CORRIGENDUM: Impact of Different Therapeutic Strategies With Left Ventricular Assist Devices on Health-Related Quality of Life During Prolonged Device-Based Support.

[This corrects the article DOI: 10.1253/circrep.CR-22-0126.].

Can right ventricular endomyocardial biopsy predict left ventricular fibrosis beforehand in dilated cardiomyopathy?

AIMS: Myocardial fibrosis of the left ventricle (LV) is a prognostic factor in dilated cardiomyopathy (DCM). This study aims to evaluate whether fibrosis of right ventricular (RV) endomyocardial biopsy (EMB) can predict the degree of LV fibrosis beforehand in DCM. METHODS AND RESULTS: Fibrosis extent in 70 RV-EMB specimens of DCM diagnosis was compared with that in the whole cross-sectional LV of excised hearts in the same patients (52 explanted hearts for transplant and 18 autopsied hearts). The median interval between biopsy and excision was 4.1 (0.13-19.3) years. The fibrosis area ratio of the EMBs and excised hearts were evaluated via image analysis. The distribution of cardiovascular magnetic resonance-late gadolinium enhancement (LGE) in the intraventricular septum was classified into four quartile categories. The fibrosis area ratio in RV-EMB correlated significantly with that in the short-axis cut of the LV of excised hearts (r = 0.82, P < 0.0001) and with a diffuse pattern of LGE (r = 0.71, P = 0.003). In a multivariate model, after adjusting for the interval between biopsy performance and heart excision, the fibrosis area ratio in RV-EMB was associated with that in LV-excised heart (regression coefficient, 0.82; 95% confidence interval, 0.68-0.95; P < 0.0001). CONCLUSIONS: The fibrosis observed in RV-EMB positively correlated with the extent of fibrosis in the LV of excised hearts in patients with DCM. The study findings may help predict LV fibrosis, considered a prognostic factor of DCM through relatively accessible biopsy techniques.

Successful echocardiography-guided medical management of severe early post-implant right ventricular failure in a patient with left ventricular assist device support: a case report.

BACKGROUND: Post-implant right heart failure (RHF) has been recognized as a crucial prognostic factor in patients receiving left ventricular assist devices (LVADs), and its management has long attracted attention from cardiologists and surgeons. CASE PRESENTATION: This report described an 18-year-old female with acutely deteriorating heart failure due to dilated cardiomyopathy who underwent paracorporeal pulsatile-flow LVAD and developed early post-implant RHF. At postoperative day (POD) six, she was almost asymptomatic at rest on 2.5 mg/kg/min of dobutamine; however, the echocardiogram, performed as part of the daily postoperative care, revealed a severely enlarged right ventricle with a decompressed left ventricle, implying the development of post-implant RHF. Bolus infusion of saline and reduction of pump flow (6.0 L/min to 3.0 L/min) led to normalization of both ventricular shapes in 30 s, suggesting that RHF could be managed without surgical interventions. Milrinone was started on POD six, followed by sildenafil administration on POD seven. Fluid balance was strictly adjusted under the close observation of daily echocardiograms. Milrinone and dobutamine were discontinued on PODs 18 and 21, respectively. The patient was listed for a heart transplant on POD 40. Despite reduced right ventricular function (right ventricular stroke work index of 182.34 mmHg*ml/m- 2, body surface area 1.5 m2), she was successfully converted to implantable LVAD on POD 44 with no recurrence of post-implant RHF thereafter for four years. CONCLUSIONS: In post-implant RHF management, early detection, together with proper and prompt medical management, is crucial to avoiding any surgical intervention. Close observation of daily echocardiograms might be helpful in detecting subclinical RHF and is useful for post-implant medical management.

Efficacy of catheter cleaning methods using intravenous indwelling catheter, 10% silver nitrate solution and a monofilament nylon thread for deeply progressed superficial driveline infections: case series.

Driveline infection (DLI) is treated by local irrigation via driveline exit site (DLES) and surgical debridement is considered in patients with deep DLI. We describe three cases of deeply progressed superficial DLI that were considered to require surgical debridement but could be treated with a unique catheter cleaning method using intravenous indwelling catheter, a cotton swab with 10% silver nitrate solution and a monofilament nylon thread. Case 1 was a 60-y-old man with ischemic cardiomyopathy with left ventricular assist device implantation 2 y before. Daily bedside debridement with 10% silver nitrate solution was performed via the DLES. Case 2 was a 43-y-old man with ischemic cardiomyopathy who had recurrent DLI with methicillin-resistant Staphylococcus aureus, and case 3 was a 49-y-old woman with hypertrophic cardiomyopathy, who also showed improvement in their DLI with Pseudomonas aeruginosa. These cleaning methods may be useful for the deeply progressed superficial DLI.

