The primary impact of ventilation and ventilatory efforts on left ventricular (LV) function in left ventricular dysfunction relate to how changes in intrathoracic pressure (ITP) alter the pressure gradients for venous return into the chest and LV ejection out of the chest. Spontaneous inspiratory efforts by decreasing ITP increase both of these pressure gradients increasing venous blood flow and impeding LV ejection resulting in increased intrathoracic blood volume. In severe heart failure states when lung compliance is reduced, or airway resistance is increased these negative swings in ITP can be exacerbated leading to LV failure and acute cardiogenic pulmonary edema. By merely reversing these negative swings in ITP by the use of non-invasive continuous positive airway pressure (CPAP), these profoundly detrimental forces can be immediately reversed, and cardiovascular stability can be restored in moments. This forms the clinical rationale for the immediate use of CPAP for the treatment of acute cardiogenic pulmonary edema. Increasing ITP during positive pressure ventilation decreases the pressure gradients for venous return and LV ejection decreasing intrathoracic blood volume. In a hypovolemic patient even with LV dysfunction this can result in hypotension due to inadequate LV preload. Minor increases in ITP as occur using pressure-limited positive-pressure ventilation primarily reverse the increased LV afterload of negative swings in ITP and if fluid overload was already present, minimally alter cardiac output. The effect of changes in lung volume on LV function are related primarily to its effects on right ventricular (RV) function through changes in pulmonary vascular resistance and overdistention (hyperinflation). In acute lung injury with alveolar collapse, positive pressure ventilation may reduce pulmonary vascular resistance if alveolar recruitment predominates. Hyperinflation, however, impedes diastolic filling while simultaneously increasing pulmonary vascular resistance. Thus, increasing lung volume can reduce RV afterload by reversing hypoxic pulmonary vasoconstriction or increase afterload by overdistention. Hyperinflation can also impede RV filling. All of these processes can be readily identified at the bedside using echocardiography. Understanding the hemodynamic coupling of the heart and lungs plays a significant role in managing patients in the critical care setting. The basic heart-lung physiology has been discovered earlier in the collection of papers. Understanding diastolic and systolic left heart failure is of upmost importance when treating patients with a variety of other common medical conditions such as sleep apnea, ARDS and COPD as these conditions are deeply intertwined. These interactions are magnified in the setting of decreased left ventricular (LV) function. Here we seek to explain how clinical presentations affect the left ventricle and how management of these conditions can have a profound effect on LV function. For simplistic sake, the forces that cause clinically relevant heart-lung interactions are illustrated in There are multiple aspects of cardiopulmonary physiology that affect patients with heart failure. Lung volume and hyperinflation affect autonomic tone and pulmonary vascular resistance. In 1966 de Burgh Daly et al. showed that the correlation between systemic vascular resistance and ventilation was secondary to reflexes from intrapulmonary receptors altered by changes in lung volume. Lung inflation by either negative or positive intrathoracic pressure (ITP), in the setting of blocked carotid sinus and aortic arch baroreceptors, led to an immediate decrease in systemic vasomotor tone . FurtherHere we will discuss the importance of heart-lung interactions in various clinical scenarios including acute cardiogenic pulmonary edema (ACPE), ventilatory weaning, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), and acute respiratory distress syndrome (ARDS).Left heart failure can be characterized by systolic dysfunction, diastolic dysfunction, or both. In developed countries, systolic ventricular failure is most commonly associated with ischemia  and hypertension, which also contributes to diastolic dysfunction. In other parts of the world, Chagas disease and rheumatic heart disease are more prevalent causes. Understanding heart lung interactions is essential for the management of all left heart failure patients. Negative intrathoracic pressure leads to increased LV transmural pressure increasing LV afterload. In patients with left heart failure, negative swings in intrathoracic pressure can markedly decrease LV ejection leading to rapid increases in LV filling pressure and secondary (hydrostatic) pulmonary edema. The spontaneous breathing efforts also represent a metabolic stress on the body. During periods of increased work of breathing, spontaneous ventilation increases oxygen demand of respiratory muscles as well as of the myocardium and may induce circulatory insufficiency and visceral organ ischemia .Based on these principles the primary treatment of acute cardiogenic pulmonary edema should be the immediate abolishment of negative swings in ITP. While hypovolemic patients may decrease their cardiac output when positive pressure ventilation is initiated due to the decrease in preload (moving leftward on the ventricular function curve), these effects are minimized if continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) are used in patients with acute heart failure, because the spontaneous inspiratory efforts remain but the negative swings in ITP are markedly diminished or abolished. Thus, CPAP and BiPAP selectively reduce LV afterload shifting the ventricular function curve upward in patients with acute heart failure without decreasing venous return. Numerous clinical trials have shown the immediate beneficial cardiovascular effects of initiating CPAP or BiPAP. These findings were reinforced by a meta-analysis by Weng et al. showing less need for endotracheal intubation and a trend toward reduced mortality when non-invasive ventilation is initiated on patients presenting with acute cardiogenic pulmonary edema . UnfortuPatients subjected to hyperinflation and increased juxtacardiac pressure will experience a drop in biventricular volumes. Furthermore, some of these effects, including decreased vasomotor tone, may be affected by induction of anesthesia during initiation of mechanical ventilation. Lung inflation with volumes less than 10 mL per kilogram of body weight leads to vagal tone withdrawal and, consequently, an increase in heart rate. This is known as respiratory sinus arrhythmia. On the other hand, lung hyperinflation with volumes greater than 15 mL per kilogram of body weight leads to vagal tone activation and sympathetic tone withdrawal. In such cases, patients exhibit a decrease in blood pressure secondary to vasodilation from a decrease in systemic vasomotor tone. Many patients with LV failure are also hypervolemic owing to increased antidiuretic hormone activation. Thus, in volume overloaded patients with heart failure, initiation of mechanical ventilation and some degree of lung hyperinflation will decrease preload, cause vasodilation and, thereby, decrease intrathoracic blood volume. In those settings, the slight decrease in LV afterload may augment LV ejection keeping cardiac output constant despite a sustained increase in ITP. These are the reasons why patients with LV failure usually tolerate intubation and positive-pressure ventilation well without secondary post-intubation hypotension .Weaning patients from positive pressure ventilation results in several processes occurring simultaneously. First, respirations change from positive swings in ITP to negative swings in ITP. This must increase venous return and LV afterload. The combined effects of these two processes lead to an increase in intrathoracic blood volume. Second, metabolic demand increases as respiratory muscles resume their normal activity. Patients with increased work of breathing during weaning will experience sympathetic hyperactivation and catecholamine surge leading to increased heart rate and hypertension, which in turn will increase myocardial oxygen demand. If the work of breathing is excessive or LV functional reserve is too limited, then the patient will fail weaning. Weaning failure will manifest as acute cardiovascular collapse, hypotension, tachycardia, and even acute cardiogenic pulmonary edema. These hemodynamic changes can be ameliorated by restricting fluids, having the patients slightly hypovolemic and treating bronchospasm prior to extubation. Optimizing bronchodilation, avoiding volume overload and controlling afterload prior to weaning trials will facilitate liberation from mechanical ventilation .Patients with COPD can also have LV failure. Both COPD and obesity are associated with terminal airway collapse with increased shunt. COPD patients are more likely to experience hyperinflation owning to the increased airway resistance combined with increased lung compliance. These patients experience limitations in expiratory flow secondary to airway collapse. Both hyperinflation and dynamic hyperinflation can increase pulmonary vascular resistance and compress the heart within the cardiac fossa. The combined effects can worsen RV dysfunction by minimizing RV end-diastolic volume (EDV) while simultaneously increasing RV afterload. Patients with LV failure need a higher LV filling pressure and EDV to sustain LV stroke volume. Since hyperinflation compresses the heart, LV end-diastolic volume also decreases, and thus cardiac output often decreases during acute exacerbations of COPD in patients with LV dysfunction .Commonly, patients with LV failure develop RV failure. In such cases, increases in transpulmonary pressure secondary to lung hyperinflation lead to increased RV afterload and decreased RV ejection and RV stroke volume leading to systemic hypotension. In these circumstances, patients may experience acute cor pulmonale and RV ischemia. COPD exacerbations can cause hypoxemia, hypercapnia and increased sympathetic tone. Passive increases in pulmonary artery pressure due to increased LV filling pressure rarely cause enough increases in pulmonary artery pressure to result in acute RV failure. These three mechanisms increase pulmonary vasomotor tone. Patients with COPD may also have chronic pulmonary hypertension leading to RV hypertrophy. Increasing RV afterload increases RV end-systolic volume and, by extension, RV EDV. Clinically, these patients may present with increased jugular venous distension during spontaneous inspiration (Kussmaul’s sign) and the shift in the intraventricular septum will decrease LV end diastolic compliance leading to decreased cardiac output  Mooney . LimitataCO2 beyond the apneic threshold. Furthermore, episodes of hypoxia and waking from sleep lead to sympathetic activation, which further increases LV afterload and contributes to an increase in myocardial oxygen demand. Patients with OSA have intermittent hypoxemia and formation of free radicals and inflammatory molecules that lead to vascular remodeling. The negative swings in ITP during OSA lead to a combined increase in LV afterload and systemic hypoxemia. Thus, at the time that LV wall stress is increasing, myocardial oxygen delivery is being compromised. Over months, these repetitive OSA events lead to the development of congestive heart failure and a downward shift in the ventricular function curve. Acutely, the negative swings in ITP, hypoxia, and sympathetic surge lead to increased LV afterload and reactive systemic hypertension leading to increased myocardial metabolic demand. Chronically, these factors worsen LV hypertrophy, which in turn affects LV diastolic function. OSA has been associated with LV remodeling and increased incidence of cardiovascular disease . Nocturnal CPAP or BiPAP have been shown to improve outcomes in patients with disordered sleep. Specifically, OSA patients with heart failure demonstrate improvement in daytime off-CPAP LV function if the CPAP treatment abolishes the obstructive breathing patterns .Noncardiogenic pulmonary edema or ARDS is characterized by decreased lung volumes secondary to alveolar collapse and pulmonary congestion, increased dead space ventilation, hypoxemia and increased work of breathing. Often hypoxemia is not responsive to non-invasive ventilation and intubation with positive end-expiratory pressure (PEEP) is required to sustain gas exchange and minimize receptive alveolar collapse at end-expiration. The resultant higher mean and end-inspiratory airway pressure often further increase dead space ventilation. Dead space ventilation along with hypoxic pulmonary vasoconstriction secondary to alveolar collapse lead to increased pulmonary vascular resistance. This must impede RV ejection and increase RV EDV, which in turn decreases LV diastolic compliance by the process of ventricular interdependence. Indeed, Jardin et al. demonstrated many years ago that when ARDS patients were given high levels of PEEP their LV stroke volume decreased despite a high pulmonary artery occlusion pressure, used as a surrogate of LV EDV. However, when these same patients were fluid resuscitated to restore their LV EDV to their pre-PEEP levels, LV stroke volume also returned to its pre-PEEP value even though PEEP was still being used. This seminal work clearly demonstrated that lung hyperinflation and high levels of PEEP impair LV filling by decreasing LV diastolic compliance through the process of ventricular interdependence and increased juxtacardiac ITP. These points are described elsewhere in this series in greater detail .2 and optimal cardiac output for a given blood volume. Titrating PEEP based on RV systolic function and lung compliance is an important technique to monitor for developing RV failure and preventing PEEP too low that would worsen alveolar collapse and hypoxia or PEEP too high that would worsen PVR and RV afterload and, consequently, worsen LV diastolic filling  and overdistention (increasing resistance). This elusive “sweet spot” mean airway pressure that balances these two opposing effects is often equated to the point where PEEP maximizes lung compliance. Clinical studies suggest that the highest PEEP associated with the best value of lung compliance is also associated with better RV systolic function as measured using transesophageal echocardiography, least dead space ventilation, assessed as end-tidal CO filling .aCO2 levels are all predictive of the development of cor pulmonale in ARDS. Clearly, all these effects are predictable based on the above logic. Driving pressure is a surrogate of lung stress due to its effect on hyperinflation and pulmonary vascular resistance. Likewise, higher PaCO2 levels are indicative of increased dead space and lead to pulmonary vasoconstriction and increased pulmonary vascular resistance. Mitigating these factors is critical to avoid right heart failure, RV dilation and, consequently, poor LV diastolic filling and low output heart failure (Other investigators looked at variables that are prominent in patients with ARDS that develop cor pulmonale. These investigators concluded that pneumonia being the etiology of ARDS, driving pressure, worsening P:F ratio and rising P failure .Heart-lung interactions play a crucial role in understanding and managing patients with left heart failure under most conditions independent of ventilatory mode.


