Inclusion of Performance Parameters and Patient Context in the Clinical Practice Guidelines for Heart Failure.

BACKGROUND: To facilitate evidence-based medicine (EBM) on an individual level, it may be important for clinical practice guidelines (CPGs) to incorporate the performance parameters of diagnostic studies and therapeutic interventions (such as likelihood ratio and absolute benefit or harm), and to incorporate relevant patient contexts that may influence decision-making. We sought to determine the extent to which heart failure CPGs currently incorporate this information. METHODS: We reviewed the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) 2013 Heart Failure CPG, the 2017 ACCF/AHA/HFSA update, and European Society of Cardiology (ESC) 2016 Heart Failure CPG. We abstracted variables for each CPG recommendation from the following domains: quality of evidence, strength of recommendation, diagnostic and therapeutic performance parameters, and patient context. RESULTS: We examined 169 recommendations from the ACCF/AHA 2013 CPGs and 2017 update and 187 recommendations from the 2016 ESC CPGs. Performance parameters for diagnostic studies (2013 ACCF/AHA: 13%; 2017 ACCF/AHA/HFSA update: 0%; 2016 ESC: 0%) and therapeutic interventions (2013 ACCF/AHA: 65%; 2017 ACCF/AHA/HFSA update: 64%; 2016 ESC: 16%) were not commonly included in CPGs. Patient context was included in about half of ACCF/AHA recommendations and a quarter of ESC recommendations. CONCLUSIONS: The majority of recommendations from heart failure CPGs lack information on diagnostic and therapeutic performance parameters and patient context. Given the importance of these components to effectively implement EBM, particularly for a heterogeneous heart failure population, innovative strategies are needed to optimize CPGs so they provide comprehensive yet succinct recommendations that can improve population-level outcomes and ensure optimal patient-centered care.

MicroRNA-195 Regulates Metabolism in Failing Myocardium Via Alterations in Sirtuin 3 Expression and Mitochondrial Protein Acetylation.

BACKGROUND: Heart failure leads to mitochondrial dysfunction and metabolic abnormalities of the failing myocardium coupled with an energy-depleted state and cardiac remodeling. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in the maintenance of mitochondrial function through regulating the mitochondrial acetylome. It is interesting to note that unique cardiac and systemic microRNAs have been shown to play an important role in cardiac remodeling by modulating key signaling elements in the myocardium. METHODS: Cellular signaling was analyzed in human cardiomyocyte-like AC16 cells, and acetylation levels in rodent models of SIRT3-/-and transgenic microRNA-195 (miR-195) overexpression were compared with wild type. Luciferase assays, Western blotting, immunoprecipitation assays, and echocardiographic analysis were performed. Enzymatic activities of pyruvate dehydrogenase (PDH) and ATP synthase were measured. RESULTS: In failing human myocardium, we observed induction of miR-195 along with decreased expression of the mitochondrial deacetylase SIRT3 that was associated with increased global protein acetylation. We further investigated the role of miR-195 in SIRT3-mediated metabolic processes and its impact on regulating enzymes involved in deacetylation. Proteomic analysis of the total acetylome showed increased overall acetylation, and specific lysine acetylation of 2 central mitochondrial metabolic enzymes, PDH and ATP synthase, as well. miR-195 downregulates SIRT3 expression through direct 3'-untranslated region targeting. Treatments with either sirtuin inhibitor nicotinamide, small interfering RNA-mediated SIRT3 knockdown or miR-195 overexpression enhanced acetylation of PDH complex and ATP synthase. This effect diminished PDH and ATP synthase activity and impaired mitochondrial respiration.SIRT3-/- and miR-195 transgenic mice consistently showed enhanced global protein acetylation, including PDH complex and ATP synthase, associated with decreased enzymatic activity. CONCLUSIONS: Altogether, these data suggest that increased levels of miR-195 in failing myocardium regulate a novel pathway that involves direct SIRT3 suppression and enzymatic inhibition via increased acetylation of PDH and ATP synthase that are essential for cardiac energy metabolism.

