Basic Res Cardiol · 2023 Nov · PMID 37930434 · Full text
Barth Syndrome (BTHS) is an inherited cardiomyopathy caused by defects in the mitochondrial transacylase TAFAZZIN (Taz), required for the synthesis of the phospholipid cardiolipin. BTHS is characterized by heart failure,...
Barth Syndrome (BTHS) is an inherited cardiomyopathy caused by defects in the mitochondrial transacylase TAFAZZIN (Taz), required for the synthesis of the phospholipid cardiolipin. BTHS is characterized by heart failure, increased propensity for arrhythmias and a blunted inotropic reserve. Defects in Ca-induced Krebs cycle activation contribute to these functional defects, but despite oxidation of pyridine nucleotides, no oxidative stress developed in the heart. Here, we investigated how retrograde signaling pathways orchestrate metabolic rewiring to compensate for mitochondrial defects. In mice with an inducible knockdown (KD) of TAFAZZIN, and in induced pluripotent stem cell-derived cardiac myocytes, mitochondrial uptake and oxidation of fatty acids was strongly decreased, while glucose uptake was increased. Unbiased transcriptomic analyses revealed that the activation of the eIF2α/ATF4 axis of the integrated stress response upregulates one-carbon metabolism, which diverts glycolytic intermediates towards the biosynthesis of serine and fuels the biosynthesis of glutathione. In addition, strong upregulation of the glutamate/cystine antiporter xCT increases cardiac cystine import required for glutathione synthesis. Increased glutamate uptake facilitates anaplerotic replenishment of the Krebs cycle, sustaining energy production and antioxidative pathways. These data indicate that ATF4-driven rewiring of metabolism compensates for defects in mitochondrial uptake of fatty acids to sustain energy production and antioxidation.
Clinical Outcomes by Sex After Pulsed Field Ablation of Atrial Fibrillation.
Turagam MK, Neuzil P, Schmidt B … +47 more , Reichlin T, Neven K, Metzner A, Hansen J, Blaauw Y, Maury P, Arentz T, Sommer P, Anic A, Anselme F, Boveda S, Deneke T, Willems S, van der Voort P, Tilz R, Funasako M, Scherr D, Wakili R, Steven D, Kautzner J, Vijgen J, Jais P, Petru J, Chun J, Roten L, Füting A, Lemoine MD, Ruwald M, Mulder BA, Rollin A, Lehrmann H, Fink T, Jurisic Z, Chaumont C, Adelino R, Nentwich K, Gunawardene M, Ouss A, Heeger CH, Manninger M, Bohnen JE, Sultan A, Peichl P, Koopman P, Derval N, Kueffer T, Reddy VY
JAMA Cardiol · 2023 Dec · PMID 37910101 · Full text
IMPORTANCE: Previous studies evaluating the association of patient sex with clinical outcomes using conventional thermal ablative modalities for atrial fibrillation (AF) such as radiofrequency or cryoablation are controv...
IMPORTANCE: Previous studies evaluating the association of patient sex with clinical outcomes using conventional thermal ablative modalities for atrial fibrillation (AF) such as radiofrequency or cryoablation are controversial due to mixed results. Pulsed field ablation (PFA) is a novel AF ablation energy modality that has demonstrated preferential myocardial tissue ablation with a unique safety profile. OBJECTIVE: To compare sex differences in patients undergoing PFA for AF in the Multinational Survey on the Methods, Efficacy, and Safety on the Postapproval Clinical Use of Pulsed Field Ablation (MANIFEST-PF) registry. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of MANIFEST-PF registry data, which included consecutive patients undergoing postregulatory approval treatment with PFA to treat AF between March 2021 and May 2022 with a median follow-up of 1 year. MANIFEST-PF is a multinational, retrospectively analyzed, prospectively enrolled patient-level registry including 24 European centers. The study included all consecutive registry patients (age ≥18 years) who underwent first-ever PFA for paroxysmal or persistent AF. EXPOSURE: PFA was performed on patients with AF. All patients underwent pulmonary vein isolation and additional ablation, which was performed at the discretion of the operator. MAIN OUTCOMES AND MEASURES: The primary effectiveness outcome was freedom from clinically documented atrial arrhythmia for 30 seconds or longer after a 3-month blanking period. The primary safety outcome was the composite of acute (<7 days postprocedure) and chronic (>7 days) major adverse events (MAEs). RESULTS: Of 1568 patients (mean [SD] age, 64.5 [11.5] years; 1015 male [64.7%]) with AF who underwent PFA, female patients, as compared with male patients, were older (mean [SD] age, 68 [10] years vs 62 [12] years; P < .001), had more paroxysmal AF (70.2% [388 of 553] vs 62.4% [633 of 1015]; P = .002) but had fewer comorbidities such as coronary disease (9% [38 of 553] vs 15.9% [129 of 1015]; P < .001), heart failure (10.5% [58 of 553] vs 16.6% [168 of 1015]; P = .001), and sleep apnea (4.7% [18 of 553] vs 11.7% [84 of 1015]; P < .001). Pulmonary vein isolation was performed in 99.8% of female (552 of 553) and 98.9% of male (1004 of 1015; P = .90) patients. Additional ablation was performed in 22.4% of female (124 of 553) and 23.1% of male (235 of 1015; P = .79) patients. The 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was similar in male and female patients (79.0%; 95% CI, 76.3%-81.5% vs 76.3%; 95% CI, 72.5%-79.8%; P = .28). There was also no significant difference in acute major AEs between groups (male, 1.5% [16 of 1015] vs female, 2.5% [14 of 553]; P = .19). CONCLUSION AND RELEVANCE: Results of this cohort study suggest that after PFA for AF, there were no significant sex differences in clinical effectiveness or safety events.
