State of Gene Therapy for Monogenic Cardiovascular Diseases.

Over the past 2 decades, significant efforts have been made to advance gene therapy into clinical practice. Although successful examples exist in other fields, gene therapy for the treatment of monogenic cardiovascular diseases lags behind. In this review, we (1) highlight a brief history of gene therapy, (2) distinguish between gene silencing, gene replacement, and gene editing technologies, (3) discuss vector modalities used in the field with a special focus on adeno-associated viruses, (4) provide examples of gene therapy approaches in cardiomyopathies, channelopathies, and familial hypercholesterolemia, and (5) present current challenges and limitations in the gene therapy field.

Super-refractory status epilepticus, rhabdomyolysis, central hyperthermia and cardiomyopathy attributable to spinal anesthesia: a case report and review of literature.

BACKGROUND: There are only six past reports of super-refractory status epilepticus induced by spinal anesthesia. None of those patients have died. Only < 15 mg of bupivacaine was administered to all six of them and to our case. Pathophysiology ensuing such cases remains unclear. CASE PRESENTATION: A 27 year old gravida 2, para 1, mother at 37 weeks of gestation came to the operating theater for an elective cesarean section. She had no significant medical history other than controlled hypothyroidism and one episode of food allergy. Her current pregnancy was uneventful. Her American Society of Anesthesiologists (ASA) grade was 2. She underwent spinal anesthesia and adequate anesthesia was achieved. After 5-7 min she developed a progressive myoclonus. After delivery of a healthy baby, she developed generalized tonic clonic seizures that continued despite the induction of general anesthesia. She had rhabdomyolysis, one brief cardiac arrest and resuscitation, followed by stress cardiomyopathy and central hyperthermia. She died on day four. There were no significant macroscopic or histopathological changes in her brain that explain her super refractory status epilepticus. Heavy bupivacaine samples of the same batch used for this patient were analyzed by two specialized laboratories. National Medicines Quality Assurance Laboratory of Sri Lanka reported that samples failed to confirm United States Pharmacopeia (USP) dextrose specifications and passed other tests. Subsequently, Therapeutic Goods Administration of Australia reported that the drug passed all standard USP quality tests applied to it. Nonetheless, they have detected an unidentified impurity in the medicine. CONCLUSIONS: After reviewing relevant literature, we believe that direct neurotoxicity by bupivacaine is the most probable cause of super-refractory status epilepticus. Super-refractory status epilepticus would have led to her other complications and death. We discuss probable patient factors that would have made her susceptible to neurotoxicity. The impurity in the drug detected by one laboratory also would have contributed to her status epilepticus. We propose several possible mechanisms that would have led to status epilepticus and her death. We discuss the factors that shall guide investigators on future such cases. We suggest ways to minimize similar future incidents. This is an idiosyncratic reaction as well.

Outcomes of subsequent pregnancy in women with peripartum cardiomyopathy: a systematic review and meta-analysis.

INTRODUCTION: The primary concern for women who have experienced peripartum cardiomyopathy (PPCM) is the safety of a subsequent pregnancy (SSP). To maximie decision-making, facilitate effective patient counselling, and ultimately improve maternal and fetal outcomes as a whole, it is critical to comprehend the outcomes of SSP in women who have previously experienced PPCM. This study aimed to evaluate the outcomes of SSP in women with PPCM. METHODS: Three databases (PubMed, Scopus, and ScienceDirect) were used to identify relevant studies prior to 17 October 2023. A total of 662 studies were reviewed. Following the abstract and full-text screenings, 18 observational studies were included, out of which 2 were deemed suitable for inclusion in this meta-analysis. The quality assessment was conducted using the Newcastle-Ottawa Scale. RESULTS: This study has a total of 487 SSPs. Although recovered left ventricular (LV) function before entering SSP has the potential to be a beneficial prognostic factor, recovered LV function still has a substantial risk of relapse. The mortality rate of PPCM in an SSP ranged from 0% to 55.5%. Persistent LV dysfunction was significantly associated with an increased mortality rate (OR 13.17; 95% CI 1.54 to 112.28; p=0.02) and lower LV ejection fraction (MD -12.88; 95% CI -21.67 to -4.09; p=0.004). Diastolic and right ventricular functions remained unchanged before SSP and at follow-up. The majority of the SSP was observed alongside hypertension, while pre-eclampsia emerged as the predominant hypertensive complication in most studies. CONCLUSION: SSP increases the risk of relapse and mortality in women with a previous history of PPCM. Persistent LV dysfunction prior to the SSP has a higher mortality risk compared with recovered LV function. SSP was also associated with the worsening of LV echocardiography parameters.

