Positron emission tomography myocardial perfusion imaging (PET MPI) findings predictive of post-liver transplant major adverse cardiac events.

Positron emission tomography myocardial perfusion imaging (PET MPI) is a noninvasive diagnostic test capable of detecting coronary artery disease, structural heart disease, and myocardial flow reserve (MFR). We aimed to determine the prognostic utility of PET MPI to predict post-liver transplant (LT) major adverse cardiac events (MACE). Among the 215 LT candidates that completed PET MPI between 2015 and 2020, 84 underwent LT and had 4 biomarker variables of clinical interest on pre-LT PET MPI (summed stress and difference scores, resting left ventricular ejection fraction, global MFR). Post-LT MACE were defined as acute coronary syndrome, heart failure, sustained arrhythmia, or cardiac arrest within the first 12 months post-LT. Cox regression models were constructed to determine associations between PET MPI variable/s and post-LT MACE. The median LT recipient age was 58 years, 71% were male, 49% had NAFLD, 63% reported prior smoking, 51% had hypertension, and 38% had diabetes mellitus. A total of 20 MACE occurred in 16 patients (19%) at a median of 61.5 days post-LT. One-year survival of MACE patients was significantly lower than those without MACE (54% vs. 98%, p =0.001). On multivariate analysis, reduced global MFR ≤1.38 was associated with a higher risk of MACE [HR=3.42 (1.23-9.47), p =0.019], and every % reduction in left ventricular ejection fraction was associated with an 8.6% higher risk of MACE [HR=0.92 (0.86-0.98), p =0.012]. Nearly 20% of LT recipients experienced MACE within the first 12 months of LT. Reduced global MFR and reduced resting left ventricular ejection fraction on PET MPI among LT candidates were associated with increased risk of post-LT MACE. Awareness of these PET-MPI parameters may help improve cardiac risk stratification of LT candidates if confirmed in future studies.

Evaluation and Management of Aortic Stenosis in Chronic Kidney Disease: A Scientific Statement From the American Heart Association.

Aortic stenosis with concomitant chronic kidney disease (CKD) represents a clinical challenge. Aortic stenosis is more prevalent and progresses more rapidly and unpredictably in CKD, and the presence of CKD is associated with worse short-term and long-term outcomes after aortic valve replacement. Because patients with advanced CKD and end-stage kidney disease have been excluded from randomized trials, clinicians need to make complex management decisions in this population that are based on retrospective and observational evidence. This statement summarizes the epidemiological and pathophysiological characteristics of aortic stenosis in the context of CKD, evaluates the nuances and prognostic information provided by noninvasive cardiovascular imaging with echocardiography and advanced imaging techniques, and outlines the special risks in this population. Furthermore, this statement provides a critical review of the existing literature pertaining to clinical outcomes of surgical versus transcatheter aortic valve replacement in this high-risk population to help guide clinical decision making in the choice of aortic valve replacement and specific prosthesis. Finally, this statement provides an approach to the perioperative management of these patients, with special attention to a multidisciplinary heart-kidney collaborative team-based approach.

Management of cardiac diseases in liver transplant recipients: Comprehensive review and multidisciplinary practice-based recommendations.

Cardiac diseases are one of the most common causes of morbidity and mortality following liver transplantation (LT). Prior studies have shown that cardiac diseases affect close to one-third of liver transplant recipients (LTRs) long term and that their incidence has been on the rise. This rise is expected to continue as more patients with advanced age and/or non-alcoholic steatohepatitis undergo LT. In view of the increasing disease burden, a multidisciplinary initiative was developed to critically review the existing literature (between January 1, 1990 and March 17, 2021) surrounding epidemiology, risk assessment, and risk mitigation of coronary heart disease, arrhythmia, heart failure, and valvular heart disease and formulate practice-based recommendations accordingly. In this review, the expert panel emphasizes the importance of optimizing management of metabolic syndrome and its components in LTRs and highlights the cardioprotective potential for the newer diabetes medications (e.g., sodium glucose transporter-2 inhibitors) in this high-risk population. Tailoring the multidisciplinary management of cardiac diseases in LTRs to the cardiometabolic risk profile of the individual patient is critical. The review also outlines numerous knowledge gaps to pave the road for future research in this sphere with the ultimate goal of improving clinical outcomes.

