Citations

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.

Background A multidisciplinary approach improves guideline‐directed medical therapy in systolic heart failure (HF), but its efficacy in patients with HF due to cardiac sarcoidosis is unreported. Methods and Results In a retrospective cohort study, we reviewed 848 patients from our institutional cardiac sarcoidosis clinics, identifying those with a cardiac sarcoidosis diagnosis, HF (left ventricular ejection fraction <50%) at index evaluation, and echocardiograms within 90 days and 11 to 36 months. Patients were stratified by participation in a pharmacist‐led medication therapy management (MTM) program for guideline‐directed medical therapy optimization (MTM versus non‐MTM [NMTM]) without randomization. Demographics, left ventricular ejection fraction, guideline‐directed medical therapy (quantified by Kansas City Medical Optimization score), and immunosuppressive therapy were assessed. Primary outcomes included changes in Kansas City Medical Optimization score, left ventricular ejection fraction, and cardiovascular event–free survival (unplanned HF hospitalization, left ventricular assist device /heart transplant, or death). The final cohort included 111 patients (median age, 57 years; 34% women; 64% New York Heart Association class I–II); 43 (39%) were MTM and 68 (61%) were NMTM. Mean Kansas City Medical Optimization score was similar at index evaluation (MTM, 23.2; NMTM, 29.6; P =0.83). At follow‐up (median, 16 months), the Kansas City Medical Optimization score increased significantly in both groups (MTM, 23.2 to 74.8; P <0.001; NMTM, 29.6 to 58.7; P <0.001) but was higher in MTM ( P =0.001). Mean left ventricular ejection fraction trended toward higher values in MTM (44.4% versus 40.0%, P =0.05). The primary clinical outcome occurred in 1 MTM (2.3%) and 16 NMTM (23.5%) patients, with higher risk in NMTM (hazard ratio, 11.97 [95% CI, 1.58–90.54]; P =0.002). Conclusions In this retrospective cohort study, a pharmacist‐led MTM program was associated with favorable guideline‐directed medical therapy optimization and lower risk of adverse cardiovascular outcomes in patients with cardiac sarcoidosis with HF.

Background: Pulmonary vascular resistance (PVR) is commonly considered to reflect opposition to lung blood flow caused by the arteries (PVRa), but downstream venous resistance (PVRv) may also contribute to pulmonary hypertension (PH) associated with left heart diseases (PH-LHD). In patients referred for right heart catheterization, we investigated PVR distribution and its pathophysiologic implications in PH-LHD and other forms of PH. Methods: Patients with PH-LHD (n=292), pulmonary veno-occlusive disease (PVOD, n=10), chronic thromboembolic PH (CTEPH, n=36) and controls without PH (Ctrl, n=28) were included. Pulmonary capillary pressure (Pc) was calculated using the pulmonary artery occlusion technique. PVR was partitioned into PVRa ((mPAP-Pc)/CO) and PVRv ((Pc-PAWP)/CO) with each expressed as % of PVR. PH-LHD was divided into isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). Further, PH-LHD was categorized as heart failure with preserved (HFpEF, EF≥50%) or reduced (HFrEF, EF<50%) ejection fraction or left valvular heart disease (L-VHD). In subsets, functional tests (n=71-81) and histological pulmonary venous (PV) remodeling (autopsy, n=15) were performed to investigate correlations with PVR distribution. Results: PVR distribution showed an arterial predominance in Ctrl and CTEPH, and increasing venous contribution in PH-LHD (both IpcPH and CpcPH) and PVOD (Figure A-F). In PH-LHD, patients with HFpEF had proportionately greater venous contribution to PVR than HFrEF and L-VHD (Figure G-I), though not to the extent observed in PVOD. In subsets, PVRv was more strongly correlated with E/e’, extravascular lung water estimated by sonographic B-lines, arterial PO 2 , pulmonary dead space fraction (VD/VT), DLCO, and, among the autopsy series, PV intimal thickness as compared to PVRa (Figure J-O). Conclusions: Pulmonary venous contributions to PVR are amplified in patients with PH-LHD, which is correlated with greater lung congestion, ventilatory and gas exchange abnormalities, and histological venous remodeling. Further study is required to determine the molecular mechanism and novel therapeutics of pulmonary venous disease in PH-LHD.

