Preliminary efficacy and safety analysis of tafamidis in post-liver transplant patients with hereditary transthyretin cardiac amyloidosis.

Hereditary transthyretin cardiac amyloidosis (ATTRv-CA) after liver transplantation remains challenging to treat due to residual amyloid deposits in extrahepatic organs, including the heart. Tafamidis, a transthyretin tetramer stabilizer, has shown promise in the treatment of ATTRv-CA; however, its efficacy and safety after liver transplantation are uncertain. In this preliminary retrospective review, we assessed the efficacy and safety of tafamidis (80 mg) in three ATTRv-CA cases after liver transplantation. Following one year of treatment, all patients experienced improvement in dyspnea, New York Heart Association functional class, brain natriuretic peptide levels, and cardiac troponin T levels. No significant changes in echocardiographic parameters were observed. Notably, no cardiovascular or drug-related adverse events occurred during treatment. Our findings suggest that tafamidis may benefit post-liver transplant patients with ATTRv-CA and warrant further investigation through randomized controlled trials with larger cohorts. This study highlights a potential therapeutic avenue for the management of cardiovascular involvement in this challenging patient population.

Interplay of the heart, spleen, and bone marrow in heart failure: the role of splenic extramedullary hematopoiesis.

Improvements in therapies for heart failure with preserved ejection fraction (HFpEF) are crucial for improving patient outcomes and quality of life. Although HFpEF is the predominant heart failure type among older individuals, its prognosis is often poor owing to the lack of effective therapies. The roles of the spleen and bone marrow are often overlooked in the context of HFpEF. Recent studies suggest that the spleen and bone marrow could play key roles in HFpEF, especially in relation to inflammation and immune responses. The bone marrow can increase production of certain immune cells that can migrate to the heart and contribute to disease. The spleen can contribute to immune responses that either protect or exacerbate heart failure. Extramedullary hematopoiesis in the spleen could play a crucial role in HFpEF. Increased metabolic activity in the spleen, immune cell production and mobilization to the heart, and concomitant cytokine production may occur in heart failure. This leads to systemic chronic inflammation, along with an imbalance of immune cells (macrophages) in the heart, resulting in chronic inflammation and progressive fibrosis, potentially leading to decreased cardiac function. The bone marrow and spleen are involved in altered iron metabolism and anemia, which also contribute to HFpEF. This review presents the concept of an interplay between the heart, spleen, and bone marrow in the setting of HFpEF, with a particular focus on extramedullary hematopoiesis in the spleen. The aim of this review is to discern whether the spleen can serve as a new therapeutic target for HFpEF.

Clinical clues for suspecting wild-type transthyretin cardiac amyloidosis in patients with monoclonal gammopathy of undetermined significance: a case report.

BACKGROUND: Myeloproliferative disorders, including monoclonal gammopathy of undetermined significance (MGUS), are often associated with amyloid light-chain (AL)-type cardiac amyloidosis (CA) but occasionally with wild-type transthyretin (ATTR) CA. In recent years, ATTR amyloidosis has attracted necessity for its reliable diagnosis with the addition of new treatments. Usually, both wild-type ATTR CA and AL-type CA present with marked cardiac hypertrophy, but renal dysfunction is milder in wild-type ATTR amyloidosis than in AL-type amyloidosis. Peripheral neurologic and autonomic symptoms such as numbness and dysesthesia are moderately present in AL-type amyloidosis, but less so in wild-type ATTR amyloidosis. Furthermore, the prognosis of ATTR-type amyloidosis is better than that of AL-type amyloidosis. CASE PRESENTATION: A 72-year-old man with cardiac hypertrophy presented with New York Heart Association functional class III dyspnea and leg edema. He had no history of carpal tunnel syndrome. An electrocardiogram showed atrial fibrillation and low voltage. The N-terminal pro-B-type natriuretic peptide level was 3310 pg/mL, and troponin T was elevated to 0.073 ng/mL. However, the glomerular filtration rate was only slightly decreased at 69.0 mL/min/1.73 m2. The serum free light-chain assay revealed a significant increase in the kappa chain, with positive results in Bence Jones proteins and serum immunoelectrophoresis. Bone marrow examination confirmed the diagnosis of monoclonal gammopathy of undetermined significance (MGUS). AL-type amyloidosis associated with a myeloproliferative disorder was suspected, and the prognosis was initially predicted to be poor, classified as Mayo stage IV. Contrary to this prognosis, the patient showed a slow progression of heart failure. Further imaging modalities and cardiac tissue findings confirmed the diagnosis as transthyretin type amyloidosis, and a favorable prognosis was established with the use of tafamidis. CONCLUSIONS: MGUS occasionally coexists with wild-type ATTR CA. Scant autonomic symptoms, mild renal dysfunction, and slow progression of heart failure might be clues that the CA associated with the myeloproliferative disease is wild-type ATTR amyloidosis.

