Myocardial strain is associated with adverse cardiac events in patients treated with chimeric antigen receptor (CAR) T-cell therapy.

BACKGROUND: Cardiovascular events, including heart failure and arrhythmias, following chimeric antigen receptor (CAR) T-cell therapy are increasingly recognized. Although global longitudinal strain (GLS) has demonstrated prognostic utility for other cancer therapy-related cardiac dysfunction, less is known regarding the association of GLS with adverse cardiac events following CAR T-cell therapy. OBJECTIVES: To determine the association of baseline GLS with adverse cardiovascular events in adults receiving CAR-T cell therapy. METHODS: Patients who had an echocardiogram within 6 months prior to receiving CAR T-cell therapy were retrospectively identified. Clinical data and cardiac events were collected via chart review. Echocardiograms were analyzed offline for GLS, left ventricular ejection fraction, and Doppler parameters. Multivariable logistic regression was used to determine the association between adverse cardiovascular events and echocardiographic parameters. RESULTS: Among 75 CAR T-cell therapy patients (mean age 63.9, 34.7% female), nine patients (12%) experienced cardiac events (CEs) including cardiovascular death, new/worsening heart failure, and new/worsening arrhythmia within 1 year of treatment. In univariable models, higher baseline GLS (OR 0.78 [0.63, 0.96], p = .021) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.40 [1.08, 1.81], p = .012) was associated with a higher risk of CE. After adjusting for age and LDH, higher baseline GLS (OR 0.65 [0.48-0.88], p = <.01) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.56 [1.06, 2.29], p = .024) was associated with a higher risk of CE. CONCLUSION: Lower GLS and higher mitral E/e' on a baseline echocardiogram were associated with higher risk for CEs in patients receiving CAR T-cell therapy.

Syndromes of Concurrent Hypertension, Diastolic Dysfunction, and Pulmonary or Peripheral Edema in Cardio-Oncology: Case Studies, Literature Review, and New Classification System.

OPINION STATEMENT: Individuals who have ever been diagnosed with cancer are at increased risk for cardiovascular conditions during and after cancer treatment. Especially during cancer treatment, cardiovascular conditions can manifest in many ways, including peripheral or pulmonary edema. Edema can indicate volume overload affecting the heart even without other unequivocal evidence of apparent diastolic or systolic left ventricular dysfunction, particularly at rest. We propose a novel algorithm to streamline the diagnostic evaluation and cardiovascular classification for cancer patients with edema. We initially advise prompt evaluation with a chest X-ray and echocardiogram. We then suggest classification into one of five categories based on the timing of presentation of edema relative to cancer treatment, as well as echocardiography results and the presence or absence of hypertension or lymphatic causes of edema. This classification tool can then be utilized to guide further cardiovascular management suggestions. These concurrent syndromes presenting as edema may indicate the development or aggravation of undiagnosed diastolic dysfunction with or without hypertension, even if transiently present only while on cancer treatment.

In ischemic LV dysfunction, adding PCI to medical therapy did not reduce a composite of death or aborted sudden death.

SOURCE CITATION: Perera D, Morgan HP, Ryan M, et al; REVIVED-BCIS2 Investigators. Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction: prespecified analyses from the REVIVED-BCIS2 trial. Circulation. 2023;148:862-871. 37555345.

Is "moderate" aortic stenosis still the right name? A review of the literature.

Current guidelines recommend aortic valve replacement for symptomatic or selected asymptomatic high-risk patients with severe aortic stenosis. Conversely, a watchful waiting attitude applies to patients with moderate aortic stenosis, regardless of their risk profile and symptoms, until the echocardiographic thresholds of severe aortic stenosis are reached. This strategy is based on data reporting high mortality in untreated severe symptomatic aortic stenosis, whereas moderate aortic stenosis has always been perceived as a non-threatening condition, with a benefit-risk balance against surgery. Meanwhile, numerous studies have reported a worrying event rate in these patients, surgical techniques and outcomes have improved significantly and the use of transcatheter aortic valve replacement has become more widespread and extended to lower-risk patients, leaving this strategy open to question, especially for patients with moderate aortic stenosis and left ventricular dysfunction. In this review, we summarize the current state of knowledge about moderate aortic stenosis progression and prognosis. We also discuss the particular case of moderate aortic stenosis associated with left ventricular dysfunction, and the ongoing trials that that might change our paradigm for the management of this "moderate" valvular heart disease.

