Arrhythmic prognosis according to left ventricular systolic dysfunction severity in cardiac sarcoidosis.

BACKGROUND: Current guidelines present varying classes of recommendations for implantable cardioverter-defibrillator (ICD) utilization in patients with cardiac sarcoidosis (CS) and left ventricular ejection fraction (LVEF) <50%. OBJECTIVE: The purpose of this study was to investigate the ventricular arrhythmia risk in CS patients with ICDs and varying degrees of left ventricular systolic dysfunction. METHODS: The study included CS patients with an ICD and LVEF <50% at index evaluation. The primary outcome was survival free of sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) after ICD implantation and was assessed comparatively for LVEF ≤35% vs 36%-49% and for primary vs secondary prevention ICD indication. RESULTS: The study included 61 patients (median age 57 years; 61% male) with LVEF 36%-49% (n = 23) or LVEF ≤35% (n = 38). An ICD was implanted for secondary prevention in 24% and 44% of the LVEF ≤35% and 36%-49% groups, respectively (P = .11). The primary outcome did not differ between the 2 groups in univariable analysis (LVEF ≤35% vs 36%-49%: hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.39-1.82; P = .67). In multivariable analysis, secondary prevention ICD indication was the only significant predictor of incident sustained VT/VF (HR 2.86; 95% CI 1.23-6.67; P = .015). Mean sustained VT/VF event burden was higher in the secondary compared with the primary prevention ICD patients (0.47 vs 0.11 events per patient-year; P = .005) but did not differ significantly between LVEF ≤35% and 36%-49% patients. CONCLUSION: CS patients with ICD indications and LVEF 36%-49% carry similarly high arrhythmic risk as those with LVEF ≤35%. Patients with secondary prevention ICDs have the highest overall risk.

An magnetic resonance imaging-pathology correlation case report of cardiac sarcoidosis mimicking arrhythmogenic biventricular cardiomyopathy.

Background: Cardiac sarcoidosis (CS) is a granulomatous disease that can manifest as conduction defects, ventricular arrhythmias, and heart failure. The diagnosis of CS is inherently difficult due to variable presentations; as such, endomyocardial biopsy is often required but lacks sensitivity due to patchy myocardial involvement. Moreover, the diagnostic criteria of CS and arrhythmogenic cardiomyopathy overlap, particularly in right-side dominant or biventricular presentations, which further complicates an already challenging differential diagnosis. Case summary: A 53-year-old man with no prior chronic medical conditions presented with ventricular tachycardia (VT) and heart failure with reduced ejection fraction. He was found to have biventricular cardiomyopathy and late gadolinium enhancement on cardiac magnetic resonance imaging, resulting in an initial diagnosis of arrhythmogenic cardiomyopathy. Implantable cardioverter-defibrillator was placed, but he was readmitted for recurrent VT 2 months later. Despite an aggressive VT therapy (combination of antiarrhythmic drugs, epicardial and endocardial ablation, and stellate ganglion block), he continued with refractory VT and developed cardiogenic shock. Extra-corporeal membrane oxygenation was initiated as a bridge to heart transplantation. Pathology of the explanted heart revealed the underlying disease to be CS. Discussion: Cardiac sarcoidosis can mimic arrhythmogenic biventricular cardiomyopathy and may be difficult to distinguish by the proposed diagnostic criteria. High clinical suspicion and thorough investigation are necessary for an earlier diagnosis and initiation of treatment.

Reduction in Balloon Pump Size Reduces Axillary Intraaortic Balloon Pump Failure Risk.