Recurrent fulminant non-rheumatic streptococcal myocarditis proven by endomyocardial biopsy and autopsy.

A 42-year-old man with a history of acute myocarditis after streptococcal pharyngitis developed recurrent fulminant myocarditis. Endomyocardial biopsy revealed myocyte degeneration, interstitial edema, and neutrophil infiltration. The patient's cardiac function deteriorated rapidly, and he died despite mechanical circulatory support. Autopsy revealed neutrophil infiltration, interstitial edema, and micro-abscesses containing masses of streptococci and neutrophilic phagocytosis within the myocardium. The patient did not meet the diagnostic criteria for acute rheumatic fever; thus, he was diagnosed with non-rheumatic streptococcal myocarditis. Non-rheumatic streptococcal myocarditis rarely recurs, but it can be fulminant upon recurrence. Learning objective: We report a rare case of recurrent fulminant non-rheumatic streptococcal myocarditis. Endomyocardial biopsy and autopsy revealed neutrophil infiltration and micro-abscesses containing bacterial masses of streptococci and neutrophilic phagocytosis in the myocardium. The patient did not meet the diagnostic criteria for acute rheumatic fever; thus, he was diagnosed with non-rheumatic streptococcal myocarditis. Non-rheumatic streptococcal myocarditis rarely recurs, but it can be fulminant upon recurrence.

Comparisons between biopsy-proven versus clinically diagnosed cardiac sarcoidosis.

OBJECTIVES: Diagnosis of cardiac sarcoidosis (CS) without histological evidence remains controversial. This study aimed to compare characteristics and outcomes of histologically proven versus clinically diagnosed cases of CS, which were adjudicated using Heart Rhythm Society or Japanese Circulation Society criteria. METHODS: A total of 512 patients with CS (age: 62±11 years, female: 64.3%) enrolled in the multicentre registry were studied. Histologically confirmed patients were classified as 'biopsy-proven CS', while those with the presence of strongly suggestive clinical findings of CS without histological evidence were classified as 'clinical CS'. Primary outcome was a composite of all-cause death, heart failure hospitalisation and ventricular arrhythmia event. RESULTS: In total, 314 patients (61.3%) were classified as biopsy-proven CS, while 198 (38.7%) were classified as clinical CS. Patients classified under clinical CS were associated with higher prevalence of left ventricular dysfunction, septal thinning, and positive findings in fluorodeoxyglucose-positron emission tomography or Gallium scintigraphy than those under biopsy-proven CS. During median follow-up of 43.7 (23.3-77.3) months, risk of primary outcome was comparable between the groups (adjusted HR: 1.24, 95% CI: 0.88 to 1.75, p=0.22). Similarly, the risks of primary outcome were comparable between patients with clinical isolated CS who did not have other organ/tissue involvement, and biopsy-proven isolated CS (adjusted HR: 1.23, 95% CI: 0.56 to 2.70, p=0.61). CONCLUSIONS: A substantial number of patients were diagnosed with clinical CS without confirmatory biopsy. Considering the worse clinical outcomes irrespective of the histological evidence, the diagnosis of clinical CS is justifiable if imaging findings suggestive of CS are observed.

A retrospective investigation to establish new screening approach for the detection of patients at high risk of Fabry disease in male left ventricular hypertrophy patients.