Oxidized phospholipids in cardiovascular disease.
Tsimikas S, Witztum JL
Nat Rev Cardiol · 2024 Mar · PMID 37848630 · Publisher ↗
Prolonged or excessive exposure to oxidized phospholipids (OxPLs) generates chronic inflammation. OxPLs are present in atherosclerotic lesions and can be detected in plasma on apolipoprotein B (apoB)-containing lipoprote...
Prolonged or excessive exposure to oxidized phospholipids (OxPLs) generates chronic inflammation. OxPLs are present in atherosclerotic lesions and can be detected in plasma on apolipoprotein B (apoB)-containing lipoproteins. When initially conceptualized, OxPL-apoB measurement in plasma was expected to reflect the concentration of minimally oxidized LDL, but, surprisingly, it correlated more strongly with plasma lipoprotein(a) (Lp(a)) levels. Indeed, experimental and clinical studies show that Lp(a) particles carry the largest fraction of OxPLs among apoB-containing lipoproteins. Plasma OxPL-apoB levels provide diagnostic information on the presence and extent of atherosclerosis and improve the prognostication of peripheral artery disease and first and recurrent myocardial infarction and stroke. The addition of OxPL-apoB measurements to traditional cardiovascular risk factors improves risk reclassification, particularly in patients in intermediate risk categories, for whom improving decision-making is most impactful. Moreover, plasma OxPL-apoB levels predict cardiovascular events with similar or greater accuracy than plasma Lp(a) levels, probably because this measurement reflects both the genetics of elevated Lp(a) levels and the generalized or localized oxidation that modifies apoB-containing lipoproteins and leads to inflammation. Plasma OxPL-apoB levels are reduced by Lp(a)-lowering therapy with antisense oligonucleotides and by lipoprotein apheresis, niacin therapy and bariatric surgery. In this Review, we discuss the role of role OxPLs in the pathophysiology of atherosclerosis and Lp(a) atherogenicity, and the use of OxPL-apoB measurement for improving prognosis, risk reclassification and therapeutic interventions.
Serial Changes in Cardiopulmonary Exercise Testing Parameters in Untreated Patients With Transthyretin Cardiac Amyloidosis.
Argirò A, Silverii MV, Burgisser C … +11 more , Fattirolli F, Baldasseroni S, di Mario C, Zampieri M, Biagioni G, Mazzoni C, Chiti C, Allinovi M, Ungar A, Perfetto F, Cappelli F
Can J Cardiol · 2024 Mar · PMID 37793568 · Publisher ↗
BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is associated with a progressive reduction of functional capacity. The progression of cardiopulmonary exercise testing (CPET) parameters over time is still unkno...
BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is associated with a progressive reduction of functional capacity. The progression of cardiopulmonary exercise testing (CPET) parameters over time is still unknown. METHODS: In this study, 55 patients with ATTR-CM underwent 2 serial cardiologic evaluations and CPETs in a national referral center for cardiac amyloidosis (Careggi University Hospital, Florence). RESULTS: Forty-three patients (78%) had wild-type ATTR. Median age was 80 years (interquartile range [IQR] 76-83 years), and 50 of the patients (91%) were men. At baseline, median peak oxygen consumption (pVO) was 15 mL/kg/min (IQR 12-18 mL/kg/min), percentage of predicted pVO (%ppVO) was 71% (IQR 60%-83%) and VE/VCO slope was 31 (IQR 26-34). After a median follow-up of 14 months (IQR 13-16 months), pVO, %ppVO and VE/VCO slope were significantly worsened (-1.29 mL/kg/min [95% confidence interval (CI): -1.85 to -0.74; P < 0.01], -4.5% [95% CI: -6.9 to -2.02; P < 0.01], and 8.6 [95% CI 6-11; P < 0.01], respectively). Furthermore, exercise time (-39 s, 95% CI: -59 to -19; P < 0.01), exercise tolerance (-0.47 metabolic equivalents, 95% CI: -0.69 to -0.2; P < 0.01), and peak systolic pressure (-10.8 mm Hg, 95% CI: -16.2 to -5.4; P < 0.01) were significantly reduced. The worsening in CPET variables did not correspond with a significant change in echocardiographic parameters. CONCLUSIONS: Cardiorespiratory response to exercise significantly worsened over a short period of time in patients with ATTR-CM. Serial CPET may be useful to identify early disease progression.
