Cardiomyopathies may be hereditary and associated with a familial predilection. Morbidity and mortality can be caused by heart failure, sudden death, or arrhythmias. Sometimes these events are the first manifestations of cardiovascular disease. Hypertrophic cardiomyopathy and arrhythmogenic cardiomyopathy are perhaps most thoroughly studied in that context. Dilated cardiomyopathy, although most frequently of secondary etiology, has a significant familial cluster. Noncompaction of the left ventricle can sometimes be seen in healthy individuals and, in other instances, is associated with severe LV dysfunction. Genetic testing is of utmost importance, since it might allow for the identification of individuals carrying mutations predisposing them to these diseases. In addition, certain variants may benefit from tailored therapeutic regimens, and thus searching for a causal mutation can impact clinical practice and is recommended for all patients with HCM or ACM. Patients with DCM and positive family history should be included as well. Regular follow-ups are advised, even in those with negative phenotypes, because these disorders are often age dependent. During pregnancy and in the case of athletes, special consideration should be made as well. We intend to summarize the most current evidence regarding their management. The term cardiomyopathy refers to a complex and heterogenous group of conditions that present with functional and or structural myocardial anomalies without predisposing factors, such as volume/pressure overload or coronary atherosclerosis . The genMost cardiomyopathies tend to present in adulthood and have autosomal dominant inheritance. In the pediatric age group, other patterns of transmission are more relevant. Autosomal recessive, X-linked, or mitochondrial inheritance appear at higher rates than in adults ,3. GivenWe reviewed the available literature on the PubMed database, using terms such as “genetics/cardiomyopathies”, “Cardiomyopathy, Hypertrophic”, “Cardiomyopathy, Dilated”, “Arrhythmogenic Right Ventricular Dysplasia”, and “Isolated Noncompaction of the Ventricular Myocardium”, up until the end of February 2023. To garner specific information regarding “epidemiology”, “genetics”, “pregnancy”, “athletes”, and “sudden death”, those terms were added to the search. In this narrative review, we included case reports, observational studies, clinical trials, and systematic reviews according to what we deem to be most pertinent. In addition, we analyzed various clinical guidelines from international scientific societies, including the European Society of Cardiology, the American Heart Association, and the American Heart Failure Society.The hallmark of hypertrophic cardiomyopathy (HCM) is the thickening of the left ventricular wall. Besides this imaging finding, electrocardiographic abnormalities, fibrotic infiltrates in the myocardium, as well as valvular and coronary artery anomalies may be present .Usually, HCM has an autosomal dominant mode of inheritance and, in most cases, involves sarcomere proteins. In some instances, heredity may be recessive, appear de novo, or have low penetrance, hindering the recognition of a familial predisposition .A vast spectrum of clinical findings has been described. HCM constitutes one of the main causes of sudden death in young people. On the other hand, it may lead to severe left ventricular function impairment and cause heart failure. Given its highly complex clinical manifestations, establishing a prognosis can present an intricate dilemma .HCM is the most prevalent genetic cardiomyopathy. Still, it is estimated that most individuals carrying a mutation associated with HCM are not identified. In the general population, the prevalence of HCM is thought to be 0.2%. Estimates may vary, depending on whether only clinically evident disease or asymptomatic carriers are considered. In addition, population characteristics such as age may be relevant . Some stIn up to 60% of cases, a disease-causing mutation is identified. Nowadays, regular genetic testing involves at least eight sarcomere or sarcomere-related genes: MYH7 (cardiac beta-myosin heavy chain), MYBPC3 (cardiac myosin binding protein C3), TNNT2 (cardiac troponin T), TNNI3 (cardiac troponin I), TPM1 , ACTC (encoding cardiac actin), and MYL2 and MYL3 (myosin light chains). Most often than not, these mutations are missense, although loss and gain of function are possible .Consequently, a significant percentage of HCM cases remains without a definitive genetic cause. Within a subset of individuals, neither a genetic cause nor a familial predisposition occurs, meaning that other genes or pathophysiological mechanisms of HCM have yet to be discovered .Classical descriptions of the hypertrophy observed in HCM refer to asymmetrical growth of the interventricular septum. Other less frequent forms affect the free wall, the anterolateral wall of the left ventricle (LV), or the apex. Ultimately, the papillary muscles and the right ventricle may be involved .All in all, a diagnosis in adults can be established by 2D echocardiography or cardiac magnetic resonance (CMR) once a maximal end-diastolic wall thickness (MEDWT) of 15 mm is found anywhere in the LV, seeing as though other causes of left ventricular hypertrophy (LVH) have been excluded. In patients with a family history or positive genetic testing, less restrictive diagnostic criteria of 13 or 14 mm can be used ,17.In children, the measurement of the LV dimension must be adjusted for, among other things, age and size. Thus, a z-score (number of standard deviations from the mean population) adjusted for a body surface greater than two is, usually, considered diagnostic. Yet, the American guidelines only consider that threshold adequate in cases with a definite family history or positive genetic testing and require a z-score ≥ 2.5 in asymptomatic children or negative family history ,17.Dilated cardiomyopathy (DCM) is the most frequent indication for cardiac transplantation. It can be defined by the presence of an enlarged and poorly contractile LV. Nonetheless, circumstances that could result in severe LV impairment such as significant coronary artery disease or abnormal loading conditions must be excluded to meet DCM criteria ,19.Therefore, a rigorous differential diagnosis of ischemic heart disease must be completed before safely establishing a diagnosis. In that case, angiography (or computed tomography coronary angiography) can show stenosis of the coronary vessels. Cardiovascular magnetic resonance can be of help, showing late gadolinium enhancement (LGE) compatible with previous myocardial infarction ,21.In addition, the same patterns of cardiac remodeling can appear in different nonischemic DCM or as a maladaptive response to environmental factors, so those situations ought to be ruled out. Toxins such as alcohol, amphetamines, or cocaine; some infections; and metabolic and inflammatory factors are potential etiologies of DCM .Some unique yet relevant signs should raise suspicion of a multisystemic disease. A few examples of those constitute the presence of a unique pigmentation of the skin and scars, seen in hemochromatosis; the presence of muscle weakness or abnormal gait, suggesting a neuromuscular disease; and neurosensorial deafness, suggesting a mitochondrial disease .The most up-to-date assessments predict DCM prevalence to be around 1:250. That is to say, DCM is no less common than HCM. When at least two individuals in the same family, either first- or second-degree, develop DCM without a clear etiology, it is defined as familial dilated cardiomyopathy (FDM) . SporadiAs seen with HCM, the recognition of FDM can be thwarted by incomplete pedigree assessment, the occurrence of de novo mutations, age-dependent phenotypes, or incomplete penetrance of existing mutations .DCM has been associated with nearly 40 different genes. Mutations related to the cytoskeletal complex, proteins of the nuclear envelope, sarcomere, ion channels, and transcription factors have been reported; however, up to 25% of all cases involve titin (TTN). Regarding the cytoskeletal complex proteins, the dystrophin gene is commonly impaired. This gene is, simultaneously, the cause of Duchenne muscular dystrophy (DMD). Desmin (DES) is related to the myocardium’s cytoskeleton architecture but also to the skeleton and smooth muscle. DES mutations have been reported in patients with skeletal or myocardial myopathies . FurtherRBM20 is an RNA binding protein. Autosomal dominant mutations have been described, typically associated with early onset disease and with a more severe clinical presentation .Of all cases of FDM, up to 10% will carry a heterozygous mutation of a sarcomere gene, such as an MYH7 chain or ACTC. This means that FDM and HCM share some genetic causes. Currently, it has been proposed that in HCM, force generation is impaired, affecting the movement of contractile proteins, whereas in FDM, the mechanisms for relaying contractile force to the z-disks/cell membrane are altered .Lastly, the interplay of multiple genes, for example due to digenetic inheritance, could significantly impact the severity of the phenotype. Recently it has been reported that a patient carrying both TTN and RBM20 mutations had an earlier and more severe onset of disease .The proposed mechanism of DCM has long been understood to be the dilation of the LV due to fibrosis and other remodeling processes. Set structural changes result in pump failure, namely, decreased cardiac output and impaired ventricular filling with increased end-diastolic ventricular pressure. In response, various systemic compensatory adjustments arise. Often the diseases will slowly, but definitely, lead to heart failure .Diagnostic criteria include LV or biventricular dysfunction and dilation, with an end-diastolic volume or diameter with a z-score > 2. Body surface area, age, and ejection fraction are frequent confounders to adjust for . A similIn some instances, to clarify the etiology, cardiac resonance imaging can be useful, since the detention of fibrosis and edema can point to an inflammatory cause, though with residual sensitivity. Ultimately, ECG is usually unnoteworthy, though repolarization anomalies, left bundle branch block, or auriculoventricular conduction prolongation can occur .Morbidity and mortality in DCM are attributed to the development of heart failure or are consequences of a fatal arrhythmia .Arrhythmogenic cardiomyopathy (ACM) is an inherited disease with autosomal dominant traits frequently associated with desmosome proteins. It affects predominantly the right ventricle, where cardiomyocytes are replaced by the fibrotic extracellular matrix and adipocytes. Typically, these histological changes occur mainly on the right side of the heart, though left ventricle disease can happen, and, in limited cases, can be the predominant location ,31.Patients are predisposed to severe ventricular dysfunction and life-threatening arrhythmias. Accordingly, ACM is regarded as a leading cause of sudden death in young people and athletes ,31. MoreACM prevalence in the general population could be 1:5000, making it a rare genetic disease ,33.Current estimates are that 50% of patients have a positive family history. However, familial predisposition is thought to be higher, which can be explained by incomplete penetrance and limited phenotypic expression .ACM is commonly associated with desmosomal gene mutations. Plakophilin 2 (PKP2) is the most frequent, followed by desmoplakin (DSP), desmoglein 2 (DSG2), and desmocollin 2 (DSC2). However, when searching for individuals meeting international diagnostic criteria for ACM, not more than half will meet these criteria. Unfortunately, even adding non-desmosomal mutations will only marginally help identify causal mutations .Spatial transcriptomics studies have helped to corroborate some pathophysiological mechanisms of ACM. For example, it has been proven that PKP2 mutations are related to biventricular remodeling with fibro-fatty deposition in the myocardium, cardiomyocyte degeneration, and loss of desmosomes between cardiomyocytes .One example of non-desmosomal mutations is transmembrane protein 43 (TMEM43), a nuclear envelope protein, with one specific mutation (TMEM43-p.S358L) known to cause a highly penetrant and lethal phenotype, although very rare and endemic in a specific region of Canada .Integrin-linked kinase (ILK) is a serine/threonine protein kinase, with various mutations previously described in patients with ACM. Studies in zebrafish found that