BACKGROUND: The prevalence of Fabry disease (FD) in male patients with left ventricular hypertrophy (LVH) is about 1%. From the perspective of performing more efficient screening with measurement of α-galactosidase (α-Gal) activity, it is important to raise the pretest probability. METHODS: We retrospectively investigated the prevalence of FD in 701 male patients with LVH who already had been screened by measurement of α-Gal activity in eight hospitals. From the viewpoint of enzymatic screening, we validated previously reported clinical features of FD including the electrocardiographic and echocardiographic characteristics with comparing each clinical determinant between patients with FD and non-FD patients. We finally aimed to establish a new screening approach for the detection of patients at high risk of FD. RESULTS: There were five FD patients (0.7%) in the 701 male patients with LVH. Those five patients with FD all had the cardiac variant type and age at detection of LVH was ≥35 years in all patients. In LVH patients with LV ejection fraction (EF) ≥ 50%, Pend-Q interval < 40 msec, SV1 + RV5 > 4.0 mV, and diffuse LVH were important determinants of FD. In LVH patients with LVEF < 50%, asymmetric septal hypertrophy and posterior wall motion abnormality seemed to be associated with FD. CONCLUSIONS: In our retrospective study, the prevalence of FD in male patients with LVH was found to be 0.7%. We established the efficient combinations of clinical determinants using age at detection of LVH, Pend-Q interval, high voltage, and LVH pattern in an echocardiogram.

Fingolimod-associated severe bilateral cystoid macular edema.

Purpose: To report a rare case in which a patient undergoing long-term oral fingolimod treatment for multiple sclerosis (MS) developed late-onset severe bilateral cystoid macular edema (ME) at 3-weeks post cataract surgery. Observations: This study involved a 61-year-old female undergoing long-term oral fingolimod treatment for MS in whom at 4-years post initiation of treatment and the treatment being tapered to a 0.5 mg twice-weekly dose severe bilateral cystoid ME occurred at 3-weeks post cataract surgery. Although the patient was administered the proper treatments for pseudophakic ME, including a 20-mg sub-Tenon's-capsule triamcinolone acetonide injection, it took 13 months for the ME to ultimately resolve with continued oral fingolimod treatment. Conclusions and importance: The findings in this study show that severe bilateral cystoid ME can occur even several years after initiating fingolimod treatment, thus indicating that detailed follow-up is necessary post cataract surgery.

Serum autotaxin as a novel prognostic marker in patients with non-ischaemic dilated cardiomyopathy.

AIMS: Autotaxin (ATX) promotes myocardial inflammation, fibrosis, and the subsequent cardiac remodelling through lysophosphatidic acid production. However, the prognostic impact of serum ATX in non-ischaemic dilated cardiomyopathy (NIDCM) has not been clarified. We investigated the prognostic impact of serum ATX in patients with NIDCM. METHODS AND RESULTS: We enrolled 104 patients with NIDCM (49.8 ± 13.4 years, 76 men). We divided the patients into two groups using different cutoffs of median serum ATX levels for men and women: high-ATX group and low-ATX group. Cardiac events were defined as a composite of cardiac death and heart failure resulting in hospitalization. Median ATX level was 203.5 ng/mL for men and 257.0 ng/mL for women. Brain natriuretic peptide levels [224.0 (59.6-689.5) pg/mL vs. 96.5 (40.8-191.5) pg/mL, P = 0.010] were higher in the high-ATX group than low-ATX group, whereas high-sensitivity C-reactive protein and collagen volume fraction levels in endomyocardial biopsy samples were not significantly different between the two groups. Kaplan-Meier survival analysis revealed that the event-free survival rate was significantly lower in the high-ATX group than low-ATX group (log-rank; P = 0.007). Cox proportional hazard analysis revealed that high-ATX was an independent determinant of composite cardiac events. In both sexes, serum ATX levels did not correlate with high-sensitivity C-reactive protein levels and collagen volume fraction but had a weak correlation with brain natriuretic peptide levels (men; spearman's rank: 0.274, P = 0.017, women; spearman's rank: 0.378, P = 0.048). CONCLUSION: High serum ATX levels can be associated with increasing adverse clinical outcomes in patients with NIDCM. These results indicate serum ATX may be a novel biomarker or therapeutic target in NIDCM.

Methods for confirming the safety of radiation therapy in patients with left ventricular assist device: a case of extranodal NK/T-cell lymphoma, nasal type.