Cardiac MRI-Enriched Phenomapping Classification and Differential Treatment Outcomes in Patients With Ischemic Cardiomyopathy.

BACKGROUND: Significant controversy continues to confound patient selection and referral for revascularization and mitral valve intervention in patients with ischemic cardiomyopathy (ICM). Cardiac magnetic resonance (CMR) enables comprehensive phenotyping with gold-standard tissue characterization and volumetric/functional measures. Therefore, we sought to determine the impact of CMR-enriched phenomapping patients with ICM to identify differential outcomes following surgical revascularization and surgical mitral valve intervention (sMVi). METHODS: Consecutive patients with ICM referred for CMR between 2002 and 2017 were evaluated. Latent class analysis was performed to identify phenotypes enriched by comprehensive CMR assessment. The primary end point was death, heart transplant, or left ventricular assist device implantation. A multivariable Cox survival model was developed to determine the association of phenogroups with overall survival. Subgroup analysis was performed to assess the presence of differential response to post-magnetic resonance imaging procedural interventions. RESULTS: A total of 787 patients were evaluated (63.0±11.2 years, 24.8% women), with 464 primary events. Subsequent surgical revascularization and sMVi occurred in 380 (48.3%) and 157 (19.9%) patients, respectively. Latent class analysis identified 3 distinct clusters of patients, which demonstrated significant differences in overall outcome (P<0.001). Latent class analysis identified differential survival benefit of revascularization in patients as well as patients who underwent revascularization with sMVi, based on phenogroup classification, with phenogroup 3 deriving the most survival benefit from revascularization and revascularization with sMVi (hazard ratio, 0.61 [0.43-0.88]; P=0.0081). CONCLUSIONS: CMR-enriched unsupervised phenomapping identified distinct phenogroups, which were associated with significant differential survival benefit following surgical revascularization and sMVi in patients with ICM. Phenomapping provides a novel approach for patient selection, which may enable personalized therapeutic decision-making for patients with ICM.

Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL) / Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis

Introducción y objetivos: La amiloidosis cardiaca (AC) es una patología asociada a un elevado número de ingresos hospitalarios. Dada la escasa información disponible al respecto, planteamos un análisis de la incidencia y las causas de hospitalización en esta enfermedad.Material y métodosSe evaluaron 143 pacientes (128 por transtiretina [AC-ATTR] y 15 por cadenas ligeras [AC-AL]) incluidos en el Registro de Amiloidosis Cardiaca de Galicia (AMIGAL), recogiendo todas sus hospitalizaciones.ResultadosDurante un seguimiento mediano de 959 días se produjeron 179 hospitalizaciones no programadas (tasa de incidencia [TI] 512,6 ingresos hospitalarios por 1.000 pacientes-año), siendo las más habituales las de causa cardiovascular (n=109, TI 312,2). El motivo individual de ingreso hospitalario más frecuente fue la insuficiencia cardiaca (IC) (n=87, TI 249,2).La AC-AL se asoció con una TI de hospitalizaciones no programadas más elevada que la AC-ATTR (TI 781 vs. 483,2; HR 1,62; p=0,029) a expensas de las de causa no cardiovascular (TI 376 vs. 181,2; HR 2,07; p=0,027). La supervivencia libre de hospitalización no programada al año y a los tres años en la AC-AL fue menor que en la AC-ATTR (46,7 y 20,0% vs. 73,4 y 35,2%, respectivamente; p=0,021). (AU)

Introduction and objetives: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease.Material and methodsOne hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations.ResultsDuring a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2).AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). (AU)

Medical Decision-Making and Revascularization in Ischemic Cardiomyopathy.