Prognostic impact of lung computed tomography density in cardiogenic shock patients with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Pulmonary complications often occur in patients receiving veno-arterial extracorporeal membrane oxygenation (VA ECMO). However, the prognostic impact of lung damage has not been fully elucidated. METHODS: This single-center retrospective observational study targeted patients with cardiogenic shock who received VA ECMO between 2012 and 2021. This study included 65 patients who underwent chest computed tomography (CT) on VA ECMO, followed by escalation to central mechanical circulatory support (MCS) with left ventricular venting. The average density of lung CT images was measured using region-of-interest methods, and the primary endpoint was 180-day all-cause death after escalation to the central MCS. RESULTS: Twenty-two patients (34%) developed 180-day all-cause death. According to the Cox regression analysis, age (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03-1.14; p = 0.001), ischemic etiology (HR, 5.53; 95% CI, 2.09-14.62; p < 0.001), duration of VA ECMO support (HR, 1.19; 95% CI, 1.00-1.40; p = 0.045), and lung CT density (≥ -481 Hounsfield unit [HU]) (HR, 6.33; 95% CI, 2.26-17.72; p < 0.001) were independently associated with all-cause death. Receiver operating characteristic curve analysis determined that lung CT density ≥ -481 HU is an optimal cutoff value for predicting all-cause death (area under the curve [AUC], 0.72). The 180-day overall survival rate for patients with high lung CT density (≥ -481 HU) was significantly lower than that for those with low lung CT density (< -481 HU) (44.4% vs. 81.6%, respectively, p = 0.002). CONCLUSIONS: Higher lung CT density could be a useful predictor of death in patients with VA ECMO requiring central MCS escalation.

Impact of Different Therapeutic Strategies With Left Ventricular Assist Devices on Health-Related Quality of Life During Prolonged Device-Based Support.

Background: Left ventricular assist device (LVAD) implantation improves survival and health-related quality of life (HRQoL) of patients with heart failure. However, the impact of LVADs or different LVAD-based therapeutic strategies on long-term HRQoL has not been investigated. We evaluated the long-term HRQoL of Japanese patients who were treated with different LVAD-based therapeutic strategies. Methods and Results: Patients whose data were recorded in the Japanese Registry for Mechanical Assisted Circulatory Support between January 2010 and December 2018 were divided into 3 groups: primary implantable LVAD (G-iLVAD; n=483), primary paracorporeal LVAD (n=33), and bridge-to-bridge from paracorporeal to implantable LVAD (n=65). HRQoL was evaluated using the EuroQoL 5-dimension 3-level (EQ-5D-3L) before and 3 and 12 months after LVAD implantation; the mean EQ-5D-3L visual analog scale (VAS) score in the G-iLVAD group at these time points was 47.4, 71.1, and 72.9, respectively (where scores of 0 and 100 indicate worst and best imaginable health state, respectively). Changes in the least squares means of the VAS scores at 3 and 12 months after implantation differed significantly among the 3 groups. Social function, disability, and physical and mental problems were significantly lower in the G-iLVAD than other groups. Conclusions: HRQoL improved significantly at 3 and 12 months after LVAD implantation in all groups. Physical function showed a stronger improvement than did social function, disability, and mental function.

Novel Scoring System to Risk Stratify Patients Receiving Durable Left Ventricular Assist Device From J-MACS Registry Data.

BACKGROUND: Recently, destination therapy (DT) was approved in Japan, and patients ineligible for heart transplantation may now receive durable left ventricular assist devices (LVADs). Several conventional risk scores are available, but a risk score that is best to select optimal candidates for DT in the Japanese population remains unestablished.Methods and Results: A total of 1,287 patients who underwent durable LVAD implantation and were listed for the Japanese registry for Mechanically Assisted Circulatory Support (J-MACS) were eligible for inclusion. Finally, 494 patients were assigned to the derivation cohort and 487 patients were assigned to the validation cohort. According to the time-to-event analyses, J-MACS risk scores were newly constructed to predict 3-year mortality rate, consisting of age, history of cardiac surgery, serum creatinine level, and central venous pressure to pulmonary artery wedge pressure ratio >0.71. The J-MACS risk score had the highest predictability of 3-year death compared with other conventional scores in the validation cohort, including HeartMate II risk score and HeartMate 3 risk score. CONCLUSIONS: We constructed the J-MACS risk score to estimate 3-year mortality rate after durable LVAD implantation using large-scale multicenter Japanese data. The clinical utility of this scoring to guide the indication of DT should be validated in the next study.