A left ventricular assist device (LVAD) is a treatment option for patients with end-stage heart failure; however, a certain number of patients on durable LVADs are diagnosed with malignancy. Radiation therapy (RT) for patients with durable LVADs has safety concerns, because RT may interfere with the device. Herein, we report a case of RT during durable LVAD management. A 48-year-old man with a durable LVAD was diagnosed with sinusitis. As his symptoms were resistant to drug therapy, endoscopic sinus surgery was performed, and extranodal NK/T-cell lymphoma, nasal type (ENKL) was pathologically detected. Since RT was the first-line treatment for ENKL, we conducted two types of irradiation experiments to determine whether RT can be safely performed in patients with durable LVADs as follows: (1) assessing the extent of the radiation levels at each site and evaluating device malfunction by irradiating the lesion sites in the patient model with the same protocol as planned, and (2) evaluating device malfunction by directly irradiating the durable LVAD equipment once at the scheduled total dose. The radiation doses at the pump, driveline, system controller, power cable, and power module of the durable LVAD reached 7.86 cGy, 6.34 cGy, 0.66 cGy, 0.38 cGy, and 0.14 cGy, respectively. In both experiments, durable LVAD malfunction or any type of alarm was not observed. We concluded that RT could be safely performed with chemotherapy in this patient and our irradiation experiments can be applied to RT for other malignancies.

Differences in Prognosis and Cardiac Function According to Required Percutaneous Mechanical Circulatory Support and Histological Findings in Patients With Fulminant Myocarditis: Insights From the CHANGE PUMP 2 Study.

Background Prognoses and long-term cardiac function of patients with fulminant myocarditis have not been fully elucidated. Therefore, we clarified the prognoses and long-term cardiac function according to required percutaneous mechanical circulatory support and histological findings among patients with fulminant myocarditis. Methods and Results We conducted a multicenter retrospective medical record review of 216 patients with fulminant myocarditis requiring percutaneous mechanical circulatory support. Sixty-one patients were treated with intra-aortic balloon pump or Impella alone, and 155 patients received veno-arterial extracorporeal membrane oxygenation and were treated with or without intra-aortic balloon pump or Impella. Histologically, 107 patients had lymphocytic myocarditis; 34, eosinophilic myocarditis; and 4, giant cell myocarditis. Freedom from composite end point (death, durable left ventricular assist device implantation, and heart transplantation) was 66% at 90 days, 62% at 1 year, and 57% at 6 years. Veno-arterial extracorporeal membrane oxygenation use was associated with poor prognosis in the multivariable analysis (hazard ratio [HR], 5.27; 95% CI, 1.60-17.36). The eosinophilic myocarditis subgroup showed better prognosis (HR, 0.28; 95% CI, 0.10-0.80) compared with the lymphocytic myocarditis subgroup but not in the multivariable analysis. Ventricular tachycardia/ventricular fibrillation rhythm at admission, high C-reactive protein level, and no endomyocardial biopsy were also associated with poor prognosis. The left ventricular ejection fraction at 1 year was ≤50% in 16% of patients and was lower in patients with eosinophilic myocarditis (median: 57.9% [48.8-65.0%]) than in those with lymphocytic myocarditis (65.0% [58.6-68.7%]) (P=0.036). Conclusions Patients with fulminant myocarditis who received veno-arterial extracorporeal membrane oxygenation had a poor prognosis. Long-term cardiac function was impaired in some patients, especially those with eosinophilic myocarditis.

Biopsy-Proven Fulminant Myocarditis Requiring Mechanical Circulatory Support Following COVID-19 mRNA Vaccination.

A 48-year-old woman suffered from cardiogenic shock with fulminant myocarditis following the second dose of COVID-19 vaccine (mRNA-1273). Venoarterial extracorporeal membrane oxygenation and Impella support were essential in achieving hemodynamic stability. Endomyocardial biopsy revealed lymphocytic infiltration with predominant immunostaining for CD8- and CD68-positive cells. The left ventricular ejection fraction improved significantly after treatment with mechanical circulatory support. Myocarditis following COVID-19 mRNA vaccination may also occur in middle-aged women; it may be fulminant and require mechanical circulatory support. Although our results suggest the involvement of cytotoxic T lymphocytes and macrophages, further investigation is needed before these can be established as pathogenetic mechanisms.

Une femme de 48 ans a souffert d'un choc cardiogène accompagné d'une myocardite fulminante après avoir reçu la deuxième dose du vaccin contre la COVID-19 (ARNm-1273). L'oxygénation par membrane extracorporelle veino-artérielle et l'assistance par Impella ont joué un rôle essentiel pour atteindre la stabilité hémodynamique. Une biopsie endomyocardique a révélé la présence d'infiltrats lymphocytaires avec une immunocoloration prédominante pour les cellules exprimant CD8 et CD68. La fraction d'éjection ventriculaire gauche s'est améliorée considérablement après un traitement par assistance circulatoire mécanique. Des cas de myocardite peuvent également survenir chez des femmes d'âge moyen après l'administration d'un vaccin à ARNm contre la COVID-19; ils peuvent être fulminants et nécessiter une assistance circulatoire mécanique. Bien que nos résultats laissent croire à une participation des lymphocytes T cytotoxiques et des macrophages, une étude approfondie s'impose avant de pouvoir cerner les mécanismes pathogènes.