some mutations in this gene were associated with higher rates of premature death caused by heart failure .Desmin (DES) is a protein of the cytoskeleton, and its function is related to the Z-discs in the sarcomeres but also desmosome plaque proteins. It has been associated with myofibrillar myopathies; thus, some have suggested that filament assembly defects could be involved in the pathophysiology of ACM .ACM is defined by the presence of an “arrhythmogenic heart muscle” and is not caused by vascular, hypertensive, or ischemic disease .The deposition of fibrofatty tissue initially occurs in the epicardium and then propagates toward the endocardium. Consequently, cardiac chamber walls become thinner to the point of aneurysmal dilation. The most common locations within the right ventricle are the sub-tricuspid and infundibular regions as well as the apex .Initial clinical presentations are the onset of palpitations or even syncope with exertion coupled with electrocardiographic anomalies, for example, repolarization anomalies such as T-wave inversions, or depolarization anomalies such as a left bundle branch block. Long-standing patients may develop heart failure either limited to the right side or biventricular .Currently, the gold standard for the diagnosis of ACM is histology, whether from biopsy or post-mortem autopsy. In fairness, imaging studies are more important in clinical practice. Echocardiography might show global ventricular dilation, systolic akinesia, dyskinesia, or diastolic bulging. CMR with gadolinium enhancement allows for detailed tissue characterization, non-invasively, making it the preferred method .The European Society of Cardiology, in its Task Force Criteria for the diagnosis of ACM, proposed a mixture of ECG, imaging, clinical symptoms, family history, and genetic testing criteria to define the disease .Left ventricular noncompaction (LVNC) may be a congenital disease with a genetic predisposition. Patients present with an excessively trabecular ventricle, forming recesses or sinusoids directly in communication with the left cavity due to abnormal embryogenesis ,42.Although sometimes isolated in some cases, LVNC can be associated with other cardiac anomalies, such as complex cyanotic congenital heart disease .Imaging techniques, namely, 2D echocardiography, CMR, and angiography, can be employed to establish a diagnosis ,42.Heart failure, sudden death, and cardioembolism comprise the three main courses of the disease. LV systolic dysfunction can progress, and a heart transplant might be indicated. Besides that, thromboembolic complications are also important to be accounted for .Though classical descriptions define LVNC as a congenital cardiomyopathy, “acquired” LVNC has been reported in patients with the onset of the disease later in life .Generally, it is said that the prevalence of LVNC is unknown. Estimates depend greatly on population characteristics and the diagnostic criteria used, including imagological modality. Published evidence ranges widely, from 0.14% to 1.26% of patients referred to a given echocardiography laboratory .Several genes have been linked to LVNC and with various patterns of inheritance. Both autosomal dominant and recessive, also X-linked, and mitochondrial inheritance are possible. Most commonly, it is autosomal dominant and involves mitochondrial, cytoskeletal, sarcomere, or ion channel genes .When studied, a mere 30% of probands revealed a positive family history . Thus, iTaffazin (TAZ) or the G4.5 gene is a known genetic cause of LVNC. Particularly, this gene is identified in pediatric age, associated with myopathies such as Barth syndrome, but not in adults. Z-line protein, LIM domain binding protein 3 (LBD3), and lamin A/C protein genes have established a mutual genetic etiology between DCM and LVNC. An overlap with HCM also exists, with some sarcomere protein genes also being implied in LVNC .LVNC in conjunction with congenital heart disease is often attributed to a mutation in the α-dystrobrevin gene codifying a cytoskeletal protein .Mutations in the DES gene in the context of LVNC are rare; however, they tend to present simultaneously with neuromuscular and myocardial disease, having a poorer prognosis ,49.The literature regarding the median age of diagnosis of LVNC is extremely incoherent. In some studies, the authors have estimated it to be as little as 7 years old (from 11 months to 22 years), whereas in others, they calculated it to be 58 years (from 28 to 80 years). Currently, a growing number of patients are diagnosed in adulthood; however, when compared to the other cardiomyopathies mentioned above, LVNC is identified more prematurely ,51.Echocardiography in LVNC will show a two-layered myocardium in the LV. The layer adjacent to the epicardium is thin, whereas the one closest to the endocardium is thicker and replenished with prominent trabeculations and recesses. A Doppler sign can be found in set recesses, proving the connection to the main chamber of the LV .International echocardiographic criteria have been published to differentiate from trabeculation seen in normal individuals. Given that, LVNC is diagnosed, although with significant limitations, when the ratio between the two layers at end-diastole is greater than 2. In contrast, in a CMR, a ratio, in diastole, of noncompacted and compacted myocardium of at least 2.3 has been shown to be very reasonable at identifying pathological noncompaction, exemplified in Some patients will end up developing LV dysfunction. Diastolic compromise has been reported as well due to abnormal relaxation, excessive trabeculation, or fibrosis. Arrhythmias, either ventricular tachyarrhythmias (more frequent) or atrial fibrillation, in association with the development of thrombi in the trabeculae are regarded as potential causes of morbidity . All in Anticoagulation is recommended if the LV ejection fraction is under 40%, there is atrial fibrillation, or there is a history of thromboembolic events .Nowadays, genetic testing is of paramount importance in the management of cardiomyopathies. First, certain variants might cause more severe phenotypes and have a higher risk of sudden death and thus must be addressed. Secondly, testing of family members will allow for the identification of at-risk individuals and provide them with proper vigilance ,55.Genetic testing in families should begin with the most affected individual, i.e., the one with the most severe manifestations or with the earliest onset of disease. Thereafter, the patient and their relatives should receive appropriate genetic counseling as well as cascade testing of other at-risk individuals. Nowadays, genetic testing comprises next-generation sequencing of multi-gene panels according to the individual’s phenotype. The timeframe has not been largely studied; however, it is generally considered reasonable at diagnosis .Often, a single mutation can be responsible for any given cardiomyopathy. Nevertheless, compound heterozygous mutations have been reported in 5% of HCM cases and up to 20% of ACM cases .Multi-gene panels offer a greater likelihood of finding the causal variant(s) but increase the chance of finding results of undetermined clinical significance. From single variant testing to whole exome sequencing, physicians benefit from a large array of possible options, and the selection of the specific type should be tailored to each situation. Not always will the addition of more genes prove to be beneficial. For example, when testing for DCM, even with a large panel containing more than 20 genes, a molecular diagnosis is achieved only in 10–40% of patients ,58. In cAccording to the Heart Failure Society guidelines for cardiomyopathy genetic testing, LVNC should be seen more as a phenotype rather than a primary cardiomyopathy itself. Often, it appears in conjunction with all other primary cardiomyopathies. Hence genetic testing in LVNC should be directed by the cardiomyopathy phenotype presented in that case . IndicatIn cardiovascular genetics, the focus of diagnostic and treatment has moved from being solely on the index case and expanded to include the family. Often, probands when diagnosed are at late-stage disease, leaving few interventions available . In addiGenerally, a three-generation pedigree is recommended, with three main objectives: to determine if a familial predisposition is present, to ascertain the pattern of inheritance, and to identify at-risk individuals ,55.A detailed family inquiry, including cardiovascular symptoms such as shortness of breath, palpitations, syncope, and its relationship with exercise is advised. In addition, attributed diagnosis, namely, heart failure, and the history of prior procedures such as implantable cardioverter defibrillators, pacemakers, heart surgery, and transplantation with the respective age of onset are relevant. When it comes to sudden death, it should be especially relevant when under 40 years of age, in the context of single-vehicle accidents, drowning, or in infancy .A clinical evaluation of first-degree relatives is recommended at baseline to classify them as clinically affected, clinically unaffected, or reportedly clinically unaffected (meaning asymptomatic but have not completed phenotype screening). This last category is relatively important because disease development is age dependent and requires successive assessments. If they have the phenotype of the disease, then expanded genetic testing could be required. Even individuals who test negative for a known familial variant are advised to be evaluated at baseline. However, if no signs or symptoms arise, there is no need for further follow-up .Likewise, clinically unaffected individuals who are known to carry a family variant are advised to be regularly tested for the development of the phenotype. Clinical phenotype screening is comprised of four parts: medical history, physical examination, ECG, and a 2D echocardiogram, possibly with Doppler and CMR if the first imaging is equivocal ,63.Baseline phenotype screening for at-risk relatives also includes Holter monitoring, both in HCM and ACM, CK-MM  in case of HCM and LVNC (to rule out syndromic and neuromuscular disease), and exercise treadmill testing if HCM. Lastly, in HCM and DCM, metabolic disease screening is recommended to exclude fatty acid oxidation defects and mitochondrial oxidative phosphorylation disorders .The American Heart Failure Society has published guidelines applicable to first-degree relatives of individuals with established genetic cardiomyopathy . They reIt is commonly known that pregnancy is associated with multiple hemodynamic changes, namely, significant increases in cardiac output, total plasma volume, and a reduction in peripheral resistance. Moreover, it determines a hypercoagulable state .Usually, contraception is advised for females with cardiomyopathies at the onset of fertility, since that will allow for better planning of an adequate timeframe for the pregnancy. Factors such as disease stability and symptoms will be pondered in that decision. In addition, many drugs are risks for the unborn, requiring modifications to the therapeutic regimen . AssessmAn initial risk assessment with the modified World Health Organization (WHO) classification of maternal cardiovascular risk is strongly suggested because a contraindication to pregnancy can be issued if Class IV and periodic outpatient cardiology evaluations are recommended in the following timelines: WHO class II—each trimester, class III—monthly or every 2 months ,66.Even women with established cardiomyopathies end up, in most cases, having no major events during pregnancy . The limWhen it comes to FDM, the literature is very sparse. Few studies have been conducted, and often they are regarding idiopathic DCM. Nevertheless, the outcomes for genetic vs. idiopathic DCM are probably the same. In that case, asymptomatic and mildly symptomatic patients tend to have limited risk associated with pregnancy. Indicators to look for are severe LV dysfunction and poor New York Heart Association (NYHA) functional class . So far,A 2022 retrospective, longitudinal study found that pregnancy did not accelerate disease progression in women carrying LMNA mutations, nor did it lead to worsening of electrical disease and ventricular arrhythmias (VAs), and it also did not increase the odds of needing a left ventricular assist device, a heart transplant, or even dying .Peripartum cardiomyopathy (PPCM) is a diagnosis of exclusion. It can be understood as an idiopathic de novo cardiomyopathy with severe