Pulmonary Vascular Reverse Remodeling After Left Ventricular Assist Device Implantation in Patients With Pulmonary Hypertension.

Prevalence of combined pre- and post-capillary (Cpc) pulmonary hypertension (PH) in patients with PH due to left heart disease (PH-LHD) and the long-term impact of left ventricular assist device (LVAD) implantation in patients with Cpc-PH are not fully elucidated. Eighty-nine patients with PH-LHD who underwent LVAD implantation were retrospectively analyzed. Patients were divided into two groups according to their preoperative pulmonary vascular resistance (PVR) and diastolic pressure gradient (DPG) values (Cpc-PH group, PVR >3 wood units [WU], or DPG ≥7 mmHg; isolated postcapillary [Ipc]-PH group, PVR ≤3 WU, and DPG <7 mmHg). There were 50 patients with Cpc-PH (PVR >3 WU [group A, n = 41]; PVR >3 WU and DPG ≥7 mmHg [group B, n = 8]; DPG ≥7 mmHg [group C, n = 1]), and 39 patients with Ipc-PH. Despite a successful LVAD implantation in all participants, 13 and two patients remained in groups A and B, respectively, early after LVAD implantation, whereas two patients each remained in groups A and B 1 year postoperatively. Values of PVR and DPG in the Cpc-PH group returned to normal levels by 3 years postoperatively. Over 50% of patients with PH-LHD had Cpc-PH, and PVR and DPG normalized in all participants within 3 years after LVAD implantation.

Treatment of advanced heart failure in adults with congenital heart disease: a narrative review and clinical cases.

Background and Objective: The number of adults with congenital heart disease (ACHD) is increasing worldwide. Almost all congenital cardiac lesions can be successfully treated due to the progress in neonatal surgery and pediatric cardiology with a high likelihood of surviving until adulthood. However, ACHD frequently develop sequelae related to the initial cardiac anomaly. Heart failure (HF) is one of the most common complications associated with a high morbidity and mortality. Methods: The authors did search the PubMed database regarding relevant content covering publications up to March 2022. Relevant manuscripts were classified according to the impact factor of the journal, being a guideline manuscript, a position paper by a society or a comprehensive review of the current literature. Key Content and Findings: Optimal HF treatment remains an unmet need in ACHD. In particular, advanced HF therapy with cardiac resynchronization therapy, ventricular assist devices or organ transplantation is still very different and more specific in ACHD compared to non-ACHD. This review aims to compile international views and evidence from the literatures on the treatment of advanced HF in ACHD. Current challenges, but also the success of different treatment strategies in ACHD are illustrated by clinical cases. Conclusions: The main finding of the review is that data is still scarce regarding ACHD with advanced HF and international efforts to collect data regarding these patients needed to improve the current standard of care.

Successful recovery from refractory hypoxia due to right-to-left shunting associated with iatrogenic atrial septal defect after catheter ablation in a patient with a left-ventricular assist device: a case report.

Background: Catheter ablation (CA) has been reported to be an effective therapeutic option for ventricular arrhythmias, even in patients with a left-ventricular assist device (LVAD). However, the issues of right-to-left shunting due to iatrogenic atrial septal defect (iASD) associated with procedures for CA have not been well documented. We describe a rare case of refractory hypoxia associated with right-to-left shunting via iASD after CA through the transseptal approach in an LVAD patient. Case summary: A 52-year-old Asian man with a continuous-flow implantable LVAD and progressive right ventricular (RV) dysfunction was admitted because of refractory ventricular tachycardia (VT) and subsequent right heart failure. Since VT could not be controlled by intravenous administration of multiple antiarrhythmic drugs, VT ablation via the transseptal approach was performed. Ventricular tachycardia was terminated to the sinus rhythm after VT ablation; however, hypoxia associated with significant right-to-left shunting across the iASD was detected. Intensive medical management, such as an adjusted mechanical ventilator to increase pulmonary vascular compliance and adjustment of LVAD pump speed, as well as the use of intravenous inotropes to support impaired RV function successfully stabilized the haemodynamic and improved hypoxia for the disappearance of right-to-left shunting. Echocardiography at 7 months after CA showed that the significant iASD and right-to-left shunting had disappeared. Discussion: The evaluation of RV function prior to VT ablation via the transseptal approach is important in the postoperative management of patients with LVAD, because RV dysfunction may cause refractory hypoxia due to iASD.