Axillary artery intra-aortic balloon pump (axIABP) placement has been implemented as a bridging solution before heart transplantation. This study evaluates complications associated with axIABP support and describes an approach to minimize adverse events. We previously described a percutaneous approach for axIABP placement. However, patients receiving axIABP between September 1, 2017, and September 26, 2019 (n = 32) demonstrated a high rate of balloon pump malfunction (8/32; 25%) and other complications (totaling 15/32; 47%). Sixty-four patients were sequentially treated under a revised protocol. Compared to the initial cohort, no significant differences in demographics were noted. A significant reduction in rate of balloon malfunction (8/32, 25% vs. 1/64, 2%; p < 0.001) and total complications (15/32, 47% vs. 10/64, 16%; p = 0.0025) during the period of support were noted after intervention. Subsequent analysis of total complications per device size (40 vs. ≤ 34 ml balloon) revealed significantly reduced complications in patients with smaller devices (40% vs. 13%, respectively; p = 0.0022). This study provides guidelines to limit complications in patients supported with axIABP, facilitating a protracted period of bridging support.

Arrhythmic manifestations and outcomes of definite and probable cardiac sarcoidosis.

BACKGROUND: The 2014 Heart Rhythm Society consensus statement defines histological (definite) and clinical (probable) diagnostic categories of cardiac sarcoidosis (CS), but few studies have compared their arrhythmic phenotypes and outcomes. OBJECTIVE: The purpose of this study was to evaluate the electrophysiological/arrhythmic phenotype and outcomes of patients with definite and probable CS. METHODS: We analyzed the arrhythmic/electrophysiological phenotype in a single-center North American cohort of 388 patients (median age 56 years; 39% female, n = 151) diagnosed with definite (n = 58) or probable (n = 330) CS (2000-2022). The primary composite outcome was survival to first ventricular tachycardia/fibrillation (VT/VF) event or sudden cardiac death. Key secondary outcomes were also assessed. RESULTS: At index evaluation, in situ cardiac implantable electronic devices and antiarrhythmic drug use were more common in definite CS. At a median follow-up of 3.1 years, the primary outcome occurred in 22 patients with definite CS (38%) and 127 patients with probable CS (38%) (log-rank, P = .55). In multivariable analysis, only a higher ratio of the 18F-fluorodeoxyglucose maximum standardized uptake value of the myocardium to the maximum standardized uptake value of the blood pool (hazard ratio 1.09; 95% confidence interval 1.03-1.15; P = .003, per 1 unit increase) was associated with the primary outcome. During follow-up, patients with definite CS had a higher burden of device-treated VT/VF events (mean 2.86 events per patient-year vs 1.56 events per patient-year) and a higher rate of progression to heart transplant/left ventricular assist device implantation but no difference in all-cause mortality compared with patients with probable CS. CONCLUSION: Patients with definite and probable CS had similarly high risks of first sustained VT/VF/sudden cardiac death and all-cause mortality, though patients with definite CS had a higher overall arrhythmia burden. Both CS diagnostic groups as defined by the 2014 Heart Rhythm Society criteria require an aggressive approach to prevent arrhythmic complications.

Imaging of Cardiac Sarcoidosis: An Update and Future Aspects.

Cardiac sarcoidosis (CS), an increasingly recognized disease of unknown etiology, is associated with significant morbidity and mortality. Given the limited diagnostic yield of traditional endomyocardial biopsy (EMB), there is increasing reliance on multimodality cardiovascular imaging in the diagnosis and management of CS, with EMB being largely supplanted by the use of 18F-fluorodeoxyglucose (FDG-PET) and cardiac magnetic resonance imaging (CMR). This article aims to provide a comprehensive review of imaging modalities currently utilized in the screening, diagnosis, and monitoring of CS, while highlighting the latest developments in each area.

Biventricular catheterization combined with pressure-volume loop monitoring provides insight into the dynamic effects of left ventricular assist devices ramp on right ventricular function.

Ramp studies are utilized for speed optimization of continuous flow left ventricular assist devices (CF-LVADs). We here report the utility of combined left and right heart catheterization during a ramp study to ensure a comprehensive understanding of the hemodynamic implications on both ventricles. Pressure-volume loop (PV loop) monitoring uncovered compromised systolic and mildly compromised right ventricular function with increasing LVAD speeds, despite improvement in left ventricular unloading. These findings informed patient management and highlight the potential utility of PV loop monitoring as an adjunct to left and right heart catheterization during ramp studies of next-generation LVADs.

Novel Left Ventricular Unloading Strategies in Patients on Peripheral Venoarterial Extracorporeal Membrane Oxygenation Support.