Relationship between spleen size and exercise tolerance in advanced heart failure patients with a left ventricular assist device.

OBJECTIVE: Spleen volume increases in patients with advanced heart failure (HF) after left ventricular assist device (LVAD) implantation. However, the relationship between spleen volume and exercise tolerance (peak oxygen consumption [VO2]) in these patients remains unknown. In this exploratory study, we enrolled 27 patients with HF using a LVAD (median age: 46 years). Patients underwent blood testing, echocardiography, right heart catheterization, computed tomography (CT), and cardiopulmonary exercise testing. Spleen size was measured using CT volumetry, and the correlations/causal relationships of factors affecting peak VO2 were identified using structural equation modeling. RESULTS: The median spleen volume was 190.0 mL, and peak VO2 was 13.2 mL/kg/min. The factors affecting peak VO2 were peak heart rate (HR; ß = 0.402, P = .015), pulmonary capillary wedge pressure (PCWP; ß = - 0.698, P = .014), right ventricular stroke work index (ß = 0.533, P = .001), blood hemoglobin concentration (ß = 0.359, P = .007), and spleen volume (ß = 0.215, P = .041). Spleen volume correlated with peak HR, PCWP, and hemoglobin concentration, reflecting sympathetic activity, cardiac preload, and oxygen-carrying capacity, respectively, and was thus related to peak VO2. These results suggest an association between spleen volume and exercise tolerance in advanced HF.

Splenic size as an indicator of hemodynamics and prognosis in patients with heart failure.

The spleen is an important immune organ that releases erythrocytes and monocytes and destroys aged platelets. It also reserves 20-30% of the total blood volume, and its size decreases in hypovolemic shock. However, the clinical significance of splenic size in patients with heart failure (HF) remains unclear. We retrospectively analyzed the data of 206 patients with clinically stable HF gathered between January 2001 and August 2020 and recorded in a single-center registry. All patients underwent right heart catheterization and computed tomography (CT). Splenic size was measured using CT volumetry. The primary outcomes were composite cardiac events occurring for the first time during follow-up, namely, cardiac death and hospitalization for worsening HF. The median splenic volume and splenic volume index (SVI) were 118.0 mL and 68.9 mL/m2, respectively. SVI was positively correlated with cardiac output (r = 0.269, P < 0.001) and stroke volume (r = 0.228, P = 0.002), and negatively correlated with systemic vascular resistance (r = - 0.302, P < 0.001). Seventy cardiac events occurred, and the optimal receiver operating characteristic curve SVI cutoff value for predicting cardiac events was 68.9 mL/m2. The median blood adrenaline concentration was higher in the low-SVI group than the high-SVI group (0.039 ng/mL vs. 0.026 ng/mL, respectively; P = 0.004), and the low-SVI group experienced more cardiac events (log-rank test, P < 0.001). Multivariate Cox proportional hazards regression revealed that a low SVI was an independent predictor of cardiac events, even when adjusted for the validated HF risk score, blood-brain natriuretic peptide concentration, blood catecholamine concentrations, and hemodynamic parameters. Splenic size reflects hemodynamics, including systemic circulating blood volume status and sympathetic nerve activity, and is associated with HF prognosis.

LPL/AQP7/GPD2 promotes glycerol metabolism under hypoxia and prevents cardiac dysfunction during ischemia.

In the heart, fatty acid is a major energy substrate to fuel contraction under aerobic conditions. Ischemia downregulates fatty acid metabolism to adapt to the limited oxygen supply, making glucose the preferred substrate. However, the mechanism underlying the myocardial metabolic shift during ischemia remains unknown. Here, we show that lipoprotein lipase (LPL) expression in cardiomyocytes, a principal enzyme that converts triglycerides to free fatty acids and glycerol, increases during myocardial infarction (MI). Cardiomyocyte-specific LPL deficiency enhanced cardiac dysfunction and apoptosis following MI. Deficiency of aquaporin 7 (AQP7), a glycerol channel in cardiomyocytes, increased the myocardial infarct size and apoptosis in response to ischemia. Ischemic conditions activated glycerol-3-phosphate dehydrogenase 2 (GPD2), which converts glycerol-3-phosphate into dihydroxyacetone phosphate to facilitate adenosine triphosphate (ATP) synthesis from glycerol. Conversely, GPD2 deficiency exacerbated cardiac dysfunction after acute MI. Moreover, cardiomyocyte-specific LPL deficiency suppressed the effectiveness of peroxisome proliferator-activated receptor alpha (PPARα) agonist treatment for MI-induced cardiac dysfunction. These results suggest that LPL/AQP7/GPD2-mediated glycerol metabolism plays an important role in preventing myocardial ischemia-related damage.