Introduction: Cardiac sarcoidosis (CS) often results in systolic heart failure (HF) and responds favorably to guideline directed medical therapy (GDMT). A multidisciplinary team approach to HF care is recommended but few published examples exist in CS patients. Methods: We queried an institutional registry of 599 CS patients (2000-2023) for patients with index LVEF < 50% (within 90 d of index CS evaluation) and follow-up TTE within 11-36 months. In our CS medication therapy management (MTM) program (started 1/8/2019), pharmacists conduct independent visits with CS patients (in person or remote), discuss GDMT tolerance and symptoms, review monitoring laboratory studies, and adjust GDMT (ACEi/ARB/ARNi, beta-blocker, MRA, and/or SGLT2i) via collaborative practice agreement with the CS cardiologists. Patients were classified as MTM (≥1 MTM encounter) or NMTM patients (0 encounters). We compared (1) GDMT, (2) cardiac remodeling, and (3) clinical outcomes (event free survival to first heart failure hospitalization, LVAD, heart transplant, or death). Results: Nineteen percent (113/599) CS patients met inclusion criteria (34% female, 92% white, median age 57 y, 19% definite CS, 58% probable CS, 31% presumed CS), with 44 MTM (median 11.5 encounters, IQR 11) and 69 NMTM patients. Both MTM and NMTM patients were on a median 2 GDMT agents at index evaluation (p=0.21). At follow-up (median 19 mo MTM, 15 mo NMTM, p=0.05), MTM patients were on more GDMT agents than NMTM (median 3.0 vs 2.0, p<0.001), with higher % target dose of ACEi/ARB/ARNi (98% vs 71%, p=0.009), beta-blocker (87% vs 57%, p=0.004), and SGLT2i use (30% vs 9%, p=0.004), but similar MRA use (48% vs 32%, p=0.09). Immunosuppressive therapy was used in 88% patients (89% MTM vs 87% NMTM, p=0.79). Index LVEF was similar (MTM 36%, NMTM 32%, p=0.07). Mean change in LVEF (excluding LVAD/transplant patients) demonstrated a non-significant trend towards improved remodeling in MTM (+8.6%) vs NMTM patients (+5.5%; p=0.39). MTM patients exhibited lower risk of the clinical outcome (1/44 MTM vs 16/69 MTM patients; univariable HR 0.08 [95%CI 0.01 - 0.63], log-rank p=0.016). Conclusions: A pharmacist MTM program for CS patients with HF is associated with improved GDMT uptitration and clinical outcomes, emphasizing the value of collaborative multidisciplinary CS care.

Background: Differentiating between causes of non-ischemic cardiomyopathy is important for disease-directed treatment. Cardiac MRI (CMR) and the use of late gadolinium enhancement (LGE) have proven useful for enhancing diagnostic accuracy. Definitive assessment of cardiomyopathy etiology by explant pathology facilitates direct evaluation of CMR utility. Hypothesis: We hypothesized direct comparison between pre-transplant (Tx) CMR and explant pathology will improve the characterization of undifferentiated cardiomyopathy through examination of cases where pre- and post-Tx diagnoses were discordant. Aims: To evaluate discrepant cases to describe imaging patterns in relation to post-Tx diagnosis. Methods: Institutional Tx recipients between 2000 and June 2023 were queried for pre-Tx MRI (n=122). Discrepant cases were identified (n=8). Pre-Tx diagnostic modalities, including CMR, were reviewed, and CMR patterns were evaluated in association with ultimate explant diagnosis. Results: Of the eight patients with discrepant diagnoses, five carried clinical diagnosis of dilated cardiomyopathy, one hypertrophic cardiomyopathy, one peripartum cardiomyopathy, and one congenital heart disease having undergone tricuspid valve and ASD repair. Pathologic evaluation most frequently identified biventricular or left ventricular arrhythmogenic cardiomyopathy (ARVC) (n=6), where CMR disclosed a diffuse pattern of subepicardial LGE and pre-Tx diagnosis of DCM was most common. Two of these pathologic descriptions represented a different disease on genetic evaluation: one patient had Danon disease, another had a LMNA pathogenic variant. The presumed peripartum cardiomyopathy was identified as Fabry’s disease on pathology (however, genetic testing consistent with Danon disease). Both Danon disease patients had primarily subendocardial LGE on CMR. One patient with a DCM phenotype had HCM pathologically. Results summarized in Table 1. Conclusions: Cardiac MRI can be a useful modality for the evaluation of underlying cardiomyopathy and should prompt appropriate genetic testing. Diffuse subepicardial LGE frequently accompanied the diagnosis of ARVC whereas a non-subepicardial pattern reflected alternative etiologies identified only through genetic testing.

Introduction: Unexplained high-grade AV block (AVB) in patients age <65 years is among the salient features of cardiac sarcoidosis (CS). Guidelines recommend that CS patients with high-grade AVB should receive an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) rather than a permanent pacemaker (PPM). However, in clinical practice, CS may be recognized after PPM implantation for high-grade AVB. Aims: To evaluate the characteristics and outcomes of patients diagnosed with CS after PPM implantation for high-grade AVB and assess the decision-making and rationale for upgrade to ICD/CRT-D. Methods: Retrospective review of the Mayo Clinic Sarcoid Registry (n=848) was performed to identify all patients for which a PPM was implanted for high-grade AVB prior to the diagnosis of CS. Baseline clinical and imaging characteristics were collected during index evaluation at our institution. Decision-making for ICD upgrade, lead management strategy, immunosuppression initiation, and outcomes were assessed. Results: Overall, 29 of 848 (3.4%) of CS patients (62% probable/definite CS; 77% male; median (IQR) age 56 (48-61) years; and median (IQR) LVEF 58% (50-62) received a PPM for high-grade AVB prior to a CS diagnosis. Median (IQR) interval between PPM implant and index evaluation was 10 (3-23) months. Eight of 29 patients underwent upgrade to ICD (n=4) or CRT-D (n=4). Among them, the pacing lead was extracted in 4. All patients were upgraded for primary prevention of sudden cardiac death (SCD), with 3 of them also having LVEF<50% requiring upgrade to CRT-D. Twenty-two (79%) patients in the total cohort were treated with immunosuppression. During median (IQR) follow-up 37 months (11-74), 1 patient in the upgrade group had sustained VT appropriately treated with anti-tachycardia pacing. No events were documented among patients in the non-upgrade group. At last follow-up, 6 (75%) patients in the upgrade group and 12 (57%) in the non-upgrade group were pacemaker dependent. Median LVEF change was 0% in patients who underwent upgrade to CRT-D and –0.2% in those who underwent upgrade to ICD or no upgrade. Conclusions: In this cohort of patients diagnosed with CS several months after a PPM had been implanted for high-grade AVB, incident VT/VF was infrequent with contemporary CS management. In the absence of other SCD risk factors, CS patients who received a PPM for high-grade AVB prior to their CS diagnosis may not require ICD upgrade.