left ventricular systolic dysfunction in late pregnancy or the puerperium. PPCM can have similar characteristics with DCM and familial cases of PPCM have been reported. Both PPCM and pregnancy-associated cardiomyopathy can be an initial manifestation of FCM. The course of the disease can worsen; however, virtually half of the affected individuals will achieve normalized ventricular function in 2 years ,71,72.Lastly, regarding LVNC and ACM, current evidence is even scarcer. Of the case reports published about the latter in asymptomatic patients, no serious risk of disease progression with the pregnancy was found. It, most likely, poses a severe risk when associated with VAs or heart failure, though formal evidence is still lacking. When it comes to LVNC, due to its increased risk of thromboembolic events, anti-coagulation therapy has been conducted during pregnancy, yet without proper data .Exercise has always been associated with multiple health benefits. However, high-intensity exercise has been proven to be correlated with SCD events , which hRecently, new evidence has emerged suggesting that the relationship between physical activity and SCD could have been, previously, overestimated. For example, in individuals with HCM that participate in sports, defibrillators did not register a higher number of shocks than those implanted in patients not participating in sports . In a crNowadays, it is reasonable that asymptomatic individuals carrying an HCM mutation, without any imaging finding of LVH, take part in competitive athletics without meaningful restriction ,78. OnceHowever, when it comes to ACM, the evidence seems to sustain a dose-dependent relationship between endurance training and the development of ACM. In a 2013 cross-sectional study, of 87 desmosome mutation carriers, those participating in endurance training and regular exercise were more likely to develop the phenotype at an earlier age than those who did not exercise or did it at a lower intensity. Patients in the highest quartile of exercise showed an odds ratio (OR) = 25.3, with a 95% confidence interval (CI) of 4.21–153. In addition, time free of VAs and heart failure was significantly higher in nonathletes . Other sWhen it comes to DCM, high-intensity and competitive sports are contraindicated in those carrying LMNA or FLNC mutations or with histories of cardiac arrest, unexplained syncope, LVEF < 45%, frequent VAs, or >20% LGE on CMR . BesidesLV hypertrabeculation is commonly found in athletes, with 8% of them meeting diagnostic criteria . HoweverAll in all, limited evidence has been produced to justify banning indiscriminately all individuals from participating in recreational sports. High-intensity exercise likely confers an increased risk of sudden death events in patients with a predisposition to developing arrhythmias. Nonetheless, a personalized decision based on appropriate testing is preferred, and low to moderate physical activity could be useful to prevent further health burdens attributed to sedentarism ,78.As many as 30% of all sudden deaths are the first cardiac symptoms a patient may experience . SCD canIn HCM, rates of sudden death are greater at younger ages and decrease into adulthood. The current state-of-the-art treatment has had a major impact on the number of those fatalities due to the usage of ICD devices, better advanced life support outcomes, and higher rates of heart transplantations . To asseIn the case of DCM, SCD occurs in as many as 12% of patients, representing up to 30% of all mortality ,87. LMNAACM is associated with VAs and sudden death. A higher predisposition is seen in younger patients and those presenting with right ventricle dysfunction or syncope, ECG anomalies such as QRS fragmentation, or non-sustained ventricular tachycardia. Out of all possible measures, ICD implantation seems to be the most successful at preventing SCD . Thus, eIn a study of LNVC patients, of those who died, half were from SCD. The main predictor of that occurrence was heart failure. Therefore, ICD implantation is indicated in those with LV ejection fraction ≤35%, NYHA functional class II or III, a family history of sudden death, a personal history of syncope, or the presence of nonsustained ventricular tachycardia .Lastly, another factor that impacts the risk of SCD is the presence of multiple mutations. For example, triple sarcomeric mutations in HCM individuals conferred higher rates of SCD . In addiAlthough the management of genetic cardiomyopathies requires a high level of expertise, some key principles apply to all. First, the recognition of a familial predisposition is essential. Secondly, providing at-risk relatives with appropriate genetic testing and follow-up is another important step. Lastly, patients with an increased risk of sudden death must be identified and offered preventative options.Due to their relative specificity, current recommendations tend to lack robust data. Some emerging areas of research are the relationship between genotype and phenotype, as well as their respective prognostic value.


Performance of cardiovascular magnetic resonance (CMR) in the planning phase of percutaneous pulmonary valve implantation (PPVI) is needed for the accurate delineation of the right ventricular outflow tract (RVOT), coronary anatomy and the quantification of right ventricular (RV) volume overload in patients with significant pulmonary regurgitation (PR). This helps to find the correct timings for the intervention and prevention of PPVI-related complications such as coronary artery compression, device embolization and stent fractures. A defined CMR study protocol should be set for all PPVI candidates to reduce acquisition times and acquire essential sequences that are determinants for PPVI success. For correct RVOT sizing, contrast-free whole-heart sequences, preferably at end-systole, should be adopted in the pediatric population thanks to their high reproducibility and concordance with invasive angiographic data. When CMR is not feasible or contraindicated, cardiac computed tomography (CCT) may be performed for high-resolution cardiac imaging and eventually the acquisition of complementary functional data. The aim of this review is to underline the role of CMR and advanced multimodality imaging in the context of pre-procedural planning of PPVI concerning its current and potential future applications. Pulmonary valve replacement (PVR) is indicated in selected cases to treat the chronic volume overload on the right cardiac chambers secondary to severe pulmonary regurgitation (PR). The pulmonary valve (PV) consists of three semilunar cusps, one anterior and two posteriors, which connect through the fibrous interleaflet triangles to the right ventricular outflow tract (RVOT). PR may occur as a sequela of the surgical repair of congenital heart diseases (CHD), such as tetralogy of Fallot (TOF), where surgical correction consists of closing the ventricular septal defect and widening the pulmonary outflow tract . Other cPercutaneous pulmonary valve implantation (PPVI) has emerged in recent decades and has shown earlier treatment promise in PR compared to surgery before irreversible RV failure occurs . PPVI caAn extensive clinical and instrumental pre-procedural workup is essential to select the optimal timing and possible candidates for PPVI. A meticulous preprocedural analysis of the RVOT and PA anatomy is needed, as percutaneous prosthetic valves are available in defined types of shape and dimension, while the anatomy and sizes of the RVOT are very heterogeneous. This could also help in avoiding possible PPVI-related complications such as stent fractures, device embolization, conduit rupture, and coronary artery compression .Different non-invasive imaging modalities are applied in the routine clinical practice for PPVI planning ,7. AmongTherefore, second-level imaging with cardiovascular magnetic resonance (CMR) or cardiac computed tomography (CCT) is fundamental for PPVI planning. Principal advantages of CMR are that it can provide both anatomical and hemodynamic information, with accurate quantification of RV volumes and function, precise quantification of PR, and a 3D anatomical definition of the RVOT, PA and coronary arteries. Unlike echocardiography, CMR allows unrestricted views on cardiac and extracardiac structures, such as conduits, and is independent from geometric assumptions for volume quantification. In the last few years, CCT has been increasingly applied before PPVI as an alternative to CMR. Its principal role relies on high-resolution 3D evaluation of cardiovascular anatomy and the delineation of coronary arteries. Despite anatomical data, recent evolution technology allows CCT to acquire functional data related to blood flows and ventricular volumes ,10.A multimodality imaging approach is fundamental to optimally plan complex percutaneous procedures over the PV . Among aThe aim of this review is to underline the role of CMR in the context of pre-procedural planning of PPVI concerning its current and potential applications in the future.CMR is currently considered the gold standard for ventricular volume quantification and the assessment of systolic function. A reduction in RV volume overload has been shown in CMR studies after successful PPVI treatment; an example is given in In recent decades, numerous attempts have been made to identify reasonable cut-offs of RV dilatation in terms of end-diastolic volume (RVEDV) and end-systolic volume (RVESV) for PVR indication in patients with relevant PR, as, in most cases, patients can remain clinically asymptomatic for years despite relevant PR and severe RV dilatation and/or initial deterioration of its contractile function ,13. FollIn asymptomatic patients, indications for PVR are based essentially on the entity and trend of RV dilatation and dysfunction.2, and/or indexed RVESV ≥ 80 mL/m2, and/or the development of at least moderate tricuspid regurgitation; progressive RV contractile dysfunction (recommendation IIa) . Fi. Fi29]. For the RVOT anatomy, different anatomical CMR sequences can be performed, such as contrast-enhanced MR angiography (ceMRA) and 3-dimensional (3D) whole-heart sequences .3D whole-heart sequences are preferable in children as they do not require breath-holding or a contrast medium ,32. AddiThe main limitations of 3D whole-heart sequences are their high susceptibility to metallic devices (stents or protheses), relatively long acquisition times, and RVOT measurement variations of up to 5 mm between systole and diastole, as demonstrated in a recent study . ceMRA iThe different timings of image acquisition between 3D whole-heart and ceMRA inevitably introduce a clear difference in RVOT measurement. Ferrari et al. compared RVOT measurements by ceMRA and 3D steady-state-free-precession (SSFP) sequences at end-systole (ES) and end-diastole (ED) in a retrospective study of 31 CHD patients with moderate to severe PR, in native or patched RVOTs and significant RV dilatation. This study demonstrated that 3D SSFP diameters at ES were significantly higher than those taken at ED and with ceMRA. In this study, ES diameters with whole-heart imaging also showed the best agreement with cardiac catheterization data . A studyMoreover, ES data showed the best correlation with cardiac catheterization to quantify RVOT dilatation. In contrast, mid-diastolic measures seemed to underestimate the RVOT size when compared to angiographic data . In anotAt our institution, all potential candidates for PPVI underwent a complete CMR protocol for the evaluation of the PV, RVOT and PA anatomy, quantification of PR and biventricular volumes, and assessment of coronary anatomy .