Prognostic Importance of Pulmonary Arterial Capacitance in Acute Decompensated Heart Failure With Preserved Ejection Fraction.

Background Although the prognostic importance of pulmonary arterial capacitance (PAC; stroke volume/pulmonary arterial pulse pressure) has been elucidated in heart failure with reduced ejection fraction, whether its significance in patients suffering from heart failure with preserved ejection fraction is not known. We aimed to examine the association of PAC with outcomes in inpatients with heart failure with preserved ejection fraction. Methods and Results We prospectively studied 705 patients (median age, 83 years; 55% women) registered in PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction). We investigated the association of echocardiographic PAC at discharge with the primary end point of all-cause death or heart failure rehospitalization with a mean follow-up of 384 days. We further tested the acceptability of the prognostic significance of PAC in a subgroup of patients (167/705 patients; median age, 81 years; 53% women) in whom PAC was assessed by right heart catheterization. The median echocardiographic PAC was 2.52 mL/mm Hg, with a quartile range of 1.78 to 3.32 mL/mm Hg. Univariable and multivariable Cox regression testing revealed that echocardiographic PAC was associated with the primary end point (unadjusted hazard ratio, 0.82; 95% CI, 0.72-0.92; P=0.001; adjusted hazard ratio, 0.86; 95% CI, 0.74-0.99; P=0.035, respectively). Univariable Cox regression testing revealed that PAC assessed by right heart catheterization (median calculated PAC, 2.82 mL/mm Hg) was also associated with the primary end point (unadjusted HR, 0.70; 95% CI, 0.52-0.91; P=0.005). Conclusions A prospective cohort study revealed that impaired PAC diagnosed with both echocardiography and right heart catheterization was associated with adverse outcomes in inpatients with heart failure with preserved ejection fraction. Registration URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024414. Unique identifier: UMIN000021831.

Comparison of Impella 5.0 and extracorporeal left ventricular assist device in patients with cardiogenic shock.

INTRODUCTION: Choice of mechanical circulatory support to stabilize hemodynamics until cardiac recovery or next treatment is a strategic cornerstone for improving outcomes in patients with severe cardiogenic shock. We aimed to clarify the difference in treatment course and outcomes with the use of Impella 5.0 and an extracorporeal left ventricular assist device (eLVAD) in patients with cardiogenic shock refractory to medical therapy or other mechanical circulatory support. METHODS: We performed a retrospective medical record review of consecutive patients who were implanted with Impella 5.0 or eLVAD as a bridge to decision at our medical center. RESULTS: A total of 26 patients (median age 40 years, 16 males) were analyzed. Of seven patients managed with Impella 5.0, the Impella 5.0 was removed successfully in two patients and five patients underwent surgery for durable LVAD implantation. Of 19 patients managed with eLVAD, the eLVAD was successfully removed in 3 patients, 9 patients required durable LVAD, and 7 patients died during eLVAD management. The period between Impella 5.0 or eLVAD implantation to durable LVAD surgery was significantly shorter with Impella 5.0 (58 vs 235 days, p = 0.001). Cardiopulmonary bypass time was significantly shorter and a significantly smaller amount of red blood cell transfusion was required with Impella 5.0 (149 vs 192 min, p = 0.042; 7.0 vs 15.0 units, p = 0.019). There were four massive stroke events with eLVAD, but no massive stroke event with Impella 5.0. CONCLUSION: Impella 5.0 facilitates smoother management as a bridge to decision and reduces surgical invasiveness during durable LVAD implantation.

Prognostic impact of immune-related adverse events on patients with and without cardiovascular disease: a retrospective review.