Prevalence and determinants of Hyperpolypharmacy in adults with heart failure: an observational study from the National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: While an expanding armamentarium of pharmacologic therapies has contributed to improved outcomes among adults with heart failure (HF) over the past two decades, this has also been accompanied by an increase in the number of medications taken by adults with HF. The use of at least 10 medications, defined as hyperpolypharmacy, is particularly notable given its association with adverse outcomes. We aimed to assess the prevalence and identify determinants of hyperpolypharmacy among adults with HF. METHODS: We studied adults aged ≥50 years with self-reported HF from the National Health And Nutrition Examination Survey (NHANES) in 2003-2014. We calculated weighted means and percentages to describe patient characteristics. We conducted a multivariable Poisson regression analysis to identify factors independently associated with hyperpolypharmacy; we adjusted for survey sampling, socio-demographics, comorbidity, geriatric conditions, and health care utilization. We examined 947 participants, representing 4.6 million adults with HF. RESULTS: The prevalence of hyperpolypharmacy was 26%. In a multivariable regression analysis, comorbidity count, ≥10 ambulatory contacts, and ≥ 3 hospitalizations were independently associated with hyperpolypharmacy. Interestingly, functional impairment and cognitive impairment were not independently associated with hyperpolypharmacy; while low annual household income and low educational status were each associated with an almost 2-fold increase in hyperpolypharmacy. CONCLUSION: Hyperpolypharmacy is a common condition among adults with HF. We additionally found that low household income and low educational status are independently associated with hyperpolypharmacy, suggesting that non-medical factors may be contributing to this potentially harmful condition.

Eligibility of Pacemaker Patients for Subcutaneous Implantable Cardioverter Defibrillators.

INTRODUCTION: The subcutaneous implantable cardioverter defibrillator (ICD) has emerged as a viable therapeutic option for patients who are deemed high risk for sudden cardiac death. Previous studies have shown that 7-15% of patients are not candidates for the S-ICD based on their intrinsic QRS/T-wave morphology. Presently, it is not known if the S-ICD can be considered as supplementary therapy in patients who are ventricularly paced. We sought to determine the proportion of ventricularly paced patients who would qualify for an S-ICD. METHODS AND RESULTS: We evaluated 100 patients with transvenous pacemakers/ICDs, including 25 biventricular devices to determine S-ICD candidacy during right ventricular (RV) pacing and biventricular pacing based on the recommended QRS:T-wave ratio screening template. Fifty-eight percent of patients qualified for an S-ICD based on their QRS morphology during ventricular pacing. More patients during biventricular pacing met criteria compared to during RV pacing alone (80% vs. 46%, P <0.01). Patients that were paced from the RV septum were more likely to qualify compared to those paced from the RV apex (67% vs. 37%, respectively, P <0.01). CONCLUSION: While S-ICD implantation may be considered as supplemental therapy in select patients with preexisting transvenous devices, relatively fewer candidates who are paced from the RV apex qualify. QRS morphologies generated from biventricular pacing as well as from septal RV pacing are more likely to screen in based on the recommended S-ICD template.

Exercise capacity, physical activity, and morbidity.

Muscle weakness and atrophy are key characteristics of the aging adult but can also be found in chronically ill patients with heart failure, cancer, renal failure, and chronic infectious diseases all associated with an accelerated level of muscle dysfunction. Reduced physical activity levels and exercise intolerance increase muscle loss and decrease quality of life in both the aging and heart failure populations. The purpose of this review is to provide an overview of the effects of aging and heart failure on skeletal muscle function and how exercise training can improve long-term outcomes associated with skeletal muscle dysfunction.

Analysis of Skeletal Muscle Torque Capacity and Circulating Ceramides in Patients with Advanced Heart Failure.

BACKGROUND: Heart failure (HF)-related exercise intolerance is thought to be perpetuated by peripheral skeletal muscle functional, structural, and metabolic abnormalities. We analyzed specific dynamics of muscle contraction in patients with HF compared with healthy, sedentary controls. METHODS: Isometric and isokinetic muscle parameters were measured in the dominant upper and lower limbs of 45 HF patients and 15 healthy age-matched controls. Measurements included peak torque normalized to body weight, work normalized to body weight, power, time to peak torque, and acceleration and deceleration to maximum strength times. Body morphometry (dual energy X-ray absorptiometry scan) and circulating fatty acids and ceramides (lipodomics) were analyzed in a subset of subjects (18 HF and 9 controls). RESULTS: Extension and flexion time-to-peak torque was longer in the lower limbs of HF patients. Furthermore, acceleration and deceleration times in the lower limbs were also prolonged in HF subjects. HF subjects had increased adiposity and decreased lean muscle mass compared with controls. Decreased circulating unsaturated fatty acids and increased ceramides were found in subjects with HF. CONCLUSIONS: Delayed torque development suggests skeletal muscle impairments that may reflect abnormal neuromuscular functional coupling. These impairments may be further compounded by increased adiposity and inflammation associated with increased ceramides.