®, Siemens Healthineers, Erlangen, Germany) or a 3 T scanner , both with a cardiac phased array coil placed on the thorax. A standardized CMR dataset was set for all patients to minimize acquisition times, along with a CMR study that can be performed in approximately 30–40 min. The presence of well-trained technicians and direct on-site supervision by an experienced cardiac imager are fundamental to check acquired images and eventually add further sequences or scanning planes if needed. The CMR study protocol for PPVI candidates essentially consists of 2D cine SSFP in multiple cardiac planes, and 3D SSFP for anatomical imaging and phase contrast (PC) sequences for flow quantification (Our experience was based on the performance of CMR studies using a 1.5-tesla (T)  . CCT proIn the context of PPVI evaluation, the role of high-resolution cardiovascular imaging by CCT principally consists of an anatomical assessment. CCT can clearly demonstrate the anatomy of the RVOT and distribution of the PA  and is cHowever, no consensus exists on CCT measurements that should be used to best assess valve size and patients’ suitability. A recent retrospective study by Curran et al. evaluated CCT parameters such as the minimum and maximum diameter of the PV , the cross-sectional area and the circumference-derived diameter in patients who had already undergone PPVI. Of these, the cross-sectional area and the circumference-derived diameter were best associated with the real PV anulus size . RadiatiSchievano et al. evidenced the wide variability of RVOT/PA morphology, size and dynamics through 4D CCT examinations which provided 3D deformation data in 12 patient candidates for PPVI. When compared to standard static images by 3D CMR, a high disagreement was evidenced, mainly due to complex anatomy and deformation forces . In anotAlthough its principal role consists of a pure anatomical assessment, CCT can assess biventricular volume and function quantification as well as the evaluation of RV contraction abnormalities, and may be used as an alternative to CMR when this is contraindicated ,10. For In last few years, 3D data, principally through CMR and CCT studies, have satisfied the clinical need to overcome the standard 2D assessment of cardiac structures to better appreciate complex intracardiac relationships in CHD patients. This has hugely facilitated a patient-tailored approach in surgical and interventional planning .3D printing can provide patient-specific physical 3D reconstructions of the entire heart or of specific regions of interest. Acquired 3D CMR (whole-heart or ceMRA) or multidetector CCT images are transformed into 3D surface files after an accurate post-processing analysis, and sent to the printer for the final result. Good image quality with high contrast between cardiac and vessel structures, low noise and high spatial resolution are fundamental for adequate 3D printing . ImportaRecently introduced virtual and augmented reality technologies have offered 3D visualization and simulation of complex congenital defects in real-time . MoreoveEssential goals of CMR studies before PPVI are the definition of the origin, course, and take-off angle of the coronary arteries, the RVOT morphology and dimensions, the grading of PR severity, and the quantification of RV volumes and ejection fraction. All these data can be achieved through standard 2D and 3D CMR sequences and should be routinely addressed for patients’ selection and to optimize PPVI planning. Innovative imaging approaches, such as 4D flow CMR sequences and the application of artificial intelligence algorithms, may further impact our future workflow in CMR scanning. However, these are still mainly restricted to the research area and further studies are warranted to assure their full integration into routine clinical practice.


Atrial septal defect (ASD) is characterized by a left-to-right shunt causing dilatation of the right atrium and right ventricle as well as pulmonary hyperperfusion. The detection of ASDs often occurs late in childhood or adulthood. Little is known about cardiac structure and function in neonates with ASD.p < 0.001; RV basal dimension end-diastole: 14.9 mm vs. 13.8 mm, p < 0.001; and RV outflow tract diameter 13.6 mm vs. 12.4 mm, p < 0.001). Atrial volumes were larger in neonates with ASD compared to controls . Tricuspid annular plane systolic excursion was larger in neonates with ASD than in controls . Left ventricular dimensions and function did not differ between neonates with ASD and controls. In conclusion, ASDs were associated with altered cardiac dimensions already in the neonatal period, with larger right ventricular dimensions and larger atrial volumes at echocardiography within the first 30 days after birth.We analyzed neonatal echocardiograms from the Copenhagen Baby Heart Study, a multicenter, population-based cohort study of 27,595 neonates. We included 716 neonates with secundum-type ASDs and matched them 1:1 on sex and age at examination with neonates without ASD from the same birth cohort. Neonates with an ASD  had larger right ventricular (RV) dimensions than matched controls .The online version contains supplementary material available at 10.1007/s00246-023-03211-z. Atrial septal defects (ASD) are among the most common congenital heart defects. The morphological defect in the atrial septum will in most cases lead to a left-to-right shunt, due to higher pressure in the left atrium. The shunt results in an increased volume load on the right side of the heart. By the time of diagnosis, several other morphological changes in the heart are frequently found. Right ventricular dilatation and right atrial enlargement are among the most common changes . Due to Little is known about cardiac structure very early in life in patients with ASD since symptoms and diagnosis often occur later . In uterThis study aims to investigate if cardiac morphology and function in patients with ASD are different from matched controls as early as within the first month after birth. We explore this topic by examining an unselected cohort of neonates with ASD found in a large echocardiographic screening study of neonates.We conducted a case–control study of echocardiographic parameters in neonates with ASD included in the Copenhagen Baby Heart Study.st, 2016, to October 31st, 2018 [The Copenhagen Baby Heart Study (CBHS) is a multicenter, population-based cohort study with prenatal inclusion. All expectant parents in the Capital Region of Denmark were offered inclusion in the study in the period April 1st, 2018 . A totalIn the CBHS, the neonatal echocardiographies were performed by sonographers and specialists trained in pediatric echocardiography using Vivid E9 ultrasound equipment . The CBHS echocardiographic protocol was established in accordance with the American Society of Echocardiography’s guidelines for pediatric echocardiography . CardiacParents who had given consent to be included in CBHS were reminded by text message after giving birth to a live-born infant and booked an appointment for the echocardiographic examination using a secure website. Neonatal echocardiograms in CBHS were performed while the infants were calm or sleeping.After the inclusion period, echocardiograms were reviewed offline using EchoPAC clinical software . To determine whether neonates had an ASD, two investigators systematically analyzed subxiphoid echocardiographic images of the atrial septum using a novel algorithm for the echocardiographic assessment of interatrial communications that was developed and validated in the CBHS and was recently published . CategorNeonates with ASD were matched 1:1 with controls from the CBHS study cohort on sex and age at the time of echocardiographic examination. We excluded neonates with syndromes, chromosomal abnormalities, or other congenital heart disease.For this study, we chose to investigate echocardiographic parameters of particular interest in patients with ASD. Namely, we investigated right ventricular (RV) dimensions  diameter), tricuspid annular plane systolic excursion (TAPSE), atrial volumes ; left atrial end-systolic volume (LAESV)), left ventricular dimensions ; left ventricular internal diameter end-systole (LVIDs); left ventricular posterior wall end-systole (LVPWs); left ventricular outflow tract(LVOT); interventricular septum end-diastole (IVSd)) as well as diameters for the inferior vena cava (IVC), and the main pulmonary artery (MPA). We also measured left ventricular ejection fraction (LVEF) and fractional shortening (FS). Measurements and analyses of echocardiographic parameters were done in accordance with the Recommendations for Quantification Methods During the Performance of a Pediatric Echocardiogram from the American Society of Echocardiography . For theAnalyses and measurements of echocardiographic outcome parameters were made by two investigators blinded to the presence of ASD, as they did not assess images of the atrial septum with Color Doppler. Echocardiograms from neonates with ASD and matched controls were randomly distributed between the two investigators. Echocardiographic analyses were frequently supervised by a third investigator to minimize the risk of inter- and intraobserver variability.p values < 0.003 were considered statistically significant .Continuous variables are presented as mean values (SD) or median values (IQR), where appropriate. Categorical variables are presented as absolute numbers (percentages). Comparison between cases (neonates with ASD) and matched controls was performed using Student’s t test. Bonferroni’s correction for multiple testing was applied, and We performed subgroup analyses on the influence of the size of the ASD, the neonates’ age at examination, and the influence of fenestrated defects vs. single defects. For analyses on the influence size of the ASD, we looked further into the subgroup where the ASD diameter measurement was feasible. We plotted the echocardiographic outcome variables that showed a difference in means between neonates with ASD and controls in the main analysis against the ASD diameters to identify potential associations and applied a linear regression model with a 95% confidence interval. For subgroup analyses on the neonates’ age at examination, we compared neonates examined at age 0–7 days old with neonates examined at age 8–30 days old. For analyses on the influence of fenestrated defects, we performed analyses on a subgroup of neonates with ASD, who had complete data on all RV parameters and atrial volumes. We compared the echocardiographic outcome variables that differed between neonates with ASD and controls in the main analysis using Student’s t test with Bonferroni’s correction for multiple testing.Statistical analyses were performed using R statistical software v. 1.2.1335 .We included 716 neonates with secundum-type ASD  and 716 controls matched on sex and age at examination. Descriptive characteristics are shown in Table n = 644; 90%), while a smaller proportion of neonates had an additional component of right-to-left shunting . None of the neonates had exclusively right-to-left shunting. The direction of shunting in neonates with ASD was left-to-right in the majority of cases  were plotted against the size of the ASD and are shown in Supplementary Fig. 2. No clear correlation between the size of the defect and the increase in right ventricular dimensions or atrial volumes was seen. However, when fitting linear regression models to the plots, a slight positive association between the diameter of ASD and RAESV was found (p = 0.02). TAPSE also increased slightly with increasing diameter of ASD (p = 0.01).To investigate whether differences in echocardiographic parameters between neonates with and without ASD were present at birth or developed during the first month of life, we divided the cohort into two subgroups based on the neonates’ age at examination. Specifically, we compared neonates with ASD examined during the first week after birth (0 to 7 days old) with neonates from the control group examined at the same age. Likewise, we compared neonates with ASD examined at age 8 to 30 days with controls  and neonates with fenestrated defects (n = 134) apart from a slightly larger RAESV in neonates with single defects compared to neonates with fenestrated defects .We found no differences in right ventricular dimensions or atrial volumes between neonates with single defects  [The RVOT is recommended to be part of the assessment of the RV in adults  but norm8 years) . An incrn = 200, age range 0–21 years) and found no significant difference when compared to a control group [TAPSE is a recommended tool for assessing right ventricular systolic function in standard echocardiographic exams , even thol group .We also found the left atrial volume to be larger in neonates with ASDs than in neonates without ASD. Left atrial enlargement in patients with ASD has previously been described as a consequence of the volume overload similar to right-sided enlargements . An alteThe dimensions and function of the LV, LVOT, and interventricular septum did not differ between neonates with ASD and controls, which is in accordance with earlier studies .A limitation of all echocardiographic studies includes interobserver variability. For the present study, we sought to minimize interobserver variability by having the echocardiographic analyses performed by only two investigators, who had received equal training