Apical hypertrophic cardiomyopathy (ApHCM) can result in the formation of a left ventricular apical aneurysm and progressive myocardial fibrosis, which is associated with a worse prognosis. We present the case of a 76-year-old man previously diagnosed with ApHCM seven years ago, who has been under clinical follow-up. Serial cardiac magnetic resonance (CMR) imaging was performed in 2013 and 2020 due to suspected apical aneurysm formation based on echocardiographic evaluation. The 2020 CMR imaging revealed an increase in myocardial fibrosis observed through late-gadolinium enhancement images and, for the first time, a small apical aneurysm that was not clearly visualized on two-dimensional echocardiography. The time course leading to the development of an ApHCM aneurysm is not well-defined and may impact the clinical course. The genetic etiology of this condition involves mutations in genetic sarcomeric proteins Herein, we present the case of a 76-year-old male who has been undergoing clinical and periodic imaging follow-ups since his diagnosis of ApHCM in 2013. He remained asymptomatic for dyspnea, chest pain, palpitations, and arrhythmic episodes. In a two-dimensional echocardiography examination conducted in 2020, normal LV basal thickness was observed, with hypertrophy involving the septum and lateral walls at mid-ventricular and apical levels, resulting in mid-cavity obliteration. Paradoxical dynamic obstruction with a systolic jet flow from the basal LV chamber to the apex (and vice versa in diastole) was detected . Three-dThese findings raised suspicion of apical aneurysm formation, although it could not be definitively confirmed through two-dimensional echocardiography. Therefore, a further assessment was conducted using CMR imaging, which revealed the presence of a small apical aneurysm that was not observed in the previous examination in 2013 .Comparing the CMR findings from 2013 and 2020, a progressive extension of myocardial fibrosis was observed, with a higher amount of late-gadolinium enhancement estimated to have increased from 13% to 24.9%. Maximal wall thickness was estimated at the septal-apical segment (18.4 mm), and no significant changes were observed in LV mass (from 123 g to 130 g) and LVEF (from 64% to 60%) .In our patient, new apical aneurysm detection allowed oral permanent anticoagulants indication without any thromboembolic or cardiovascular events. The patient remained asymptomatic under clinical, one-year follow-up.Despite being less frequent compared to other types of HCM, the ApHCM phenotype is not as rare as initially believed, accounting for up to 25% of HCM in Asian populations and 1% to 10% in non-Asians ,In contrast to classic HCM, ApHCM does not typically exhibit left ventricular outflow tract obstruction resulting from systolic anterior motion of the mitral valve and is not associated with concomitant mitral regurgitation. However, midventricular obstruction and cavity obliteration may or may not be present, accompanied by the formation of an apical aneurysm. Mid-ventricular obstruction arises from hypertrophy of the mid-apical lateral and septal regions The presence of apical aneurysms and obstruction can be attributed to regional myocardial scarring, which arises due to repeated exposure of the apical region to increased LV wall stress, high systolic pressures, elevated oxygen consumption, altered coronary perfusion, and the ischemia. Consequently, dyskinetic/akinetic aneurysms pose a risk of apical thrombus formation and thromboembolic events The use of CMR imaging allows for accurate phenotypic characterization of HCM, enabling clarification of inconclusive cases from echocardiography and the exclusion of alternative diagnoses as outlined in the 2020 guidelines. CMR imaging is a valuable technique for evaluating maximal wall thickness, LV ejection fraction, the presence of LV apical aneurysms, and the extent of myocardial fibrosis for the purpose of SCD risk stratification The size of the aneurysm does not consistently correlate with clinical outcomes. Even in small aneurysms, approximately 20% of patients experience thromboembolic events and apical clot formation. Therefore, anticoagulation should be considered in all patients with aneurysms, regardless of the size. No embolic events or apical thrombus formation have been reported during the follow-up period when prophylactic anticoagulation was administered to these patients Despite the absence of definitive data regarding the development of aneurysm apical formation in ApHCM current guidelines recommend serial CMR evaluation for re-stratification of these patients. Non-specific trials were developed by repeating systemically CMR imaging to elucidate the timeline of apical aneurysm formation. In a recent pilot serial CMR study of 76 patients with ApHCM, aneurysm formation was related to four stages for its development, starting with systolic apical cavity obliteration, then broadening of the apical slit in systole, further developing into an apical outpouching, and finally forming an apical aneurysm. Nevertheless, further investigations are required to clarify time progression and established specific CMR follow-up recommendations.In conclusion, apical aneurysm detection in ApHCM is a valuable strategy for identifying patients at higher risk of cardiovascular events. Echocardiography is the primary modality for assessment and monitoring, while CMR imaging plays a confirmatory role in inconclusive cases. Regular imaging follow-up is recommended to detect aneurysm formation and assess the progression of myocardial fibrosis, enabling re-evaluation of the risk of SCD. In this case, CMR imaging played a crucial role in re-stratification.