Activation of PPARδ signaling improves skeletal muscle oxidative metabolism and endurance function in an animal model of ischemic left ventricular dysfunction.

Exercise intolerance in heart failure has been linked to impaired skeletal muscle oxidative capacity. Oxidative metabolism and exercise capacity are regulated by PPARδ signaling. We hypothesized that PPARδ stimulation reverts skeletal muscle oxidative dysfunction. Myocardial infarction (MI) was induced in C57BL/6 mice and the development of ventricular dysfunction was monitored over 8 wk. Mice were randomized to the PPARδ agonist GW501516 (5 mg/kg body wt per day for 4 wk) or placebo 8 wk post-MI. Muscle function was assessed through running tests and grip strength measurements. In muscle, we analyzed muscle fiber cross-sectional area and fiber types, metabolic gene expression, fatty acid (FA) oxidation and ATP content. Signaling pathways were studied in C2C12 myotubes. FA oxidation and ATP levels decreased in muscle from MI mice compared with sham- operated mice. GW501516 administration increased oleic acid oxidation levels in skeletal muscle of the treated MI group compared with placebo treatment. This was accompanied by transcriptional changes including increased CPT1 expression. Further, the PPARδ-agonist improved running endurance compared with placebo. Cell culture experiments revealed protective effects of GW501516 against the cytokine-induced decrease of FA oxidation and changes in metabolic gene expression. Skeletal muscle dysfunction in HF is associated with impaired PPARδ signaling and treatment with the PPARδ agonist GW501516 corrects oxidative capacity and FA metabolism and improves exercise capacity in mice with LV dysfunction. Pharmacological activation of PPARδ signaling could be an attractive therapeutic intervention to counteract the progressive skeletal muscle dysfunction in HF.

Cardiac myostatin upregulation occurs immediately after myocardial ischemia and is involved in skeletal muscle activation of atrophy.

UNLABELLED: Myostatin (MSTN), a negative regulator of muscle growth and size, is increased after acute myocardial infarction (AMI) but timing of upregulation after injury is not known. In this study, we investigated the timing of the MSTN/AKT/p38 pathway activation in heart and skeletal muscle after AMI, as well as the potential effect of cardiac injury-related MSTN endocrine signaling on skeletal muscle and other circulating growth factors. METHODS: Coronary artery ligation was performed in C57BL/6 mice at age 8 weeks to induce AMI. Mice were sacrificed at different time points (10 m, 1 h, 2 h, 6 h, 12 h, 24 h, 1 week, 2 weeks, 1 months and 2 months) after surgery (n=3 per time point, n=18 total). RESULTS: Cardiac and circulating MSTN upregulation occurred as early as 10 min after AMI. Two months after AMI, increased cardiac MSTN/SMAD2,3 and p38 together with decreased IGF-1/AKT signaling suggest an anti-hypertrophic profile. In skeletal muscle, an absence of local MSTN increase was accompanied by increased MSTN-dependent SMAD2,3 signaling, suggestive of paracrine effects due to cardiac-derived MSTN. Protein degradation by the ubiquitin-proteasome system in the skeletal muscle was also evident. Serum from 24h post-MI mice effectively induced a MSTN-dependent increase in atrogin1 and MuRF1. CONCLUSION: Our study shows that cardiac MTSN activation occurs rapidly after cardiac ischemia and may be involved in peripheral protein degradation in the skeletal muscle by activating atrogin1 and MuRF1.

Novel Biomarker Approaches for Managing Patients With Cardiac Transplantation.

Despite major advances in the medical care of patients following heart transplantation (HTx) and a steady increase in long-term survival, allograft surveillance is still based on endomyocardial biopsy, the gold standard since the 1970s. This invasive procedure calls for less burdening and more cost-effective approaches. In recent years, impressive progress has been made in utilizing blood-based biomarkers for the diagnosis and management of diseases in a variety of fields. Hence, a number of trials have been performed testing the usefulness of circulating molecules or other technical methods to overcome the need for surveillance myocardial biopsy in HTx patients. Here, we review current approaches and the state of research on novel biomarkers for the management of patients following heart transplantation.