and a thorough introduction to the measurements and methods used for this study. Also, the investigators were blinded to whether the neonates had an ASD or not, by not accessing the images with color Doppler over the atrial septum. Repeatability and reproducibility of neonatal echocardiography in the CBHS have previously been tested, showing good inter- and intraobserver agreement for most measurements . PotentiThe CBHS is presenting robust echocardiographic data on the largest cohort of neonates to date. Neonatal echocardiograms of > 25,000 neonates were performed, using a TTE protocol in accordance with international standards. However, as the cohort was not specifically set up for the assessment of children with shunts, we have limited data on right-sided dimensions. Echocardiographic techniques are steadily being improved with advanced analyses being made possible by for example 3D echocardiography and strain imaging . For optThe neonates included in our study were not diagnosed with ASD due to symptoms but found this early after birth because they were part of a large population-based cohort study with echocardiographic examination. This unselected cohort of neonates with ASD is unique, allowing us to report echocardiographic characteristics in neonates with and without ASD from the same birth cohort.In our subgroup analyses, we found a slight positive association between the diameter of the ASD and RAESV, and TAPSE, but no clear pattern for the other echocardiographic variables. Studies specifically on cohorts of patients with small ASDs show that morbidity and mortality are seen even in cases where the ASD is considered small and hemodynamically insignificant –31.The cohort of neonates with ASD in the present study might include neonates where the defects are both asymptomatic and smaller than usually seen in clinical settings. The reported morphological differences between neonates with ASD and controls found in this study may be relatively small in absolute numbers but reached convincing statistical significance due to a large number of included subjects. However, the study design with the large cohort of neonates in the CBHS and the method with thorough and blinded echocardiographic analyses for this present study validate our findings and make up the strengths of our study. This new knowledge of early morphological changes contributes to our pathophysiological and anatomical understanding of ASDs.Neonates aged 0–30 days with ASDs had larger right ventricular dimensions and larger atrial volumes than matched controls. These findings indicate that the morphological cardiac changes typical for ASDs are found very early in life after only a few days of left-to-right shunting.Supplementary file1 (DOCX 801 KB)Below is the link to the electronic supplementary material.


Atrial fibrillation (AF) has been linked to dementia risk, partly explained by cerebral small vessel disease (CSVD). Since AF and cardiovascular comorbidities were associated with cardiac dysfunction, we aimed to determine the association between echocardiographic parameters and neuroimaging markers of CSVD in patients with AF-related ischemic stroke.This cross-sectional study enrolled patients with AF-related ischemic stroke from March 2013 to December 2019 who underwent transthoracic echocardiography and brain 3T MRI, including T1, T2, Flair, and SWI imaging sequences. We assessed the presence of lacunes and cerebellar microbleeds (CMBs), the severity of white matter hyperintensity (WMH) scored by the Fazekas scale (0-6), and the severity of enlarged perivascular spaces (EPVS) in basal ganglia (BG) and centrum semiovale (CSO) classified into three categories . CSVD burden was rated on a 0-to-4 ordinal scale. Generalized linear regression analysis and post hoc comparisons with Bonferroni correction were performed to assess the association between various echocardiographic parameters and these lesions, adjusted for demographics and potential confounders.119 patients  were included for analysis, of whom 55 (46.2%) had lacunes, 40 (33.6%) had CMBs, and median severity for WMH, BG-EPVS, CSO-EPVS, and CSVD burden were 2 (IQR: 1–3), 1 (IQR: 1–2), 1 (IQR: 0–1), and 1 (IQR: 1–2) respectively. In multivariable, fully adjusted models, left ventricular posterior wall thickness (LVPW) was associated with a higher risk of lacunes  and CSVD burden . Right atrial diameter (RAD) was associated with greater CSO-EPVS . No echocardiographic parameters were revealed to be associated with CMBs and WMH.In patients with AF-related ischemic stroke, LVPW is associated with a higher risk of lacunes and CSVD burden, while RAD was associated with greater CSO-EPVS. Larger studies are required to determine these associations and to elucidate if these associations can help facilitate cognitive evaluation and brain MRI screening. Increasing evidence suggests that atrial fibrillation (AF) appears to be correlated with cognitive decline independent of clinical stroke , 2. Cereleft atrium (LA) and enlarged left ventricular (LV), and are also associated with an increased incidence of heart failure. Conversely, patients with cardiac dysfunction are known to contribute to AF development and maintenance , and followed the Declaration of Helsinki. All patients provided written consent.All patients were evaluated by 2-D transthoracic echocardiography during hospitalization, using a Philips iE33  echocardiography device. A single trained investigator with considerable echocardiographic experience performed all the echocardiographic evaluations blinded to other information. All measurements were performed according to the American Society of Echocardiography guidelines.We collected echocardiographic parameters including left atrial anteroposterior diameter (LAD), left ventricular end-diastolic diameter (LVD), right anteroposterior atrial diameter (RAD), right ventricular end-diastolic diameter (RVD), interventricular septum diameter (IVS), left ventricular posterior wall diameter (LVPW), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular cardiac and stroke volume (SV) and the left ventricular ejection fraction (LVEF) was calculated using two-plane Simpson method.MRI was performed on a 3.0-T GE scanner Discovery or Architect scanner at West China Hospital of Sichuan University. The MRI protocol included: (1) axial T1 weighted: TE = 24 ms, TR = 1,750 ms, echo train length (ETL) = 10, bandwidth (BW) = 41.67KHz, matrix = 320 × 224, slice thickness = 5 mm, filed-of-view = 240 mm, spacing = 1, number of excitations (NEX) = 1; (2) axial T2 weighted: TE = 93 ms, TR = 5,727 ms, ETL = 32, BW = 83.3 KHz, matrix = 512 × 512, filed-of-view = 240 mm, slice thickness = 5 mm, spacing = 1, NEX = 1.5; (3) FLAIR weighted: TE = 145 ms, TR = 8,400 ms, inversion time (TI) = 2,100 ms, BW = 83.3 KHz, flip angle (FA) = 145°, matrix = 320 × 224, slice thickness = 5 mm, filed-of-view = 240 mm, spacing = 1, NEX = 1; (4) Between March 2013 and May 2018, SWI weighted: TE = 20 ms, TR = 27 ms, Flip angle = 15°, slices = 64, slice thickness = 2 mm, and field of view = 185 × 220 mm); between April 2018 and December 2019, the parameters were: SWI .MRI measurements were made in accordance with the consensus criteria of the Standards for Reporting Vascular changes on neuroimaging (STRIVE) . Lacunesp =0.002), lacunes , the severity of WMH , BG-EPVS , and CSO-EPVS .Visualization and evaluation of MRI images were performed by a single rater (K.L.Y) blinded to clinical data. For the purpose of assessing inter-rater agreement, a second rater (W.D.T.) evaluated 25 randomly selected patients for the presence of CMBs , heart disease , prior antithrombotic agents  use, smoking and alcohol status. CHA2DS2-VASc score was calculated as previously described . HyperteData are presented as means ± SD or medians with interquartile ranges, and as proportions for categorical variables as appropriate. Inter-rater reliability of the neuroimaging variable was tested using the kappa statistic.Univariate analysis for the association of clinical characteristics and echocardiographic parameters with MRI markers of CSVD was assessed by using generalized linear models (GLM). The Spearman χ2 test was used for categorical variables comparison. Multivariate analysis was performed to determine the contribution of echocardiographic parameters to neuroimaging burden of CSVD using generalized linear models (GLM) adjusted for age, sex, and factors with statistical significance by univariate analysis. Due to colinearity issues, both the CHA2DS2-VASc score and its sub-variables were entered into separate multivariate models. We used a regression model with a logit link function for the association of echocardiographic parameters with the presence of lacunes and CMBs. Analysis for the association of echocardiographic parameters with severity for WMH, BG-EPVS, CSO-EPVS, and CSVD burden was performed using a regression model with a probit link function. Risk ratios (RR) per standard deviation change and 95% confidence intervals (CI) were presented.P-value < 0.05 was considered statistically significant. Again, a Bonferroni correction (Bonferroni correction = 0.05/number of subsamples = 0.004) was applied to 12 echocardiographic variables for multiple comparisons.All analyses were performed using SPSS 25.0 . A A total of 378 AIS patients who underwent transthoracic echocardiography and 3T MRI were registered in the present analysis. The following patients were excluded: 133 because they had a non-cardioembolic stroke, 25 because bilateral stroke infarcts affected the identification of CSVD on neuroimaging, 30 because of no evidence of AF, and 51 because of time from admission to stroke onset over 14 days. Furthermore, 20 patients had unavailable MRI imaging, leading to the final study sample of 119 as shown in The mean age of eligible patients was 68.38 ± 12.692 years, and 45.4% were male. Median CHA2DS2-VASc score was 2 (IQR: 1–3). The median time interval between echocardiogram and diagnosis of AF was 1 month (IQR: 0–36 months). The baseline characteristics and echocardiographic parameters are shown in P < 0.05). Age, hypertension, cardiac valve disease, and CHA2DS2-VASc score were significantly associated with the risk of greater WMH . Age and CHA2DS2-VASc score were significantly associated with the risk of CMBs (P < 0.05). Besides, age, hypertension, diabetes, coronary artery disease, cardiac valve disease, CHA2DS2-VASc score, and prior anticoagulant therapy were significantly associated with BG-EPVS severity , while age, hypertension, cardiac valve disease, CHA2DS2-VASc score, and current drinkers were significantly associated with CSO-EPVS severity . Cardiac valve disease, congestive heart failure, and CHA2DS2-VASc score were significantly associated with CSVD burden .The univariate analysis of the clinical characteristics presented in P = 0.049), IVS , and LVPW  were significantly associated with the risk of lacunes. With Bonferroni correction, the associations between LAD and IVS and lacunes were attenuated. LAD , IVS , and LVPW  were significantly associated with greater WMH, whereas the statistically significant difference in these associations was no longer significant after Bonferroni correction. LVPW  was significantly associated with BG-EPVS severity, and RAD  was significantly associated with CSO-EPVS severity, while a Bonferroni correction attenuated these associations. In addition, LAD  and LVPW  were significantly associated with CSVD burden. Bonferroni correction reduced the association between LAD and CSVD burden.Univariate analysis for the association of echocardiographic parameters with MRI markers of CSVD as shown in P = 0.020) and WMH , while both IVS and LVPW were positively correlated with lacunes  and WMH . LVPW was positively correlated with BG-EPVS severity , while RAD was positively correlated with CSO-EPVS severity . In addition, LAD and LVPW were positively correlated with CSVD burden .Spearman correlation matrix as shown in P < 0.001), greater WMH , and CSVD burden . RAD is significantly associated with CSO-EPVS severity . After Bonferroni correction, there was no significant difference between LVPW and greater WMH. No significant associations were observed with any echocardiographic parameters and CMBs  LVPW was associated with a higher risk of lacunes and CSVD burden. (2) RAD was associated with greater CSO-EPVS. These associations remained significant after adjusting for age, sex, and potential confounders. We emphasized the importance of echocardiographic assessment in clinical practice to