Clinical impact of the pathological quantification of myocardial fibrosis and infiltrating T lymphocytes using an endomyocardial biopsy in patients with hypertrophic cardiomyopathy.

BACKGROUND: The impact of quantitative pathological findings derived from endomyocardial biopsies (EMB) on clinical prognosis in patients with hypertrophic cardiomyopathy (HCM) remains unclear. METHODS: We retrospectively studied 55 consecutive HCM patients who underwent EMB. We quantified the collagen area fraction (CAF), the cardiomyocyte diameter, the nuclear area and circularity, and the number of myocardial infiltrating CD3+ cells using EMB samples by image analyzing software. The primary clinical endpoint was defined as a composite including cardiovascular death, admission due to heart failure and ventricular arrhythmia. RESULTS: During the median follow-up of 37.2 months, the primary endpoint was found in 12 patients. No significant difference in the risk score of 5-year sudden cardiac death was observed between the event-occurrence group and the event-free group. In the multivariable Cox proportional-hazard analysis, CAF [hazard ratio (HR) per 10% increase: 1.555, 95% CI: 1.014-2.367, p = 0.044] and the number of infiltrating CD3+ cells (HR per 10% increase: 1.231, 95% CI: 1.011-1.453, p = 0.041) were the independent predictors of the primary endpoint, while the myocardial diameter and the nuclear irregularity had no significant prognostic impact. Kaplan-Meier survival curves demonstrated that patients with both higher CAF and higher number of CD3+ cells had the worst prognosis (log-rank, P < 0.001). CONCLUSIONS: The higher CAF and the higher number of infiltrating CD3+ cells quantified using EMB samples were the independent predictors of poor clinical outcomes in patients with HCM. Cardiomyocyte diameter and nuclear irregularity did not significantly impact the clinical prognosis.

Ventricular Sigmoid Septum as a Risk Factor for Anthracycline-Induced Cancer Therapeutics-Related Cardiac Dysfunction in Patients With Malignant Lymphoma.

Background: Identifying risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) is essential for the early detection and prompt initiation of medial therapy for CTRCD. No study has investigated whether the sigmoid septum is a risk factor for anthracycline-induced CTRCD. Methods and Results: We enrolled 167 patients with malignant lymphoma who received a CHOP-like regimen from January 2008 to December 2017 and underwent both baseline and follow-up echocardiography. Patients with left ventricular ejection fraction (LVEF) ≤50% were excluded. CTRCD was defined as a ≥10% decline in LVEF and LVEF <50% after chemotherapy. The angle between the anterior wall of the aorta and the ventricular septal surface (ASA) was measured to quantify the sigmoid septum. CTRCD was observed in 36 patients (22%). Mean LVEF and global longitudinal strain (GLS) were lower, left ventricular mass index was higher, and ASA was smaller in patients with CTRCD. In a multivariable Cox proportional hazard analysis, GLS (hazard ratio [HR] per 1% decrease 1.20; 95% confidence interval [CI] 1.07-1.35) and ASA (HR per 1° increase 0.97; 95% CI 0.95-0.99) were identified as independent determinants of CTRCD. An integrated discrimination improvement evaluation confirmed the significant incremental value of ASA for developing CTRCD. Conclusions: Smaller ASA was an independent risk factor and had significant incremental value for CTRCD in patients with malignant lymphoma who received the CHOP-like regimen.

Multimorbidity, polypharmacy, and mortality in older patients with pacemakers.

