Impact of sleep-disordered breathing on ventricular tachyarrhythmias after left ventricular assist device implantation.

Sleep-disordered breathing (SDB) is associated with an increased risk of adverse events in patients with heart failure (HF); however, its impact in patients implanted with a left ventricular assist device (LVAD) remains unclear. We aimed to investigate the prevalence of SDB in patients with LVAD and its impact on their clinical outcomes. Fifty consecutive patients with LVAD who underwent portable sleep monitoring between September 2017 and April 2018 were prospectively enrolled, and they were followed up for 170 ± 36 days. According to their respiratory disturbance indexes (RDIs), they were categorized into the SDB group (RDI ≥ 15, n = 12) and the non-SDB group (RDI < 15, n = 38). The incidence of adverse events during the follow-up period was investigated after enrollment. Multivariate logistic regression analysis revealed significant differences in SDB in LVAD-implanted patients in terms of the logarithmic transformation brain natriuretic peptide (BNP) values (p = 0.005). The optimal BNP cut-off value for SDB prediction in LVAD-implanted patients was 300 pg/mL (sensitivity: 58.3%, specificity: 94.7%). During follow-up, ventricular tachyarrhythmias (VTas) occurred significantly more frequently in the SDB group (4 [33%] vs. 2 [5%] patients, p = 0.02); Atrial tachyarrhythmia (ATa) also tended to occur more frequently in the SDB group (2 [25%] vs. 2 [2%] patients, p = 0.07). SBD was prevalent in 24% of the LVAD-implanted patients with advanced HF. Furthermore, SDB was significantly associated with high BNP levels and was also potentially associated with subsequent incidence of VTa in patients with LVAD.

Discordance between immunofluorescence and immunohistochemistry C4d staining and outcomes following heart transplantation.

BACKGROUND: Capillary deposition of C4d is an important marker of antibody-mediated rejection (AMR) following heart transplantation (HT). There are two immunopathologic assay methods for detecting C4d: frozen-tissue immunofluorescence (IF) and paraffin immunohistochemistry (IHC). The clinical significance of discrepancy between the results of IF and IHC has not been understood. METHODS AND RESULTS: We reviewed 2187 biopsies from 142 HT recipients who had biopsies with assessment of both IF and IHC staining. Among them, 103 (73%) patients had negative IF and IHC C4d staining (Negative Group) and 32 (23%) patients had positive IF but negative IHC staining (Discordant Group). At the time of positive biopsy, 6 (19%) Discordant patients had graft dysfunction, compared to 5 (5%) Negative patients (p = .022). Cumulative incidence of cellular rejection at 1 year was comparable (31% vs. 29%, p = .46); however, cumulative incidence of AMR was significantly higher in the Discordant group (21% vs. 4%, p = .004). Overall 1-year survival was comparable (90% vs. 96%, p = .24); however, freedom from heart failure (HF) was significantly lower in the Discordant group (70% vs. 96%, p < .001). CONCLUSION: The Discordant group showed higher rates of graft dysfunction, AMR and HF admission than the Negative group.

Hypogammaglobulinemia following heart transplantation: Prevalence, predictors, and clinical importance.

Hypogammaglobulinemia (HGG) can occur following solid organ transplantation. However, there are limited data describing the prevalence, risk factors, and clinical outcomes associated with HGG following heart transplantation. We retrospectively reviewed data of 132 patients who had undergone heart transplantation at our institution between April 2014 and December 2018. We classified patients into three groups based on the lowest serum IgG level post-transplant: normal (≥700 mg/dL), mild HGG (≥450 and <700 mg/dL), and severe HGG (<450 mg/dL). We compared clinical outcomes from the date of the lowest IgG level. Mean age was 57 (47, 64) years, and 94 (71%) patients were male. Prevalence of severe HGG was the highest (27%) at 3-6 months following heart transplantation and then decreased to 5% after 1 year. Multivariate analysis showed that older age and Caucasian race were independent risk factors for HGG. Overall survival was comparable between the groups; however, survival free of infection was 73%, 60%, and 45% at 1 year in the normal, mild HGG, and severe HGG groups, respectively (P = .013). In conclusion, there is a high prevalence of HGG in the early post-heart transplant period that decreases over time. HGG is associated with an increased incidence of infection.