facilitate cognitive evaluation and brain MRI screening of AF-related patients.Mechanisms linking the association between LVPW and prevalent lacunes and CSVD burden in patients with AF-related ischemic stroke may involve various aspects, as follows. First, this association may be partially mediated by abnormal perfusion of the brain microvasculature. Compared to sinus rhythm, AF could trigger a higher variability, which would lead to critical cerebral hemodynamic events (hypoperfusion or hypertensive events) at the capillary level during AF . CardiacAnother interesting finding of the present study was that RAD was associated with greater CSO-EPVS. Fewer studies involved the association between right atrium diameter and neuroimaging markers of CSVD previously. In fact, AF can also result in enlargement and fibrosis of the right atrium, which may interfere with the function of the right atrium , 17. RigOur study should be considered in light of several limitations. Firstly, due to the current study's cross-sectional design, we cannot examine causal relationships between echocardiographic characteristics and neuroimaging markers of CSVD in AF-related patients, but only document associations. Secondly, echocardiography is known to have limited precision, while the cost and ease of echocardiography make it an ideal examination for admission to a hospital by individuals. Thirdly, patients with permanent or persistent AF may have very different echocardiographic parameters to those with paroxysmal and that has been shown in several prior papers, while the retrospective design represents a limitation of the current study to obtain information on the type of AF. Lastly, it was done in a single center with a relatively small number of patients which may cause selection bias.In patients with AF-related ischemic stroke, LVPW is associated with a higher risk of lacunes and CSVD burden, while RAD was associated with greater CSO-EPVS. Further studies with a larger sample size and a longitudinal design were needed to continue to determine these associations and to elucidate if these associations can help facilitate cognitive evaluation and brain MRI screening.The original contributions presented in the study are included in the article/The study was approved by the Ethics Committee of West China Hospital, Sichuan University Scientific Research. The patients/participants provided their written informed consent to participate in this study.KY: study concept, data analysis, statistics, and paper writing. WT: study concept, patient recruitment, data analysis, statistics, and study protocol development. ZW and DL: imaging data acquisition and interpretation of data. MX: study protocol design and data analysis. JL: data analysis and informed consent acquisition. ML: study concept and guidance. All authors contributed to the article and approved the submitted version.


Native T1 mapping is used to assess myocardial tissue characteristics without gadolinium contrast agents. The focal T1 high-intensity region can indicate myocardial alterations. This study aimed to identify the association between the native T1 mapping including the native T1 high region and left ventricular ejection fraction (LVEF) recovery in patients with dilated cardiomyopathy (DCM). Patients with newly diagnosed DCM (LVEF of < 45%) who underwent cardiac magnetic resonance imaging with native T1 mapping were included in the analysis. Native T1 high region was defined as a signal intensity of > 5 SD in the remote myocardium. Recovered EF was defined as a follow-up LVEF of ≥ 45% and an LVEF increase of ≥ 10% after 2 years from baseline. Seventy-one patients met the inclusion criteria for this study. Forty-four patients (61.9%) achieved recovered EF. Logistic regression analysis showed that the native T1 value  and the native T1 high region , but not late gadolinium enhancement, were independent predictors of recovered EF. Compared with native T1 value alone, combined native T1 high region and native T1 value improved the area under the curve from 0.703 to 0.788 for predicting recovered EF. Myocardial damage, which was quantified using native T1 mapping and the native T1 high region were independently associated with recovered EF in patients with newly diagnosed DCM. Dilated cardiomyopathy (DCM) is a myocardial disease commonly diagnosed based on impaired left ventricular ejection fraction (LVEF) and LV dilation . LVEF reCardiac magnetic resonance (CMR) imaging is suitable for investigating cardiac properties, functions and geometry. Late gadolinium enhancement (LGE)-CMR imaging is a standard technique for evaluating myocardial fibrosis . MoreoveECV is a surrogate measure of extracellular space and is equivalent to the myocardial volume of gadolinium contrast medium distribution. It is used to assess extracellular space, which is occupied by the extracellular matrix. Therefore, it can reflect diffuse myocardial fibrosis in the absence of protein deposition or oedema . The natThis single-centre, retrospective, observational study assessed patients with newly diagnosed DCM who underwent CMR imaging at Kitasato University Hospital in Japan between October 2016 and December 2019. DCM was defined as an LVEF of < 45% at baseline echocardiography. Patients with significant coronary artery disease , cardiac amyloidosis, sarcoidosis, acute myocarditis, metabolic disorders, endocrine dysfunction, neuromuscular diseases, peripartum cardiomyopathy, organic heart valve disease, use of cardiotoxic drugs and alcohol abuse were excluded. The Ethics Committee of Kitasato University Medical approved this study and the use of clinically acquired data. Moreover, the need for a written informed consent was waived.All CMR imaging procedures were performed with a 3.0T scanner  using a standard protocol. All images were obtained during breath holding at expiration. The cine images included the acquisition of three long-axis slices (two- and four-chamber) and a stack of short-axis slices covering the whole LV using a balanced steady-state free precession (bSSFP) sequence. Native T1 mapping was performed on a standard LV short-axis slice at the mid-ventricular level using the modified Look-Locker inversion recovery sequence combined with motion correction before contrast injection. The sequence parameters were as follows:2; flip angle (FA): 35°; bandwidth: 1085 Hz/pixel and slice thickness: 8 mm.For an RR interval of > 700 ms, repetition time (TR)/echo time (TE): 280.6/1.1 ms; matrix: 256 × 169; field of view (FOV): 360 × 307 mm2: FA: 35°; bandwidth: 1085 Hz/pixel and slice thickness: 8 mm.For an RR interval of < 700 ms, TR/TE: 263.9/1.0 ms; matrix: 192 × 154; FOV: 360 × 307 mm2; FA, 55°; bandwidth, 1,175 Hz/pixel; slice thickness, 8 mm and slice gap, 2 mm. Parallel imaging with GeneRalized Autocalibrating Partially Parallel Acquisitions was used for the sequence. The optimal inversion time (TI) was determined with a TI-scout sequence. This pulse sequence was used to determine optimal TI to null the signal intensity of the normal myocardium.LGE images were acquired 10–15 min after the intravenous injection of 0.2 mmol/kg gadolinium using the phase-sensitive inversion recovery bSSFP sequence. The sequence parameters were as follows: TR/TE, 2.7/1.1 ms; matrix, 224 × 180; FOV, 340 × 340 mmLV volumetric analysis was performed with a commercially available software . The presence of LGE was defined by an experienced observer. The native T1 values were determined by drawing the region-of-interest (ROI) manually in each segment of the participants on a dedicated workstation with an ROI measuring tool , according to the six regions of the mid-ventricle in the 17-segment model . The ROIAt baseline, blood pressure, heart rate and laboratory parameters were evaluated upon undergoing CMR imaging and echocardiography was performed. Patients were treated according to the current guidelines. Recoveret-test was used to compare continuous variables and the Mann–Whitney U test was utilised to evaluate non-normally distributed continuous variables. The Pearson’s chi-square test was applied to assessed categorical variables. A two-tailed P value of < 0.05 was considered statistically significant. Multivariate logistic regression analysis was performed to identify variables correlated with recovered EF among all baseline variables. The univariate analysis included potential covariates affecting LVEF recovering, as shown in a previous study [Data were presented as mean ± standard deviation or as frequency (percentage). The Student’s us study . ClinicaIn total, 71 patients met the inclusion criteria of this study. After 2 years from baseline, 44 patients (61.9%) achieved recovered EF  patients presented with native T1 high regions despite the absence of LGE Fig. A. In patAccording to the results of the univariate analysis, mineralocorticoid receptor antagonist, complete left bundle branch block, LGE, native T1 value and native T1 high region were included in the multivariate model. Two multivariate models, one containing the native T1 value and one containing the native T1 high region, were constructed. In model 1, the native T1 value  was considered an independent factor associated with recovered EF. In model 2, the presence of the native T1 high region  was identified as an independent factor associated with recovered EF Table . Based oFigure The current study showed the clinical significance of native T1 mapping in patients with newly diagnosed DCM. There were no significant differences in LV volumes and the presence of LGE between patients with recovered EF and those without. However, patients without recovered EF had a higher native T1 value than those with recovered EF. Furthermore, both the native T1 value and the presence of the native T1 high region were independently associated with recovered EF. The native T1 high region had an incremental prognostic value for predicting recovered EF. Thus, the native T1 high region and the native T1 value might be important markers for predicting recovered EF in patients with DCM.A high native T1 value indicates oedema (increased tissue water content caused by different factors including inflammation) and high interstitial components (e.g. fibrosis and amyloid deposition) . In the Both native T1 and ECV fractions are correlated with histological collagen volume fractions. ECV quantifies the interstitial uptake of gadolinium contrast agent relative to the plasma. Native T1 mapping can be an effective alternative option to ECV measurement if a shorter scan time and non-contrast material requirements are considered . Thus, nLGE is the gold standard method for assessing focal myocardial damage representative of fibrosis . LGE is In the current study, the native T1 high region was associated with LVEF recovery. Two previous studies revealed that the native T1 value of the segments with LGE was higher than that of the segments without LGE in patients with DCM , 28. HowIn a previous study, the native T1 value significantly decreased after GDMT. This finding indicates reduced collagen volume fraction and serum myocardial collagen accumulation index in patients with DCM after GDMT . The curNative T1 mapping can be performed on all patients eligible for CMR imaging because it does not require gadolinium contrast agents. In addition, the native T1 high region had an additive predictive value for predicting LVEF recovery. In relation to this reason, it might be helpful to focus on the native T1 value and the native T1 high region in determining appropriate treatment strategies in patients with newly diagnosed DCM.The current study had several limitations that must be acknowledged. First, this was a single-centre study with a limited number of patients. This could have resulted in patient selection bias and a lower statistical power. Second, only patients undergoing CMR imaging were included in the analysis, which could have posed a risk of bias. Third, the statistical power was limited because of the small number of events. Fourth, T1 mapping images of LV were acquired only at the mid-ventricular level. Therefore, the whole LV myocardium could not be evaluated.The quantitative value of native T1 mapping and the presence of a high-signal intensity region were independent predictors of LVEF improvement in patients with newly diagnosed DCM. Combined native T1 value and native T1 high region was more accurate in predicting LVEF improvement than native T1 value alone. Hence, T1 mapping might be useful in identifying therapeutic options for patients with DCM.