The purpose of this study was to evaluate left ventricular (LV) unloading strategies in patients supported with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). A retrospective review was conducted of all consecutive patients requiring VA-ECMO support for any indication, who underwent novel LV unloading strategies with either direct left atrial venoarterial (LAVA) cannulation or pulmonary artery venoarterial (PAVA) venting, in comparison to Impella and intra-aortic balloon pump (IABP). The primary outcome was successful bridge to transplant, LV assist device, or myocardial recovery. Forty-six patients (63% male, mean age 52.8 ± 17.6 years) were included. Fourteen patients (30%) underwent novel unloading with either LAVA or PAVA, 11 patients (24%) underwent IABP placement, and 21 patients (46%) underwent Impella insertion. In the novel LV unloading cohort, 10 patients (71%) survived to hospital discharge. Four patients (29%) were weaned from ECMO and eight patients (57%) underwent cardiac transplantation. Although a trend favoring cannula-based unloading for the primary outcome was noted, the cohort was too small for statistical significance (79% LAVA/PAVA, 57% Impella, 45% IABP; p = 0.21). However, probability of survival was greater in the LAVA/PAVA cohort compared to Impella and IABP ( p < 0.05). Thus, we demonstrate the efficacy of LA and PA cannulation as an alternative LV unloading strategy for patients supported with peripheral VA-ECMO.

Inhibition of angiogenesis in the management of refractory gastrointestinal bleeding in patients with LVAD support.

BACKGROUND: Gastrointestinal bleeding (GIB) in patients with continuous flow left ventricular assist devices (CF-LVADs) is often related to GI angiodysplasia (GIAD). We previously reported data on VEGF inhibition with IV bevacizumab in the treatment of LVAD-associated GIAD bleeding, and now present follow-up data on patients treated with IV bevacizumab and/or low-dose oral pazopanib. METHODS: All consecutive adult patients with LVAD-associated GIB from GIAD treated with bevacizumab or pazopanib, from July 20, 2017 to June 22, 2022, were included in the analysis. Data on hospitalizations, GI endoscopic procedures, and blood transfusions were obtained from first admission for GIB up to a median of 35.7 months following treatment initiation (range 1.3-59.8 months). RESULTS: Eleven patients (91% male, mean 69.5 ± 8.9 years) were included. Eight patients (73%) received IV bevacizumab, two patients (18%) received oral pazopanib, and one patient (9%) received bevacizumab followed by pazopanib therapy. We observed a significantly decreased number of annualized hospitalizations for GIB (median difference - 2.87, p = 0.002), blood transfusions (median difference - 20.9, p = 0.01), and endoscopies (median difference - 6.95, p = 0.007) in patients pre- and post-anti-angiogenic therapy (bevacizumab and/or pazopanib). Similarly, a significant improvement in these clinical outcomes was noted in the bevacizumab group with decreased annualized hospitalizations (median difference - 2.75, p = 0.014), blood transfusions (median difference - 24.5, p = 0.047), and number of endoscopies (median differences -6.88, p = 0.006). CONCLUSION: Anti-angiogenic therapy with IV bevacizumab and/or low-dose oral pazopanib appears to provide benefits in patients with LVAD-associated GIB with reduced hospitalizations, blood transfusions, and need for GI endoscopic procedures.

Cardiac fludeoxyglucose-18 positron emission tomography in genotype-positive arrhythmogenic cardiomyopathy.