Influence of Induction Therapy Using Basiliximab With Delayed Tacrolimus Administration in Heart Transplant Recipients　- Comparison With Standard Tacrolimus-Based Triple Immunosuppression.

BACKGROUND: Appropriate indications and protocols for induction therapy using basiliximab have not been fully established in heart transplant (HTx) recipients. This study elucidated the influence of induction therapy using basiliximab along with delayed tacrolimus (Tac) initiation on the outcomes of high-risk HTx recipients.Methods and Results:A total of 86 HTx recipients treated with Tac-based immunosuppression were retrospectively reviewed. Induction therapy was administered to 46 recipients (53.5%) with impaired renal function, pre-transplant sensitization, and recipient- and donor-related risk factors (Induction group). Tac administration was delayed in the Induction group. Induction group subjects showed a lower cumulative incidence of acute cellular rejection grade ≥1R after propensity score adjustment, but this was not significantly different (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.37-1.08, P=0.093). Renal dysfunction in the Induction group significantly improved 6 months post-transplantation (P=0.029). The cumulative incidence of bacterial or fungal infections was significantly higher in the Induction group (HR: 10.6, 95% CI: 1.28-88.2, P=0.029). CONCLUSIONS: These results suggest that basiliximab-based induction therapy with delayed Tac initiation may suppress mild acute cellular rejection and improve renal function in recipients with renal dysfunction, resulting in its non-inferior outcome, even in high-risk patients, when applied to the appropriate recipients. However, it should be carefully considered in recipients at a high risk of bacterial and fungal infections.

Role of Gallium-SPECT-CT in the Management of Patients With Ventricular Assist Device-Specific Percutaneous Driveline Infection.

BACKGROUND: Percutaneous driveline infection is a major complication of left ventricular assist device (LVAD). This study evaluated the role of gallium-67 single-photon emission computed tomography (Ga-SPECT)-CT in LVAD-specific percutaneous driveline infection. METHODS: Thirty-six patients with implantable continuous-flow LVAD, who underwent Ga-SPECT-CT to evaluate percutaneous driveline infections, were enrolled and divided into uptake and no-uptake groups based on tracer concentration uptake on Ga-SPECT-CT. Primary outcomes were surgical intervention and readmission for driveline infection. RESULTS: Twenty-two patients had uptake on Ga-SPECT-CT. No significant differences were noted in patient characteristics, wound appearance, or laboratory results. The prevalence of positive skin culture at the driveline exit site (DLES), and usage and duration of antibiotics did not differ. However, the uptake group had higher 1-year event rates (surgical intervention: 39% vs 0%, P = .019; readmission: 74% vs 6.9%, P = .0016). In addition to positive skin culture at DLES and short duration of antibiotic therapy, uptake on Ga-SPECT-CT was a risk factor for surgical intervention (odds ratio 9.00; P = .018) and readmission (odds ratio 7.86; P = .0051). CONCLUSIONS: Ga-SPECT-CT could be one of the clinical modalities for guiding the treatment of driveline infection in patients with a LVAD.

Heart Transplantation Ameliorates Ambulation Capacity in Patients With Muscular Dystrophy　- An Analysis of 9 Cases.

BACKGROUND: Heart transplantation (HTx) is reported to have a comparable effect on the prognosis of heart failure patients without muscular disease and for those with muscular dystrophy (MD). However, little is known about the changes in muscular diseases in patients with MD after HTx. Methods and Results: We assessed the ambulatory capacity of 9 patients with MD who underwent HTx. All patients demonstrated improvement in ambulation to varying degrees and 1 patient successfully climbed Mount Fuji 3.8 years after HTx. CONCLUSIONS: HTx potentially improves not only the prognosis but also the ambulatory capacity of patients with MD.

