Coexistence of variant-type transthyretin and immunoglobulin light-chain amyloidosis: a case report.

Background: Determining the type of amyloid deposits is clinically important for choosing the specific therapies for cardiac amyloidosis. Case summary: A 78-year-old woman who had been experiencing fluid retention and dyspnoea on exertion for 6 months was referred to our hospital for the management of heart failure with left ventricular hypertrophy. Since 99mTc-hydroxymethylene diphosphonate scintigraphy showed mild cardiac uptake and significant elevation of serum free lambda chain (with a difference of 263 mg/L in free light chain), we suspected immunoglobulin light-chain amyloidosis (AL), and endomyocardial biopsy was performed. The deposit site within the myocardial tissue exhibited positive for Congo red staining and transthyretin immunostaining, however negative or non-specific for light-chain immunostaining including lambda and kappa staining. Genetic testing confirmed a mutation in V122I, variant-type transthyretin amyloidosis (ATTRv). Despite the administration of patisiran, her condition exhibited progressive deterioration. Additionally, she displayed macroglossia, an atypical manifestation in ATTRv amyloidosis. Further biopsies from tongue and abdominal wall fat culminated in a final diagnosis: the coexistence of ATTRv and AL (of the lambda type). Although treatment with melphalan and dexamethasone was started, she passed away 24 months after the initial visit. When the endomyocardial biopsy specimen underwent mass spectrometry as a post hoc analysis, both ATTR and AL amyloid were significantly detected. Discussion: Coexistence of ATTRv and AL within cardiac amyloidosis is extremely uncommon. In situations where incongruities arise between the amyloid type determined via immunohistochemistry findings and the amyloid type assumed based on other clinical findings, mass spectrometry should be considered.

Non-dilated left ventricular cardiomyopathy vs. dilated cardiomyopathy: clinical background and outcomes.

AIMS: Non-dilated left ventricular cardiomyopathy (NDLVC) was proposed as a new category of cardiomyopathy that included patients with non-left ventricular (LV) dilatation, LV wall motion abnormality, or LV scar. However, the clinical background and event rates of NDLVC were unclear. The aim of this study was to examine the characteristics and event rates of patients with NDLVC and reduced LV ejection fraction (NDLVC-REF) in comparison with those with dilated cardiomyopathy (DCM). METHODS AND RESULTS: We retrospectively included 363 patients with newly diagnosed non-ischaemic cardiomyopathy and reduced LV ejection fraction (<50%) between December 2004 and January 2018. Patients who did not have LV dilatation (LV dimension index of ≦31 mm/m2 in men and ≦34 mm/m2 in women) were categorized as NDLVC-REF (n = 80, 22.2%), and the remaining patients were categorized as DCM. Cardiac events were defined as sudden cardiac death and rehospitalization for heart failure. Patients with NDLVC-REF had a higher prevalence of atrial fibrillation and a higher LV ejection fraction than those with DCM at baseline. LV ejection fraction was higher and LV end-diastolic diameter was smaller in patients with NDLVC-REF than in those with DCM at all time points after diagnosis. During the median follow-up period of 68.8 months (interquartile range: 33.0-93.7 months), 44 patients experienced cardiac events. The Kaplan-Meier curves showed no significant differences in the probability of cardiac events among NDLVC-REF and DCM patients (P = 0.349). However, patients with NDLVC-REF and LV dilatation after diagnosis (14%) had a higher risk of cardiac events than those with NDLVC-REF without LV dilatation (P = 0.049). CONCLUSIONS: There was no significant difference in the incidence of cardiac events between NDLVC-REF and DCM. Among NDLVC-REF patients, 18% of patients who showed LV dilatation after diagnosis had poor outcomes. Therefore, both NDLVC-REF and DCM patients may require equivalent attention to follow-up and regular assessment of LV function.

Characteristics and incidence of cardiac events across spectrum of age in cardiac sarcoidosis.

Background: Clinical characteristics and the risk of cardiovascular events in patients with cardiac sarcoidosis (CS) according to the age of initial diagnosis are unclear. Methods: This study is a sub-analysis of the ILLUMINATE-CS registry, which is a retrospective, multicenter registry that enrolled patients with CS between 2001 and 2017. Patients were divided into three groups according to the tertile of age at the time of initial diagnosis of CS. The study compared the clinical background at the time of CS diagnosis and the incidence rate of cardiac events across age categories. Results: A total of 511 patients were analyzed in this study. In baseline, older patients were more likely to be female. History of hypertension, heart failure admission, and atrioventricular block were more common in patients with older age. There was no significant difference in the history of ventricular arrhythmias and left ventricular ejection fraction among all age groups. During a median follow-up period of 3.2 [IQR: 1.7-4.2] years, 35 deaths, 56 heart failure hospitalization, and 98 fatal ventricular arrhythmias was observed. The incidence rate of all-cause death and heart failure hospitalization was significantly higher in patients with older age (p < 0.001), while there was no significant difference in the incidence rate of ventricular arrhythmia among age groups (p = 0.74). Conclusions: In patients with CS, the risk of all-cause death and heart failure hospitalization was higher in older patients compared with other age groups; however, the risk of ventricular arrhythmia was comparable across all age groups.

Efficacy of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Clinical Parameters in Patients with Heart Failure.

Background and Objectives: Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors have been approved as an oral drug for treating anemia in chronic kidney disease (CKD). However, the clinical effect of HIF-PH inhibitors in patients with heart failure (HF) is unclear. Thus, this study investigated the effect of HIF-PH inhibitors in patients with HF and CKD. Materials and Methods: Thirteen patients with HF complicated by renal anemia who were started on vadadustat were enrolled. Clinical parameters were compared before and 1 month after vadadustat was started. Results: The mean left ventricular ejection fraction was 49.8 ± 13.9%, and the mean estimated glomerular filtration rate was 29.4 ± 10.6 mL/min/1.73 m2. The hemoglobin level was significantly increased (9.7 ± 1.3 mg/dL vs. 11.3 ± 1.3 mg/dL, p < 0.001), and the N-terminal prohormone of B-type natriuretic peptide was significantly decreased after the introduction of vadadustat [4357 (2651-15182) pg/mL vs. 2367 (1719-9347) pg/mL, p = 0.002]. Furthermore, the number of patients with New York Heart Association functional class ≥ 3 was also decreased after the introduction of vadadustat [8 (61.5%) vs. 1 (7.7%), p = 0.008]. No thromboembolic adverse events or new tumors were observed in any patient during the study period. Conclusions: The introduction of vadadustat in patients with HF complicated by renal anemia led to improvements in anemia and symptoms of HF.

The efficacy and safety of sacubitril/valsartan in heart failure with reduced ejection fraction patients with hypotension.

Despite previous studies showing that patients with low systolic blood pressure (sBP) in heart failure with reduced ejection fraction (HFrEF) has a poor prognosis, it has few treatment options. This study aimed to investigate the efficacy and safety of sacubitril/valsartan (S/V) in HFrEF patients with hypotension. We included 43 consecutive HFrEF patients with sBP < 100 mmHg despite guideline-directed medical therapy for at least 3 months and who received S/V between September 2020 and July 2021. Patients admitted for acute heart failure were excluded and 29 patients were evaluated for safety endpoints. Furthermore, patients who performed non-pharmacological therapy or died within 1 month were excluded, finally, 25 patients were evaluated for efficacy endpoints. The mean initial S/V dose was 53.0 ± 20.5 mg/day and the mean dosage was increased to 84.0 ± 34.5 mg/day in 1 month. Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) values significantly decreased from 2200 [interquartile range (IQR): 1462-3666] pg/ml to 1409 (IQR: 964-2451) pg/ml. (p < 0.0001). No significant change in sBP occurred (pre-sBP: 93.2 ± 4.9 mmHg, post-sBP: 93.4 ± 9.6 mmHg, p = 0.91), and no patients discontinued the S/V due to symptomatic hypotension in 1 month after S/V initiation. S/V can be safely introduced in HFrEF patients with hypotension to reduce serum NT-proBNP values. Thus, S/V may be useful for the treatment of HFrEF patients with hypotension.

Native T1 high region and left ventricular ejection fraction recovery in patients with dilated cardiomyopathy.

Native T1 mapping is used to assess myocardial tissue characteristics without gadolinium contrast agents. The focal T1 high-intensity region can indicate myocardial alterations. This study aimed to identify the association between the native T1 mapping including the native T1 high region and left ventricular ejection fraction (LVEF) recovery in patients with dilated cardiomyopathy (DCM). Patients with newly diagnosed DCM (LVEF of < 45%) who underwent cardiac magnetic resonance imaging with native T1 mapping were included in the analysis. Native T1 high region was defined as a signal intensity of > 5 SD in the remote myocardium. Recovered EF was defined as a follow-up LVEF of ≥ 45% and an LVEF increase of ≥ 10% after 2 years from baseline. Seventy-one patients met the inclusion criteria for this study. Forty-four patients (61.9%) achieved recovered EF. Logistic regression analysis showed that the native T1 value (OR: 0.98; 95% CI: 0.96-0.99; P = 0.014) and the native T1 high region (OR: 0.17; 95% CI: 0.05-0.55; P = 0.002), but not late gadolinium enhancement, were independent predictors of recovered EF. Compared with native T1 value alone, combined native T1 high region and native T1 value improved the area under the curve from 0.703 to 0.788 for predicting recovered EF. Myocardial damage, which was quantified using native T1 mapping and the native T1 high region were independently associated with recovered EF in patients with newly diagnosed DCM.

Re-worsening left ventricular ejection fraction after response to cardiac resynchronization therapy.

BACKGROUND: Although cardiac resynchronization therapy (CRT) provided functional and clinical improvement in patients with heart failure (HF) and electrical intraventricular conduction disturbances, some patients had re-worsening left ventricular (LV) function after a favorable CRT response. We analyzed the clinical variables and cardiac outcomes associated with this re-worsening LV function after CRT. METHODS: In this study, 71 patients with CRT response who received CRT between 2006 and 2017 were included. CRT response was defined as a "≥ 10% improvement in LV ejection fraction (LVEF) on follow-up." Patients were classified into two groups: (i) persistent: (n = 48, 68%), defined as those with a CRT response and (ii) re-worsening: (n = 23, 32%), consisting of those who fell out of the definition of a CRT response after an initial CRT response. RESULTS: Half of the patients in the re-worsening group failed to maintain a CRT response from two years upwards. A longer duration from HF diagnosis to CRT implantation, nonspecific intraventricular conduction delay (NIVCD) on electrocardiogram at CRT implantation, and a lower increased LVEF at initial CRT response were independent predictors for the re-worsening group. Patients in the re-worsening group had a higher incidence rate for HF hospitalization and cardiac deaths, compared with those in the persistent group. CONCLUSION: One-third of CRT responders experienced re-worsening LVEF, which was associated with poor outcomes. CRT responders with NIVCD, longer HF duration, and a lower increased LVEF at initial CRT response should be monitored with caution.

Perioperative Management of Takayasu Arteritis for Cardiac Surgery in a Patient Treated With Tocilizumab.

We describe the case of a young woman with Takayasu arteritis with severe stenosis in the main trunk of the left coronary artery. After administration of prednisolone and tocilizumab to control disease activity, coronary artery bypass grafting was performed. Here, we report the successful perioperative management of this cardiac surgery. (Level of Difficulty: Advanced.).