BACKGROUND: The emergence of immune checkpoint inhibitors (ICIs) has brought about a paradigm shift in cancer treatment as the use of these drugs has become more frequent and for a longer duration. As a result of T-cell-mediated inflammation at the programmed cell death-1, programmed death-ligand-1, and cytotoxic T-lymphocyte antigen-4 pathways, immune-related adverse events (irAEs) occur in various organs and can cause a rare but potentially induced cardiotoxicity. Although irAEs are associated with the efficacy of ICI therapy and better prognosis, there is limited information about the correlation between irAEs and cardiotoxicity and whether the benefits of irAEs apply to patients with underlying cardiovascular disease. This study aimed to investigate the association of irAEs and treatment efficacy in patients undergoing ICI therapy with and without a cardiovascular history. METHODS: We performed a retrospective review of the medical records of 409 consecutive patients who received ICI therapy from September 2014 to October 2019. RESULTS: Median patient age was 69 years (29.6% were female). The median follow-up period was 278 days. In total, 69 (16.9%) patients had a history of any cardiovascular disease and 14 (3.4%) patients experienced cardiovascular irAEs after ICI administration. The rate of cardiovascular irAEs was higher in patients with prior non-cardiovascular irAEs than without. The prognosis of patients with irAEs ( +) was significantly better than that of the patients without irAEs (P < 0.001); additionally, this tendency did not depend on the presence or absence of a cardiovascular history. Furthermore, the Cox proportional hazards analysis revealed that irAEs were an independent predictor of mortality. CONCLUSIONS: Although cardiovascular irAEs may be related to prior non-cardiovascular irAEs under ICI therapy, the occurrence of irAEs had a better prognostic impact and this tendency was not affected by cardiovascular history.

Multidisciplinary Approaches for Transthyretin Amyloidosis.

Amyloidosis caused by systemic deposition of transthyretin (TTR) is called ATTR amyloidosis and mainly includes hereditary ATTR (ATTRv) amyloidosis and wild-type ATTR (ATTRwt) amyloidosis. Until recently, ATTRv amyloidosis had been considered a disease in the field of neurology because neuropathic symptoms predominated in patients described in early reports, whereas advances in diagnostic techniques and increased recognition of this disease revealed the presence of patients with cardiomyopathy as a predominant feature. In contrast, ATTRwt amyloidosis has been considered a disease in the field of cardiology. However, recent studies have suggested that some of the patients with ATTRwt amyloidosis present tenosynovial tissue complications, particularly carpal tunnel syndrome, as an initial manifestation of amyloidosis, necessitating an awareness of this disease among neurologists and orthopedists. Although histopathological confirmation of amyloid deposits has traditionally been considered mandatory for the diagnosis of ATTR amyloidosis, the development of noninvasive imaging techniques in the field of cardiology, such as echocardiography, magnetic resonance imaging, and nuclear imaging, enabled nonbiopsy diagnosis of this disease. The mechanisms underlying characteristic cardiac imaging findings have been deciphered by histopathological studies. Novel disease-modifying therapies for ATTR amyloidosis, such as TTR stabilizers, short interfering RNA, and antisense oligonucleotides, were initially approved for ATTRv amyloidosis patients with polyneuropathy. However, the indications for the use of these disease-modifying therapies gradually widened to include ATTRv and ATTRwt amyloidosis patients with cardiomyopathy. Since the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, occurred, the minimization of hospital visits and telemedicine have become increasingly important. As older age and cardiovascular disease are major factors associated with increased disease severity and mortality of COVID-19, many ATTR amyloidosis patients are at increased risk of disease aggravation when they are infected with SARS-CoV-2. From this viewpoint, close interspecialty communication to determine the optimal interval of evaluation is needed for the management of patients with ATTR amyloidosis.

Heart Failure Association, Heart Failure Society of America, and Japanese Heart Failure Society Position Statement on Endomyocardial Biopsy.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumors. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples has significantly improved the diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (1) an overview of the practical approach to EMB, (2) an update on indications for EMB, (3) a revised plan for heart transplant rejection surveillance, (4) the impact of multimodality imaging on EMB, and (5) the current clinical practice in the worldwide use of EMB.

Heart Failure Association of the ESC, Heart Failure Society of America and Japanese Heart Failure Society Position statement on endomyocardial biopsy.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples have significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (i) an overview of the practical approach to EMB, (ii) an update on indications for EMB, (iii) a revised plan for HTx rejection surveillance, (iv) the impact of multimodality imaging on EMB, and (v) the current clinical practice in the worldwide use of EMB.