Cardiac phenotype in familial partial lipodystrophy.

OBJECTIVES: LMNA variants have been previously associated with cardiac abnormalities independent of lipodystrophy. We aimed to assess cardiac impact of familial partial lipodystrophy (FPLD) to understand the role of laminopathy in cardiac manifestations. STUDY DESIGN: Retrospective cohort study. METHODS: Clinical data from 122 patients (age range: 13-77, 101 females) with FPLD were analysed. Mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with an LMNA variant were studied as proof-of-concept for future studies. RESULTS: Subjects with LMNA variants had a higher prevalence of overall cardiac events than others. The likelihood of having an arrhythmia was significantly higher in patients with LMNA variants (OR: 3.77, 95% CI: 1.45-9.83). These patients were at higher risk for atrial fibrillation or flutter (OR: 5.78, 95% CI: 1.04-32.16). The time to the first arrhythmia was significantly shorter in the LMNA group, with a higher HR of 3.52 (95% CI: 1.34-9.27). Non-codon 482 LMNA variants were more likely to be associated with cardiac events (vs. 482 LMNA: OR: 4.74, 95% CI: 1.41-15.98 for arrhythmia; OR: 17.67, 95% CI: 2.45-127.68 for atrial fibrillation or flutter; OR: 5.71, 95% CI: 1.37-23.76 for conduction disease). LMNA mutant hiPSC-CMs showed a higher frequency of spontaneous activity and shorter action potential duration. Functional syncytia of hiPSC-CMs displayed several rhythm alterations such as early afterdepolarizations, spontaneous quiescence and spontaneous tachyarrhythmia, and significantly slower recovery in chronotropic changes induced by isoproterenol exposure. CONCLUSIONS: Our results highlight the need for vigilant cardiac monitoring in FPLD, especially in patients with LMNA variants who have an increased risk of developing cardiac arrhythmias. In addition, hiPSC-CMs can be studied to understand the basic mechanisms for the arrhythmias in patients with lipodystrophy to understand the impact of specific mutations.

Management of heart failure in patients with end-stage kidney disease on maintenance dialysis: a practical guide.

End-stage kidney disease (ESKD) and heart failure (HF) often coexist and must be managed simultaneously. Multidisciplinary collaboration between nephrology and cardiology is critical when treating patients with such complicated physiology. There is no "one-size-fits-all" approach to the evaluation of patients with new left ventricular systolic dysfunction, and diagnostic testing should be adapted to an individual's risk factors. Guideline-directed medical therapy (GDMT) for systolic heart failure should be employed in these patients. While limited randomized data exist, observational data and post hoc analyses suggest that GDMT, including renin angiotensin aldosterone system inhibitors, is associated with improved cardiovascular outcomes and can be safely initiated at low doses with close monitoring of kidney function in this population. Volume status is typically managed through ultrafiltration, so close communication between cardiology and nephrology is necessary to achieve a patient's optimal dry weight and mitigate intradialytic hypotension. Patient education and engagement regarding sodium and fluid restriction is crucial, and symptom burden should be reassessed following changes to the dialysis regimen.

Practical Guide to Evaluating Myocardial Disease by Cardiac MRI.

OBJECTIVE. A spectrum of pathophysiologic mechanisms can lead to the development of myocardial disorders including ischemia, genetic abnormalities, and systemic disorders. Cardiac MRI identifies different myocardial disorders, provides prognostic information, and directs therapy. In comparison with other imaging modalities, cardiac MRI has the advantage of allowing both functional assessment and tissues characterization in a single examination without the use of ionizing radiation. Newer cardiac MRI techniques including mapping can provide additional information about myocardial disease that may not be detected using conventional techniques. Emerging techniques including MR spectroscopy and finger printing will likely change the way we understand the pathophysiology mechanisms of the wide array of myocardial disorders. CONCLUSION. Imaging of myocardial disorders encompasses a large variety of conditions including both ischemic and nonischemic diseases. Cardiac MRI sequences, such as balanced steady-state free precession and late gadolinium enhancement, play a critical role in establishing diagnosis, determining prognosis, and guiding therapeutic management. Additional sequences-including perfusion imaging, T2*, real-time cine, and T2-weighted sequences-should be performed in specific clinical scenarios. There is emerging evidence for the use of mapping in imaging of myocardial disease. Multiple other new techniques are currently being studied. These novel techniques will likely change the way myocardial disorders are understood and diagnosed in the near future.

Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States.

BACKGROUND: Patients with end-stage kidney disease (ESKD) on dialysis were excluded from clinical trials of direct oral anticoagulants for atrial fibrillation (AF). Recent data have raised concerns regarding the safety of dabigatran and rivaroxaban, but apixaban has not been evaluated despite current labeling supporting its use in this population. The goal of this study was to determine patterns of apixaban use and its associated outcomes in dialysis-dependent patients with ESKD and AF. METHODS: We performed a retrospective cohort study of Medicare beneficiaries included in the United States Renal Data System (October 2010 to December 2015). Eligible patients were those with ESKD and AF undergoing dialysis who initiated treatment with an oral anticoagulant. Because of the small number of dabigatran and rivaroxaban users, outcomes were only assessed in patients treated with apixaban or warfarin. Apixaban and warfarin patients were matched (1:3) based on prognostic score. Differences between groups in survival free of stroke or systemic embolism, major bleeding, gastrointestinal bleeding, intracranial bleeding, and death were assessed using Kaplan-Meier analyses. Hazard ratios (HRs) and 95% CIs were derived from Cox regression analyses. RESULTS: The study population consisted of 25 523 patients (45.7% women; 68.2±11.9 years of age), including 2351 patients on apixaban and 23 172 patients on warfarin. An annual increase in apixaban prescriptions was observed after its marketing approval at the end of 2012, such that 26.6% of new anticoagulant prescriptions in 2015 were for apixaban. In matched cohorts, there was no difference in the risks of stroke/systemic embolism between apixaban and warfarin (HR, 0.88; 95% CI, 0.69-1.12; P=0.29), but apixaban was associated with a significantly lower risk of major bleeding (HR, 0.72; 95% CI, 0.59-0.87; P<0.001). In sensitivity analyses, standard-dose apixaban (5 mg twice a day; n=1034) was associated with significantly lower risks of stroke/systemic embolism and death as compared with either reduced-dose apixaban (2.5 mg twice a day; n=1317; HR, 0.61; 95% CI, 0.37-0.98; P=0.04 for stroke/systemic embolism; HR, 0.64; 95% CI, 0.45-0.92; P=0.01 for death) or warfarin (HR, 0.64; 95% CI, 0.42-0.97; P=0.04 for stroke/systemic embolism; HR, 0.63; 95% CI, 0.46-0.85; P=0.003 for death). CONCLUSIONS: Among patients with ESKD and AF on dialysis, apixaban use may be associated with a lower risk of major bleeding compared with warfarin, with a standard 5 mg twice a day dose also associated with reductions in thromboembolic and mortality risk.

Right ventricular strain in pulmonary arterial hypertension: a 2D echocardiography and cardiac magnetic resonance study.

BACKGROUND: Right ventricular (RV) strain is a potentially useful prognostic marker in patients with pulmonary arterial hypertension (PAH). However, published reports regarding the accuracy of two-dimensional echocardiography (2DE)-derived RV strain against an independent reference in this patient population are limited. The aims of this study were: (1) to study the relationship between 2DE RV longitudinal strain and cardiovascular magnetic resonance (CMR)-derived RV ejection fraction (RVEF) in patients with PAH; (2) to compare 2DE-derived and CMR-derived RV longitudinal strain in these patients; and (3) to determine the reproducibility of these measurements. METHODS: Thirty patients with PAH underwent 2DE and CMR imaging within a 2-hour time period. 2DE RV longitudinal strain was measured from a focused RV apical four-chamber view using speckle tracking software. CMR RV longitudinal strain was measured from short-axis slices acquired using fast-strain-encoded sequence. Global peak systolic RV longitudinal strain was calculated for both 2DE and CMR. RESULTS: RV longitudinal strain using 2DE software correlated well with CMR-derived RVEF (R = 0.69, P = 0.0006). There was moderate agreement when comparing 2DE to CMR RV longitudinal strain (R = 0.74, P = 0.0002; bias -1%, limits of agreement -9 to 7%). Inter-observer variability and intra-observer variability for RV longitudinal strain were lower for 2DE than CMR. CONCLUSIONS: RV longitudinal strain by 2DE provides a good alternative for CMR-derived RVEF in patients with PAH. The moderate agreement in strain measurements between 2DE and CMR suggests that further software improvements are needed before these measurements can be used interchangeably in clinical practice.