ANP is mainly synthesized by the atria, and upon excretion, it serves two primary purposes: vasodilation and increasing the renal excretion of sodium and water. The understanding of ANP’s role in cardiac systems has improved considerably in recent decades. This review focuses on several studies demonstrating the importance of analyzing the regulations between the endocrine and mechanical function of the heart and emphasizes the effect of ANP, as the primary hormone of the atria, on atrial fibrillation (AF) and related diseases. The review first discusses the available data on the diagnostic and therapeutic applications of ANP and then explains effect of ANP on heart failure (HF) and atrial fibrillation (AF) and vice versa, where tracking ANP levels could lead to understanding the pathophysiological mechanisms operating in these diseases. Second, it focuses on conventional treatments for AF, such as cardioversion and catheter ablation, and their effects on cardiac endocrine and mechanical function. Finally, it provides a point of view about the delayed recovery of cardiac mechanical and endocrine function after cardioversion, which can contribute to the occurrence of acute heart failure, and the potential impact of restoration of the sinus rhythm by extensive ablation or surgery in losing ANP-producing sites. Overall, ANP plays a key role in heart failure through its effects on vasodilation and natriuresis, leading to a decrease in the activity of the renin-angiotensin-aldosterone system, but it is crucial to understand the intimate role of ANP in HF and AF to improve their diagnosis and personalizing the patients’ treatment. In recent decades, the understanding of the role of natriuretic peptides (NPs) in cardiac pathophysiology has improved considerably, increasing their importance both for diagnostic and therapeutic purposes. The natriuretic peptide family consists of three peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), and they represent the main cardiac endocrine function, as far as we currently know. Among these peptides, ANP is mainly synthesized by the atria, where the precursor form of these peptides split into prohormones and is stored in secretory granules in atrial cardiomyocytes ,2. Upon The diagnostic value of natriuretic peptides in cardiovascular disease, including AF and HF, has been extensively studied. ANP excretion is primarily regulated by mechanical stretch of the atrium during increased exercise, as observed in heart failure, and may also be influenced by the rate of atrial contraction. ANP release can also be stimulated by factors such as myocardial ischemia, adrenergic agonists, angiotensin II, and vasopressin. The half-life of ANP in plasma is approximately 2–4 min, and it is inactivated by neutral endopeptidase and lysosomal degradation. Elevated ANP levels are associated with left ventricular diastolic dysfunction and left ventricular end-diastolic pressure and may be a risk factor for AF recurrence. ANP levels also correlate with left atrial volume (LA) as determined by echocardiography and cardiac magnetic resonance. After an AF episode, plasma ANP levels decrease rapidly in response to filling pressure, and a steady normalization of ANP concentration occurs in association with improvement in atrial mechanical function .Measurement of NP levels can be useful in the clinical management of cardiovascular disease. In patients with HF, NP is a tool for diagnosis, prognosis, and therapy management, and there are established cut-off values. In addition, NP is useful in the management of AF by screening for new-onset AF, predicting the success of cardioversions and pulmonary vein isolations, and assessing the risk of stroke . In a stANP levels are typically very low in healthy individuals (20 pg/mL), but increase significantly in HF or AF patients. Measurement of the bioactive form of ANP can be challenging due to its short half-life (2 min), whereas the more stable N-terminal prohormone form (NT-proANP) is readily degraded. Therefore, the mid-region of NT-proANP (MR-proANP), which is less susceptible to degradation, is used in the clinical evaluation of HF patients. Measurement of the bioactive form of ANP can be challenging due to its short half-life (2 min) and the more stable N-terminal prohormone form (NT-proANP) is readily degraded. Therefore, the mid-region of NT-proANP (MR-proANP), which is less susceptible to degradation, is used in the clinical evaluation of HF patients . Figure p = 0.007). The higher NT-proANP levels persisted even after adjustment for underlying heart disease (p < 0.0001). In another study, Büttner et al. [In a study, Rossi et al.  aimed tor et al. , investir et al. , MeasureThere are also many studies on the most stable fragment of pro-ANP, namely MR-proANP in HF or AF patients, showing the diagnostic value of this peptide . Gohar eThe diagnostic value of MR-proANP was also reported by Yagmur et al.  in critiLast but not least, Schweizer et al.  in a recIn conclusion, ANPs have important diagnostic applications in AF and HF. They have been shown to be useful biomarkers for the diagnosis and severity assessment of these diseases. ANPs may also be a useful tool for predicting the risk of hospitalization and mortality in patients with HF. However, further studies are needed to explore the clinical utility of ANPs in these conditions.Since the PARADIGM randomized control trial showed that inhibition of neprilysin (NEP) improved outcomes in patients with HF, understanding the role of natriuretic peptides in this context has gained increasing interest . Data frOn the basis of these assumptions, several studies have examined the effect of sacubitril/valsartan on natriuretic peptide activity. Data from the PROVE-HF and EVALUATE HF studies confirmed a sustained decrease in NT-proBNP associated with positive remodeling as measured by left ventricular ejection fraction and left atrial dimensions ,20.On the other hand, the association between inhibition of NEP and BNP levels was weaker, and the change in the effector pathway of cyclic guanylate cyclase was somewhat independent of BNP trajectory . Two stuFor example, the aforementioned study by Nougué et al. confirmed a strong inhibition of the activity of NEP and showed a sustained 4-fold increase in ANP levels during sacubitril/valsartan therapy. Similarly, a biomarker substudy  of the POverall, these findings support the concept that ANP has an underlying biological effect in heart failure and those strategies that restore its physiological properties could improve the clinical outcomes. This concept applies to NEP inhibition, because ANP appears to be a more potent substrate for NEP and a more potent activator of the cGMP pathway than BNP but could as well pave the way for more targeted ANP substitutive therapy. Such strategies are currently under investigation and could in the future open a new chapter in the treatment of heart failure .Heart failure (HF) is a clinical and pathophysiological syndrome caused by ventricular dysfunction, leading to a different combination of volume overload and decreased cardiac output. The hemodynamic changes of HF lead to activation of renin-angiotensin-aldosterone and the sympathetic nervous system to restore homeostasis. Activation of neurohormonal systems causes sodium and water retention along with vasoconstriction to restore blood flow. However, in chronic heart failure, these mechanisms lead to a dysfunctional adaptation that further exacerbates hemodynamic derangement and pathological cardiac remodeling.Natriuretic peptides play an important role in heart failure through their effects on vasodilation and natriuresis, leading to a decrease in the activity of the renin-angiotensin-aldosterone system . Among NIn heart failure, volume overload leads to atrial distension, which promotes the release of ANP in response to these hemodynamic changes. However, it has been reported that patients with heart failure may have a significant deficiency of ANP and an attenuated renal response to ANP, leading to retention of sodium and water . AccordiRenal ANP resistance is caused by several mechanisms, including decreased ANP availability at the renal site, decreased binding of ANP to its receptor (NPR), or degradation of ANP at the renal site; these mechanisms can result in sodium and water retention at elevated ANP levels. Interestingly, both left ventricular dysfunction and renal failure, which is promoted by impaired renal response, are important markers of heart failure, to the extent that renal failure is considered one of the strongest markers of mortality . SeveralAF is the most common cardiac arrhythmia worldwide with multifactorial etiology. Several factors contribute to the disease, including aging, left atrial enlargement, left atrial dysfunction, heart failure, respiratory conditions, or mitral valve disease. AF induces irregular contractions in the atrium, resulting in electrical and structural remodeling. AF is also reported to be associated with endothelial damage, inflammation, and fibrosis ,32,33. SAtrial fibrillation causes the atria to lose efficiency in pumping blood to the ventricles , resulting in increased stress on the atrial walls and mechanical stretch. Therefore, ANP is secreted to stabilize hemodynamics through natriuresis and vasodilation, and this increase is directly related to the increase in left atrial stretching. Although ANP concentration increases during AF, it has been reported that a prolonged AF leads to a decrease in ANP level, due to the structural changes in the left atrium leading to a loss of ANP production sites . MaartenAs shown in These seemingly contradictory results should be considered in light of the different patient population, as catheter ablation is generally performed in subjects with less advanced atrial remodeling, and the difficulty in defining the natural history of atrial remodeling in AF. Detailed assessment of the time course of loss of atrial “integrity” will be an important milestone in this topic, and further studies are needed. Interestingly, ANP production itself could contribute to the development of atrial fibrosis by amyloid deposition. Amyloid deposits (misfolded proteins) can result from aging and various diseases. Among the types of amyloidosis, isolated atrial amyloidosis (IAA) is characterized by misfolded ANP proteins. Maarten et al.  discusseHowever, despite this potential mechanism, strong clinical evidence is lacking, and the interplay between these entities and their pathophysiology is yet to be elucidated. These complex interactions are illustrated in Current treatments for AF focus on restoring the sinus rhythm of the heart, which is not as effective because atrial remodeling and structural damage are the leading causes of AF, which can be irreversible if not diagnosed and treated in time ,42. An iIn another study, Nishino et al.  analyzedAccording to these results, the recovery of atrial contraction  takes about one month. In contrast, the concentration of ANP (as an indicator of endocrine function) drops rapidly and recovers within a week. With a similar behavior, peak A-wave velocity should increase to higher values as ANP drops to almost zero within 4 h. However, we have no such increase in mechanical function, showing a mismatch between recovery times. The