Ischemic cardiomyopathy (ICM) is the most common underlying etiology of heart failure in the United States and is a significant contributor to deaths due to cardiovascular disease worldwide. The diagnosis and management of ICM has advanced significantly over the past few decades, and the evidence for medical therapy in ICM is both compelling and robust. This contrasts with evidence for coronary revascularization, which is more controversial and favors surgical approaches. This review will examine landmark clinical trial results in detail as well as provide a comprehensive overview of the current epidemiology, diagnostic approaches, and management strategies of ICM.

Peripartum cardiomyopathy: A case report of decompensated heart failure in a hypertensive patient.

RATIONALE: Peripartum cardiomyopathy (PPCM) occurring in the context of hypertension presents a unique clinical challenge. This case contributes to the medical literature by highlighting the complexities of managing heart failure in postpartum women with pre-existing hypertensive disorders, particularly when complicated by a history of preeclampsia. PATIENT CONCERNS: Mrs. O.O., a 34-year-old hypertensive woman, presented with progressive dyspnea, bilateral leg swelling, and orthopnea. Notably, she had a history of previous preeclampsia and exhibited worsening symptoms over several months. DIAGNOSES: The patient was diagnosed with decompensated heart failure secondary to PPCM, exacerbated by hypertension and anemia. INTERVENTIONS: Therapeutic interventions included diuretics, angiotensin receptor-neprilysin inhibitors, digoxin, and anticoagulation. Additionally, lifestyle modifications and dietary restrictions were implemented. OUTCOMES: Following treatment adjustments, the patient demonstrated significant improvement in symptoms, exercise tolerance, and cardiac function. The transition from NYHA class III to class II heart failure indicated successful management. LESSONS: This case underscores the importance of a comprehensive approach to managing PPCM in hypertensive patients, with attention to cardiovascular and obstetric factors. It highlights the effectiveness of multidisciplinary care in achieving positive outcomes and emphasizes the need for heightened vigilance in postpartum women with cardiovascular risk factors.

Cardiomyopathies in children and adolescents: aetiology, management, and outcomes in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Registry.

BACKGROUND AND AIMS: Childhood-onset cardiomyopathies are rare and poorly characterized. This study examined the baseline characteristics and 1-year follow-up of children with cardiomyopathy in the first European Cardiomyopathy Registry. METHODS: Prospective data were collected on individuals aged 1-<18 years enrolled in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis long-term registry (June 2014-December 2016). RESULTS: A total of 633 individuals aged ≤18 years with hypertrophic [HCM; n = 388 (61.3%)], dilated [DCM; n = 206 (32.5%)], restrictive [RCM; n = 28 (4.4%)], and arrhythmogenic right ventricular cardiomyopathy [ARVC; n = 11 (1.7%)] were enrolled by 23 referral centres in 14 countries. Median age at diagnosis was 4.0 [interquartile range (IQR) 0-10] years, and there was a male predominance [n = 372 (58.8%)] across all subtypes, with the exception of DCM diagnosed <10 years of age; 621 (98.1%) patients were receiving cardiac medication and 80 (12.6%) had an implantable cardioverter-defibrillator. A total of 253 patients (253/535, 47.3%) had familial disease. Genetic testing was performed in 414 (67.8%) patients with a pathogenic or likely pathogenic variant reported in 250 (60.4%). Rare disease phenocopies were reported in 177 patients (28.0%) and were most frequent in patients under 10 years [142 (30.9%) vs. 35 (19.6%); P = .003]. Over a median follow-up of 12.5 months (IQR 11.3-15.3 months), 18 patients (3.3%) died [HCM n = 9 (2.6%), DCM n = 5 (3.0%), RCM n = 4 (16.0%)]. Heart failure events were most frequent in RCM patients (36.0%). CONCLUSIONS: The findings confirm the heterogeneous aetiology of childhood cardiomyopathies and show a high frequency of familial disease. Outcomes differed by cardiomyopathy subtype, highlighting a need for disease-specific evaluation and treatment.