Assessing trends and variability in outpatient dual testing for chronic kidney disease with urine albumin and serum creatinine, 2009-2018: a retrospective cohort study in the Veterans Health Administration System.

BACKGROUND: Simultaneous urine testing for albumin (UAlb) and serum creatinine (SCr), that is, 'dual testing,' is an accepted quality measure in the management of diabetes. As chronic kidney disease (CKD) is defined by both UAlb and SCr testing, this approach could be more widely adopted in kidney care. OBJECTIVE: We assessed time trends and facility-level variation in the performance of outpatient dual testing in the integrated Veterans Health Administration (VHA) system. DESIGN, SUBJECTS AND MAIN MEASURES: This retrospective cohort study included patients with any inpatient or outpatient visit to the VHA system during the period 2009-2018. Dual testing was defined as UAlb and SCr testing in the outpatient setting within a calendar year. We assessed time trends in dual testing by demographics, comorbidities, high-risk (eg, diabetes) specialty care and facilities. A generalised linear mixed-effects model was applied to explore individual and facility-level predictors of receiving dual testing. KEY RESULTS: We analysed data from approximately 6.9 million veterans per year. Dual testing increased, on average, from 17.4% to 21.2%, but varied substantially among VHA centres (0.3%-43.7% in 2018). Dual testing was strongly associated with diabetes (OR 10.4, 95% CI 10.3 to 10.5, p<0.0001) and not associated with VHA centre complexity level. However, among patients with high-risk conditions including diabetes, <50% received dual testing in any given year. As compared with white veterans, black veterans were less likely to be tested after adjusting for other individual and facility characteristics (OR 0.93, 95% CI 0.92 to 0.93, p<0.0001). CONCLUSIONS: Dual testing for CKD in high-risk specialties is increasing but remains low. This appears primarily due to low rates of testing for albuminuria. Promoting dual testing in high-risk patients will help to improve disease management and patient outcomes.

Association of Cardiopulmonary Hemodynamics and Outcomes in Pulmonary Hypertension Following Kidney Transplant: A Multicenter Retrospective Cohort Study.

BACKGROUND: Pulmonary Hypertension (PH) frequently complicates the evaluation of kidney transplant (KT) candidates, and is associated with increased adverse outcomes (mortality, delayed graft function (DGF), and major adverse cardiovascular events (MACE)) following KT. RESEARCH QUESTION: What is the relationship between cardiopulmonary hemodynamics and post-KT outcomes? STUDY DESIGN AND METHODS: We conducted a multicenter retrospective cohort study of adults undergoing KT between 10/1/11 and 10/1/21, who underwent right heart catheterization (RHC) to assess cardiopulmonary hemodynamics within a year of transplantation. Frailty models and logistic regression models were used to evaluate the association between cardiopulmonary hemodynamics and outcomes (mortality, DGF, MACE) following KT. RESULTS: A total of 117 patients were included in the final analysis, predominantly male (72%), with a median age of 57 years. PH, defined as mean pulmonary artery pressure (mPAP) > 20mmHg, was present in the majority of the cohort (N=93, 79%). The cohort was followed for a median of 29.9 months post-KT, during which about one-fourth experienced mortality (23%) or DGF (25%) events, and approximately one-third (34%) experienced MACE. Though echocardiographic measures of pulmonary artery pressure failed to identify post-KT outcomes, a mPAP of ≥ 30mmHg on RHC was associated with post-KT MACE (Hazard Ratio 2.60, 95% Confidence Interval [1.10, 6.10]) and more prevalent in those experiencing post-KT mortality (63% vs 32%, p=0.001). Pre-capillary pulmonary hypertension was also associated with post-KT mortality (Hazard Ratio 3.71, 95% Confidence Interval [1.07, 12.90]). INTERPRETATION: Pre-capillary pulmonary hypertension and a mPAP of ≥ 30mmHg on RHC, but not echocardiographic evidence of PH, was associated with mortality and MACE following KT. These data suggest that RHC hemodynamics are superior to echocardiographic measures of PH in associating with outcomes following KT, and RHC-derived mPAP in particular may have value in predicting MACE and mortality post-KT.

