Rosenbaum, Andrew

Abstract Isolated cardiac sarcoidosis (iCS), defined by granulomatous inflammation limited to the myocardium, represents the most diagnostically challenging and prognostically adverse form of sarcoidosis. As it is fundamentally a diagnosis of exclusion, iCS diagnosis relies on the absence of extracardiac sarcoid and the integration of multimodality imaging, endomyocardial biopsy, and molecular testing, each with inherent limitations. Cardiac magnetic resonance and positron emission tomography provide complementary assessment of inflammation, fibrosis, and ventricular function, enhancing diagnostic confidence. Electroanatomic mapping-guided biopsy may improve histologic yield, whereas genetic testing helps exclude phenocopies such as arrhythmogenic, hypertrophic, or dilated cardiomyopathies. Circulating biomarkers remain non-specific but may complement imaging-based algorithms. Future research should focus on harmonized imaging protocols, non-FDG radiotracers, and molecular tissue profiling to refine activity assessment and guide therapy. Multimodal, probability-based frameworks represent the most promising approach for earlier, more accurate diagnosis and risk stratification in iCS.

Introduction: The Impella 5.5 is frequently employed to provide temporary mechanical circulatory support as bridge to recovery or durable therapy. Optimization of device management relies on understanding ventricular pressure-volume (PV) relationships. Aim: The aim of this study was to evaluate the biventricular (BiV) relationship with PV loop assessment during Impella 5.5 support in non-myopathic ventricles. Methods: Six domestic Yorkshire Pigs were used for this study. The Impella 5.5 (J&J MedTech, NJ) was inserted percutaneously under ultrasound and fluoroscopic guidance through either the carotid artery or aortic arch, using a 26Fr DrySeal Sheath (Gore, AZ). BiV PV loop conductance catheters (Sigma-M, CD Leycom, Hengelo, The Netherlands) were inserted via femoral venous access. The LV PV loop catheter is positioned via transeptal puncture and with intracardiac echocardiogram guidance. BiV PV loops are generated for each level of Impella 5.5 support. Results: With increasing levels of Impella 5.5 support, left ventricular (LV) PV loops shifted increasingly to the left and right ventricular (RV) loops to the right. Accordingly, LV end-diastolic volume (EDV) decreased (110±4 ml to 90±8 ml; p<0.001) and RV EDV increased (121±7 ml to 147±13 ml; p<0.001), from baseline to P9. Native LV systolic function decreased with increasing Impella 5.5 support, as demonstrated by a reduction in stroke volume (SV) (56±5 ml to 49±5 ml; p<0.001), cardiac output (CO) (3.4±0.8 ml/min to 2.0±0.3 ml/min; p<0.001), ejection fraction (EF) (51±4% to 44±6%; p<0.001), stroke work (SW) (4483±1023 ml*mmHg to 2383±719 ml*mmHg; p<0.001), and LV peak positive dP/dt (825 ± 184 mmHg/s to 523 ± 99 mmHg/s; p<0.001). Conversely, the native RV experienced preload-mediated increase in SV (65±7 ml to 86±20 ml; p<0.001), CO (3.7±0.8 ml/min to 4.3±0.9 ml/min; p<0.001), EF (53±4% to 58±11%; p<0.001), SW (918±143 ml*mmHg to 1529±365 ml*mmHg; p<0.001), and RV dP/dt (164±16 mmHg/s to 228±29 mmHg/s, p<0.001). Load independent contractility was assessed in the LV (1.64±0.33 mmHg/ml to 1.71±0.41 mmHg/ml; p=0.2) and RV (0.25±0.04 mmHg/ml to 0.29±0.05 mmHg/ml; p<0.001). Conclusions: This study highlights ventricular interdependence with Impella 5.5 support with opposing BiV trends. In a healthy heart, the RV can adequately compensate for increased preload offered by the device.