Clinical Outcomes by Consolidation of Bone Marrow Stem Cell Therapy and Coronary Artery Bypass Graft in Patients With Heart Failure With Reduced Ejection Fraction: A Meta-analysis.

Bone marrow stem cell (BMSC) transplantation during coronary artery bypass graft (CABG) is an innovative treatment for ischemic heart disease (IHD). We conduct a meta-analysis to examine whether patients with IHD presenting heart failure with reduced ejection fraction (HFrEF) can be beneficent from CABG with additional BMSC transplantation. Electronic searches were performed on PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov from their inception to July 2021. The efficacy was based on left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), and 6-min walk test (6MWT) change after treatment. Eight randomized-controlled trials (RCTs) were included in this meta-analysis, with a total of 350 patients. Results showed BMSC transplantation significantly improved the LVEF [mean difference (MD) = 6.23%, 95% confidence interval (CI): 3.22%-9.24%, P < 0.0001], LVEDVi (MD = -20.15 ml/m2, 95% CI: -30.49 to -9.82 ml/m2, P < 0.00001), and LVESVi (MD = -17.69 ml/m2, 95% CI: -25.24 to -10.14 ml/m2, P < 0.00001). There was no statistically significant difference in the improvement of LVEDD, LVEDV, and 6MWT between the cell transplantation group and control groups. Subgroup analysis revealed that the intervention for control group could affect the efficacy of BMSC transplantation. Sensitivity analysis found the conclusion of LVEDD, LVEDV, and 6MWT changes was not stable. Therefore, among patients with IHD presenting HFrEF, BMSC transplantation during CABG is promising to be beneficial for postoperative left ventricular (LV) function improvement. However, according to the unstable results of the sensitivity analysis, it cannot be concluded whether the extra step has a positive effect on left ventricular remodeling and exercise capacity. RCTs with larger cohorts and more strict protocols are needed to validate these conclusions.

Low left ventricular ejection fraction, complication rescue, and long-term survival after coronary artery bypass grafting.

OBJECTIVES: To evaluate the association between low left ventricular ejection fraction (LVEF), complication rescue, and long-term survival after isolated coronary artery bypass grafting. METHODS: National cohort study of patients who underwent isolated coronary artery bypass grafting (2000-2016) using Veterans Affairs Surgical Quality Improvement Program data. Left ventricular ejection fraction was categorized as ≥35% (n = 55,877), 25%-34% (n = 3893), or <25% (n = 1707). Patients were also categorized as having had no complications, 1 complication, or more than 1 complication. The association between LVEF, complication rescue, and risk of death was evaluated with multivariable Cox regression. RESULTS: Among 61,477 patients, 6586 (10.7%) had a perioperative complication and 2056 (3.3%) had multiple complications. Relative to LVEF ≥35%, decreasing ejection fraction was associated with greater odds of complications (25%-34%, odds ratio, 1.30 [1.18-1.42]; <25%, odds ratio, 1.65 [1.43-1.92]). There was a dose-response relationship between decreasing LVEF and overall risk of death (≥35% [ref]; 25%-35%, hazard ratio, 1.46 [1.37-1.55]; <25%, hazard ratio, 1.68 [1.58-1.79]). Among patients who were rescued from complications, there were decreases in 10-year survival, regardless of LVEF. Among those rescued after multiple complications, LVEF was no longer associated with risk of death. CONCLUSIONS: While decreasing LVEF is associated with post-coronary artery bypass grafting complications, patients rescued from complications have worse long-term survival, regardless of left ventricular function. Prevention and timely treatment of complications should remain a focus of quality improvement initiatives, and future work is needed to mitigate their long-term detrimental impact on survival.

Validation of mitral regurgitation reversibility in patients with HeartMate 3 LVAD implantation.

The resolution of functional mitral valve regurgitation (MR) in patients awaiting left ventricular assist device (LVAD) implantation is discussed controversially. The present study analyzed MR and echocardiographic parameters of the third-generation LVAD HeartMate 3 (HM3) over 3 years. Of 135 LVAD patients (with severe MR, n = 33; with none, mild, or moderate MR, n = 102), data of transthoracic echocardiography were included preoperatively to LVAD implantation, up to 1 month postoperatively, and at 1, 2, and 3 years after LVAD implantation. Demographic data and clinical characteristics were collected. Severe MR was reduced immediately after LVAD implantation in all patients. The echocardiographic parameters left ventricular end-diastolic diameter (P < .001), right ventricular end-diastolic diameter (P < .001), tricuspid annular plane systolic excursion (P < .001), and estimated pulmonary artery pressure (P < .001) decreased after HM3 implantation independently from the grade of MR prior to implantation and remained low during the 2 years follow-up period. Following LVAD implantation, right heart failure, ventricular arrhythmias, ischemic stroke as well as pump thrombosis and bleeding events were comparable between the groups. The incidences of death and cardiac death did not differ between the patient groups. Furthermore, the Kaplan-Meier analysis showed that survival was comparable between the groups (P = .073). HM3 implantation decreases preoperative severe MR immediately after LVAD implantation. This effect is long-lasting in most patients and reinforces the LVAD implantation without MR surgery. The complication rates and survival were comparable between patients with and without severe MR.

Improvement of left ventricular function with surgical revascularization in patients eligible for implantable cardioverter-defibrillator.

INTRODUCTION: Left ventricular ejection fraction (EF) ≤ 35% is the cornerstone criterion for implantable cardioverter-defibrillator (ICD) eligibility. Improvement in EF may occur in ICD-eligible patients after coronary artery bypass graft surgery (CABG). However, the incidence, predictors, and outcomes of this process are unclear. METHODS AND RESULTS: We studied 427 patients with EF ≤ 35% who underwent CABG in the Surgical Treatment for Ischemic Heart Failure (STICH) trial and had a systematic pre- and postoperative (4 months) EF assessment using the identical cardiac imaging modality. All imaging studies were interpreted at a core laboratory. Improvement in EF was defined as postoperative EF > 35% and >5% absolute improvement from baseline. Of the 427 patients (mean age 61.8 ± 9.5 and 50 women), 125 (29.2%) had EF improvement. Their mean EF increased from 26.8% (±5.8%) to 43.3% (±6.5%) (p < .0001). EF improvement occurred in only 20% of patients with a preoperative EF < 25%. The odds of EF improvement were 1.96 times higher (95% confidence interval [CI]: 0.91-4.23, p = .09) in patients with myocardial viability. In adjusted analyses, EF improvement was associated with a significantly lower risk of all-cause mortality (hazard ratio [HR]: 0.58, 95% CI: 0.35-0.96; p = .03) and heart failure mortality (HR: 0.31, 95% CI: 0.11-0.87; p = .027). CONCLUSION: Nearly 1/3rd of ICD-eligible patients undergoing CABG had significant improvement in EF, obviating the need for primary prevention ICD implantation. These results provide patients and clinicians data on the likelihood of ICD eligibility after CABG and support the practice of reassessment of EF after revascularization.

Cardiac resynchronisation therapy in anthracycline-induced cardiomyopathy.