Evaluation of left ventricular structure and function by three-dimensional echocardiography.

PURPOSE OF REVIEW: To summarize research on the use of 3-dimensional (3D) echocardiography for quantifying left ventricular (LV) volumes, ejection fraction, and mass, and to describe emerging applications of the technology. RECENT FINDINGS: Several publications have provided reference values for LV volumes and ejection fraction by 3D transthoracic echocardiography (3DTTE) in normal patients. SUMMARY: With real-time 3DTTE, one can acquire and display a 3D image encompassing the entire LV within seconds. Because 3DTTE aids in identification of the true LV apex, it provides more accurate LV volumes than its 2D counterpart. As compared with a cardiovascular magnetic resonance standard, 3DTTE tends to slightly underestimate LV volumes, in part because its spatial resolution is limited, making identification of the true endocardial border more difficult. As compared with 2DTTE, 3DTTE is advantageous for identifying and assessing the extent of regional wall motion abnormalities. For quantification of LV mass, 3DTTE is superior to both 2DTTE and M-mode echocardiography. Emerging applications of 3DTTE include speckle-tracking strain assessment, dyssynchrony analysis, and LV shape analysis, which appear to have prognostic value in patients with a variety of cardiac conditions.

Prognostic value of normal regadenoson stress perfusion cardiovascular magnetic resonance.

BACKGROUND: Regadenoson is a vasodilator stress agent that selectively activates the A2A receptor. Compared to adenosine, regadenoson is easier to administer and results in fewer side effects. Although extensively studied in patients undergoing nuclear perfusion imaging (MPI), its use for perfusion cardiovascular magnetic resonance (CMR) is not well described. The aim of this study was to determine the prognostic value of a normal regadenoson perfusion CMR in patients with known or suspected coronary artery disease. METHODS: Patients with known or suspected coronary artery disease were prospectively enrolled to receive perfusion CMR (Philips 1.5 T) with regadenoson. Three short-axis slices of the left ventricle (LV) were obtained during first pass of contrast using a hybrid GRE-EPI pulse sequence (0.075 mmol/kg Gadolinium-DTPA-BMA at 4 ml/sec). Imaging was performed 1 minute after injection of regadenoson (0.4 mg) and repeated 15 minutes after reversal of hyperemia with aminophylline (125 mg). Perfusion defects were documented if they persisted for ≥ 2 frames after peak enhancement of the LV cavity. CMR was considered abnormal if there was a resting wall motion abnormality, decreased LVEF (<40%), presence of LGE, or the presence of a perfusion defect during hyperemia. All patients were followed for a minimum of 1 year for major adverse cardiovascular event (MACE) defined as coronary revascularization, non-fatal myocardial infarction, and cardiovascular death. RESULTS: 149 patients were included in the final analysis. Perfusion defects were noted in 43/149 (29%) patients; 59/149 (40%) had any abnormality on CMR. During the mean follow-up period of 24 ± 9 months, 17/149 (11.4%) patients experienced MACE. The separation in the survival distributions for those with perfusion defects and those without perfusion defects was highly significant (log-rank p = 0.0001). When the absence of perfusion defects was added to the absence of other resting CMR abnormalities, the negative predictive value improved from 96% to 99%. CONCLUSION: Regadenoson perfusion CMR provides high confidence for excellent prognosis in patients with normal perfusion.