Cardiac Troponin T and NT-proBNP for Prediction of 30-Day Readmission or Death in Patients with Acute Dyspnea: Data from the Akershus Cardiac Examination 2 Study.
Bhatnagar R, Berge K, Røysland R … +6 more , Høiseth AD, Brynildsen J, Christensen G, Omland T, Røsjø H, Lyngbakken MN
Cardiology · 2023 · PMID 37544298 · Full text
INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) measurements are recommended in patients with acute dyspnea. We aimed to assess the prognostic merit of cTnT compared to N...
INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) measurements are recommended in patients with acute dyspnea. We aimed to assess the prognostic merit of cTnT compared to NT-proBNP for 30-day readmission or death in patients hospitalized with acute dyspnea. METHODS: We measured cTnT and NT-proBNP within 24 h in 314 patients hospitalized with acute dyspnea and adjudicated the cause of the index admission. Time to first event of readmission or death ≤30 days after hospital discharge was recorded, and cTnT and NT-proBNP measurements were compared head-to-head. RESULTS: Patients who died (12/314) or were readmitted (71/314) within 30 days had higher cTnT concentrations (median: 32.6, Q1-Q3: 18.4-74.2 ng/L vs. median: 19.4, Q1-Q3: 8.4-36.1 ng/L; p for comparison <0.001) and NT-proBNP concentrations (median: 1,753.6, Q1-Q3: 464.2-6,862.0 ng/L vs. median 984, Q1-Q3 201-3,600 ng/L; for comparison p = 0.027) compared to patients who survived and were not readmitted. cTnT concentrations were associated with readmission or death within 30 days after discharge both in the total cohort (adjusted hazard ratio [aHR]: 1.64, 95% confidence interval [CI]: 1.30-2.05) and in patients with heart failure (HF) (aHR: 1.58, 95% CI: 1.14-2.18). In contrast, NT-proBNP concentrations were not associated with short-term events, neither in the total cohort (aHR: 1.10, 95% CI: 0.94-1.30) nor in patients with adjudicated HF (aHR: 1.06, 95% CI: 0.80-1.40). CONCLUSION: cTnT concentrations are associated with 30-day readmission or death in patients hospitalized with acute dyspnea, as well as in patients adjudicated HF.
The heterocellular heart: identities, interactions, and implications for cardiology.
Lother A, Kohl P
Basic Res Cardiol · 2023 Jul · PMID 37495826 · Full text
The heterocellular nature of the heart has been receiving increasing attention in recent years. In addition to cardiomyocytes as the prototypical cell type of the heart, non-myocytes such as endothelial cells, fibroblast...
The heterocellular nature of the heart has been receiving increasing attention in recent years. In addition to cardiomyocytes as the prototypical cell type of the heart, non-myocytes such as endothelial cells, fibroblasts, or immune cells are coming more into focus. The rise of single-cell sequencing technologies enables identification of ever more subtle differences and has reignited the question of what defines a cell's identity. Here we provide an overview of the major cardiac cell types, describe their roles in homeostasis, and outline recent findings on non-canonical functions that may be of relevance for cardiology. We highlight modes of biochemical and biophysical interactions between different cardiac cell types and discuss the potential implications of the heterocellular nature of the heart for basic research and therapeutic interventions.
Quality of Life Measures in Aortic Stenosis Research: A Narrative Review.
Frank D, Kennon S, Bonaros N … +11 more , Romano M, Di Mario C, van Ginkel DJ, Bor W, Kasel M, Backer O, Hachaturyan V, Lüske CM, Kurucova J, Bramlage P, Styra R
Cardiology · 2023 · PMID 37442111 · Full text
BACKGROUND: Elderly patients with aortic stenosis (AS) not only have a reduced life expectancy but also a reduced quality of life (QoL). The benefits of an AS intervention may be considered a balance between a good QoL a...
BACKGROUND: Elderly patients with aortic stenosis (AS) not only have a reduced life expectancy but also a reduced quality of life (QoL). The benefits of an AS intervention may be considered a balance between a good QoL and a reasonably extended life. However, the different questionnaires being used to determine the QoL were generally not developed for the specific situation of patients with AS and come with strengths and considerable weaknesses. The objective of this article was to provide an overview of the available QoL instruments in AS research, describe their strengths and weaknesses, and provide our assessment of the utility of the available scoring instruments for QoL measurements in AS. SUMMARY: We identified and reviewed the following instruments that are used in AS research: Short Form Health Survey (SF-36/SF-12), EuroQol-5D (EQ-5D), the Illness Intrusiveness Rating Scale (IIRS), the HeartQoL, the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Minnesota Living with Heart Failure Questionnaire (MLHF), the MacNew Questionnaire, and the Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ). KEY MESSAGES: There is no standardized assessment of QoL in patients with AS. Many different questionnaires are being used, but they are rarely specific for AS. There is a need for AS-specific research into the QoL of patients as life prolongation may compete for an improved QoL in this elderly patient group.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe