Incidence, Predictors, and Outcomes of New-Onset Left Ventricular Systolic Dysfunction After Orthotopic Liver Transplantation.

BACKGROUND: Adverse cardiovascular events after liver transplantation (LT) are relatively common and are a significant source of early mortality. Although new-onset systolic dysfunction after LT is a reported phenomenon, there is little data regarding its incidence, risk factors, and outcomes. METHODS AND RESULTS: This single-center retrospective study included all adult patients from January 2002 to March 2015 with deceased-donor LT and available preoperative transthoracic echocardiograms (TTEs). In total, 1,760 patients were included in the study, 602 (34.2%) of whom had a postoperative TTE. The primary end point was development of new-onset cardiomyopathy, defined as a new left ventricular ejection fraction (LVEF) of <40% within 180days of transplant. Sixty-nine (11.4%) of the patients who received post-LT TTE had a reduction in LVEF to <40% within 6 months. Clinical parameters of donor and recipient did not show significant impact on development of post-LT LV systolic dysfunction (LVSD). Presence of wall motion abnormalities (P = .004) on preoperative TTE was predictive of development of post-LT LVSD. These patients did not have longer hospitalizations, but they had worse survival. CONCLUSIONS: Post-LT LV systolic dysfunction occurs at higher rates than previously suspected and may develop more frequently in patients with underlying cardiac structural abnormalities, which appear to adversely affect post-LT survival.

Myocardial functional changes in transfemoral versus transapical aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has greatly expanded the treatment options available for patients with severe aortic stenosis at high surgical risk. MATERIALS AND METHODS: We compared changes in myocardial function in TAVR with a transfemoral (TF) versus a transapical (TA) approach at a major tertiary hospital from 2012-2016. Traditional echocardiographic measures of cardiac structure and function were tracked, alongside the use of two-dimensional speckle tracking echocardiography to measure myocardial strain and strain rates. RESULTS: For the entire cohort with complete data at all time points (n = 42), between the pre-TAVR baseline (mean: 20.1 d) and the post-TAVR 1-mo follow-up (mean: 32.7 d), global longitudinal strain significantly increased (from -15.6% to -18.2%, P < 0.001). When comparing the TF (n = 31) and TA (n = 11) groups, TA patients showed persistently impaired apical longitudinal strain at the 1-mo follow-up (-15.9% versus -22.3%, P < 0.05). In terms of clinical outcomes, both groups (n = 131 for TF, n = 53 for TA) were similar in terms of 30-d mortality, readmission rate, and risk of post-TAVR acute kidney injury. However, TA patients experienced significantly longer length of hospitalization (7.58 versus 3.92 d, P = 0.02), intensive care unit hours (105.4 versus 47.1 h, P = 0.02), and were at a greater risk of long-term (>72 h) intensive care unit stay (45% versus 25%, P = 0.01). CONCLUSIONS: Patients undergoing TA-TAVR exhibit impaired apical longitudinal strain, although global myocardial function is similar to TF-TAVR otherwise. Myocardial strain measured by two-dimensional speckle tracking echocardiography appears to be a sensitive method to detect subtle cardiac remodeling after TAVR.

Cardiac Amyloidosis: Diagnosis and Treatment Strategies.

Cardiac amyloidosis in the United States is most often due to myocardial infiltration by immunoglobulin protein, such as in AL amyloidosis, or by the protein transthyretin, such as in hereditary and senile amyloidosis. Cardiac amyloidosis often portends a poor prognosis especially in patients with systemic AL amyloidosis. Despite better understanding of the pathophysiology of amyloid, many patients are still diagnosed late in the disease course. This review investigates the current understanding and new research on the diagnosis and treatment strategies in patients with cardiac amyloidosis. Myocardial amyloid infiltration distribution occurs in a variety of patterns. Structural and functional changes on echocardiography can suggest presence of amyloid, but CMR and nuclear imaging provide important complementary information on amyloid burden and the amyloid subtype, respectively. While for AL amyloid, treatment success largely depends on early diagnosis, for ATTR amyloid, new investigational agents that reduce production of transthyretin protein may have significant impact on clinical outcomes. Advancements in the non-invasive diagnostic detection and improvements in early disease recognition will undoubtedly facilitate a larger proportion of patients to receive early therapy when it is most effective.

Changes in myocardial deformation after transcatheter and surgical aortic valve replacement.

Speckle tracking echocardiography (STE) has emerged as a novel angle-independent modality in assessing myocardial velocity, deformation, and strain. Its role in assessing change before and after aortic valve replacement in patients with aortic stenosis (AS) has recently generated interest. This review summarizes the practical utility and clinical implications of myocardial deformation by STE after surgical or transcatheter aortic valve replacement (TAVR). Overall, atrial strain and ventricular strain as measured by STE improve after surgical and transcatheter aortic intervention in short- and long-term follow-up with evidence of a more pronounced acute improvement in patients who undergo TAVR. STE assessment of strain, particularly global longitudinal strain, can detect subtle changes in myocardial systolic function prior to conventional variables such as left ventricular ejection fraction and is clinically useful in predicting mortality and symptom development in patients with AS. This underscores the emerging role of STE in monitoring post-procedural improvements in cardiac function as well as the potential value in guiding optimal timing of AS intervention.

Echocardiography and Alternative Cardiac Imaging Strategies for Long-Term Cardiotoxicity Surveillance of Cancer Survivors Treated with Chemotherapy and/or Radiation Exposure.

Cardiotoxicity from chemotherapy is a leading cause of morbidity and mortality in cancer survivors. Cardiotoxic effects include left ventricular systolic dysfunction, coronary artery disease, hypertension, bradycardia, arrhythmias, pericardial disease, valvular disease, and radiation-induced restrictive cardiomyopathy. Noninvasive cardiac imaging has been at the forefront of detecting cardiotoxicity in patients receiving chemotherapeutic agents known to adversely affect cardiac structure and function. Regimens for cardiotoxicity surveillance prior to and during chemotherapy administration have been proposed; however, optimal screening for and treatment of long-term cancer survivors have yet to be clarified. This review focuses on the most common imaging modalities for assessing cardiac dysfunction along with newer imaging technologies, and reviews suggested long-term surveillance strategies in cancer survivors following chemotherapy and radiation therapy.

Concepts in cardio-oncology: definitions, mechanisms, diagnosis and treatment strategies of cancer therapy-induced cardiotoxicity.

There has been considerable improvement in cancer survival rates, primarily through improved preventive strategies and novel anticancer drugs. Cancer is now becoming a chronic illness and as such both short and long-term cardiotoxic effects of cancer therapy are becoming more apparent. This has led to the emergence of a new multidisciplinary specialty known as cardio-oncology, with the purpose of identifying patients who are at a higher risk for developing cardiotoxicity so that appropriate surveillance, treatment and follow-up strategies may be instituted early. The mechanisms of cardiotoxicity caused by commonly used anticancer agents are reviewed, along with the latest advances in diagnostic and preventative strategies, with the overall objective of allowing cancer patients to continue both lifesaving and palliative treatments for their malignancy.

Comprehensive hemodynamic performance and frequency of patient-prosthesis mismatch of the St. Jude Medical Trifecta bioprosthetic aortic valve.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the performance of a new stented pericardial bioprosthesis, the Trifecta (St. Jude Medical, St. Paul, MN, USA), for aortic valve replacement (AVR) with respect to valvular hemodynamics and frequency of patient-prosthesis mismatch (PPM). PPM has been reported in a wide range of bioprosthetic valves following AVR, and has been associated with multiple adverse outcomes. It was hypothesized that the Trifecta aortic valve would have superior hemodynamics and an acceptable incidence of PPM following AVR. METHODS: A prospective cohort study was performed between January 2010 and May 2012, following 75 patients (mean age 71.9 _ 11.1 years) who had undergone AVR with a Trifecta valve for aortic stenosis (88%) or regurgitation (12%) at the authors' institutions. Intraoperative three-dimensional and Doppler transesophageal echocardiography were used to evaluate hemodynamic variables before and after AVR, as well as pre-discharge. RESULTS: Echocardiographic evaluation showed a preoperative average mean gradient (MG) of 40.6 ± 21.6 mmHg, an average peak gradient (PG) of 72.1 ± 19.4 mmHg, and an average effective orifice area index (EOAI) of 0.39 ± 0.20 cm2/m2. Postoperative mean pressure gradient measurements showed a postoperative average MG of 8.76 ± 3.75 mmHg (p < 0.001), an average PG of 19.4 ± 8.6 mmHg (p < 0.001), and EOAI of 1.09 ± 0.36 cm2/m2 (p < 0.001), which demonstrated a significantly improved hemodynamic performance across all valve sizes. Postoperative MG versus measured EOAI demonstrated a fairly linear relationship (R2 = 0.0703), rather than a rapid increase in MG with EOAI < 0.85 and < 0.65, as was seen with previous valve designs. Severe PPM (defined as EOAI ≤ 0.65 cm2/m2) was found in four patients (6%), while moderate PPM (EOAI > 0.65 and < 0.85 cm2/m2) was seen in 11 patients (16%). CONCLUSION: The Trifecta pericardial valve demonstrated excellent hemodynamic performance at all valve sizes, and resulted in very low postoperative transvalvular pressure gradients and PPM, without the need for aortic root enlargement.

Small molecule disruption of G beta gamma signaling inhibits the progression of heart failure.

RATIONALE: Excess signaling through cardiac Gbetagamma subunits is an important component of heart failure (HF) pathophysiology. They recruit elevated levels of cytosolic G protein-coupled receptor kinase (GRK)2 to agonist-stimulated beta-adrenergic receptors (beta-ARs) in HF, leading to chronic beta-AR desensitization and downregulation; these events are all hallmarks of HF. Previous data suggested that inhibiting Gbetagamma signaling and its interaction with GRK2 could be of therapeutic value in HF. OBJECTIVE: We sought to investigate small molecule Gbetagamma inhibition in HF. METHODS AND RESULTS: We recently described novel small molecule Gbetagamma inhibitors that selectively block Gbetagamma-binding interactions, including M119 and its highly related analog, gallein. These compounds blocked interaction of Gbetagamma and GRK2 in vitro and in HL60 cells. Here, we show they reduced beta-AR-mediated membrane recruitment of GRK2 in isolated adult mouse cardiomyocytes. Furthermore, M119 enhanced both adenylyl cyclase activity and cardiomyocyte contractility in response to beta-AR agonist. To evaluate their cardiac-specific effects in vivo, we initially used an acute pharmacological HF model (30 mg/kg per day isoproterenol, 7 days). Concurrent daily injections prevented HF and partially normalized cardiac morphology and GRK2 expression in this acute HF model. To investigate possible efficacy in halting progression of preexisting HF, calsequestrin cardiac transgenic mice (CSQ) with extant HF received daily injections for 28 days. The compound alone halted HF progression and partially normalized heart size, morphology, and cardiac expression of HF marker genes (GRK2, atrial natriuretic factor, and beta-myosin heavy chain). CONCLUSIONS: These data suggest a promising therapeutic role for small molecule inhibition of pathological Gbetagamma signaling in the treatment of HF.

Aberrant penetrating posterior descending artery from proximal right coronary artery.

We report a rare variant of the posterior descending artery (PDA) in a 51-year-old African-American male discovered in coronary CT angiography. Arising from the proximal right coronary artery near its ostium, the anomalous PDA penetrated posteriorly toward the atrioventricular junction septum, exited through the inferior pyramidal space into the posterior interventricular groove and continued in the groove as a short PDA. Along its course it gave rise to small branches to the medial wall of the right atrium, the atrioventricular node region, and the inferoseptal wall of the right ventricle.

Change in Invasively Measured Mean Pulmonary Artery Pressure After Transcatheter Mitral Valve Repair Is Associated With Heart Failure Readmission.

BACKGROUND: Pre-existing pulmonary hypertension is associated with poor outcomes after transcatheter mitral valve repair (TMVr) for mitral regurgitation (MR). However, the impact of an immediate change in mean pulmonary artery pressure (ΔmPAP) following TMVr on outcomes is unknown. METHODS: Patients who underwent TMVr from December 2015 to February 18, 2020 at our institution for symptomatic 3-4+ MR and who had invasive hemodynamics measured immediately pre- and post-TMVR were included. Multivariate Cox regression analysis was performed to examine the association of ΔmPAP (post-TMVr - pre-TMVr mPAP) with the primary endpoint of heart failure (HF) readmission at 1 year. Secondary endpoints included all-cause mortality and the composite endpoint of HF readmission or all-cause mortality at 1 year. RESULTS: Among 55 patients, 55% were men, mean age was 72 ± 14.2 years, and mean ΔmPAP was -1.4 ± 8.2 mm Hg. Overall, HF readmission occurred in 14 (25%), death in 10 (18%), and the composite endpoint in 20 (36%) patients. In multivariable analyses, higher ΔmPAP was significantly associated with HF readmission (hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.00 - 1.21; P = 0.04). ΔmPAP was not associated with death (HR = 1.04, 95% CI: 0.96 - 1.14; P = 0.33), though there was a numerical but statistically non-significant trend towards the composite endpoint (HR = 1.06, 95% CI: 1.00 - 1.13; P = 0.06) driven by HF readmission. CONCLUSION: Higher ΔmPAP immediately following TMVr was associated with increased HF readmission at 1 year. Larger prospective studies are needed to validate these data and further explore the utility of ΔmPAP as a novel hemodynamic parameter to predict post-TMVR outcomes.

Incidence and prognostic implication of unrecognized myocardial scar characterized by cardiac magnetic resonance in diabetic patients without clinical evidence of myocardial infarction.

BACKGROUND: Silent myocardial infarctions (MIs) are prevalent among diabetic patients and inflict significant morbidity and mortality. Although late gadolinium enhancement (LGE) imaging by cardiac magnetic resonance (CMR) can provide sensitive characterization of myocardial scar, its prognostic significance in diabetic patients without any clinical evidence of MI is unknown. METHODS AND RESULTS: We performed clinically indicated CMR imaging in 187 diabetic patients who were grouped by the absence (study group, n=109) or presence (control group, n=78) of clinical evidence of MI (clinical history of MI or Q waves on ECG). CMR imaging and follow-up were successful in 107 study patients (98%) and 74 control patients (95%). Cox regression analyses were performed to associate LGE with major adverse cardiovascular events (MACE), including death, acute MI, new congestive heart failure or unstable angina, stroke, and significant ventricular arrhythmias. LGE by CMR was present in 30 of 107 study patients (28%). At a median follow-up of 17 months, 38 of 107 patients (36%) experienced MACE, which included 18 deaths. Presence of LGE was associated with a >3-fold hazards increase for MACE and for death (hazard ratio, 3.71 and 3.61; P<0.001 and P=0.007, respectively). Adjusted to a model that combines patient age, sex, ST or T changes on ECG, and left ventricular end-systolic volume index, LGE maintained a >4-fold hazards increase for MACE (adjusted hazard ratio, 4.13; 95% confidence interval, 1.74 to 9.79; P=0.001). In addition, LGE provided significant prognostic value with MACE and with death adjusted to a diabetic-specific risk model for 5-year events. The presence of LGE was the strongest multivariable predictor of MACE and death by stepwise selection in the study patients. CONCLUSIONS: CMR imaging can characterize occult myocardial scar consistent with MI in diabetic patients without clinical evidence of MI. This imaging finding demonstrates strong association with MACE and mortality hazards that is incremental to clinical, ECG, and left ventricular function combined.

Significance of Coronary Artery Calcium Found on Non-Electrocardiogram-Gated Computed Tomography During Preoperative Evaluation for Liver Transplant.

Guidelines to evaluate patients for coronary artery disease (CAD) during preoperative evaluation for orthotopic liver transplantation (OLT) are conflicting. Cardiac catheterization is not without risk in patients with end-stage liver disease. No study to date has looked at the utility of non-electrocardiogram-gated chest computed tomography (CT) in the preliver transplant population. Our hypothesis was that coronary artery calcium scores (CACSs) from chest CT scans ordered during the liver transplant workup can identify patients who would benefit from invasive angiography. Nine hundred and fifty-three patients who underwent coronary angiography as part of their OLT workup were considered. Charts were randomly selected and reviewed for the presence of a chest CT performed before coronary angiography during the OLT workup. Agatston and Weston scores were calculated. CACS results were compared with coronary angiography findings. Nine of 54 patients were found to have obstructive CAD by angiography. Receiver-operating characteristic analysis demonstrated that an Agatston score of 251 and a Weston score of 6 maximized sensitivity and specificity for detection of obstructive coronary disease. An Agatston score <4 or Weston score <2 excluded the presence of obstructive CAD; using these thresholds, 13 patients (24%) or 15 patients (28%), respectively, could have theoretically avoided catheterization without missing significant CAD. In conclusion, our data identify the strength of CACS in ruling out coronary disease in patients being evaluated for OLT. Calcium scoring from non-electrocardiogram-gated CT studies may be integrated into preoperative algorithms to rule out obstructive CAD and help avoid invasive angiography in this high-risk population.

Brugada syndrome with marked conduction disease: dual implications of a SCN5A mutation.

A 51-year-old woman presented with an episode of syncope. Upon further review she was found to have a typical Brugada type pattern on her electrocardiogram. She did not have evidence for structural heart disease. At electrophysiological testing she was found to have marked infrahisian conduction disease and had easily inducible polymorphic ventricular tachycardia. She underwent implantation of a dual-chamber implantable cardioverter defibrillator (ICD) and family screening was recommended. Genetic analysis revealed a novel nonsense mutation in the gene encoding for the sodium channel (SCN5A). Five months after ICD implantation the patient had an episode of ventricular fibrillation documented on ICD interrogation. This case is unique as it is consistent with an overlap syndrome, namely both Brugada Syndrome and distal atrioventricular (AV) conduction disease secondary to a novel SCN5A mutation in a young female. This finding highlights the phenotypic heterogeneity of novel SCN5A mutations.

Ruptured Papillary Muscles After Chordae-Preserving Bioprosthetic Mitral Valve Replacement.

Bioprosthetic valve-associated masses in the perioperative period are rare. This report describes the case of a 68-year-old man with perivalvular masses that were initially discovered on a routine postoperative transthoracic echocardiogram 7 days after chordae-preserving mitral valve replacement and coronary artery bypass grafting. An intraoperative transesophageal echocardiogram demonstrated ruptured papillary muscles. This case report describes the differential diagnosis and surgical management of this rare finding.