Postextrasystolic potentiation in low-gradient, severe aortic stenosis: a poor man's stress echo?

An elderly man with dyspnea and syncope was found to have severe aortic stenosis (AS) by the continuity equation, despite a transaortic gradient that was only moderately elevated, in the setting of severe left ventricular dysfunction. The transaortic gradient increased during postextrasystolic beats, suggesting that his that his AS was truly severe; this was confirmed by dobutamine echocardiography. He underwent transcatheter aortic-valve replacement (TAVR), with subsequent improvement in left ventricular systolic function. The diagnostic and prognostic significance of postextrasystolic potentiation, with associated increase in aortic stenosis gradient, deserves renewed attention in the TAVR era.

Inflammatory and thrombotic valvulopathies in autoimmune disease.

Rheumatologic diseases are characterised by loss of immune tolerance, resulting in systemic inflammation. Inflammation and scarring of the endocardium, which lines the inner surface of the heart chambers and valves, can result in valvular thickening and dysfunction. Estimates of prevalence vary depending on the sensitivity of the screening methodology used and range from 30%-50% in systemic lupus and rheumatoid arthritis to 10%-30% in ankylosing spondylitis. Progression of valve disease is a slow process but can result in haemodynamically significant complications. Thromboembolic complications such as cerebrovascular occlusions pose a serious risk of morbidity. The presence of antiphospholipid antibodies increases the risk of valvular disease and thrombotic complications. Anticoagulation is recommended in the presence of antiphospholipid antibodies, but the guidance on the role of immunosuppressive therapy to treat valvular disease is lacking. Surgical valve therapy may be considered in severe disease, but there is increased risk in patients with an autoimmune disease which includes a higher risk of infection, thromboembolic and bleeding complications, as well as cardiovascular events in the setting of premature atherosclerotic heart disease. Therefore, management should be provided in a multidisciplinary team that includes a rheumatologist, a cardiologist and a cardiothoracic surgeon; medical therapy should be optimised before considering a high-risk valve surgery.

Considerations when measuring myocardial perfusion reserve by cardiovascular magnetic resonance using regadenoson.

BACKGROUND: Adenosine cardiovascular magnetic resonance (CMR) can accurately quantify myocardial perfusion reserve. While regadenoson is increasingly employed due to ease of use, imaging protocols have not been standardized. We sought to determine the optimal regadenoson CMR protocol for quantifying myocardial perfusion reserve index (MPRi) - more specifically, whether regadenoson stress imaging should be performed before or after rest imaging. METHODS: Twenty healthy subjects underwent CMR perfusion imaging during resting conditions, during regadenoson-induced hyperemia (0.4 mg), and after 15 min of recovery. In 10/20 subjects, recovery was facilitated with aminophylline (125 mg). Myocardial time-intensity curves were used to obtain left ventricular cavity-normalized myocardial up-slopes. MPRi was calculated in two different ways: as the up-slope ratio of stress to rest (MPRi-rest), and the up-slope ratio of stress to recovery (MPRi-recov). RESULTS: In all 20 subjects, MPRi-rest was 1.78 ± 0.60. Recovery up-slope did not return to resting levels, regardless of aminophylline use. Among patients not receiving aminophylline, MPRi-recov was 36 ± 16% lower than MPRi-rest (1.13 ± 0.38 vs. 1.82 ± 0.73, P = 0.001). In the 10 patients whose recovery was facilitated with aminophylline, MPRi-recov was 20 ± 24% lower than MPRi-rest (1.40 ± 0.35 vs. 1.73 ± 0.43, P = 0.04), indicating incomplete reversal. In 3 subjects not receiving aminophylline and 4 subjects receiving aminophylline, up-slope at recovery was greater than at stress, suggesting delayed maximal hyperemia. CONCLUSIONS: MPRi measurements from regadenoson CMR are underestimated if recovery perfusion is used as a substitute for resting perfusion, even when recovery is facilitated with aminophylline. True resting images should be used to allow accurate MPRi quantification. The delayed maximal hyperemia observed in some subjects deserves further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00871260.