point of view here is that due to the rapid drop in ANP concentration (within 4 h) in comparison with left atrial stretch and mechanical dysfunction, acute heart failure may occur.There are numerous studies on the effects of catheter ablation on ANP and its prognostic role. Sacher et al.  studied An interesting finding that emerged from the studies is the kinetics of ANP after catheter ablation. These data  showed tData from both cardioversion and catheter ablation consistently demonstrated delayed recovery of mechanical and endocrine atrial function estimated from ANP kinetics. These findings provide the basis for formulating hypotheses about the interplay between these aspects of atrial physiology after restoration of the sinus rhythm. Data from surgical treatment of atrial fibrillation with the Maze procedure  show thaThe production of natriuretic peptides represents the major endocrine function of the heart. While the role of BNP in the diagnosis and treatment of HF is currently well established, the assessment of ANP levels is still a subject of research without any clinical implication. Among the various factors hampering this, such as a shorter half-life, the most important is most likely the higher complexity of the endocrine function of the atria combined with several unresolved questions in the available literature regarding the mechanism of regulation during different diseases (such as HF and AF), the presence of a specific site for ANP secretion, the specific interplay between filling pressure, atrial contraction, and the presence of fibrosis. The intriguing link between AF, ANP, and atrial amyloidosis can be a possible explanation not only for the AF phenomenon , but we


Radiotherapy has significantly improved cancer survival rates, but it also comes with certain unavoidable complications. Breast and thoracic irradiation, for instance, can unintentionally expose the heart to radiation, leading to damage at the cellular level within the myocardial structures. Detecting and monitoring radiation-induced heart disease early on is crucial, and several radionuclide imaging techniques have shown promise in this regard. In this 10-year review, we aimed to identify nuclear medicine imaging modalities that can effectively detect early cardiotoxicity following radiation therapy. Through a systematic search on PubMed, we selected nineteen relevant studies based on predefined criteria. The data suggest that incidental irradiation of the heart during breast or thoracic radiotherapy can cause early metabolic and perfusion changes. Nuclear imaging plays a prominent role in detecting these subclinical effects, which could potentially serve as predictors of late cardiac complications.However, further studies with larger populations, longer follow-up periods, and specific heart dosimetric data are needed to better understand the relationship between early detection of cardiac abnormalities and radiation-induced heart disease. However1.199mTc]-sestamibi or [99mTc]-tetrofosmin are absorbed by healthy myocardial cells. Following RT, regions with reduced uptake indicate impaired myocardial blood flow (MBF), typically due to radiation-caused damage to the endothelium and capillary disturbances  was proposed as an accurate tool to detect and monitor RIHD. Several studies report evidence of early radiation-associated cardiac changes identified with MPS after adjuvant RT –10. MPS urbances , 12.15O]-H2O, [13N]-ammonia and [18F]-flurpiridaz are particularly useful for monitoring changes in MBF and myocardial flow reserve (MFR)  can be used to measure MBF and therefore detect perfusion abnormalities. Radiotracers such as rubidium 82, [5O]-H2O, N-ammoniave (MFR) . These P1.2123I]-BMIPP) is correlated with adenosine triphosphate; single photon emission computed tomography (SPECT) [123I]-BMIPP appears a reliable tool to detect decreased oxidative metabolism of free fatty acids as a surrogate marker of myocardial ischemia. While [123I]-BMIPP has only been used as an investigational agent, it shows promise in assessing both the severity and extent of myocardial damage  positron emission tomography ([18F]‐FDG-PET/CT) provides a unique assessment of myocardial metabolism by detecting changes in cardiomyocytes at an early stage before cardiotoxicity. Uptake of 18FDG correlates with changes in the cellular myocardial metabolism together with inflammation extent within the coronary arteries wall, preceding possible atherosclerotic plaque rupture and could also reflect macrophages content within the vulnerable plaque . To be included in our systematic review studies had to meet specific inclusion criteria: i/patients had to have received breast or thoracic RT; ii/nuclear imaging was performed within the year after RT; and iii/the full text of the study was available in English. Exclusion criteria included the following: i/patients without a history of RT; ii/the use of non-human subjects; iii/case studies; iv/review articles; v/abstracts alone; and vi/editorials. Two reviewers  independently screened all titles and abstracts. Disagreement between the two reviewers was resolved with discussion between them, or with a third reviewer (GN). From each article, the following data were collected: the number of patients, sex, age, primary cancer, RT modalities, nuclear imaging modalities, time interval between nuclear imaging and RT, cardiac dose, systemic cancer therapy, cardiac outcome, and nuclear imaging results.The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines . DatabasOverall, 238 articles were retrieved. Among them, 219 articles were excluded because they did not meet the inclusion criteria. Ultimately, 19 studies were included. Among them, 11 evaluated radiation-induced myocardial metabolic dysfunctions , and 8 evaluated radiation-induced myocardial perfusion dysfunctions (6 with SPECT and 1 with PET) Figure 133.13.1.1A total of 365 patients underwent MPS, among whom 347 were treated for breast cancer (BC) (232 left-sided breast cancer (LSBC)/115 right-sided breast cancer (RSBC)) and 18 for esophageal cancer. The sex ratio was 14 males and 351 females since most studies were about BC. The median age varied from 45.3 to 62.2 years old. Only one study reported performance status (PS), with PS < 2 and Karnofsky performance scale (KPS) > 70% as inclusion criteria  to 50.00 Gy for breast/chest and lymph nodes, with one study using a 10 Gy boost. For esophageal cancer, the dose was 60–64 Gy. All studies used three-dimensional conformal radiation therapy (3DCRT), while three employed intensity-modulated radiotherapy (IMRT) , 24, 27.3.1.437Gy–V40Gy (Four studies reported perfusion defects (PD) after RT, with rates ranging from 17% to 43% at 6 months for LSBC and 44% during RT for esophageal cancer –26. WallGy–V40Gy . No sign3.1.5Two studies did not report clinical outcomes , 27. Abr3.23.2.1One study assessed perfusion PET imaging in 15 females with BC (6 RSBC/9 LSBC), aged 32-68 years . Four pa3.2.215O]-H2O PET imaging were conducted for each patient.Perfusion PET imaging was performed pre-irradiation and at 2- and 8-months post-RT. Resting and pharmacological stress with adenosine -BMIPP. One study performed SPECT before irradiation and 6 months after RT  level, ECG, and pericardial effusion in all patients after RT. None of the 17 patients exhibited clinical symptoms. One study showed no significant change in BNP level , while t3.43.4.1A total of 542 patients  underwent PET/CT evaluation early after RT. The median age ranged from 45.3 to 62.2 years. The primary cancers included thoracic malignancies , esophag3.4.218F]‐FDG-PET/CT without specific preparation for cardiologic evaluation. Preparation methods typically involved fasting for >4 or 6 hours and a threshold glucose dose. The time interval between RT and PET ranged from 11 days to 17 months.All studies used -H2O PET/CT effectively analyzed early subclinical changes in heart perfusion (A study on BC patients found that [erfusion . Howevererfusion .4.2123I]-BMIPP. While most studies indicate an increase in myocardial FDG uptake, it is essential to acknowledge that some research points to a reduced FDG uptake in the myocardium (Radiation-induced damage can affect myocardial perfusion and metabolic function, leading to changes in energy sources and metabolism , 44. Higocardium , 39, 40.ocardium , 39. Fro18F]‐FDG-PET/CT oncologic applications and cardiac inflammatory imaging applications (Standardized PET preparation protocols for evaluating myocardial damage in the irradiated myocardium are lacking. Differences in fasting and imaging protocols exist between [ications . Variousications . Despite4.3123I]-BMIPP studies showed early myocardial metabolic disorder after high-dose irradiation, but at 1-year post-CRT, there was no association between myocardial metabolic impairment and radiation dose. This suggests that other factors such as cardiovascular risk factors or chemotherapy may influence long-term myocardial metabolism, making it challenging to predict long-term radiation-induced heart disease based solely on radiation dose.Previous studies have shown that PD occurs in the irradiation field and is correlated with cardiac exposure , 9. One Previous literature on metabolic PET imaging found dose-response relationships in head and neck cancer  and lung4.3.1The impact of different techniques on preventing new PD is still controversial. Zellers et al. found no benefit of DBIH in relation to PD occurrence, but the heart was not consistently excluded from the RT field . Convers4.3.2Stress/rest MPS is a sensitive examination used for monitoring and detecting cardiac diseases , 55. It Contradictory findings exist regarding the relationship between myocardial FDG uptake and cardiac toxicity. Some studies have shown that increased FDG uptake in the right ventricle wall is associated with cardiotoxicity after anthracycline or trastuzumab therapy . FDG uptDespite rigorous efforts and the significant importance of the topic, the current body of research in this field has yielded largely inconclusive results. Numerous studies present contrasting findings, with only a handful suggesting any tangible correlation between nuclear medicine data and outcomes. These discrepancies underscore the pressing need for standardized methodologies, robust data collection, and a more coordinated approach to research in this domain. As it stands, the collective findings provide limited guidance for detecting early post-RT cardiac damage, a testament to the nascent and challenging nature of this research area.5Data suggest that incidental irradiation of the heart after breast or thoracic RT can result in early metabolic and perfusion changes. Nuclear imaging in nuclear medicine has a prominent place in the detection of these subclinical effects that could possibly predict late cardiac complications. Prospective studies with larger populations, longer follow-up, and specific heart dosimetric data are mandatory to understand the relationship between early detection of cardiac abnormalities and RIHD.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.Conceptualization: JE, CB, and GN. Methodology: JE, CB, and GN. Writing: JE. Review and editing: CB, FH, CL, IC, DA, OM, and GN. Supervision: CB and GN. All authors contributed to the article and approved the submitted version.


Consequently, much remains to be elucidated regarding the concomitant development and progression of cardiac and renal dysfunction.Cardiovascular and renal physiology are closely linked, and disruptions in one system can have significant effect on the functioning of the other. Accordingly, advanced disease states in these systems, such as congestive heart failure and CKD, likely precipitate and exacerbate one another.et al. present their work with the Cardiovascular Health Study,2 in which they investigated associations between echocardiographic parameters and eGFR in an older population 65 years or older and free of known HF. The study design included both cross-sectional (N of subjects=3516) and longitudinal analysis (n of subjects=2135), which examined baseline echocardiographic parameters in relation to the presence of CKD at baseline and a 30% decline in eGFR over a 7-year follow-up period, respectively. In addition, sensitivity analysis was conducted to examine the association between 2D speckle-tracking echocardiography parameters and rapid decline in eGFR, defined as an annual decline rate of >3 ml/min per 1.73 m2 per year. Though no correlation was found between diastolic indices and decline in eGFR as continuous variables in adjusted linear regression, the study found that diastolic function indices were associated with both rapid annual decline and >30% total decline in eGFR. The authors have thus demonstrated a link between decline in renal function and subnormal diastolic function assessed by multiple echocardiographic parameters in an older general population.In this issue, Mehta The authors have conducted a scientifically sound and thorough exploratory study with strengths that include a large study population and a long follow-up period. The population-based, multicentre, and longitudinal study design of the Cardiovascular Health Study provides a robust basis for testing the hypothesis that subclinical cardiac dysfunction assessed by echocardiography is associated with decline in kidney function over time. The limitations of this study were addressed by the authors in a well-balanced discussion, in which it was highlighted that causality cannot be established from the results, and further that the findings might not be directly reproducible in contemporary settings because of medical and technological advances after the time of original data collection.et al. has potential implications of both physiological and clinical significance. Physiologically, it supports a potential role of diastolic function in relation to a decrease in renal function which cannot be attributed solely to age-related decline. As formerly stated, causality cannot be established from this finding, but the extent to which it contributes to current understanding may be explored through three criteria for a causal link between two variables as proposed by Mill3: (1) temporal precedence of the independent variable, (2) covariance between the variables, and (3) exclusion of tertiary confounding factors. First, the results demonstrate temporal precedence of subclinical diastolic dysfunction before decline in eGFR. This is in line with the recent results of the German population-based Gutenberg Health Study, in which the diastolic parameter E/e was strongly associated with decline in eGFR over a 5-year period and further predicted higher rate of decline.4 Second, the results demonstrate covariance between diastolic function indices and prevalence of CKD at baseline. The interpretation of this, however, particularly regarding directionality of the interaction, is challenging. For instance, the Shanghai Heart Health Study found no association between clinical diastolic dysfunction and eGFR in a general older population,5 which would otherwise have been expected if diastolic dysfunction was able to affect kidney function. Beyond the general population, although it has previously been established that in patients with manifest CKD, diastolic dysfunction is highly prevalent and a strong predictor of mortality.6 In addition, diastolic function has been found to correlate with progressive stages of CKD, even in early stages,7 and further to gradually deteriorate in parallel with kidney function.8 The covariance between diastolic function and renal function thus seems strongest in subjects with manifest kidney disease. The work of Mehta et al. provides interesting new insight into this because it shows that baseline diastolic parameters are associated with eGFR in a general population, not only cross-sectionally but also with a longitudinal decline in eGFR. However, it seems unlikely that diastolic dysfunction is independent of renal function. Finally, although this study includes thorough adjusted analysis, the interwoven and complex nature of the cardiorenal relationship precludes the possibility of excluding all confounding factors. In continuation of this, it would, for instance, be of interest to investigate the concomitant decline of both cardiac and renal parameters because diastolic parameters might affect systolic parameters over time, which in turn might impose confounding effects on the perceived link between diastolic and renal function. In addition to the three aforementioned criteria may be added that one or several plausible underlying mechanisms for physiological interaction should be present. The authors propose several potential mechanisms to explain their results, including both direct interaction and underlying systemic mechanisms that result in adverse effects in both organ systems. The abundance of potential mechanisms highlights the need for further investigation, particularly with the aim of disproving some of the existing theories. As a final criterion for causality may be added that the relationship should involve proportional variation between diastolic and renal function, analogous to a dose-response relationship. Such proportional variation was explored in this study, and adjusted linear regression failed to show correlation between diastolic parameters and decline in eGFR as continuous variables. Although it is uncertain whether the link might instead follow a nonlinear relationship, the finding does not support causality between diastolic dysfunction and decline in renal function.The finding from Mehta et al. suggests potential utility of echocardiographic assessment of diastolic function in the effort to identify at-risk subjects free of manifest CKD in whom early monitoring and treatment might be beneficial. Future studies might aim to establish a threshold for diastolic parameters at which an association with future decline in eGFR arises and which could guide the need for potential intervention. As stated by the authors, Sodium-glucose co-transporter 2 (SGLT2) inhibitors have gained widespread use, especially because of their renoprotective properties in patients with CKD and HF10 as well as cardioprotective properties.11 Accordingly, the latest clinical practice guidelines for the management of HF now recommend SGLT2 inhibitors for patients with HF with preserved ejection fraction (HFpEF).12 Because HFpEF is generally regarded a clinical manifestation of diastolic dysfunction,13 this leaves a narrow potential target population with subclinical diastolic dysfunction, in which intervention with SGLT2 inhibitors might be initiated and tested. Furthermore, the effects of SGLT2 inhibitors on cardiac remodeling and diastolic function still require further investigation, and the underlying processes and effects have yet to be fully established.14 As such, the basis for future interventional studies needs to be expanded.Of clinical significance, the finding by Mehta et al. adds to current knowledge of the cardiorenal link and contributes to laying the groundwork for future mechanistic and, perhaps in time, interventional studies. From the work can be gathered a new hypothesis that subclinical diastolic dysfunction might precipitate decline in renal function, which can now be tested and explored.In conclusion, the work by Mehta


Impaired physical functional status is one of the typical long-term sequelae of COVID-19 infection that significantly affects the quality of life and work capacity. Minor changes in cardiac structure and function that are unable to cause the manifestation of overt heart failure may remain undetected in COVID-19 convalescents, at the same time potentially contributing to the persistence of symptoms and development of long COVID syndrome.To study the typical features and short-term dynamics of cardiac remodeling and possible signs of cardiac dysfunction following hospitalization for COVID-19.n = 53) matched to the subset of non-hypertensive study participants (n = 106).This is a combined cross-sectional and longitudinal cohort study in which 176 hospitalized patients  with COVID-19 infection underwent comprehensive transthoracic echocardiography pre-discharge (22.6 ± 7.1 days from the onset of symptoms) with repeated evaluation after 1 month. The control group included 88 age-, sex-, height- and weight-matched healthy individuals, with a subset of those (p < 0.001), worsening of diastolic indices  and global longitudinal strain . No significant improvement was found on re-evaluation at 1 month.Concentric left ventricular geometry was revealed in 59% of participants, including 43% of non-hypertensive subjects; predominantly Grade I diastolic dysfunction was found in 35 and 25% of patients, respectively. Other findings were naturally following from described phenotype of the left venticle and included a mild increase in the absolute and relative wall thickness (0.45 ± 0.07 vs. 0.39 ± 0.04, Hospitalized patients recovering from COVID-19 were characterized by a high prevalence of left ventricular concentric remodeling, predominantly Grade I diastolic dysfunction, and a mild decrease in the longitudinal systolic function. These changes were less frequent but still prevalent in the non-hypertensive subgroup and largely persisted throughout the 1-month follow-up.  To daSome of the mentioned uncertainties could be potentially related to differences in enrolled populations. Geography, gender, age, ethnicity, locally prevailing SARS-CoV-2 variants, reserve capacity of the health care system at the time the study was recruiting participants, and available logistics for the follow-up visits all inevitably affect characteristics of the observed populations in terms of disease severity and existing comorbidities, including those that have been associated with adverse prognosis both short-term in the acute COVID-19 setting , 20 and The purpose of the current study was to identify possible echocardiographic patterns and markers of cardiac impairment in the short-term follow-up of post-acute COVID-19 patients with an additional focus on the role of hypertension as a potential confounding factor.2.2.1.By design, this is a combined cross-sectional and longitudinal cohort study. Between January and November 2021, eligible patients who were hospitalized at the pulmonological department of Kharkiv City Hospital #13  were invited to participate in the study. Eligibility criteria included the age of ≥18 years and the diagnosis of COVID-19 pneumonia that had been confirmed with a positive polymerase chain reaction test. Exclusion criteria included stage D chronic heart failure, acute heart failure, history of myocardial infarction, permanent atrial fibrillation, stroke within 6 months, severe uncontrolled hypertension (defined as systolic BP ≥ 180 mm Hg and/or diastolic BP ≥ 110 mm Hg), significant valvular heart disease , active cancer or systemic autoimmune pathology, inability to provide informed consent, and persisting O2 supplementation dependence by the time of discharge.Out of a total of 265 consecutive eligible patients, 89 declined participation  and 176 were enrolled in the study, being a source of data for cross-sectional analysis. After the exclusion of 50 patients who were unable/unwilling to do a follow-up visit, the final cohort that was used for longitudinal comparisons included 126 participants—see n = 53) was additionally compared to the cohort of non-hypertensive study participants to properly exclude the possible confounding effect of hypertension on the studied parameters.The control group included 88 individuals (Control 1) selected from the internal database representative of the local population from the 2018–2019 (pre-COVID) period. These subjects were individually matched to the study group at a 1:2 ratio using a nearest-neighbor strategy to adjust for age, sex, height, weight, and prevalence of hypertension and diabetes mellitus  and achievement of clinical criteria of epidemic safety  . During The follow-up visit for re-assessment of symptoms, changes in clinical parameters, structural and functional state of the cardiovascular system was carried out at 1 month.2.3.Transthoracic echocardiography was performed using the Radmir ULTIMA Expert ultrasound system . Linear and volumetric measurements were performed in accordance with the current guidelines for chamber