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Purpose: Until recently, it has been believed that donating a kidney not represents any risk for development of cardiovascular disease. However, a recent Norwegian epidemiological study suggests that kidney donors have an increased long-term risk of cardiovascular mortality. The pathophysiological mechanisms linking reduced kidney function to cardiovascular disease are not known. Living kidney donors are screened for cardiovascular morbidity before unilateral nephrectomy, and are left with mildly reduced glomerular filtration rate (GFR) after donation. Therefore, they represent an unique model for investigating the pathogenesis linking reduced GFR to cardiovascular disease and cardiovascular remodelling. We present the study design of Cardiovascular rEmodelling in living kidNey donorS with reduced glomerular filtration rate (CENS), which is an investigator-initiated prospective observational study on living kidney donors. The hypothesis is that living kidney donors develop cardiovascular remodelling due to a reduction of GFR.Materials and methods: 60 living kidney donors and 60 age and sex matched healthy controls will be recruited. The controls will be evaluated to fulfil the Norwegian transplantation protocol for living kidney donors. Investigations will be performed at baseline and after 1, 3, 6 and 10 years in both groups. The investigations include cardiac magnetic resonance imaging, echocardiography, bone density scan, flow mediated dilatation, laser Doppler flowmetry, nailfold capillaroscopy, office blood pressure, 24-h ambulatory blood pressure, heart rate variability and investigation of microbiota and biomarkers for inflammation, cardiovascular risk and the calcium-phosphate metabolism.Conclusions: The present study seeks to provide new insight in the pathophysiological mechanisms linking reduced kidney function to cardiovascular disease. In addition, we aim to enlighten predictors of adverse cardiovascular outcome in living kidney donors. The study is registered at Clinical-Trials.gov (identifier: NCT03729557).
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Enfermedades Cardiovasculares/fisiopatología , Tasa de Filtración Glomerular , Enfermedades Renales/fisiopatología , Trasplante de Riñón , Riñón/fisiopatología , Donadores Vivos , Nefrectomía/efectos adversos , Remodelación Vascular , Remodelación Ventricular , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Estudios de Casos y Controles , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/etiología , Estudios Longitudinales , Noruega , Estudios Prospectivos , Proyectos de Investigación , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
The myocardial infarction (MI) rat model plays a crucial role in modern cardiovascular research, but the inherent heterogeneity of this model represents a challenge. We sought to identify subgroups among the post-MI rats and establish simple noninvasive stratification protocols for such subgroups. Six weeks after induction of MI, 49 rats underwent noninvasive examinations using magnetic resonance imaging (MRI) and echocardiography. Twelve sham-operated rats served as controls. Increased end-diastolic left ventricular (LV) pressure and lung weight served as indicators for congestive heart failure (CHF). A clustering algorithm using 13 noninvasive and invasive parameters was used to identify distinct groups among the animals. The cluster analysis revealed four distinct post-MI phenotypes; two without congestion but with different degree of LV dilatation, and two with different degree of congestion and right ventricular (RV) affection. Among the MRI parameters, RV mass emerged as robust noninvasive marker of CHF with 100% specificity/sensitivity. Moreover, LV infarct size and RV ejection fraction further predicted subgroup among the non-CHF and CHF rats with excellent specificity/sensitivity. Of the echocardiography parameters, left atrial diameter predicted CHF. Moreover, LV end-diastolic diameter predicted the subgroups among the non-CHF rats. We propose two simple noninvasive schemes to stratify post-MI rats, based on the degree of heart failure; one for MRI and one for echocardiography.NEW & NOTEWORTHY In vivo phenotyping of rats is essential for robust and reliable data. Here, we present two simple noninvasive schemes for the stratification of postinfarction rats based on the degree of heart failure: one using magnetic resonance imaging and one based on echocardiography.