INTRODUCTION: Chemotherapy-induced cardiomyopathy has been increasingly recognised as patients are living longer with more effective treatments for their malignancies. Anthracyclines are known to cause left ventricular (LV) dysfunction. While heart failure medications are frequently used, some patients may need consideration for device-based therapies such as cardiac resynchronisation therapy (CRT). However, the role of CRT in anthracycline-induced cardiomyopathy (AIC) is not well understood. METHODS: We performed a retrospective review of all patients undergoing CRT implantation at our centre from 2003 to 2019 with a diagnosis of AIC. The LV remodelling and survival outcomes of this population were obtained and then compared with consecutive patients with other aetiologies of non-ischaemic cardiomyopathy (NICM). RESULTS: A total of 34 patients underwent CRT implantation with a diagnosis of AIC with a mean age of 60.5±12.7 years, left ventricular ejection fraction (LVEF) of 21.7%±7.4%, and 11.3±7.5 years and 10.2±7.4 years from cancer diagnosis and last anthracycline exposure, respectively. At 9.6±8.1 months after CRT implantation, there was an increase of LVEF from 21.8%±7.6% to 30.4%±13.0% (p<0.001). Patients whose LVEF increased by at least 10% post-CRT implant (42.5% of cohort) survived significantly longer than patients who failed to improve their LVEF by that amount (p=0.01). A propensity matched analysis between patients with AIC and 369 consecutive patients with other aetiologies of NICM who underwent CRT implantation during the same period revealed no significant differences in improvement in LVEF or long-term survival. CONCLUSIONS: Patients with AIC undergo LV remodelling with CRT at rates similar to other aetiologies of NICM. Furthermore, AIC post-CRT responders have a favourable long-term mortality compared with non-responders.

Viabilidade miocárdica na prática clínica / Assessing myocardial viability in clinical practice

Embora a avaliação da viabilidade miocárdica seja comum na prática do cardiologista, muitos médicos têm dúvidas a respeito dos resultados dos métodos diagnósticos. A medicina nuclear tem papel importante nos estudos de viabilidade, mas os laudos precisam ser interpretados num contexto clínico e fisiopatológico. Este artigo teve o objetivo de revisar a origem e a evolução do conceito da viabilidade miocárdica. São expostos os métodos diagnósticos com ênfase na medicina nuclear com uma explicação funcional sobre cada tipo de exame. A partir disso, são mostradas imagens como exemplos e é proposta uma maneira de atuar nesses casos baseada na clínica, na porcentagem de miocárdio acometido e na topografia das lesões coronarianas (proximais ou distais). (AU)

Although assessing myocardial viability is a common cardiology practice, many physicians question the results of diagnostic methods. Nuclear medicine plays an important role in viability studies, but the reports require interpretation in a clinical and pathophysiological context. this article was aimed at reviewing the origin and evolution of myocardial viability. Here we present diagnostic methods by emphasizing nuclear medicine and provide a functional explanation of each test type using example images. We also propose how to act in these cases based on clinic examination findings, the percentage of affected myocardium, and coronary lesion topography (proximal or distal).(AU)

Cardiogenic shock with highly complicated course after influenza A virus infection treated with vva-ECMO and Impella CP (ECMELLA): a case report.

BACKGROUND: The value of mechanical circulatory support (MCS) in cardiogenic shock, especially the combination of the ECMELLA approach (Impella combined with ECMO), remains controversial. CASE PRESENTATION: A previously healthy 33-year-old female patient was submitted to a local emergency department with a flu-like infection and febrile temperatures up to 39 °C. The patient was tested positive for type-A influenza, however negative for SARS-CoV-2. Despite escalated invasive ventilation, refractory hypercapnia (paCO2: 22 kPa) with severe respiratory acidosis (pH: 6.9) and a rising norepinephrine rate occurred within a few hours. Due to a Horovitz-Index < 100, out-of-centre veno-venous extracorporeal membrane oxygenation (vv-ECMO)-implantation was performed. A CT-scan done because of anisocoria revealed an extended dissection of the right vertebral artery. While the initial left ventricular function was normal, echocardiography revealed severe global hypokinesia. After angiographic exclusion of coronary artery stenoses, we geared up LV unloading by additional implantation of an Impella CP and expanded the vv-ECMO to a veno-venous-arterial ECMO (vva-ECMO). Clinically relevant bleeding from the punctured femoral arteries resulted in massive transfusion and was treated by vascular surgery later on. Under continued MCS, LVEF increased to approximately 40% 2 days after the initiation of ECMELLA. After weaning, the Impella CP was explanted at day 5 and the vva-ECMO was removed on day 9, respectively. The patient was discharged in an unaffected neurological condition to rehabilitation 25 days after the initial admission. CONCLUSIONS: This exceptional case exemplifies the importance of aggressive MCS in severe cardiogenic shock, which may be especially promising in younger patients with non-ischaemic cardiomyopathy and potentially reversible causes of cardiogenic shock. This case impressively demonstrates that especially young patients may achieve complete neurological restoration, even though the initial prognosis may appear unfavourable.

Tratamiento con sildenafilo en disfunción ventricular izquierda e hipertensión pulmonar asociada / Treatment with sildenafil in left ventricular dysfunction and associated pulmonary hypertension

RESUMEN Introducción: la hipertensión pulmonar es un hallazgo frecuente en la insuficiencia cardíaca. El uso del sildenafilo en estos casos es una práctica habitual, pero aún controversial por lo limitado de los estudios realizados. Objetivo: comparar las variables ecocardiográficas de hemodinamia pulmonar, en pacientes con disfunción sistólica ventricular izquierda e hipertensión pulmonar secundaria severa, antes y después del uso del sildenafilo. Materiales y métodos: se realizó un estudio de cohorte, donde se incluyeron 19 pacientes; se realizó un seguimiento de dos años. Se analizaron variables clínicas, de laboratorio y ecocardiográficas. Se evaluaron las principales variables de hemodinamia pulmonar antes del uso del sildenafilo y a las doce semanas de su indicación. Se realizó una curva de supervivencia al concluir el seguimiento. El nivel de significación estadístico empleado fue de p < 0,05. Resultados: la edad promedio fue de 56,16 ± 15,77 años y predominó el sexo masculino, con un 73,7 %. La supervivencia al término del seguimiento fue de 78,9 %. Las principales variables ecocardiográficas de hemodinamia pulmonar mostraron una reducción significativa a las doce semanas del tratamiento con sildenafilo. La supervivencia de los pacientes con una reducción del 25 % de las presiones pulmonares en el ecocardiograma realizado a las doce semanas del tratamiento, fue mayor al terminar el estudio (100 % vs 33 %, log-rank test p = 0,001). Conclusiones: posterior al uso del sildenafilo se encontró una reducción significativa de las variables de hemodinamia pulmonar en el ecocardiograma evolutivo. La sobrevida fue mayor en los pacientes que presentaron dicha reducción (AU).

ABSTRACT Introduction: pulmonary hypertension is a common finding in heart failure. The use of sildenafil in these cases is a common practice, but still controversial due to the limited number of studies carried out. Objective: to compare echocardiographic variables of pulmonary hemodynamics, in patients with left ventricular systolic dysfunction and severe secondary pulmonary hypertension, before and after the use of sildenafil. Materials and methods: a cohort study was led, including 19 patients; a two-year follow-up was carried out. Clinical, laboratory and echocardiographic variables were analyzed. The main pulmonary hemodynamics variables were evaluated before the use of sildenafil and 12 weeks after its indication. A survival curve was performed at the end of the follow-up. The statistical significance level used was p < 0.05. Results: the average age was 56.16 ± 15.77 years, and male sex predominated with 73.3 %. Survival at the end of the follow up was 78.9 %. The main echocardiographic variables of pulmonary hemodinamics showed a significant reduction at 12 weeks of treatment with sildenafil. The survival of patients with a 25 % reduction in pulmonary pressures in the echocardiogram performed at 12 weeks of treatment was greater at the end of the study (100 % vs 33 %, log-rank test p = 0.001). Conclusions: after using sildenafil, a significant reduction of pulmonary hemodynamics variables was found in the evolutionary echocardiogram. Survival was higher in patients who had this reduction (AU).

Lactobacillus plantarum probiotic induces Nrf2-mediated antioxidant signaling and eNOS expression resulting in improvement of myocardial diastolic function.

Yorkshire swine were fed standard diet (n = 7) or standard diet containing applesauce rich in caffeic acid with Lactobacillus plantarum (n = 7) for 3 wk. An ameroid constrictor was next placed around the left coronary circumflex artery, and the dietary regimens were continued. At 14 wk, cardiac function, myocardial perfusion, vascular density, and molecular signaling in ischemic myocardium were evaluated. The L. plantarum-applesauce augmented NF-E2-related factor 2 (Nrf2) in the ischemic myocardium and induced Nrf2-regulated antioxidant enzymes heme oxygenase-1 (HO-1), NADPH dehydrogenase quinone 1 (NQO-1), and thioredoxin reductase (TRXR-1). Improved left ventricular diastolic function and decreased myocardial collagen expression were seen in animals receiving the L. plantarum-applesauce supplements. The expression of endothelial nitric oxide synthase (eNOS) was increased in ischemic myocardial tissue of the treatment group, whereas levels of asymmetric dimethyl arginine (ADMA), hypoxia inducible factor 1α (HIF-1α), and phosphorylated MAPK (pMAPK) were decreased. Collateral-dependent myocardial perfusion was unaffected, whereas arteriolar and capillary densities were reduced as determined by α-smooth muscle cell actin and CD31 immunofluorescence in ischemic myocardial tissue. Dietary supplementation with L. plantarum-applesauce is a safe and effective method of enhancing Nrf2-mediated antioxidant signaling cascade in ischemic myocardium. Although this experimental diet was associated with a reduction in hypoxic stimuli, decreased vascular density, and without any change in collateral-dependent perfusion, the net effect of an increase in antioxidant activity and eNOS expression resulted in improvement in diastolic function.NEW & NOTEWORTHY Colonization of the gut microbiome with certain strains of L. Plantarum has been shown to convert caffeic acid readily available in applesauce to 4-vinyl-catechol, a potent activator of the Nrf2 antioxidant defense pathway. In this exciting study, we show that simple dietary supplementation with L. Plantarum-applesauce-mediated Nrf2 activation supports vascular function, ameliorates myocardial ischemic diastolic dysfunction, and upregulates expression of eNOS.

Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial.

BACKGROUND: Most cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility. METHODS: In this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF <45% and 15% or greater LV scar size were randomised in 2:1 ratio to receive intracoronary infusion of allogenic CDCs or placebo, respectively. Change in segmental myocardial circumferential strain (Ecc) by MRI from baseline to 6 months was compared between CDCs and placebo groups. RESULTS: In total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3 (10.8) and 108 (87.1%) men). Segmental Ecc improvement was significantly greater in patients receiving CDC (-0.5% (4.0)) compared with placebo (0.2% (3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of -0.7% (3.5) in patients receiving CDC vs 0.04% (3.7) in the placebo group, p=0.04). CONCLUSIONS: In patients with post-MI LV dysfunction, CDC administration resulted in improved segmental myocardial function. Our findings highlight the importance of segmental myocardial function indices as an endpoint in future clinical trials of patients with post-MI. TRIAL REGISTRATION NUMBER: NCT01458405.

Ultrasound-Targeted Microbubble Destruction Accelerates Angiogenesis and Ameliorates Left Ventricular Dysfunction after Myocardial Infarction in Mice.

Failure of coronary recanalization within 12 h or no flow in the myocardium after percutaneous coronary intervention is associated with high mortality from myocardial infarction, and insufficient angiogenesis in the border zone results in the expansion of infarct area. In this study, we examined the effects of ultrasound-targeted microbubble destruction (UTMD) on angiogenesis and left ventricular dysfunction in a mouse model of myocardial infarction. Fifty-four mice with MI were treated with no UTMD, ultrasound (US) alone or UTMD four times (days 1, 3, 5 and 7), and another 18 mice underwent sham operation and therapy. Therapeutic US was generated with a linear transducer connected to a commercial diagnostic US system (VINNO70). UTMD was performed with the VINNO70 at a peak negative pressure of 0.8 MPa and lipid microbubbles. Transthoracic echocardiography was performed on the first and seventh days. The results indicated that UTMD decreased the infarct size ratio from 78.1 ± 5.3% (untreated) to 43.3 ± 6.4%, accelerated angiogenesis and ameliorated left ventricular dysfunction. The ejection fraction increased from 25.05 ± 8.52% (untreated) to 42.83 ± 9.44% (UTMD). Compared with that in other groups, expression of vascular endothelial growth factor and endothelial nitric oxide synthase and release of nitric oxide were significantly upregulated after UTMD treatment, indicating angiogenesis. Therefore, UTMD is a potential physical approach in the treatment of myocardial infarction.