Pathophysiology of sepsis-related cardiac dysfunction: driven by inflammation, energy mismanagement, or both?

Sepsis is a systemic inflammatory response that follows bacterial infection. Cardiac dysfunction is an important consequence of sepsis that affects mortality and has been attributed to either elevated inflammation or suppression of both fatty acid and glucose oxidation and eventual ATP depletion. Moreover, cardiac adrenergic signaling is compromised in septic patients and this aggravates further heart function. While anti-inflammatory therapies are important for the treatment of the disease, administration of anti-inflammatory drugs did not improve survival in septic patients. This review article summarizes findings on inflammatory and other mechanisms that are triggered in sepsis and affect cardiac function and mortality. Particularly, it focuses on the effects of the disease in metabolic pathways, as well as in adrenergic signaling and the potential interplay of the latter with inflammation. It is suggested that therapeutic approaches should include combination of anti-inflammatory treatments, stimulation of energy production, and restoration of adrenergic signaling in the heart.

Myocardial Recovery With HeartMate 3 Left Ventricular Assist Device: An Attainable Goal That Needs Better Precision.

Despite advances in our understanding of myocardial recovery among left ventricular assist device (LVAD) patients, with 10-30% of patients achieving substantial myocardial improvement, the rates of LVAD support cessation remain extremely low (1-2%). These numbers are in stark contrast to clinical trial data where successful LVAD cessation is reported in up to 47% of patients. The majority of LVAD programs lack structured recovery programs and targeted protocols, likely underscoring the heterogeneity that exists among LVAD patients with myocardial recovery. This perspective summarizes the current medical and surgical challenges with respect to 1) identifying the appropriate candidates for LVAD cessation; 2) methods to wean LVAD support; 3) reviewing surgical techniques for cessation of current generation HeartMate 3 LVAD; and 4) approaching shared decision making for LVAD cessation between patients and providers given the uncertainties that remain in the field.

Effect of mechanical unloading on genome-wide DNA methylation profile of the failing human heart.

Heart failure (HF) is characterized by global alterations in myocardial DNA methylation, yet little is known about the epigenetic regulation of the noncoding genome and potential reversibility of DNA methylation with left ventricular assist device (LVAD) therapy. Genome-wide mapping of myocardial DNA methylation in 36 patients with HF at LVAD implantation, 8 patients at LVAD explantation, and 7 nonfailing (NF) donors using a high-density bead array platform identified 2,079 differentially methylated positions (DMPs) in ischemic cardiomyopathy (ICM) and 261 DMPs in nonischemic cardiomyopathy (NICM). LVAD support resulted in normalization of 3.2% of HF-associated DMPs. Methylation-expression correlation analysis yielded several protein-coding genes that are hypomethylated and upregulated (HTRA1, FBXO16, EFCAB13, and AKAP13) or hypermethylated and downregulated (TBX3) in HF. A potentially novel cardiac-specific super-enhancer long noncoding RNA (lncRNA) (LINC00881) is hypermethylated and downregulated in human HF. LINC00881 is an upstream regulator of sarcomere and calcium channel gene expression including MYH6, CACNA1C, and RYR2. LINC00881 knockdown reduces peak calcium amplitude in the beating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). These data suggest that HF-associated changes in myocardial DNA methylation within coding and noncoding genomes are minimally reversible with mechanical unloading. Epigenetic reprogramming strategies may be necessary to achieve sustained clinical recovery from heart failure.

Meta-Analysis of Point-of-Care Lung Ultrasonography Versus Chest Radiography in Adults With Symptoms of Acute Decompensated Heart Failure.

Acute decompensated heart failure (ADHF) is a primary cause of older adults presenting to the emergency department with acute dyspnea. Point-of-care lung ultrasound (LUS) has shown comparable or superior diagnostic accuracy in comparison with a chest x-ray (CXR) in patients presenting with symptoms of ADHF. The systematic review and meta-analysis aimed to elucidate the sensitivity and specificity of LUS in comparison with CXR for diagnosing ADHF and summarize the rapidly growing body of evidence in this domain. A total of 5 databases were searched through February 18, 2021, to identify observational studies that reported on the use of LUS compared with CXR in diagnosing ADHF in patients presenting with shortness of breath. Meta-analysis was conducted on the sensitivities and specificities of each diagnostic method. A total of 8 studies reporting on 2,787 patients were included in this meta-analysis. For patients presenting with signs and symptoms of ADHF, LUS was found to be more sensitive than CXR (91.8% vs 76.5%) and more specific than CXR (92.3% vs 87.0%) for the detection of cardiogenic pulmonary edema. In conclusion, LUS is more sensitive and specific than CXR in detecting pulmonary edema. This highlights the importance of sonographic B-lines, along with the accurate interpretation of clinical data, in the diagnosis of ADHF. In addition to its convenience, reduced costs, and reduced radiation exposure, LUS should be considered an effective alternative to CXR for evaluating patients with dyspnea in the setting of ADHF.