This research investigated the predictive value of combined detection of brain natriuretic peptide (BNP) and cystatin C (Cys C) in heart failure after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Sixty-five AMI patients complicated by heart failure (HF) after PCI and 79 non-heart failure (non-HF) patients were involved in this research. The levels of Cys C and BNP were measured. Risk factors for heart failure in AMI patients after PCI were analyzed by multivariate logistic regression analysis. Efficacy of BNP and Cys C on predicting heart failure were analyzed by receiver operating characteristic (ROC) curve. Cys C and BNP levels were significantly higher in the HF group than in the non-HF group. BNP and Cys C levels were the independent influencing factors causing heart failure within one year after PCI. The area under the predicted curve (AUC) of Cys C, BNP, and combined Cys C and BNP were 0.763, 0.829, and 0.893, respectively. The combined detection of Cys C and BNP was highly valuable in predicting heart failure in AMI patients after PCI, which can be regarded as the serum markers for diagnosis and treatment of heart failure. Acute myocardial infarction (AMI) refers to hypoxia-ischemia-induced myocardial injury and necrosis caused by sudden reduction or interruption of blood flow due to the blockage of coronary arteries . AMI canThe widespread use of percutaneous coronary intervention (PCI) has significantly reduced mortality in patients with AMI, but the development of heart failure after the procedure severely affects the recovery of patients after treatment . Early rBrain natriuretic peptide (BNP) is the current hematological gold standard for acute heart failure diagnosis . BNP is Most of the heart failure patients have inadequate renal blood flow . Serum cIn this research, a total of 153 AMI patients admitted to the Affiliated Hospital of Jiangnan University were recruited. Patients with AMI received standard loading dose medications (300 mg aspirin and 180 mg ticagrelor or 300 mg clopidogrel) and were treated with PCI. PCI procedures were performed by experienced cardiologists.Acute heart failure in AMI patients was diagnosed by clinical manifestations and physical examination: 1) typical clinical manifestations of new-onset heart failure (such as fatigue and varying degrees of dyspnea); 2) accelerated heart rate or the presence of gallop rhythm, and auscultation of the chest revealed moist rales; 3) chest X-ray showing pulmonary congestion, pulmonary edema, and pleural effusion; or 4) cardiogenic shock.Inclusion criteria were age ≥8 years, time to reperfusion  <12 h, patients treated with PCI, and patients that had segment elevation (ST) or non-ST segment elevation AMI by significant coronary artery stenosis. Exclusion criteria were patients that had combined old myocardial infarction or chronic heart failure, combined pulmonary heart disease or pulmonary hypertension, severe hepatic or renal insufficiency or cranial diseases, or estimated life expectancy <1 year.Blood samples were collected from patients at 48 h after PCI. All the laboratory tests were performed by the emergency laboratory of our hospital. BNP was evaluated by Elecsys electrochemiluminescent immunoassay . Cys C was measured using the Human Cystatin C ELISA Kit .The left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-diastolic diameter (LVEDD) of patients were detected by echocardiography.The data are reported as means±SD or n (percentage). The differences between groups were compared by Mann-Whitney test or Fisher's exact test. Multivariate logistic analysis was used to identify independent predictors of heart failure during a 1-year period, with heart failure occurrence  as the dependent variable and age, BMI, gender, diabetes, hypertension, hyperlipidemia, chronic obstructive pulmonary disease (COPD), pre-stroke, chronic kidney disease, heart rate, blood pressure, echocardiographic parameters, total cholesterol (TC), triglycerides (TG), high-sensitivity C-reactive protein  BNP, creatine kinase-muscle/brain (CK-MB), and Cys C as independent variables. The stepwise method was used to exclude irrelevant items (P>0.05). Receiver operating characteristic (ROC) curve was used to evaluate the prediction efficacy of serum BNP and Cyc C levels in heart failure. P<0.05 was considered statistically significant. Data analysis in this study was conducted using the SPSS 23.0 software .vs 59.7±7.8 years, P=0.039). Body mass index (BMI), gender, diabetes, hypertension, hyperlipidemia, prior stroke, chronic kidney disease, and COPD had no significant difference between the two groups .Demographic and clinical characteristics of patients are shown in vs 75.7±16.2 bpm, P=0.016). However, blood pressure showed no significant different between groups . Baseline LVEF in the HF group was lower than in the non-HF group . The LVEDD and LVEDV showed no significant difference .AMI patients in the HF group had significantly higher heart rate than those in the non-HF group , higher CK-MB levels , higher BNP levels   . Patients in the HF group had higher hs-CRP levels (13.61±4.34 P<0.001) , and higP<0.001) .The multivariate logistic regression analysis of risk factors for heart failure in AMI patients one year after undergoing emergency PCI is shown in The area under the curve (AUC) of BNP level in heart failure prediction was 0.829 (95%CI: 0.761 to 0.898), while the sensitivity was 75.38% and the specificity was 83.54% . The AUCThe main findings of our study were: 1) Cys C and BNP levels were independent factors for heart failure within one year after PCI among AMI patients; 2) the combined BNP and Cys C were good predictors of heart failure in AMI after PCI and can be used to guide clinical decisions.AMI is a common cardiovascular disease. The widespread use of emergency PCI has significantly reduced the mortality of AMI . Heart fPatients with myocardial infarction are at higher risk of heart failure due to the progression of ventricular remodeling. The patient's heart function gradually changes from compensated to decompensated , which eCys C is a small-molecule protein consisting of 120 amino acids and is an extracellular cysteine protease inhibitor that regulates the metabolism of extracellular proteins . Cys C lCys C level was significantly higher in the HF group. Multivariate logistic analysis showed that Cys C was a predictor for heart failure in AMI patients at one-year follow up.BNP is widely used in chronic heart failure diagnosis and treatment . ElevateMyocardial ischemia and necrosis after the onset of AMI lead to weakened contractility and decreased compliance, resulting in myocardial strain, accelerated heart rate, and increased atrial ventricular volume and ventricular wall tension, causing explosive synthesis and secretion of BNP . TherefoThere were several limitations in this research. This research was a single-center study, which might have led to selection bias. Second, this research was limited by a relatively small number of patients. Some of the patients were also lost to follow-up.We concluded that Cys C and BNP levels are independent influencing factors for heart failure after AMI. The combined BNP and Cys C might help in the prediction of heart failure in AMI patients after PCI and could be used to guide clinical decisions.