quantification by the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) . Linear Left ventricular global longitudinal strain was calculated as LV GLS = MAPSE/LVL* 100% using the recently proposed linear method –28. SimiMitral and tricuspid annular motion velocities, as well as parameters of transmitral and transtricuspid blood flow, were measured in pulsed-wave tissue Doppler mode according to the standard methods provided in the current guidelines , 30.Diagnosis and grading of the left ventricular diastolic dysfunction (DD) were performed in accordance with the 2016 ASE/EACVI algorithm  with inc2.4.t-test for normally distributed parameters and Mann-Whitney U-test for skewed variables; Chi-Square test was used to compare binary and categorical variables. Longitudinal comparisons were made using paired samples t-test or Wilcoxon signed-rank test. P values reported were calculated using two-sided Fisher’s exact test, the differences were considered significant if P < 0.05. Correlation analysis was performed using the linear Pearson method.The collected data was analyzed using StatSoft STATISTICA Version 12 statistical analysis software package. Data distribution was assessed using Shapiro-Wilk test. For all variables, descriptive statistics are reported as mean ± standard deviation (SD) or median [interquartile range] for normally distributed and skewed continuous variables, respectively. Categorical variables are reported as counts (percentages). Cross-sectional comparisons of continuous variables were performed using independent samples 3.3.1.The mean age of the initial 176 participants who entered the study  was 53.4 ± 13.6 years. The average time from symptoms onset was 22.6 ± 7.1 days for Visit 1 and 54.3 ± 8.2 days for Visit 2. The most frequent comorbidities were hypertension and obesity with the prevalence of both close to 40%; the complete report on comorbidities and further clinical characteristics are presented in 3.2.Echocardiographic assessment of cardiac structure in observed patients has revealed a mild increase in LA size and volume, interventricular septum (IVS) and posterior LV wall thickness, and myocardial mass parameters compared to matched control see . The obsAssessment of the LV systolic parameters in the study cohort has revealed a mild decrease in the B-mode derived indices of longitudinal function (MAPSE and GLS) and the midwall shortening vs. control. At the same time, a minimal increase in ejection fraction in the setting of a mildly decreased LV cavity resulted in the absence of changes in the cardiac output as assessed by the stroke volume index.LV diastolic function was characterized by a 20% reduction of mean e’ velocities, reaching subnormal values in 47% of participants. An E/e’ increase that was observed, however, was of little magnitude, leaving the vast majority of study subjects well below the cut-off values suggestive of increased LV filling pressures. The lack of traceable tricuspid regurgitation in the majority of patients (together with no evidence of right chambers remodeling or dysfunction) suggested normal pulmonary artery pressures but complicated the grading of diastolic dysfunction. As a result, out of 62 patients with diastolic dysfunction, 47 (26.7%) were categorized as Grade I DD and 15 (8.5%) as having indeterminate filling pressures. In the absence of data on left atrial strain, re-classification of these patients using LV GLS values , 32 withn = 106) was additionally performed to completely eliminate the possible confounding effect of differences in hypertension severity and quality of its control.Considering the similarities of changes in cardiac morphology and function that we observed in the study group to the hypertensive phenotype, a sub-analysis focused on the cohort of non-hypertensive participants  and the control group.In the proposed setting, we observed less pronounced changes that were still similar to the concentric phenotype described above see . DespiteA similar pattern was observed when assessing LV diastolic filling, with a statistically significant decrease in mitral e’ velocity and an increase in E/e’ ratio resulting in a 25% prevalence of Grade I diastolic dysfunction. MAPSE and GLS values were also mildly decreased in non-hypertensive COVID-19 patients on the background of a clinically insignificant increase in ejection fraction.3.3.Another aspect of our study was focused on the assessment of short-term post-discharge dynamics of echocardiographic parameters in observed COVID-19 patients based on the results of repeated comprehensive transthoracic echocardiography after a median of 31 days from the first visit. p < 0,001 for both indices) during a one-month follow-up , with RWT reaching values >0,42 in 64% of participants, including 55% of non-hypertensive subjects. These changes were accompanied by a mild depression of ventricular longitudinal function, manifested as a persisting 5%–10% decrease in LV GLS, MAPSE, TAPSE, and mitral annular velocities vs. control. LV diastolic dysfunction remained highly prevalent and was detected in 36% of cases in the general cohort and 30%—among non-hypertensive participants.r = 0.37) and LV MMI by height2,7 (r = 0.31). These findings implied that those were the patients with initially thicker walls who could potentially gain higher 6MWD increment vs. those in whom LV walls had a closer to normal thickness by the moment of discharge. Correlation analysis of dynamic changes in LV morphology has confirmed these suggestions, showing that the only parameters related to the increase in the 6 min walk distance % were a decrease in the IVS thickness (r = −0.31) and LV myocardial mass / MMI by height2,7 (r = −0.31).  within normal limits and therefore being hardly clinically significant when taken isolated.In the assessment of the biventricular longitudinal systolic function, we applied a recently proposed linear method that was later validated on 1266 cardiovascular disease-free individuals in the HUNT study, showing a close to linear correlation and no significant differences to the 2D speckle tracking-obtained values . The advMost of the echocardiographic studies that had been performed to date in COVID-19 patients were focused on the assessment of changes in cardiac structure and function during the acute phase of disease and on the evaluation of their prognostic significance, mostly using a hard endpoint of COVID-19-related death , 39–41. The study by Moody et al.  is amongn = 18). Similar findings were observed for mitral annular e’ velocity and E/e’ ratio that were equal between troponin-negative patients and Control 1 subjects in our study but insignificantly deteriorated in ex-troponin-positive participants in  . An indiAnother study by Ingul et al.  presentsTudoran et al.  report aWe did not identify prior studies longitudinally assessing echocardiographic dynamics within the early post-acute period of COVID-19 that would not use the parameters obtained during the early acute phase as a baseline. The current study presents data on the 1-month follow-up in the period from a median of 23–54 days after manifestation of symptoms, demonstrating no significant changes in cardiac morphology during this phase. The minimal decrease in the systolic indices that we observed was not associated with clinical deterioration and most likely resulted from the gradual reversal of a somewhat higher output state due to SARS-CoV-2-induced pulmonary affection. The same process could have explained the tendency to a minimal decrease in myocardial mass parameters . At the same time, the observed minimal changes in myocardial mass were contrasted with the expected dynamics during the period of post-hospitalization reconditioning  and coulIn the report on a long-term echocardiographic follow-up at a later phase after hospitalization for COVID-19, Ovrebotten et al.  demonstr4.1.To our knowledge, this is the first study focusing on the comprehensive assessment of echocardiographic changes in hospitalized COVID-19 patients during the early post-discharge period. Simultaneous cross-sectional comparison to the matched control allowed us to more clearly outline the existing minor changes in the cardiac structure and function that still appeared to be linked to the observed functional improvement during one month of follow-up. A sub-analysis that was performed in a cohort of non-hypertensive individuals has allowed us to more reliably mitigate the confounding effect of hypertension compared to the simple matching of its self-reported presence, given that the latter does not account for the possible differences in the severity and control of hypertension.Being a single-center study, it could be susceptible to hospital-related confounding effects. The most notable difference between the used treatment and the commonly applied standards was the high proportion of patients who received pulse therapy with Methylprednisolone during the first days of hospitalization. However, one would expect its possible effects on cardiac geometry and function to be transitory if existing at all, and to resolve by the moment of baseline evaluation, which was confirmed by the absence of any correlations between its use and the studied parameters. There was a source of selection bias in the design and protocol of the study—candidates with severe underlying cardiac pathology were specifically excluded for possible subtle changes in evaluated parameters not to get confounded by more severe manifestations of pre-existing disease that would be hard to adequately match to control. In addition, patients with a more severe course of COVID-19 could have been less likely to participate due to being still oxygen-dependent by the moment of discharge or reluctant to leave the floor and/or to engage in the 6 min walk test, and thus the study population might not truly reflect the characteristics of the general mass of consecutively hospitalized patients. Lastly, the prevailing SARS-CoV-2 variants at the time of enrollment were different compared to more recent time, and a higher proportion of patients were not vaccinated, mandating caution in generalizing the obtained results to the current setting of post-acute COVID-19 care.5.Hospitalized patients recovering from COVID-19 were characterized by the high prevalence of LV concentric remodeling, predominantly Grade I diastolic dysfunction, and a mild decrease in the longitudinal systolic function compared to matched control. The changes in LV geometry and diastolic dysfunction were less frequent but still prevalent in the non-hypertensive subgroup. The observed changes largely persisted during a one-month follow-up showing no general tendency to improvement, with a minor decrease in the IVS thickness and LV mass index correlating with an increase in the 6MWD.


To examine the direction, strength and causality of the associations of resting heart rate (RHR) with cardiac morphology and function in 20,062 UK Biobank participants.Participants underwent cardiac magnetic resonance (CMR) and we extracted CMR biventricular structural and functional metrics using automated pipelines. Multivariate linear regression adjusted for the main cardiovascular risk factors and Two-sample Mendelian Randomization analyses were performed to assess the potential relationship, grouped by heart rate and stratified by sex. Each 10 beats per minute increase in RHR was linked with smaller ventricular structure (lower biventricular end-diastolic volume and end-systolic volume), poorer left ventricular (LV) function  and unhealthy pattern of LV remodeling , but there is no statistical difference in LV wall thickness. These trends are more pronounced among males and consistent with the causal effect direction of genetic variants interpretation. These observations reflect that RHR has an independent and broad impact on LV remodeling, however, genetically-predicted RHR is not statistically related to heart failure.We demonstrate higher RHR cause smaller ventricular chamber volume, poorer systolic function and unhealthy cardiac remodeling pattern. Our findings provide effective evidence for the potential mechanism of cardiac remodeling and help to explore the potential scope or benefit of intervention. Left However, whether inappropriate RHR is a causative factor for changes in ventricular structure has rarely been studied. Although different patterns of cardiovascular disease (CVD) related to sex are widely recognized, the association of RHR-mediated sex differences is unclear .Recently, cardiac magnetic resonance (CMR) has been recognized as a better standard compared to echocardiography for assessing heart morphology and function because it can provide more accurate and detailed measurements, particularly in patients with poor RV assessment and image quality –10. MendTherefore, we sought to demonstrate the association in the UK Biobank population study stratified by sex between RHR and biventricular morphology derived from CMR imaging and assess the potential causal relevance of RHR on cardiac remodeling using MR techniques, aiming