Left atrial cardiomyopathy: Pathophysiological insights, assessment methods and clinical implications.

Atrial cardiomyopathy is defined as any complex of structural, architectural, contractile or electrophysiological changes affecting atria, with the potential to produce clinically relevant manifestations. Most of our knowledge about the mechanistic aspects of atrial cardiomyopathy is derived from studies investigating animal models of atrial fibrillation and atrial tissue samples obtained from individuals who have a history of atrial fibrillation. Several noninvasive tools have been reported to characterize atrial cardiomyopathy in patients, which may be relevant for predicting the risk of incident atrial fibrillation and its related outcomes, such as stroke. Here, we provide an overview of the pathophysiological mechanisms involved in atrial cardiomyopathy, and discuss the complex interplay of these mechanisms, including aging, left atrial pressure overload, metabolic disorders and genetic factors. We discuss clinical tools currently available to characterize atrial cardiomyopathy, including electrocardiograms, cardiac imaging and serum biomarkers. Finally, we discuss the clinical impact of atrial cardiomyopathy, and its potential role for predicting atrial fibrillation, stroke, heart failure and dementia. Overall, this review aims to highlight the critical need for a clinically relevant definition of atrial cardiomyopathy to improve treatment strategies.

Paced QRS morphology mimicking complete left bundle branch block induced by right ventricular pacing is associated with pacing-induced cardiomyopathy.

INTRODUCTION: Right ventricular (RV) pacing sometimes causes left ventricular (LV) systolic dysfunction, also known as pacing-induced cardiomyopathy (PICM). However, the association between specifically paced QRS morphology and PICM development has not been elucidated. This study aimed to investigate the association between paced QRS mimicking a complete left bundle branch block (CLBBB) and PICM development. METHODS: We retrospectively screened 2009 patients who underwent pacemaker implantation from 2010 to 2020 in seven institutions. Patients who received pacemakers for an advanced atrioventricular block or bradycardia with atrial fibrillation, baseline LV ejection fraction (LVEF) ≥ 50%, and echocardiogram recorded at least 6 months postimplantation were included. The paced QRS recorded immediately after implantation was analyzed. A CLBBB-like paced QRS was defined as meeting the CLBBB criteria of the American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society in 2009. PICM was defined as a ≥10% LVEF decrease, resulting in an LVEF of <50%. RESULTS: Among the 270 patients analyzed, PICM was observed in 38. Baseline LVEF was lower in patients with PICM, and CLBBB-like paced QRS was frequently observed in PICM. Multivariate analysis revealed that low baseline LVEF (odds ratio [OR]: 0.93 per 1% increase, 95% confidence interval [CI]: 0.89-0.98, p = 0.006) and CLBBB-like paced QRS (OR: 2.69, 95% CI: 1.25-5.76, p = 0.011) were significantly associated with PICM development. CONCLUSION: CLBBB-like paced QRS may be a novel risk factor for PICM. RV pacing, which causes CLBBB-like QRS morphology, may need to be avoided, and patients with CLBBB-like paced QRS should be followed-up carefully.

Histological Typing in Patients With Cardiac Amyloidosis: JACC Review Topic of the Week.