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.

Impact of Coronary Artery Calcification in the Donor Heart on Transmitted Coronary Artery Disease in Heart Transplant Recipients.

BACKGROUND: Coronary artery disease (CAD) after heart transplantation (HTx) develops as a combination of donor-transmitted coronary atherosclerosis (DTCA) and cardiac allograft vasculopathy. Assessing donor CAD before procurement is important. Because coronary artery calcification (CAC) is a predictor for CAD, donor-heart CAC is usually evaluated to estimate the risk of donor CAD. The usefulness of CAC for predicting DTCA, however, is not known. Methods and Results: Sixty-four HTx recipients whose donor underwent chest computed tomography before procurement or ≤2 weeks after HTx and who underwent coronary angiography and intravascular ultrasound (IVUS) ≤3 months after HTx were enrolled. Eight patients had CAC (CAC group) and 56 patients did not have CAC (no-CAC group). Patients in the CAC group were significantly older and had a higher prevalence of maximum intimal thickness (MIT) of the coronary artery ≥0.5 mm at initial IVUS than patients in the no-CAC group (100% vs. 55%, P=0.02). Adverse cardiac events and death were not significantly different. Everolimus tended to be used more often in the CAC group. CONCLUSIONS: Donor-heart CAC is a significant predictor for MIT of the coronary artery ≥0.5 mm after HTx. The presence of CAC, however, is not associated with future cardiac events. The higher prevalence of everolimus use in the CAC group may have affected the results.

Older age is associated with greater central aortic blood pressure following the exercise stress test in subjects with similar brachial systolic blood pressure.

Brachial systolic pressure (BSP) is often monitored during exercise by the stress test; however, central systolic pressure (CSP) is thought to be a more direct measure of cardiovascular events. Although some studies reported that exercise and aging may play roles in changes of both BSP and CSP, the relationship between BSP and CSP with age following the exercise stress test remains unclear. The aim of this study was to evaluate the effect of age on the relationship between BSP and CSP measured after exercise. Ninety-six subjects underwent the diagnostic treadmill exercise stress test, and we retrospectively divided them into the following 3 groups by age: the younger age group (43 ± 4 years), middle age group (58 ± 4 years), and older age group (70 ± 4 years). Subjects exercised according to the Bruce protocol, to achieve 85 % of their age-predicted maximum heart rate or until the appearance of exercise-associated symptoms. BSP, CSP, and pulse rate (PR) were measured using a HEM-9000AI (Omron Healthcare, Japan) at rest and after exercise. BSP, CSP, and PR at rest were not significantly different among the 3 groups (p = 0.92, 0.21, and 0.99, respectively). BSP and PR immediately after exercise were not significantly different among the groups (p = 0.70 and 0.38, respectively). However, CSP immediately after exercise was 144 ± 18 mmHg (younger age), 149 ± 17 mmHg (middle age), and 158 ± 19 mmHg (older age). CSP in the older age group was significantly higher than that in the younger age group (p < 0.01). Despite similar BSPs in all age groups after exercise, CSP was higher in the older age group. Therefore, older subjects have a higher CSP after exercise, which is not readily assessed by conventional measurements of BSP.

Impact of bridge-to-bridge strategies from paracorporeal to implantable left ventricular assist devices on the pre-heart transplant outcome: A single-center analysis of 134 cases.