Remote Cardiac Monitoring in Patients With Heart Failure: A Review.

Importance: Heart failure (HF) is often characterized by an insidious disease course leading to frequent rehospitalizations and a high use of ambulatory care. Remote cardiac monitoring is a promising approach to detect worsening HF early and intervene prior to an overt decompensation. Observations: Recently, a multitude of novel technologies for remote cardiac monitoring (RCM) in patients with HF have been developed and are undergoing clinical trials. This development has been accelerated by the COVID-19 pandemic. Conclusions and Relevance: This review summarizes the major clinical trials on RCM in patients with HF and present the most recent developments in noninvasive and invasive RCM technologies.

A Review on the Evolving Roles of MiRNA-Based Technologies in Diagnosing and Treating Heart Failure.

MiRNA-regulated processes are pivotal in cardiovascular homeostasis and disease. These short non-coding RNAs have ideal properties that could be utilized as potential biomarkers; moreover, their functions as post-transcriptional regulators of mRNA make them interesting therapeutic targets. In this review, we summarize the current state of miRNA-based biomarkers in a variety of diseases leading to heart failure, as well as provide an outlook on developing miRNA-based therapies in the heart failure field.

A case series analysis on the clinical experience of Impella 5.5® at a large tertiary care centre.

AIMS: We aimed to detail the early clinical experience with pVAD 5.5 at a large academic medical centre. Impella® 5.5 (Abiomed) is a temporary peripherally inserted left ventricular assist device (pVAD) used for the treatment of cardiogenic shock (CS). This system has several modifications aimed at improving deliverability and durability over the pVAD 5.0 system, but real-world experience with this device remains limited. METHODS AND RESULTS: We collected clinical and outcome data on all patients supported with pVAD 5.5 at our centre between February and December 2020, including procedural and device-related complications. Fourteen patients with pVAD 5.5 were included. Aetiology of CS was acute myocardial infarction (n = 6), decompensated heart failure (n = 6), suspected myocarditis (n = 1), and post-cardiotomy CS (n = 1). Four patients received pVAD 5.5 after being on inotropes alone, two were escalated from intra-aortic balloon pump, two were escalated from pVAD CP, and six patients were transitioned to pVAD 5.5 from extracorporeal membrane oxygenation. Median duration of pVAD 5.5 support was 12 (interquartile range 7, 25) days. Complications included axillary insertion site haematoma (n = 3), acute kidney injury (n = 3), severe thrombocytopenia (n = 1), and stroke (n = 1). No valve injury or limb complications occurred. Survival to device explant for recovery or transition to another therapy was 11/14 (79%) patients. CONCLUSIONS: In this early experience of the pVAD 5.5, procedural and device-related complications were observed but were manageable, and overall survival was high in this critically ill cohort, particularly when the device was used as a bridge to other therapies.

Longitudinal profiling of circulating miRNA during cardiac allograft rejection: a proof-of-concept study.

AIMS: Allograft rejection following heart transplantation (HTx) is a serious complication even in the era of modern immunosuppressive regimens and causes up to a third of early deaths after HTx. Allograft rejection is mediated by a cascade of immune mechanisms leading to acute cellular rejection (ACR) and/or antibody-mediated rejection (AMR). The gold standard for monitoring allograft rejection is invasive endomyocardial biopsy that exposes patients to complications. Little is known about the potential of circulating miRNAs as biomarkers to detect cardiac allograft rejection. We here present a systematic analysis of circulating miRNAs as biomarkers and predictors for allograft rejection after HTx using next-generation small RNA sequencing. METHODS AND RESULTS: We used next-generation small RNA sequencing to investigate circulating miRNAs among HTx recipients (10 healthy controls, 10 heart failure patients, 13 ACR, and 10 AMR). MiRNA profiling was performed at different time points before, during, and after resolution of the rejection episode. We found three miRNAs with significantly increased serum levels in patients with biopsy-proven cardiac rejection when compared with patients without rejection: hsa-miR-139-5p, hsa-miR-151a-5p, and hsa-miR-186-5p. We identified miRNAs that may serve as potential predictors for the subsequent development of ACR: hsa-miR-29c-3p (ACR) and hsa-miR-486-5p (AMR). Overall, hsa-miR-486-5p was most strongly associated with acute rejection episodes. CONCLUSIONS: Monitoring cardiac allograft rejection using circulating miRNAs might represent an alternative strategy to invasive endomyocardial biopsy.