Cardiac amyloidosis is increasingly recognized as a treatable form of heart failure. Highly effective specific therapies have recently become available for the 2 most frequent forms of cardiac amyloidosis: immunoglobulin light chain amyloidosis and transthyretin (ATTR) amyloidosis. Nevertheless, initiation of specific therapies requires recognition of cardiac amyloidosis and appropriate characterization of the amyloid type. Although noninvasive diagnosis is possible for ATTR cardiac amyloidosis, histological demonstration and typing of amyloid deposits is still required for a substantial number of patients with ATTR and in all patients with light chain amyloidosis and other rarer forms of cardiac amyloidosis. Amyloid histological typing can be performed using different techniques: mass spectrometry, immunohistochemistry, and immunoelectron microscopy. This review describes which patients require histological confirmation of cardiac amyloidosis along with when and how to type amyloid deposits in histologic specimens. Furthermore, it covers the characteristics and limitations of the different typing methods that are available in clinical practice.

[Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis]. / Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL).

INTRODUCTION AND OBJETIVES: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease. MATERIAL AND METHODS: One hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations. RESULTS: During a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2). AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). CONCLUSIONS: CA was associated with high incidence of hospitalizations, being heart failure the most frequent individual cause; unscheduled admission-free survival in AL-CA was lower than in ATTR-CA due mostly to non-cardiovascular admissions.

The structure and function of lamin A/C: Special focus on cardiomyopathy and therapeutic interventions.

Lamins are inner nuclear membrane proteins that belong to the intermediate filament family. Lamin A/C lie adjacent to the heterochromatin structure in polymer form, providing skeletal to the nucleus. Based on the localization, lamin A/C provides nuclear stability and cytoskeleton to the nucleus and modulates chromatin organization and gene expression. Besides being the structural protein making the inner nuclear membrane in polymer form, lamin A/C functions as a signalling molecule involved in gene expression as an enhancer inside the nucleus. Lamin A/C regulates various cellular pathways like autophagy and energy balance in the cytoplasm. Its expression is highly variable in differentiated tissues, higher in hard tissues like bone and muscle cells, and lower in soft tissues like the liver and brain. In muscle cells, including the heart, lamin A/C must be expressed in a balanced state. Lamin A/C mutation is linked with various diseases, such as muscular dystrophy, lipodystrophy, and cardiomyopathies. It has been observed that a good number of mutations in the LMNA gene impact cardiac activity and its function. Although several works have been published, there are still several unexplored areas left regarding the lamin A/C function and structure in the cardiovascular system and its pathological state. In this review, we focus on the structural organization, expression pattern, and function of lamin A/C, its interacting partners, and the pathophysiology associated with mutations in the lamin A/C gene, with special emphasis on cardiovascular diseases. With the recent finding on lamin A/C, we have summarized the possible therapeutic interventions to treat cardiovascular symptoms and reverse the molecular changes.

Rural/urban disparities in the trends and outcomes of peripartum cardiomyopathy in delivery hospitalizations.

BACKGROUND: Rural-urban disparities in peripartum cardiomyopathy (PPCM) are not well known. We examined rural-urban differences in maternal, fetal, and cardiovascular outcomes in PPCM during delivery hospitalizations. METHODS: We used 2003-2020 data from the National Inpatient Sample for delivery hospitalizations in individuals with PPCM. The 9th and 10th editions of the International Classification of Diseases were used to identify PPCM and cardiovascular, maternal, and fetal outcomes. Rural and urban hospitalizations for PPCM were 1:1 propensity score-matched using relevant clinical and sociodemographic variables. Odds of in-hospital mortality were assessed using logistic regression. RESULTS: Among 72,880 delivery hospitalizations with PPCM, 4,571 occurred in rural locations, while 68,309 occurred in urban locations. After propensity matching, there were a total of 4,571 rural-urban pairs. There was significantly higher in-hospital mortality in urban compared to rural hospitalizations (adjusted OR 1.54, 95% CI 1.10-1.89). Urban PPCM hospitalizations had significantly higher cardiogenic shock (2.9% vs. 1.3%), mechanical circulatory support (1.0% vs. 0.6%), cardiac arrest (2.3% vs. 0.9%), and VT/VF (4.5% vs. 2.1%, all p <.05). Additionally, urban PPCM hospitalizations had worse maternal and fetal outcomes as compared to rural hospitalizations, including higher preterm delivery, gestational diabetes, and fetal death (all p<.05). Notably, significantly more rural individuals were transferred to a short-term hospital (including tertiary care centers) compared to urban individuals (13.5% vs. 3.2%, p<.0001). CONCLUSIONS: There are significant rural-urban disparities in delivery hospitalizations with PPCM. Worse outcomes were associated with urban hospitalizations, while rural PPCM hospitalizations were associated with increased transfers, suggesting inadequate resources and advanced sickness.