Introduction: Microaxial flow pumps reduce mortality in myocardial infarction (MI) related cardiogenic shock (CS). The Impella 5.5 generates increased flow to provide circulatory support, and optimization relies on mechanistic understanding of pressure-volume (PV) relationships. Aim: Using a porcine model of acute MI in tandem with biventricular (BiV) PV loop conductance catheters, this study aimed to understand the impact of Impella 5.5 on BiV hemodynamics in MI CS. Methods: In 6 Domestic Yorkshire Pigs, an Impella 5.5 (J&J MedTech, NJ) was inserted percutaneously under fluoroscopic guidance via carotid or aortic access. An angioplasty balloon catheter was advanced past the first diagonal and inflated to above nominal pressure with blood flow obstruction for 90 minutes. BiV PV loop conductance catheters (Sigma-M, CD Leycom, Hengelo, The Netherlands) were inserted via femoral venous access. The left ventricle (LV) PV loop catheter is positioned via transeptal puncture using intracardiac echocardiography. BiV PV loops are generated for each level of Impella support from P1 to P7. Results: With increasing Impella 5.5 support, LV PV loops shifted to the left and right ventricular (RV) loops to the right. Without statistical significance, LV end diastolic volume (EDV) decreased by a mean of 12.3 ± 10.7% from baseline and RV EDV increased by 32 ± 40%. Native LV function decreased with increasing Impella 5.5 support, demonstrated by a reduction in stroke volume (SV) (35±13 ml to 27±14 ml; p<0.001), cardiac output (CO) derived from SV&heart rate (2.0±0.5 ml/min to 1.7±0.7 ml/min; p<0.001), and ejection fraction (EF) (37±7% to 29±12%; p<0.001). Less consistent trends were noted in peak positive dP/dt and end-systolic pressure volume relationship. Native RV function increased with higher levels of Impella 5.5 support, noted by increasing SV (27±24 ml to 41±28 ml; p=0.004), CO (1.6±1.2 ml/min to 2.3±1.4 ml/min; p=0.001), and EF (42±16% to 45±9%; p=0.04). Arterial elastance and ventriculo-arterial coupling increased in the LV from baseline to P7 (2.2±1.4 mmHg/ml to 2.8±1.0 mmHg/ml and 1.8±0.5 to 3.2±1.9, respectively; p<0.001) and decreased in the RV (1.3±0.7 mmHg/ml to 0.9±0.7 mmHg/ml (p<0.001) and 2.1±2.2 to 1.3±0.6 (p=0.004)). Conclusions: Impella 5.5 speed modulation highlights significant ventricular interdependence in the setting of acute MI. PV loop derived parameters here visualized parameters that may be utilized to improve optimization of hemodynamic support in CS.

Background Patients with cardiohepatic syndrome are at higher risk of adverse outcomes in the cardiac intensive care unit. We hypothesized that cardiohepatic syndrome phenotypes would exhibit differences in their clinical and transthoracic echocardiogram hemodynamic profiles, portending a higher risk of mortality. Methods We included unique CICU patients with an admission diagnosis of heart failure from 2007 to 2018 with available data for 1 or more admission liver function tests. Echocardiographic variables were extracted from patients who had a transthoracic echocardiogram within 1 day of admission. We assigned patients to 1 of 4 mutually exclusive cardiohepatic syndrome phenotype groups: normal, hepatocellular, cholestasis, and combined. Results We included 3992 CICU patients; 2483 had an available transthoracic echocardiogram. Patients with cholestasis had more right ventricular systolic dysfunction and congestion, whereas those with hepatocellular injury had more left ventricular systolic dysfunction and poor forward flow; hemodynamics and biventricular function were worst in the combined group. In‐hospital mortality occurred in 14.6% and was higher for patients with cholestasis or hepatocellular injury, especially those with greater extent/severity and worse biventricular function or poor hemodynamics. After adjustment, only the group with hepatocellular injury (adjusted odds ratio [OR], 1.35 [95% CI, 1.04–1.75], P =0.03) and the combined group (adjusted OR, 1.75 [95% CI, 1.30–2.34], P <0.001) remained at higher risk. One‐year mortality was highest in the combined group (adjusted hazard ratio [HR], 1.29 [95% CI, 1.10–1.51], P =0.002). Conclusions Cardiohepatic syndrome phenotypes are associated with distinct echocardiographic profiles. Patients with the combined cardiohepatic syndrome phenotype were at highest risk of mortality, particularly if this was combined with poor cardiac function.