Society for Cardiovascular Magnetic Resonance 2019 Case of the Week series.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). The SCMR web site ( https://www.scmr.org ) hosts a case series designed to present case reports demonstrating the unique attributes of CMR in the diagnosis or management of cardiovascular disease. Each clinical presentation is followed by a brief discussion of the disease and unique role of CMR in disease diagnosis or management guidance. By nature, some of these are somewhat esoteric, but all are instructive. In this publication, we provide a digital archive of the 2019 Case of the Week series as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.

A 49-Year-Old Man With Postcoital Hemoptysis.

CASE PRESENTATION: A 49-year-old man was seen in the pulmonary clinic for evaluation of postcoital hemoptysis. His medical history was significant for nonischemic cardiomyopathy and hypertension. He had red-yellow sputum with streaks of blood associated with dyspnea and wheezing for 5 years. He noted his symptoms occurred only with sexual intercourse while horizontal, but not while upright. He did not have any symptoms with other exertional activities, including heavy weight lifting. He did not have other symptoms. He had a remote history of less than 10 pack years of smoking. He had no personal or family history of pulmonary disease. He worked as a construction worker in the past, and currently as a driver. He had been incarcerated in the past but denied direct contact with TB. He was born in the United States, had always lived in the Northeastern region, and denied international travel. He had no constitutional symptoms or symptoms concerning for malignancy or autoimmune disease, including joint or skin complaints. His medications included aspirin, atorvastatin, carvedilol, furosemide, lisinopril, and spironolactone, and he endorsed adherence. He denied herbal or over-the-counter drugs use and denied illicit drug use.

Left Ventricular Recovery with Explantation of Continuous-Flow Left Ventricular Assist Device after 5 Years of Support.

Mechanical circulatory support may result in sufficient myocardial recovery to allow for explantation of the left ventricular assist device (LVAD). The duration of support associated with left ventricular recovery has generally been 6-12 months. In this report, we present a patient in whom the left ventricle recovered after 5 years of support with a LVAD. Our report demonstrates that long-term monitoring for left ventricular recovery is prudent and may allow for late device explantation.

Preclinical evidence for the therapeutic value of TBX5 normalization in arrhythmia control.

AIMS: Arrhythmias and sudden cardiac death (SCD) occur commonly in patients with heart failure. We found T-box 5 (TBX5) dysregulated in ventricular myocardium from heart failure patients and thus we hypothesized that TBX5 reduction contributes to arrhythmia development in these patients. To understand the underlying mechanisms, we aimed to reveal the ventricular TBX5-dependent transcriptional network and further test the therapeutic potential of TBX5 level normalization in mice with documented arrhythmias. METHODS AND RESULTS: We used a mouse model of TBX5 conditional deletion in ventricular cardiomyocytes. Ventricular (v) TBX5 loss in mice resulted in mild cardiac dysfunction and arrhythmias and was associated with a high mortality rate (60%) due to SCD. Upon angiotensin stimulation, vTbx5KO mice showed exacerbated cardiac remodelling and dysfunction suggesting a cardioprotective role of TBX5. RNA-sequencing of a ventricular-specific TBX5KO mouse and TBX5 chromatin immunoprecipitation was used to dissect TBX5 transcriptional network in cardiac ventricular tissue. Overall, we identified 47 transcripts expressed under the control of TBX5, which may have contributed to the fatal arrhythmias in vTbx5KO mice. These included transcripts encoding for proteins implicated in cardiac conduction and contraction (Gja1, Kcnj5, Kcng2, Cacna1g, Chrm2), in cytoskeleton organization (Fstl4, Pdlim4, Emilin2, Cmya5), and cardiac protection upon stress (Fhl2, Gpr22, Fgf16). Interestingly, after TBX5 loss and arrhythmia development in vTbx5KO mice, TBX5 protein-level normalization by systemic adeno-associated-virus (AAV) 9 application, re-established TBX5-dependent transcriptome. Consequently, cardiac dysfunction was ameliorated and the propensity of arrhythmia occurrence was reduced. CONCLUSIONS: This study uncovers a novel cardioprotective role of TBX5 in the adult heart and provides preclinical evidence for the therapeutic value of TBX5 protein normalization in the control of arrhythmia.