Hybrid Magnetic Resonance Positron Emission Tomography Is Associated With Cardiac-Related Outcomes in Cardiac Sarcoidosis.

BACKGROUND: Imaging with late gadolinium enhancement (LGE) magnetic resonance (MR) and 18F-fluorodeoxyglucose (18F-FDG) PET allows complementary assessment of myocardial injury and disease activity and has shown promise for improved characterization of active cardiac sarcoidosis (CS) based on the combined positive imaging outcome, MR(+)PET(+). OBJECTIVES: This study aims to evaluate qualitative and quantitative assessments of hybrid MR/PET imaging in CS and to evaluate its association with cardiac-related outcomes. METHODS: A total of 148 patients with suspected CS underwent hybrid MR/PET imaging. Patients were classified based on the presence/absence of LGE (MR+/MR-), presence/absence of 18F-FDG (PET+/PET-), and pattern of 18F-FDG uptake (focal/diffuse) into the following categories: MR(+)PET(+)FOCAL, MR(+)PET(+)DIFFUSE, MR(+)PET(-), MR(-)PET(+)FOCAL, MR(-)PET(+)DIFFUSE, MR(-)PET(-). Further analysis classified MR positivity based on %LGE exceeding 5.7% as MR(+/-)5.7%. Quantitative values of standard uptake value, target-to-background ratio, target-to-normal-myocardium ratio (TNMRmax), and T2 were measured. The primary clinical endpoint was met by the occurrence of cardiac arrest, ventricular tachycardia, or secondary prevention implantable cardioverter-defibrillator (ICD) before the end of the study. The secondary endpoint was met by any of the primary endpoint criteria plus heart failure or heart block. MR/PET imaging results were compared between those meeting or not meeting the clinical endpoints. RESULTS: Patients designated MR(+)5.7%PET(+)FOCAL had increased odds of meeting the primary clinical endpoint compared to those with all other imaging classifications (unadjusted OR: 9.2 [95% CI: 3.0-28.7]; P = 0.0001), which was higher than the odds based on MR or PET alone. TNMRmax achieved an area under the receiver-operating characteristic curve of 0.90 for separating MR(+)PET(+)FOCAL from non-MR(+)PET(+)FOCAL, and 0.77 for separating those reaching the clinical endpoint from those not reaching the clinical endpoint. CONCLUSIONS: Hybrid MR/PET image-based classification of CS was statistically associated with clinical outcomes in CS. TNMRmax had modest sensitivity and specificity for quantifying the imaging-based classification MR(+)PET(+)FOCAL and was associated with outcomes. Use of combined MR and PET image-based classification may have use in prognostication and treatment management in CS.

Diagnostic and management strategies in cardiac sarcoidosis.

Cardiac sarcoidosis (CS) is increasingly recognized in the context of with otherwise unexplained electrical or structural heart disease due to improved diagnostic tools and awareness. Therefore, clinicians require improved understanding of this rare but fatal disease to care for these patients. The cardinal features of CS, include arrhythmias, atrio-ventricular conduction delay and cardiomyopathy. In addition to treatments tailored to these cardiac manifestations, immunosuppression plays a key role in active CS management. However, clinical trial and consensus guidelines are limited to guide the use of immunosuppression in these patients. This review aims to provide a practical overview to the current diagnostic challenges, treatment approach, and future opportunities in the field of CS.