Specialty-Based Variability in Diagnosing and Managing Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: To quantify differences in the diagnosis and treatment of heart failure with preserved ejection fraction (HFpEF) between cardiologists and noncardiologists, who often diagnose and manage HFpEF. METHODS: Cardiologists and noncardiologists (internal medicine, medicine/pediatrics, family medicine, geriatrics) were anonymously surveyed between January 16, 2018, and March 2, 2018, regarding practices related to diagnosing and managing HFpEF at the University of Michigan and Weill Cornell Medical Center. Response data were compared using χ2 analysis. RESULTS: Of 1010 physicians surveyed, 211 completed a significant portion of the survey: 32 cardiologists and 179 noncardiologists. Most noncardiologists were unaware of HFpEF diagnostic guidelines and commonly used left ventricular diastolic dysfunction and natriuretic peptides to diagnose HFpEF. Noncardiologists (32.3%, n=52) were less likely than cardiologists (64.5%, n= 20) to prescribe an aldosterone antagonist for HFpEF (P=.001). Both groups reported similar use of ß-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and exercise programs. Noncardiologists were more likely to refer patients with HFrEF to cardiology (63.1%, n=111) compared with patients with HFpEF (33.5%, n=59; P<.001). Noncardiologists were more likely to discuss prognosis and goals of care with patients with HFrEF (84.4%, n=151) than with patients with HFpEF (65.9%, n=118; P<.001). CONCLUSION: Cardiologists and noncardiologists vary significantly in their HFpEF diagnosis and treatment practices. As diagnostic criteria continue to be evaluated for HFpEF, dissemination of these guidelines to noncardiologists, with an emphasis on the morbidity and mortality associated with HFpEF, is imperative.

A case series on inflammatory cardiomyopathy and suspected cardiac sarcoidosis: role of cardiac PET in management.

BACKGROUND: Presentation of life-threatening arrhythmias concomitantly with a new-onset non-ischaemic cardiomyopathy raises concern for an inflammatory cardiomyopathy such as cardiac sarcoidosis or cardiac manifestations of connective tissue disease. Comprehensive workup for specific aetiologies may be unrevealing except for signs of myocardial inflammation identified on cardiac positron emission tomography (PET). Here, we present five cases of such subjects and their clinical course. CASE SUMMARY: We collected clinical, imaging, pathological, and follow-up data of five subjects presenting with arrhythmias and unexplained new-onset cardiomyopathy. Mean age was 56.2 ± 5.8 years. Three subjects presented with ventricular tachycardia and two with atrial arrhythmias. Echocardiography showed a mean left ventricular ejection fraction of 37 ± 9%. Significant coronary artery disease was ruled out in all cases as the cause of the cardiomyopathy. All patients underwent cardiac magnetic resonance imaging (MRI) and PET scan at presentation and follow-up. In all patients, cardiac MRI revealed hyperenhancement in epicardial and mid-myocardial pattern in a non-coronary distribution, while PET scan revealed fluorodeoxyglucose (FDG) mismatch defects in multiple foci in a non-coronary distribution. Right ventricular biopsy was obtained in all patients and revealed interstitial fibrosis and cardiomyocyte hypertrophy. On median follow-up of 210 days, all subjects had improvement in both heart failure symptoms and arrhythmias and repeat PET in four out of five patients showed decreased inflammation. DISCUSSION: A high level of suspicion for inflammatory cardiomyopathy is needed in patients presenting with new unexplained cardiomyopathy and arrhythmias. A cardiac FDG-PET should be considered for diagnosis if cardiac inflammation is in the differential. This can inform further decisions regarding targeted immunomodulation therapy that may be helpful in this cohort.