BACKGROUND: Myocardial inflammation contributes to the pathogenesis of arrhythmogenic cardiomyopathy (ACM), a clinically and genetically heterogenous disorder. Due to phenotypic overlap, some patients with genetic ACM may be evaluated for an underlying inflammatory cardiomyopathy. However, the cardiac fludeoxyglucose (FDG) positron emission tomography (PET) findings in ACM patients have not been elucidated. METHODS: All genotype-positive patients in the Mayo Clinic ACM registry (n = 323) who received a cardiac FDG PET were included in this study. Pertinent data were extracted from the medical record. RESULTS: Collectively, 12/323 (4%; 67% female) genotype-positive ACM patients received a cardiac PET FDG scan as part of their clinical evaluation (median age at scan 49 ± 13 years). Amongst these patients, pathogenic/likely pathogenic variants were detected in LMNA (n = 7), DSP (n = 3), FLNC (n = 1) and PLN (n = 1). Of note, 6/12 (50%) had abnormal myocardial FDG uptake, including diffuse (entire myocardium) uptake in 2/6 (33%), focal (1-2 segments) uptake in 2/6 (33%) and patchy (3+ segments) in 2/6 (33%). Median myocardial standardized uptake value ratio was 2.1. Interestingly, LMNA-positive patients accounted for 3 out of 6 (50%) positive studies (diffuse uptake in 2 and focal uptake in 1). CONCLUSION: Abnormal myocardial FDG uptake is common in genetic ACM patients undergoing cardiac FDG PET. This study further supports the role of myocardial inflammation in ACM. Further investigation is needed to determine role of FDG PET in diagnosis and management of ACM and investigate the role of inflammation in ACM.

Case Series: Recurrence of Cardiac Sarcoidosis After Orthotopic Heart Transplantation.

Orthotopic heart transplantation for cardiac sarcoidosis (CS) is becoming increasingly common. Historically, there have been concerns regarding disease recurrence within the allograft. Although rarely reported in the literature, cases of recurrent CS tend to be observed in patients after dose reduction of immunosuppressive therapy and cessation of corticosteroids. Here, we present 2 cases of recurrent CS after orthotopic heart transplantation, confirmed on endomyocardial biopsy. Case 1 reports a 50-year-old man with a fulminant course of giant cell myocarditis who developed allograft recurrence with granulomas 5 years after transplantation despite maintenance corticosteroid therapy. Case 2 reports a 47-year-old man with CS who developed recurrence with the presence of giant cells 2 years after transplantation, with a benign clinical course. With these cases, we demonstrate the clinical overlap between CS and giant cell myocarditis and highlight the spectrum of the disease process. We also demonstrate that CS can recur despite corticosteroid maintenance therapy.

Infections in Patients With Left Ventricular Assist Devices: Current State and Future Perspectives.

Mechanical circulatory support is increasingly being used as bridge-to-transplant and destination therapy in patients with advanced heart failure. Technologic improvements have led to increased patient survival and quality of life, but infection remains one of the leading adverse events following ventricular assist device (VAD) implantation. Infections can be classified as VAD-specific, VAD-related, and non-VAD infections. Risk of VAD-specific infections, such as driveline, pump pocket, and pump infections, remains for the duration of implantation. While adverse events are typically most common early (within 90 days of implantation), device-specific infection (primarily driveline) is a notable exception. No diminishment over time is seen, with event rates of 0.16 events per patient-year in both the early and late periods postimplantation. Management of VAD-specific infections requires aggressive treatment and chronic suppressive antimicrobial therapy is indicated when there is concern for seeding of the device. While surgical intervention/hardware removal is often necessary in prosthesis-related infections, this is not so easily accomplished with VADs. This review outlines the current state of infections in patients supported with VAD therapy and discusses future directions, including possibilities with fully implantable devices and novel approaches to treatment.

Percutaneous Mechanical Circulatory Support as a Bridge to Transplantation in Ebstein Anomaly.

Ebstein anomaly is a rare congenital heart defect occurring in 0.0005% of the population because of mispositioning and malformation of the tricuspid valve. Here, we present the first description and associated imaging of percutaneous mechanical circulatory support in the setting of cardiogenic shock secondary to Ebstein anomaly.

Interventricular-Septal Output While Supported on Left Ventricular Assist Device Therapy.