to provide ideas for the mechanism of RHR affecting the pathogenesis of CVD and theoretical support for the treatment of heart rate control in CVD .2.2.1.http://www.ukbiobank.ac.uk) is a large population-based study cohort that incorporated data from more than 500,000 middle-aged participants between 2006 and 2010  (r2 < 0.01 within a ± 250-kb window). Coding alleles were defined as alleles associated with higher RHR. In general, thirty-two single nucleotide polymorphisms (SNPs) were identified to predict RHR, which involved in the genetics of embryonic heart development and the pathophysiology of a variety of heart diseases. The identified variants are shown in Genetic variants of RHR were selected from an authoritative published study from HRgene consortium with significantly genome-wide associations ( × 10−8) . In brie2.5.All UK Biobank participants completed a comprehensive baseline health and lifestyle assessment through self-report questionnaires, interviews and physical measurements. The following confounding factors were considered for the accuracy of RHR and population stratification. Questionnaire-based data included: sex, age, ethnicity, socioeconomic status (Townsend Deprivation Index), smoking and alcohol status , and physical activity level. Measurements of body mass index (BMI) were derived from general body measurement data. We also considered a self-reported history of CVD , diabetes mellitus, and use of heart rate altering drugs  . Essenti2.6.2.6.1.P-value <0.05 was considered statistically significant  with corresponding 95% confidence intervals (95% CI) were calculated for the association between RHR as the determinant and LV and RV parameters as outcome variables. The multivariable model was adjusted according to covariates mentioned above. In the interest of simplicity, GLS values in the analysis process are reported as absolute  values. Sex interactions were included in the regression models to investigate whether RHR was more significantly correlated with cardiovascular morphology and function in men or women. For further study on the relationship between the RHR level and CMR parameters, participants were divided into four groups by RHR level . Analysis of variance (ANOVA) was used to compare the group differences. Principal sensitivity analysis was performed on participants who excluded self-reported diabetes and CVD, on this basis, participants diagnosed with atrial fibrillation were also excluded. Additional sensitivity analysis was performed on participants who were diagnosed with essential hypertension and heart failure. All statistical analyses were performed using R version 4.0.4 and nificant .2.6.2.P-value <0.10 deemed to be evidence of polymorphic deviation  of LV image-derived phenotypes in UK Biobank. The study using the LV metrics measured from CMR studies comprised 16,923 and 19,260 European UK Biobank participants with hearts of normal structure separately , 25. Theeviation . Leave-oeviation . All MR 3.3.1.Among a total of 502,469 participants in the UK Biobank, 26,892 participants had available CMR metrics excluded poor image quality data. After exclusion, our study included 20,062 individuals. 3.2.In the demographic table, people in the lower RHR group have larger ventricular structure. Due to this, we performed linear regressions to further study their cross-sectional correlation. P < 0.001], LVEF of 0.28%  and LVM of 1.87 g . Higher RHR was also linked to significantly unhealthy LV pathological remodeling, comprising lower MCF ), LVGFI  and GLS .In the univariate unadjusted model, all CMR parameters except biventricular EF and LVWT were significantly correlated with RHR. After adjusting for covariates, higher RHR was still associated with smaller ventricular structure, lower ejection function and thinner wall thickness. Each 10 bpm increasing in RHR was correlated with a significant reduction in LVEDV of 6.99 ml  for every 10 bpm increase in RHR but only about half of that in females . After grouping the population by RHR level, more detailed and clear results are presented in β −0.62%, 95% CI (−0.90 to −0.34), P < 0.001] decreased significantly with each 10 bpm increase in RHR only in populations with RHR ≥ 80 bpm, and there were no sex differences in any group. We also found that in women, the associations between LVESV and LVM with RHR were not significant after the heart rate rose to 70 bpm or faster. For LVWT, there was a negative correlation in women with the lowest RHR and a positive correlation in men with the highest RHR. The differences between all groups were compared by ANOVA. The complete table of analysis results is shown in All cardiac structural parameter reductions were greater in males , includiSensitivity analysis was first performed on individuals without atrial fibrillation, self-reported prevalent CVD and diabetes. Similar to the previous large population-based analysis, all cardiac parameters except RVEF were significantly negatively correlated with RHR, and all parameters had sex differences except LVEF. It is worth mentioning that LVWT has no correlation with RHR in healthy individuals. Next, in a population analysis of hospital-diagnosed essential hypertension, all cardiac morphological and functional parameters except LVWT significantly decreased as RHR increased, with no sex differences in biventricular ejection fraction. Heart failure patients with a hospital diagnosis were considered for the final analysis. The results demonstrated that all cardiac parameters were not significantly correlated to RHR in females. The findings for the subgroup of patients with heart failure are reported in 3.3.P = 0.09). MR-egger analysis did not provide evidence of pleiotropy of RHR genetic variants on LV structure orientation, and further MR-egger intercept test did not show pleiotropy either. In the secondary analysis, all MR methods showed that there was no causation between RHR and heart failure. When we exclude SNPs that were closely related to possible major confounding factors by leave-one-out method, significant causal estimates were determined again. After this process, MR-egger pleiotropy test showed that directional pleiotropy was still not significant. Leave-one-out plots of genetic variants of RHR for causal estimates on each LV structural parameter are shown in In the main analysis, the inverse variance weighting method combined with selected genetic variations gave a causal estimate of LV parameters as anticipated . All par4.4.1.This is the first study which involves both clinical and genetic analyses that systematically demonstrate associations between RHR and biventricular structure and function with sex differences using CMR assessment, independent of CVD and a wide range of clinical confounders.Our clinical study suggests that higher RHR is linked with smaller ventricular structure , poorer LV function  and unhealthier pattern of LV remodeling . These trends are more pronounced among males. The impact of RHR on LVWT was negligible after grouping analysis. Additionally, MR analysis using inborn genetic instruments supported the causal effect of our clinical observational results. These observations are less affected by confounding or reverse causality, reflecting that RHR has an independent and broad impact on left ventricular remodeling.4.2.The role of RHR in long-term development of CVD has been a topic of increasing research interest. It is well known that RHR is an independent predictor of all-cause and multiple cardiovascular mortality . These oSeveral factors may influence the relationship of RHR to ventricular geometry. For the same cardiac output, it is a basic physiological principle that there is an inverse dependence between heart rate and stroke volume . The pacThe concept of the heart rate vulnerable phase proposed in 2015 suggests that patients with heart failure at discharge with an RHR greater than 75 bpm will have increased the mortality and readmission rates . We founThe clinical associations between RHR and cardiac remodeling are particularly pronounced in men. As RHR levels increased above 70 bpm, the correlations remained in men, but not in women with LVESV and LVM. This is in line with a 2019 Japanese study showing that increased RHR was not significantly associated with the development of electrocardiographic left ventricular hypertrophy (ECG-LVH) in women, but was negatively correlated in men . HoweverWe all know that RHR levels in endurance athletes are often below 60 bpm, or even below 40 bpm . Our stu4.3.The present study has several limitations. First, cardiac activity and rates may be influenced by circadian rhythms, caffeine intake, body position and illness status such as infection or fever, which were not considered in the RHR collection conditions. Second, drugs such as ivabradine were not on the list of self-reported heart rate-modifying medications with blood serum data and sex hormone values not included in the adjustment factors. Third, the sample size of the subgroup analysis of heart failure patients was limited, so that the credibility and reproducibility of the results appear to require further validation. Finally, due to the insufficient effective SNPs of LV parameters’ GWAS summary after weak instrumental variable screening and clumping, reverse causal analysis cannot be carried out.5.In this large population-based imaging study, we confirm higher RHR cause smaller ventricular chamber volume, poorer systolic function and unhealthy cardiac remodeling pattern. The differences between sex and disease subgroups complement the evidence providing validity for the underlying mechanisms of cardiac remodeling and help explore the potential scope or benefit of the intervention. However, ventricular hypertrophic remodeling caused by lower RHR poses new problems for heart rate control of clinical patients.


To determine baseline characteristics predictive of left ventricular ejection fraction (LVEF) recovery in patients diagnosed with heart failure with reduced ejection fraction (HFrEF) and presumed non-ischaemic aetiology.We prospectively recruited patients who were diagnosed with HFrEF (LVEF ≤40%) on echocardiography and subsequently underwent cardiac MRI. Patients were excluded if they had a known history of coronary artery disease (>70% on invasive coronary angiography), myocardial infarction, coronary revascularisation or anginal symptoms. At cardiac MRI assessment, patients were categorised as either ongoing HFrEF or heart failure with improved ejection fraction . Clinical characteristics were compared between the groups. Logistic regression was performed to identify variables that were associated with LVEF recovery. Optimal cut-offs in QRISK3 score and baseline LVEF for prediction of LVEF recovery were identified through receiver operating characteristic curve analysis.A total of 407 patients were diagnosed with HFrEF, and 139 (34%) attained HFimpEF at cardiac MRI assessment . Mean age of the patients was 63±12 years, and 260 (63.9%) were male. At multivariate logistic regression, both QRISK3 score  and baseline LVEF  were independent predictors of HFimpEF. Among patients with baseline LVEF ≤25%, only 22 (21.8%) recovered. In patients with baseline LVEF 25–40%, QRISK3 score >18% was associated with lack of recovery . Additionally, QRISK3 score was associated with the presence of ischaemic late gadolinium enhancement .The QRISK3 score helps identify patients with HFrEF with undiagnosed vascular disease. Patients with either a very low baseline LVEF or a high QRISK3 score have less chance of left ventricular recovery and should be prioritised for early cardiac MRI and close monitoring. In patients presenting with heart failure and reduced ejection fraction, a total of 21–40% have recovery of left ventricular ejection fraction (LVEF). This can be termed heart failure with improved ejection fraction and is typically defined as patients presenting with LVEF ≤40%, improving to LVEF >40% with ≥10% of absolute improvement.In our cohort of patients presenting with heart failure and reduced ejection fraction, a total of 34% had recovery of left ventricular function. Very low LVEF at presentation and high QRISK3 score were associated with reduced left ventricular recovery. It may be possible to use these factors to identify patients unlikely to have recovery of left ventricular function who are at higher risk and might benefit from early cardiac magnetic resonance (CMR).There is widespread variability in expertise and availability of CMR. We therefore propose that early CMR should be prioritised to those with either very low LVEF at presentation (LVEF ≤25%) or LVEF 25–40% at baseline with QRISK3 >18%.Up to 40% of patients with heart failure, particularly those with a non-ischaemic aetiology, undergo reverse remodelling with subsequent improvement in left ventricular ejection fraction (LVEF) after introduction of guideline-directed therapy. This has been termed heart failure with improved ejection fraction (HFimpEF) or heart failure with recovered ejection fraction.2CMR is increasingly used in the