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Ecocardiografía/métodos , Corazón/fisiopatología , Imagen por Resonancia Magnética/métodos , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Algoritmos , Animales , Cardiomiopatía Dilatada/fisiopatología , Pruebas de Función Cardíaca , Masculino , Ratas , Ratas Wistar , Volumen Sistólico , Disfunción Ventricular Izquierda/fisiopatología , Función Ventricular IzquierdaRESUMEN
Recent advances in cardiac imaging have revitalized the assessment of fundamental physiological concepts. In the field of cardiac physiology, invasive measurements with pressure-volume (PV) loops have served as the gold standard methodology for the characterization of left ventricular (LV) function. From PV loop data, fundamental aspects of LV chamber function are derived such as work, efficiency, stiffness and contractility. However, the parametrization of these aspects is limited because of the need for invasive procedures. Through the utilization of recent advances in echocardiography, magnetic resonance imaging and positron emission tomography, it has become increasingly feasible to quantify these fundamental aspects of LV function non-invasively. Importantly, state-of-the-art imaging technology enables direct assessment of myocardial performance, thereby extending functional assessment from the net function of the LV chamber, as is done with PV loops, to the myocardium itself. With a strong coupling to underlying myocardial physiology, imaging measurements of myocardial work, efficiency, stiffness and contractility could represent the next generation of functional parameters. The purpose of this review is to discuss how the new imaging parameters of myocardial work, efficiency, stiffness and contractility can bring cardiac physiologists, researchers and clinicians alike one step closer to underlying myocardial physiology.
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Contracción Miocárdica , Función Ventricular Izquierda , Ecocardiografía , Imagen por Resonancia Magnética , MiocardioRESUMEN
AIMS: Patients with rheumatoid arthritis (RA) have increased risk of heart failure (HF). The mechanisms and cardiac prerequisites explaining this association remain unresolved. In this study, we sought to determine the potential cardiac impact of an experimental model of RA in mice subjected to HF by constriction of the ascending aorta. METHODS: Aorta was constricted via thoracotomy and placement of o-rings with inner diameter 0.55 mm or 0.66 mm, or sham operated. RA-like phenotype was instigated by delayed-type hypersensitivity arthritis (DTHA) two weeks after surgery and re-iterated after additional 18 days. Cardiac magnetic resonance imaging (MRI) was performed before surgery and at successive time points throughout the study. Six weeks after surgery the mice were euthanized, blood and tissue were collected, organ weights were documented, and expression levels of cardiac foetal genes were analysed. In a supplemental study, DTHA-mice were euthanized throughout 14 days after induction of arthritis, and blood was analysed for important markers and mediators of RA (SAP, TNF-α and IL-6). In order to put the latter findings into clinical context, the same molecules were analysed in serum from untreated RA patients and compared to healthy controls. RESULTS: Significant elevations of inflammatory markers were found in both patient- and murine blood. Furthermore, the DTHA model appeared clinically relevant when compared to the inflammatory responses observed in three prespecified RA severity disease states. Two distinct trajectories of cardiac dysfunction and HF development were found using the two o-ring sizes. These differences were consistent by both MRI, organ weights and cardiac foetal gene expression levels. Still, no difference within the HF groups, nor within the sham groups, could be found when DTHA was induced. CONCLUSION: DTHA mediated systemic inflammation did not cause, nor modify HF caused by aortic constriction. This indicates other prerequisites for RA-induced cardiac dysfunction.
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Estenosis de la Válvula Aórtica , Artritis Experimental , Insuficiencia Cardíaca , Animales , Estenosis de la Válvula Aórtica/etiología , Estenosis de la Válvula Aórtica/fisiopatología , Artritis Experimental/complicaciones , Artritis Experimental/fisiopatología , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Humanos , RatonesRESUMEN
In heart failure (HF) management, noninvasive quantification of left ventricular (LV) function is rapidly evolving. Deformation parameters, such as strain, continue to challenge the central role of ejection fraction (EF) in diagnosis and prognostication of LV dysfunction in HF. The increasing recognition and use of deformation parameters motivates a conceptual discussion about what makes a parameter clinically valuable. To do this, we introduce a framework for parameter evaluation. The framework considers three aspects that are important for parameter value; 1) how these parameters couple with underlying myocardial function; 2) the evidence base of the parameters; and 3) the technical feasibility of their measurement. In particular, we emphasize that the coupling of each parameter to the underlying myocardial function (aspect 1) is crucial for parameter value. While EF offers information about cardiac dysfunction trough measuring changes in LV volume, deformation parameters more closely reflect underlying myocardial processes that contribute to cardiac pumping function. This is a fundamental advantage of deformation parameters that could explain why a growing number of studies supports their use. A close coupling to underlying function is, however, not sufficient for high clinical value by itself. A parameter also needs a strong evidence base (aspect 2) and a high degree of technical feasibility (aspect 3). By considering these three aspects, this review discusses the present and potential clinical value of EF and deformation parameters in HF management.