The effects of left ventricular unloading on septal function in patients with left ventricular assist devices (LVADs) have not been well characterized in vivo. The purpose of this study was to evaluate the relationship between markers of septal function with echocardiography in relationship to RV dysfunction and late RV failure after LVAD implantation. A retrospective study was conducted of patients supported on centrifugal-flow LVADs implanted over a 10-year period. Echocardiographic data were collected pre-operatively and up to 2 years after implantation. Interventricular septum (IVS) measurements were taken at end-systole and end-diastole. Interventricular-septal output (ISO) was calculated using the formula: (IVSs-IVSd)×heart rate. A total of 110 patients were included. An immediate and sustained reduction in both lateral annulus systolic velocity (RVS') and TAPSE were observed after implant ( p < 0.0001). However, ISO gradually decreased over time ( p < 0.0001). While ISO was not predictive of late RV failure, a decrease in ISO by 25% or greater from pre-implant to hospital discharge was associated with late RV failure (OR 4.8; 95% CI, 1.4-16.5; p = 0.012) even after adjusting for relevant clinical variables ( p ≤ 0.01 for each model). RV function is known to be influenced by mechanical ventricular interdependence and we demonstrate that measurement of ISO may be a useful marker in assessing RV dysfunction and predicting RV failure in patients following LVAD implantation.

The Mechanism and Natural History of Mitral Regurgitation in Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is an infl/ammatory cardiomyopathy that can present with mitral regurgitation (MR), but few studies describe the mechanisms and natural history of MR in CS. We queried an institutional registry of 512 patients with CS for moderate or greater MR at diagnosis. Baseline demographic and echocardiography (TTE) data were collected. MR was classified by Carpentier type. Positron emission tomography was analyzed for 2-deoxy-2-[fluorine-18] fluoro-d-glucose (FDG) avidity of anterolateral and posteromedial papillary muscles. Follow-up TTE and positron emission tomography imaging of patients treated with immunosuppression was analyzed for MR severity and FDG avidity changes. Fifty-four patients were identified. Mean left ventricular ejection fraction was 39.3%, effective regurgitant orifice 0.34 cm2, and MR regurgitant volume 46.3 ml. Carpentier type I was the most common MR mechanism (46.3%). Forty-one patients had follow-up TTE (median follow-up 1.7 years, interquartile range 2.6 years). Evaluating preprocedural follow-up TTE only, MR severity was significantly reduced, with 37% of patients showing reduction by at least 1 severity grade (p = 0.04). With postprocedural TTE included, 61% of patients showed alleviation of MR severity with mean decrease in grade - 0.98 (p <0.001). Sixty-eight percent of patients had anterolateral/posteromedial FDG avidity. Papillary muscle FDG avidity resolved in 80% of patients (n = 20, median follow-up 1.6 years, interquartile range 2.5 years). In conclusion, Carpentier type I functional MR is the most common MR mechanism in CS. MR severity and papillary muscle FDG avidity decrease after treatment, and MR resolution is further strengthened by procedural intervention in a minority of patients, suggesting an overall favorable natural history of MR in CS.

An intervention strategy to improve genetic testing for dilated cardiomyopathy in a heart failure clinic.

PURPOSE: Despite its clinical implications in screening and therapy, genetic testing in dilated cardiomyopathy (DCM) is underused. This study evaluated implementing a practice intervention in a heart failure clinic to automate and streamline the process of genetic testing. METHODS: Eligible patients with DCM were compared for frequency of pretest genetic education and testing during pre- and postintervention periods. The intervention comprised automated prescheduling of a cardiovascular genomics e-consult that served as a placeholder for downstream, pretest education, testing, and post-test review of genetic results. RESULTS: Patients with DCM were more likely to undergo pretest genetic education after intervention than before intervention (33.5% vs 14.8%, P < .0001). Similarly, patients with DCM were more likely to undergo genetic testing after intervention than before intervention (27.3% vs 13.0%, P = .0006). The number of patients who were diagnosed to have likely pathogenic or pathogenic genetic variants were 2 of 21 (9.5%) and 6 of 53 (11.1%) before and after intervention, respectively, and variants were present in the following genes: FLNC, TTN, DES, LMNA, PLN, and TNNT2. CONCLUSION: An intervention strategy in a heart failure clinic to increase the rates of pretest genetic education and testing in eligible patients with DCM was feasible and efficacious and may have important implications for the management of DCM.