In patients with Fontan circulation, hemorrhage can cause life-threatening circulatory collapse, since Fontan circulation strongly depends on the preload. Furthermore, parturients with placenta accreta spectrum are at a high risk of rapid and massive hemorrhage. Herein, we report the case of an intra-aortic balloon occlusion used for a Fontan-palliated parturient with placenta increta with successful anesthetic management.A 35-year-old-female with Fontan circulation diagnosed with placenta increta underwent a cesarean hysterectomy. The main goal during anesthetic management was to maintain sufficient preload. Infrarenal intra-aortic balloon occlusion was used to reduce intraoperative hemorrhage. The hemodynamic changes caused were well tolerated in this case.Intra-aortic balloon occlusion was used in a Fontan-palliated parturient with placenta increta with successful anesthetic management. Cardiac output in such patients is highly dependent on the preload; thus, they are susceptible to hypotension due to blood loss [Long-term survival rate in patients with congenital heart disease has improved; consequently, more patients with Fontan circulation are reaching child-bearing age.ood loss . Patientood loss . This caA 35-year-old woman with gravidity 2 and parity 1 was referred to our hospital at 21 weeks of gestation because of Fontan circulation. This was a suspected PAS case with a low-lying placenta that overrode the previous cesarean uterine scar. The patient underwent Blalock-Taussig shunt surgery at 0 and 2 years of age because of a single right ventricle and pulmonary atresia. She also underwent Fontan palliation at age 7 , respectively. She was on carvedilol 1.25 mg/day and not on thromboprophylaxis due to a history of subchorionic hematoma. Echocardiography showed a right ventricular fractional area change of 38% and mild aortic and atrioventricular regurgitation. The diameter of the inferior vena cava was 10 mm, and fenestration flow was 1.5 m/s. Her hemoglobin level was 12.0 g/dl, and BNP was 22 pg/ml. A cesarean hysterectomy with infrarenal IABO under general anesthesia was planned. Both neuraxial anesthesia followed by conversion to general anesthesia at hemorrhage and general anesthesia were considered. The anesthetic method was chosen in accordance with the patient’s preference and the ability to use transesophageal echocardiography (TEE).She presented with 430 ml of vaginal bleeding at 26 6/7 weeks gestational age. Red blood cells (280 ml) were transfused, and an emergency cesarean hysterectomy was performed. Standard monitors were placed in the operating room. An arterial line was inserted into the left radial artery, and arterial pressure-based cardiac index (apCI), stroke volume (apSV), and stroke volume variation (SVV) were monitored . Remifentanil 0.1 μg/kg/min, midazolam 5 mg, and fentanyl 150 μg were administered in titration, and tracheal intubation was performed with rocuronium 50 mg. Two 18-gauge peripheral venous lines were placed. A central venous catheter was placed via the right internal jugular vein, and the central venous pressure (CVP) was monitored. An intra-aortic balloon tip was placed distal to the renal artery. Anesthesia was maintained with 1.5% sevoflurane, continuous remifentanil 0.2 − 0.3 μg/kg/min, and intermittent boluses of fentanyl and rocuronium during the surgery. The inspiratory oxygen concentration was 67% throughout the surgery.Before delivery, apSV, SVV, and CVP were approximately 70 ml, 5 − 10%, and 15 mmHg, respectively. ApSV started to decrease immediately post-delivery Fig. , and a rThe total blood loss was 2000 ml; accordingly, 1400 ml of crystalloids, 840 ml of red blood cells, and 480 ml of fresh frozen plasma were infused. Oxytocin was not administered during the surgery. The Apgar scores of the neonate at 1/5 min were 1/5, respectively. The child was intubated and transferred to the neonatal intensive care unit. The mother was extubated and transferred to the intensive care unit. On post-operative day 5, she developed pulmonary edema, with a rise in BNP to 482 pg/ml, which improved with furosemide. She was discharged on post-operative day 17. Further, pathology confirmed the diagnosis of placenta increta.Dynamic physiological changes at delivery make anesthetic management very challenging in Fontan-palliated parturients . The priIn this case, apSV reflected the changing preload during rapid hemodynamic fluctuations, such as hemorrhage and IABO Fig. . NotablyAlthough CVP, SVV , and ven2 was reduced, indicating that the cardiac index was maintained. Rapid blood transfusion (900 ml) may have contributed to maintaining the cardiac index. Upon completion of IABO, the balloon was deflated by half for 3 min before complete deflation. Moreover, CVP remained below the pre-delivery value, and fenestration flow did not decrease, suggesting no signs of pulmonary hypertension. A stable pulmonary vascular resistance at deflation may be due to the gradual deflation of the balloon and the short duration of infrarenal IABO, 15 min. Further, an increase in apSV and CVP after balloon deflation may have been caused by the return of infrarenal circulation, which did not occur during IABO (Fig. The use of IABO decreases blood loss during delivery in patients with PAS , 12. HowIn summary, this case reports on the anesthetic management of a parturient with Fontan circulation who underwent a cesarean hysterectomy for placenta increta. The adverse hemodynamic effects of IABO were not significant. When the ventricular contractility and peripheral vascular resistance are adequate, arterial pressure-based SV can be a good surrogate for preload in Fontan-palliated patients.


In this case study, we present the evaluation of an orthotopic heart transplant (OHT) patient who presented with persistent shortness of breath and dizziness upon standing. The investigation uncovered the presence of progressive hypertrophic cardiomyopathy (HCM) in the transplanted heart, a condition first detected 11 years after the transplantation. Utilizing echocardiography with global longitudinal strain (GLS), we determined that the HCM likely originated from genetic predominance inherited from the heart donor rather than hypertensive disease. This finding highlights the significance of genetic factors in post-transplant complications and warrants further investigation into the long-term effects of heart transplantation on recipient health. Left ventricular apical hypertrophic cardiomyopathy (ApHCM) is a rare phenotypic variant of hypertrophic cardiomyopathy (HCM). It was initially identified in Japan in 1976 and has since gained growing recognition . The preA 75-year-old male was evaluated for shortness of breath and dizziness upon standing from a sitting position. The patient denied experiencing chest pain, orthopnea, paroxysmal nocturnal dyspnea, syncope episodes, or palpitations. He was an active smoker with a smoking history of more than 90 pack years and had chronic obstructive pulmonary disease, chronic renal disease stage IIIa, type II diabetes mellitus for over 30 years, and hypertension and was an OHT recipient on chronic immunosuppressive therapy. The OHT was performed 23 years ago to treat end-stage heart failure from dilated cardiomyopathy secondary to viral disease after he required five months of a left ventricular assist device as a bridge to transplantation. The cardiac allograft was from an 18-year-old donor. He meticulously complied with medical and immunosuppressive therapy over the past 23 years. The patient's family history was remarkable for a first-degree relative with dilated cardiomyopathy progressing to end-stage heart failure.The first instance of mild left ventricular hypertrophy was identified 10 years after OHT on routine transthoracic echocardiogram (TTE). Over the subsequent years, annual follow-up TTE revealed worsening apical left ventricular hypertrophy. Surveillance endomyocardial biopsies were performed up to five years post-transplant, all showing Grade 0 (no rejection), requiring minor adjustments to his immunosuppressive therapy. His medications mainly remained unchanged over the years, including lisinopril, rosuvastatin, finasteride, tamsulosin, levothyroxine, mycophenolate mofetil, prednisone, tacrolimus, and insulin therapy. He denied illicit drug use and alcohol consumption but became an active smoker after OHT. Although he had a history of alcohol abuse, he had been in remission for over 25 years.Vital signs were within normal limits. Blood pressure logs demonstrated well-controlled hypertension over time. Overall, his physical exam was unremarkable, and he appeared clinically euvolemic. The cardiac exam revealed a regular rate and rhythm with a prominent apical pulse but no murmurs. No jugular venous distention was evident at 45 degrees, and there was no evidence of hypoxemia on pulse oximetry. The 12-lead ECG demonstrated the criteria for ventricular hypertrophy with T-wave inversions in precordial leads Figure -1D.Laboratory parameters were remarkable for stable chronic kidney disease stage IIIb, with no elevated proteins in serum and no anemia. Urinalysis revealed very mild proteinuria in the setting of chronic diabetes mellitus for >30 years. Urine and serum protein electrophoresis showed no abnormal proteins. The baseline NT-pro-BNP level was 3,500 pg/mL. The 24-hour Holter evaluation was unremarkable for atrial or ventricular arrhythmias. The patient had no history of ventricular tachycardia or atrial fibrillation.TTE revealed a severe left ventricular ApHCM pattern with a left ventricular ejection fraction of >70%, a small left ventricular cavity, and an apical aneurysm Figure -2H. The On TTE evaluation, there was no left ventricular outflow tract (LVOT) obstruction, but mid-ventricular systolic collapse was present Figure -3C. TherTo further assess the hypertrophy as indicated by the TTE findings, a cMRI was conducted Figure . MeasureGiven the progressive nature of ApHCM, characterized by mid-cavity obliteration, the patient was started on beta-blocker therapy and adjusted to the maximum tolerable dose based on symptoms. He had no prior episodes of atrial fibrillation or ventricular tachyarrhythmias as evidenced by ambulatory electrocardiographic monitoring. Due to his age, comorbidities, and care goals, he was considered ineligible for reevaluation for a subsequent transplant. Subsequent patient follow-up prioritized comfort measures and arrhythmia monitoring.HCM encompasses various phenotypical variants, with the predominant form being asymmetric septal hypertrophy. Other classifications include concentric, reverse septal, neutral, and apical forms ,7. ApHCMConsistent with classic HCM, genetic mutations observed in ApHCM are primarily sarcomeric and exhibit an autosomal dominant inheritance pattern. These are modulated by environmental and ethnic determinants ,9. Up toApHCM is characterized by hypertrophy of the apical segments of the LV, leading to a distinct "spade-shaped" cavity during diastole. ECG patterns often show deep negative T-waves in precordial and inferolateral leads, accompanied by voltage criteria suggestive of left ventricular hypertrophy ,3,6-10. In ApHCM patients, LVOT obstruction due to anterior systolic motion of the anterior mitral valve leaflet is typically absent. However, midventricular obstruction and cavity obliteration during systole may occur . Apical TTE serves as a reliable initial diagnostic tool, allowing visualization of apical hypertrophy and differentiation between pure and mixed forms of ApHCM . It alsoTherapeutic options for symptomatic ApHCM are limited. Patients with LV mid-cavity obstruction are often treated with high-dose beta-blockers, diltiazem, or verapamil ,12. HoweLeft ventricular hypertrophy in cardiac transplants may arise from multiple mechanisms, such as increased afterload due to systemic hypertension, direct myocyte proliferation from immunosuppression, or chronic inflammation . SystemiThe emergence of an ApHCM phenotype in a transplanted heart suggests a genetic susceptibility to this form of HCM in the donor heart ,25. CurrLeft ventricular ApHCM is a rare variant of HCM characterized by localized hypertrophy of the apical segment of the LV. Due to its rarity, left ventricular ApHCM has been less extensively studied than other forms of HCM. The presented case of a heart transplant recipient diagnosed with left ventricular ApHCM after 11 years post-transplant adds to the unique nature of this condition. Long-term outcomes and prognostic factors for left ventricular ApHCM in heart transplant patients remain to be elucidated. Given the scarcity of cases and limited knowledge about the long-term outcomes of left ventricular ApHCM, continued research efforts are warranted to enhance our comprehension of its pathophysiology, natural history, and optimal therapeutic approaches. A deeper understanding of left ventricular ApHCM can potentially improve early detection, risk stratification, and patient management, ultimately leading to better clinical outcomes for affected individuals.