investigation of patients with heart failure. It can provide accurate assessment of cardiac function and characterisation of myocardial tissue with late gadolinium enhancement (LGE) which can provide insight into both the aetiology and prognosis of heart failure. European and US practice guidelines give CMR a class IIa recommendation in the assessment of patients with heart failure, in particular for differential diagnosis of the aetiology and to distinguish between ischaemic and non-ischaemic scar.7Patients with HFimpEF have a favourable prognosis compared with patients who do not experience reverse remodelling, although there can be a subsequent decline in LV function particularly in those whose heart failure medications are discontinued.8 9We therefore hypothesised that baseline risk factors could be used to predict which patients with new-onset presumed non-ischaemic cardiomyopathy would have recovery of LV function.We additionally aimed to identify the proportion of patients with HFimpEF by the time they have CMR and if they could be identified by any baseline clinical or epidemiological factors. We specifically aimed to establish if QRISK3,We prospectively recruited patients from the MATCH  registry who were clinically diagnosed with heart failure at cardiology clinics and referred for CMR assessment between 28 February 2018 and 15 December 2021. Patients were classified to have heart failure with reduced ejection fraction (HFrEF) if found to have a baseline LVEF ≤40% on echocardiography at the time of diagnosis. Patients were excluded if they had a baseline LVEF >40%, known history of coronary artery disease (>70% on invasive coronary angiography), myocardial infarction, coronary revascularisation or anginal symptoms. Other exclusion criteria included hypertrophic cardiomyopathy, amyloidosis, congenital heart disease and advanced renal failure . PatientClinical assessment, blood tests and CMR were carried out during one visit. Clinical information including patient demographics, comorbidities, smoking history and medication history was obtained through direct interview and electronic health record. Townsend Deprivation Index was calculated from the patient’s postcode and QRISK3 calculated from this and available clinical data . GlycatePatients were advised to avoid caffeine intake for 24 hours before CMR assessment. CMR images were acquired in a supine position using a 3T system . The study protocol included cine imaging, stress-perfusion imaging and motion-corrected bright-blood LGE. For stress imaging, adenosine was infused for at least 3 min, at a rate of 140 g/kg/min and if there was insufficient haemodynamic response (increase in heart rate <10 beats/min) or lack of symptomatic response, infused at an increased rate of up to 210 g/kg/min. LGE images were acquired as a short-axis stack, and in four-chamber, three-chamber and two-chamber views. When it was unclear if the enhancement on bright-blood LGE represented ischaemic changes, a dark-blood LGE stack was acquired.Image analysis was carried out on the cvi42 software . LV volumes were measured by manual segmentation of endocardial and epicardial contours at end-systole and end-diastole.The presence of LGE was confirmed if enhancement was identified on two orthogonal planes or, where available, on both bright and dark-blood LGE images. Ischaemic LGE was defined as enhancement that involved the subendocardium in a typical coronary distribution. Other patterns of fibrosis were categorised as non-ischaemic with the exception of right ventricular insertion point fibrosis which was deemed not to have fibrosis. Inducible ischaemia was defined as presence of visual perfusion defect affecting >1 myocardial segment on stress perfusion images not matched on rest perfusion or LGE images.2 test were used to compare demographic, clinical, echocardiographic and CMR variables between the two groups. Univariate logistic regression was used to evaluate the association between the recovery of LVEF and demographic variables, baseline LVEF and CMR-assessed tissue characteristics. Multivariate logistic regression was performed to assess whether QRISK3 score could predict LV recovery even after correcting for baseline LVEF.IBM SPSS Statistic V.28 was used for statistical analysis. The patients with HFrEF were divided into the group who achieved HFimpEF and the group who failed to. T-test and ΧReceiver operating characteristic (ROC) curve analysis and calculation of Youden index were used to identify the optimal cut-off in QRISK3 score and LVEF for prediction of HFimpEF. The prevalence of ischaemic LGE in patients with low and high QRISK3 scores was compared using a t-test. Additionally, the association between the QRISK3 score and ischaemic LGE was assessed through univariate logistic regression.We included 407 out of 516 patients from the registry. A total of 109 patients were excluded from the study for having baseline LVEF >40% (n=93), undisclosed history of acute coronary syndrome (n=5), amyloidosis (n=4), claustrophobia at CMR assessment (n=4) and contraindication to adenosine (n=3). Out of the 407 patients, 139 patients (34%) attained HFimpEF with GDMT at time of CMR assessment  . Table 1Mean age of the patients was 63±12 years, and 260 (63.9%) were male. The patients with HFimpEF were found to be younger  and consisted of fewer men  than the patients who failed to attain recovered LVEF. Risk factors or comorbidities, including diabetes mellitus, hypertension, hypercholesterolaemia, previous cerebrovascular events, atrial fibrillation, smoking history and the Townsend Deprivation Index, did not show statistically significant association with HFimpEF. However, when combined in the QRISK3 score, patients with HFimpEF had lower QRISK3  than those who did not recover. There was no difference in GDMT received between the two groups of patients, except patients with HFimpEF were less likely to receive diuretics .There was a lower prevalence of ischaemic  and non-ischaemic fibrosis  in patients with HFimpEF than patients with HFrEF who did not recover. The prevalence of inducible ischaemia was 2.9% in the patients with HFimpEF and 7.1% in the patients with HFrEF who did not recover, respectively (p=0.081). Furthermore, patients with ischaemic LGE had higher QRISK3 scores compared with those without it .At multivariate logistic regression, both QRISK3 score  and baseline LVEF  were identified to be predictors of HFimpEF independent of each other. Both QRISK3  and baseline LVEF  remained independent predictors of HFimpEF after correction for time between the baseline echocardiogram and CMR.Additionally, QRISK3 score was shown to be associated with the presence of ischaemic LGE .ROC curves of the QRISK3 score and baseline LVEF predicting HFimpEF were plotted. When predicting failure to achieve HFimpEF, the QRISK3 score had an area under the curve (AUC) value of 0.600 (95% CI 0.543 to 0.658) with an optimal cut-off of 18.055 (Youden index=0.22). On the other hand, when predicting for HFimpEF, the baseline LVEF had an AUC value of 0.585 (95% CI 0.528 to 0.641) with an optimal cut-off of 26.5 (Youden index=0.15).In order to implement the findings of the ROC analysis, we determined the proportion of patients who developed HFimpEF based on the thresholds baseline LVEF ≤25% and QRISK3 ≤18% . In patiThis study has shown that baseline clinical characteristics can predict short-term recovery of LV systolic function in patients with a new diagnosis of heart failure. In patients with a recent diagnosis of HFrEF referred for clinical CMR to investigate the aetiology of heart failure, by the time of CMR (median 63 days), 34% had recovery of LV function, fulfilling the criteria for HFimpEF. Several patient factors were significantly associated with recovery of LV function including younger age, female sex, lower HbA1c, lower baseline LVEF and lower QRISK3 score. LVEF >25% on baseline echocardiogram and QRISK3 score ≤18% were independently associated with subsequent recovery of LV function.Younger age, female sex and lower HbA1c were associated with the recovery of LV function in patients with HFrEF. Other clinical parameters that were associated with a non-significant trend to prediction of lack of recovery of LV function included history of diabetes mellitus, history of atrial fibrillation and Townsend Deprivation Index. Many of these factors are included in the calculation of the QRISK3 score which explains the strong association between QRISK3 and recovery of LV function.QRISK3 score was developed from primary care data from many millions of patients in the UK and is designed to predict 10-year risk of incident cases of cardiovascular disease.Using QRISK3 to identify those less likely to have recovery of LV function is attractive because it is widely and freely available; both patients and doctors are already familiar with its use (particularly regarding statin prescribing); and it has been derived and validated in the UK population.In our study, 34% of patients achieved HFimpEF, which is comparable with other published contemporary studies that report a rate of recovery between 21% and 40%.The prognosis of HFimpEF compared with HFrEF is significantly improved with a significant reduction in all-cause mortality ranging from 45% to 76%.In addition to clinical parameters, several CMR findings were associated with lack of recovery of LV function. Most prominently, the presence of ischaemic or non-ischaemic scar on LGE CMR was associated with a lack of recovery of LV function with an HR of 4.29. In this cohort, no patients had symptoms of angina, history of recognised myocardial infarction or prior revascularisation, but 19% of patients had ischaemic scar, indicating unrecognised myocardial infarction. The presence of ischaemic scar is well recognised to be a predictor of adverse outcomes both in patients with history and symptoms of ischaemic heart disease,18 19The presence of non-ischaemic fibrosis was also significantly associated with lack of recovery of LV function although with a lesser HR of 1.71. These results are consistent with previous reports in which the presence and extent of non-ischaemic fibrosis in dilated cardiomyopathy were associated with outcomes including arrhythmia, heart failure and mortality.20 21Although both ischaemic and non-ischaemic fibrosis are associated with lack of LV recovery, it is not clear whether they play a causative role or are a marker of irreversible processes.The CMR phenotype of patients without recovery of LV function also included increased LV, right ventricular and atrial volumes and poorer right ventricular function. However, as we did not have paired CMR data at baseline, it is not clear if these factors could be predictive or are merely associated factors with lack of recovery.CMR is recommended in National Institute for Health and Care Excellence and European Society of Cardiology (ESC) and American Heart Association/American College of Cardiology Foundation/Heart Failure Society of America guidelines,3There are practical challenges in implementing these recommendations relating to scanner availability and CMR expertise. The 2018 British Society for Cardiovascular Magnetic Resonance Survey revealed wide variance in the clinical use and waiting times in the UK with a >10-fold difference between the regions with the highest and lowest-level CMR activity. Our findings could be used to guide physicians in identifying patients who might benefit from early CMR and those in whom CMR could be delayed allowing recovery of LV function. Where CMR resources are limited, we propose that in patients with suspected non-ischaemic HFrEF, early CMR should be prioritised to:Patients with very low LVEF (≤25%).Patients with LVEF 25–40% but QRISK3 score >18%.The patients in our study were real-world patients with heart failure and there was variety to the extent in which they were being treated with optimal medical therapy. The majority were being treated with ACE inhibitors and beta-blockers, but use of mineralocorticoid receptor antagonists was modest. It is possible with increased prescribing of heart failure medications there would have been a greater proportion of HFimpEF.Echocardiographic data were not analysed in a core laboratory, but on-site measurement of LVEF was used. However, it was not the purpose of this study to accurately compare LVEF between the initial echocardiogram and subsequent CMR but rather identify clinical factors which might identify patients unlikely to have recovery of LV function. We have chosen to use a categorical definition of HFimpEF. The association between baseline LVEF and recovery may have been diminished if LV recovery was defined as a continuous variable.In this cohort of patients presented with HFrEF, 34% had recovery of LV function. A very low LVEF at presentation and high QRISK3 score were both predictive of patients with a lack of LV recovery. It may be possible to use these factors to identify patients unlikely to have recovery of LV function who might benefit from early CMR and close monitoring.