Introduction: The prevalence and prognostic significance of PVC and NSVT in cardiac sarcoidosis (CS), especially in patients with normal or mildly decreased LV function, are not well known and were investigated in the current study. Methods: We included 192 patients with definite and probable CS with LVEF>35%, no prior history of VT/VF or sudden cardiac death, who underwent up to 48 hours of Holter monitoring. They were followed retrospectively for the composite endpoint of sustained VT/VF, advanced heart failure therapy, and all-cause mortality. We performed multivariable analysis for the association of PVC burden and NSVT with the composite endpoint. Covariates were considered if they were present in at least 95% of the study sample and were significantly associated with the composite endpoint in univariable analysis. Results: The median PVC burden in the overall population was 0.3% (IQR 0.02-2.5%) and 36 (18.8%) patients had a PVC burden ≥5%. Sixty-two (32.3%) patients had NSVT detected during monitoring. The PVC burden and prevalence of NSVT in patient subgroups are shown in Figures 1 and 2. A total of 33 (17.2%) patients experienced one of the composite endpoints at a median follow-up of 3 years. In the multivariable analysis (Figure 3), PVC burden ≥5% versus <5% (HR 3.96 [1.19, 5.97], p-value <0.01) and presence of NSVT (HR 4.55 [2.09, 9.94], p-value <0.01) were associated with the composite outcome. Conclusion: Our results suggest that a high PVC burden and the presence of NSVT carry isolated prognostic value in CS. In addition, ventricular ectopy does not appear to be an indicator of disease activity based on abnormal uptake on PET scan.

Abstract Introduction Non-cardiovascular end-organ dysfunction is an important determinant of outcomes in cardiac intensive care unit (CICU) patients. We examined the association between in-hospital mortality with the severity and extent of admission liver function test (LFT) abnormalities in a heterogeneous CICU population. Purpose We hypothesized that a greater severity or extent of LFT abnormalities would be associated with higher in-hospital mortality. Methods We included consecutive unique adult CICU patients with available data for one or more of the admission LFT values of interest. Admission laboratory values were defined as those closest to CICU admission. We used the NIH Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 to categorize the severity of each LFT abnormality from Grade 0 (normal) to Grade 4 (life-threatening). We defined the extent of LFT abnormality as the number of individual LFTs meeting criteria for CTCAE Grade 1 or greater. The primary outcome of interest was all-cause in-hospital mortality. Odds ratio (OR) and 95% confidence interval (CI) values for in-hospital mortality were estimated using logistic regression, before and after multivariable adjustment. Results Of 12,428 unique CICU patients, 5,144 were excluded due to a lack of available data for any admission LFT values. The remaining 7,284 patients comprised the final study population. Among patients with available data for each individual LFT, abnormal values were present in: AST, 2,743/5,733 (47.8%); ALT 1,576/5,512 (28.6%); ALK 611/3,684 (16.6%); and TB 898/5,155 (17.4%). A total of 864 (11.9%) patients died during hospitalization. In-hospital mortality was higher for patients with one or more LFTs meeting criteria for CTCAE Grade 1 or greater (17.9% vs. 6.4%, adjusted OR 1.54 [1.27-1.86], p &lt;0.001). A stepwise increase in in-hospital mortality was observed with increasing CTCAE grade, both overall (adjusted OR 1.25 per each higher CTCAE grade [1.16-1.34], p &lt;0.001); (Figure 1A), and for each individual LFT (Figure 1B). Conclusion Cardiohepatic syndrome is an important predictor of prognosis in CICU patients, as the extent and severity of LFT abnormalities are strongly associated with in-hospital mortality. This is the first large-scale study to examine the association between the magnitude of hepatic biomarker derangement with in-hospital mortality in unselected CICU patients. Patients with markedly elevated LFT values exhibited the highest risk of in-hospital mortality. This analysis advocates for the inclusion of commonly obtained LFTs in future risk-prediction tools for enhanced prognostication.