BACKGROUND: In Japan, patients with heart failure who have a paracorporeal left ventricular assist device (pLVAD) and cannot be weaned from the VAD may undergo conversion to implantable continuous-flow LVAD (iLVAD) via a bridge-to-bridge (BTB) strategy for bridge-to-transplantation (BTT). This study aimed to evaluate the real-world clinical status of BTB strategies. METHODS: Among 134 patients who underwent iLVAD implantation for BTT, 34 patients underwent conversion from pLVAD to iLVAD (BTB group) and 100 patients underwent iLVAD implantation primarily (primary iLVAD group). The clinical characteristics and outcomes were compared between the two groups. RESULTS: No significant difference was found in the overall survival between the two groups (p = 0.26; log-rank test). However, the 1-year survival rate and the 1-year freedom from the composite events of death, stroke, systemic infection, and bleeding rate were lower in the BTB group than in the primary iLVAD group (survival rate, 88.2% vs. 99.0%, p = 0.0040; composite event-free survival rate, 26.1% vs. 49.8%, p = 0.030; log-rank test). Multivariate analysis indicated that the BTB strategy [hazard ratio (HR) 1.70, 95% confidence intervals (CI) 1.03-2.72; p=0.036] and serum total bilirubin levels at iLVAD implantation [HR 1.31, 95% CI 1.00-1.65; p=0.043] were independent predictors of 1-year composite events. CONCLUSIONS: The BTB strategy is useful in providing long-term survival in patients with acute critical diseases. However, the early mortality rate after conversion is higher in patients who underwent the BTB strategy.

Left ventricular assist device implantation in an adult male with Danon disease.

Danon disease is an extremely rare inherited disorder characterized by cardiac involvement, myopathy, and intellectual disability. As patients with Danon disease die at an early age, mainly as a result of cardiac involvement, implantation of a left ventricular assist device (LVAD) and/or heart transplantation are essential options. However, various comorbidities associated with Danon disease should be assessed when these patients are being considered as potential heart transplant candidates. We report the case of an adult male patient with dilated-phase hypertrophic cardiomyopathy secondary to Danon disease, who received an LVAD as a bridge to transplantation. .

De novo malignancy in heart transplant recipients: A single center experience in Japan.

BACKGROUND: Because of aggressive immunosuppression, heart transplant recipients have a high risk of de novo malignancy, which is a major cause of death and worse prognosis, regardless of the type. However, the impact of de novo malignancy on Japanese heart transplant recipients is unknown. METHODS: We analyzed 103 Japanese heart transplant recipients over 18-years-old at the time of transplantation between April 1999 and April 2017. Patient characteristics and prognosis were compared between heart transplant recipients with or without de novo malignancy after heart transplantation (HTx). Additionally, univariate and multivariate analyses for the risk factors of de novo malignancy after HTx were performed. RESULTS: De novo malignancy developed in 7 patients (6.8%; post-transplant lymphoproliferative disorders, n=3; Bowen's disease, n=1; colon cancer, n=2; bladder cancer, n=1). Follow-up time and previous antibody mediated rejection (AMR)≥grade 1 were risk factors of de novo malignancy after HTx in multivariate analysis (OR: 1.19, 95% CI: 1.00-1.42, p=0.043; and OR: 10.7, 95% CI: 1.37-83.68, p=0.038, respectively). History of malignancy was a potential risk factor, albeit not significant (OR: 23.05, 95% CI: 0.99-534.53, p=0.071). The survival rates in patients with de novo malignancy was significantly lower than in those without de novo malignancy (3-year survival rate: 100% versus 67%, p=0.0025). CONCLUSIONS: Long follow-up time and previous AMR≥grade 1 were risk factors of de novo malignancy after HTx. Japanese heart transplant recipients with de novo malignancy have worse prognosis; therefore, screening examinations are important for early diagnosis.

Massive Biventricular Myocardial Calcification in a Patient with Fulminant Myocarditis Requiring Ventricular Assist Device Support.

The natural course of myocardial calcification is unclear. We herein report a case of massive biventricular myocardial calcification associated with fulminant myocarditis and present its natural course. The patient was a 15-year-old boy. Massive calcification was detected in both ventricles on computed tomography several months after left ventricular assist device placement. Although the calcification gradually regressed, the patient's cardiac function did not recover, and he underwent heart transplantation after a waiting period of 3 years. A histological examination revealed severe fibrosis in both ventricles of the original heart. Myocardial calcification might suggest severe myocardial inflammation and injury in cases of fulminant myocarditis.