Background Disease‐causative variants in LMNA ‐encoded lamin A/C cause a genetic cardiomyopathy characterized by atrioventricular block, atrial fibrillation, ventricular arrhythmias, and systolic dysfunction. The influence of LMNA variant type/localization on late gadolinium enhancement (LGE) patterns and clinical outcomes remains unclear. Methods Retrospective analysis of 822 genotype‐positive patients with arrhythmogenic/dilated cardiomyopathy was used to identify those with disease‐causative variants in LMNA . Data on LGE distribution and prevalence of advanced heart failure, thromboembolic and sudden cardiac death/major ventricular arrhythmia events were extracted from the electronic record and analyzed by variant type/localization. Results Among the 72/116 (62%) LMNA variant‐positive patients with cardiac magnetic resonance imaging data, LGE was observed in 40/72 (56%) cases. Most exhibited a nonischemic, midmyocardial or subepicardial pattern (73%), and 6/40 (15%) showed a unique “pseudo‐infarct” transmural pattern, predominantly affecting the apical segments. All 6 patients with this distinct LGE pattern harbored C‐terminal IgD (immunoglobulin‐like domain) variants (p.Arg471His or p.Arg541His). In patients with clinically manifest disease (76/116), those with IgD‐localizing variants had a lower prevalence of atrioventricular block (25% versus 72%, P =0.002) and atrial fibrillation (50% versus 81%, P =0.019) but higher rates of thromboembolic events (42% versus 16%, P =0.038). During a median follow‐up of 37 months, IgD variant presence independently predicted sudden cardiac death/major ventricular arrhythmia (hazard ratio, 2.391 [95% CI, 1.046–5.464]; P =0.039). Conclusions LMNA missense variants localizing to IgD present a distinct apical pseudo‐infarct LGE pattern associated with increased risk of ventricular arrhythmias and thromboembolic events but reduced atrioventricular block and atrial fibrillation. Multicenter studies are warranted to develop variant‐specific risk‐stratification strategies in cardiac laminopathy.

ABSTRACTItraconazole and posaconazole are frequently prescribed following transplantation to prevent and treat fungal infections. Navigating drug interactions is challenging due to these agents’ potent CYP3A4 inhibition, and literature describing concurrent apixaban, a CYP3A4 substrate, is limited. This retrospective study of cardiothoracic transplant recipients evaluates the impact of itraconazole and posaconazole on apixaban exposure and reports clinical outcomes from routine apixaban dose reduction. Institutional practice reduces apixaban to 2.5 mg twice daily with itraconazole or posaconazole and obtains apixaban therapeutic drug monitoring (TDM), expected range 34–230 ng/mL. Eighteen levels collected in 15 patients on itraconazole displayed a median [IQR] apixaban trough of 143 ng/mL [95–195]. Fifteen levels collected in 13 patients on posaconazole displayed a median [IQR] apixaban trough of 124 ng/mL [93–174]. Two major bleed events, three VTE, two stroke, and eight instances of clot resolution were identified. Reduced‐dose apixaban resulted in apixaban exposure similar to normal dosing in the general population. Apixaban TDM is encouraged for individualized dosing when administered with itraconazole and posaconazole.