BACKGROUND: The prevalence of multimorbidity and polypharmacy and its association with all-cause mortality in older patients with pacemakers are largely unknown. We aimed to clarify the prevalence of multimorbidity and polypharmacy, and its association with all-cause mortality in patients ≥75 years of age with pacemakers. METHODS: We retrospectively investigated 256 patients aged ≥75 years (mean age 84.0 ± 5.3 years; 45.7% male) with newly implanted pacemakers. The study endpoint was all-cause mortality ("with events"). Multimorbidity was defined as a Charlson Comorbidity Index ≥3. Polypharmacy was defined as the use of ≥5 medications. RESULTS: During the follow-up period (median, 3.1 years), 60 all-cause deaths were reported. The Charlson Comorbidity Index (2.9 ± 1.9 vs. 1.7 ± 1.7, p < .001) and prevalence of multimorbidity (56.7% vs. 26.0%, p < .001) were significantly higher in deceased patients than in survivors. The number of drugs (6.9 ± 3.0 vs. 5.9 ± 3.3, p = .03) and the prevalence of polypharmacy (78.3% vs. 63.8%, p = .04) were significantly higher in patients with events than in those without events. The event-free survival rate was significantly higher among patients without multimorbidity than in those with multimorbidity (log-rank, p < .001), and was also significantly higher among patients without polypharmacy than in those with polypharmacy (log-rank, p < .001). Multimorbidity (hazard ratio [HR]: 3.21; 95% confidence interval [CI]: 1.85-5.58; p < .001) and polypharmacy (HR: 1.97; 95% CI: 1.03-3.77; p = .04) were independent predictors of all-cause mortality. CONCLUSIONS: Multimorbidity and its associated polypharmacy, which are common in the older population, are prevalent in patients with pacemakers and are independent predictors of poor prognosis.

Experience of the use of octreotide for refractory gastrointestinal bleeding in a patient with Jarvik2000® left ventricular assist device.

Gastrointestinal bleeding (GIB) is among the major complications affecting implantable continuous-flow left ventricular assist device (iLVAD) recipients and is the major cause of re-hospitalization. GIB in iLVAD recipients is sometimes critical, and controlling bleeding using conventional approaches is difficult. A 35-year-old woman developed refractory GIB from multiple gastric polyps and de novo angiodysplasia after Jarvik2000® iLVAD implantation. Discontinuation of anticoagulation and antiplatelet therapies had little effect on GIB; thus, multiple endoscopic hemostatic therapies were performed. However, bleeding recurred several times, and red blood cell (RBC) transfusion in large volumes was required for progressive anemia. Furthermore, the von Willebrand factor (VWF) multimer analysis revealed loss of the high-molecular weight multimer, which may have resulted from the high-speed rotation of the axial-flow LVAD pump. To supplement VWF, cryoprecipitate was administered, but it was effective for only several days. Finally, the patient was treated with octreotide, a somatostatin analog, on post-operative day 58. After starting octreotide, tarry stool gradually decreased, and progression of anemia slowed down within the first 14 days of treatment; thus, the total RBC transfusion volume was reduced without additional hemostatic interventions, including cryoprecipitate administration. The patient developed mediastinitis on post-operative day 68 and died of sepsis on post-operative day 72. There was no adverse effect associated with octreotide use. Although the observation period was short, octreotide appears to be useful for resolving recurrent GIB after iLVAD implantation and reducing blood transfusions.

Monitoring treatment response to tafamidis by serial native T1 and extracellular volume in transthyretin amyloid cardiomyopathy.

Tafamidis meglumine, a transthyretin (TTR) stabilizer, is effective in delaying the progression of neuropathy in TTR amyloidosis with Val30Met mutations. However, its efficacy in TTR amyloid cardiomyopathy is not fully elucidated. Herein, we report a 73-year-old Japanese man with a diagnosis of TTR amyloid cardiomyopathy with Val30Met mutation treated with tafamidis. To evaluate treatment response, cardiac magnetic resonance imaging was performed before and after 12 months of tafamidis treatment. Native T1, extracellular volume, and left ventricular mass showed no obvious worsening, and findings of other diagnostic studies also supported the efficacy of tafamidis to delay the progression of amyloid cardiomyopathy. Our case suggests that serial native T1 and extracellular volume may be novel non-invasive imaging methods to monitor the treatment response to TTR stabilizers in cardiac amyloidosis and also that tafamidis may be effective in suppressing cardiac progression in TTR amyloid cardiomyopathy with Val30Met mutation.