Abstract The expanding use of continuous‐flow left ventricular assist devices (CF‐LVADs) for end‐stage heart failure warrants familiarity with the physiologic interaction of the device with the native circulation. Contemporary devices utilize predominantly centrifugal flow and, to a lesser extent, axial flow rotors that vary with respect to their intrinsic flow characteristics. Flow can be manipulated with adjustments to preload and afterload as in the native heart, and ascertainment of the predicted effects is provided by differential pressure‐flow ( H ‐ Q ) curves or loops. Valvular heart disease, especially aortic regurgitation, may significantly affect adequacy of mechanical support. In contrast, atrioventricular and ventriculoventricular timing is of less certain significance. Although beneficial effects of device therapy are typically seen due to enhanced distal perfusion, unloading of the left ventricle and atrium, and amelioration of secondary pulmonary hypertension, negative effects of CF‐LVAD therapy on right ventricular filling and function, through right‐sided loading and septal interaction, can make optimization challenging. Additionally, a lack of pulsatile energy provided by CF‐LVAD therapy has physiologic consequences for end‐organ function and may be responsible for a series of adverse effects. Rheological effects of intravascular pumps, especially shear stress exposure, result in platelet activation and hemolysis, which may result in both thrombotic and hemorrhagic consequences. Development of novel solutions for untoward device‐circulatory interactions will facilitate hemodynamic support while mitigating adverse events. © 2021 American Physiological Society. Compr Physiol 12:1‐37, 2021.

ABSTRACT Background Addition of left heart catheterization (LHC) to exercise protocols allows for a unique focus on parameters of systolic and diastolic responses to increased activity in patients with left ventricular assist device (LVAD) support. Methods A retrospective review was conducted of all consecutive adult patients who underwent LHC with exercise for any indication from June 2017 to June 2023. For all patients, the relationship between exercise and parameters of LV systolic and diastolic response was assessed. Patients were divided into two cohorts based on the indication for testing: hemodynamic optimization (Optim, n = 5) or weaning consideration (Wean, n = 3). Results Eight patients (88% male, median age 57 years (IQR 44, 65)) were included. LVEF was 45% (IQR 45, 56) in Wean and 25% (IQR 20, 42) in Optim. LV systolic work index (LVSWI) increased more rapidly over levels of exercise in Wean vs. Optim (slope 46.3 vs. −0.625; p = 0.044) and LVSWI rose more quickly at lower levels of LV end diastolic pressure (LVEDP) in Wean vs. Optim (slope 219.5 vs. −2.008; p = 0.0026). Pulse power index was higher in Wean patients at baseline (0.046 (IQR 0.04, 0.07) vs. 0.016 (IQR 0.001, 0.04); p = 0.14) and peak exercise (0.12 (IQR 0.12, 0.12) vs. 0.06 (IQR 0.03, 0.1); p = 0.29). Conclusions Patients with favorable remodeling on LVAD support have significantly improved LV systolic and diastolic responses to exercise and a trend of higher systemic pulsatility. Improving our understanding of LV‐LVAD interactions with activity may aid in future efforts to improve exercise tolerance through speed modulation.

AbstractBackgroundThe prognosis in patients with advanced cardiac amyloidosis (CA) remains poor.ObjectivesWe sought to describe survival post heart transplantation (HT) in amyloid compared with non‐amyloid recipients, highlight waitlist times within the new allocation system across three Organ Procurement and Transplantation Network (OPTN) regions, and describe multiorgan transplantation (MOT) in hereditary amyloidosis.MethodsThis is a retrospective review of end‐stage CA patients who underwent HT at Mayo Clinic from January 2007 to December 2020. Wait time was compared in the new versus old OPTN allocation era starting December 18, 2018 by Wilcoxon rank sum test. All‐cause mortality for those with and without CA was compared using Kaplan–Meier estimates with log rank analysis, censoring December 16, 2022.ResultsFifty‐five patients with CA underwent HT between 2007 and 2020, 8 light chain amyloidosis (AL) (14.5%), 28 hereditary transthyretin (ATTRv) (50.9%), 17 wildtype transthyretin (ATTRwt) (30.9%), and 2 hereditary apolipoprotein A1 (AApoA1) amyloidosis patients (3.6%). No significant difference in overall survival post‐transplant was seen in amyloid compared with non‐amyloid (p = 0.816). Median time to HT was shorter in the new system, 45 days (IQR 24, 78) versus 174 days (IQR 76.5, 483.5), p = 0.006. There was a decline in MOT in hereditary amyloidosis over time with the concomitant rise in disease‐targeted therapies.ConclusionsHT survival in CA patients was similar to non‐amyloid patients. The new allocation system benefits this cohort with shorter wait times. There is less MOT in hereditary amyloidosis with increased utilization of disease‐targeted therapy.