Effect of Diabetes Mellitus on Outcomes in Patients With Left Ventricular Assist Device　- Analysis of Data From a Japanese National Database.

BACKGROUND: The objective of this study is to investigate the effect of preoperative diabetes on all-cause mortality and major postoperative complications among patients with continuous-flow left ventricular assist device (LVAD) by using data from a national database.Methods and Results: The 545 study patients who underwent primary HeartMateII implantation between 2013 and 2019 were divided into 2 groups according to their diabetes mellitus (DM) status; patients with DM (n=116) and patients without DM (n=429). First, the on-device survival and incidence of adverse events were evaluated. Second, after adjusting for patients' backgrounds, the change of laboratory data in the 2 groups were compared. Overall, on-device survival at 1, 2, and 3 years was almost equivalent between the 2 groups; it was 95%, 94%, and 91% in patients without DM, and 93%, 91%m and 91% in patients with DM (P=0.468) The incidence of adverse events was similar between 2 groups of patients, except for driveline exit site infection in the adjusted cohort. Cox proportional hazards regression analysis revealed younger age (HR: 0.98 (95% confidence interval (CI): 0.97-0.99, P=0.001) and presence of DM (HR: 1.83 (95% CI: 1.14-2.88), P=0.016) as significant predictors of driveline infection. Laboratory findings revealed no differences between groups throughout the periods. CONCLUSIONS: The clinical results after LVAD implantation in DM patients were comparable with those in non-DM patients, except for the driveline exit site infection.

Successful heart transplantation in a patient with adolescent-onset dilated cardiomyopathy secondary to propionic acidaemia: a case report.

Background: Propionic acidaemia (PA) is an autosomal recessive disorder resulting from deficiency of propionyl-CoA carboxylase, a mitochondrial enzyme that metabolizes propionyl-CoA. Generally, patients with PA develop symptoms in the neonatal period due to protein intake through breastfeeding; however, late-onset PA with atypical symptoms, including cardiomyopathy, has been recently reported. Case summary: We present the case of a 25-year-old male with late-onset PA complicated by advanced heart failure (HF) due to isolated secondary dilated cardiomyopathy, who required left ventricular assist device (LVAD) implantation and finally underwent heart transplantation (HTx). Initially, the patient developed HF at the age of 16 and was diagnosed with mitochondrial cardiomyopathy. Due to refractory HF, he underwent an LVAD implantation and was scheduled for HTx. During the preoperative period for HTx, the patient suffered from sepsis due to the worsening of LVAD driveline exit-site infection complicated by overt metabolic acidosis, finally leading to the diagnosis of late-onset PA. After this diagnosis, adequate nutritional interventions were introduced, and the cardiac function was partially restored enough for him to be weaned-off LVAD; however, the patient became inotrope dependent and underwent HTx. The post-HTx course was uneventful with special nutritional management, and he has experienced no adverse metabolic events in the past 3 years. Discussion: Late-onset PA can cause isolated adult-onset cardiomyopathy, and LVAD or HTx should be considered when PA is complicated by advanced HF and is unresponsive to conventional medical therapies.

Risk Assessment of Neutropenia during Low-Dose Valganciclovir Prophylaxis for Heart Transplant Recipients.

The aim of this study was to investigate whether low-dose valganciclovir (VGCV) prophylaxis for cytomegalovirus (CMV) infection increased the risk of developing neutropenia in heart transplant recipients (HTRs). Forty-three HTRs receiving VGCV were divided into two groups: those who received VGCV prophylaxis (n = 22) and those who did not (n = 21). Neutropenia was defined as an absolute neutrophil count ˂1500/µL and was monitored for approximately one year post-transplantation. In the prophylaxis group, 77.3% (17/22) of HTRs experienced neutropenia, which was significantly higher than that in the no prophylaxis group (42.9% [9/21], p = 0.031). No significant differences in the duration of VGCV administration and cumulative dose up to the first neutropenia episode were observed between the groups. Meanwhile, the cumulative dose of mycophenolate mofetil was significantly higher in the prophylaxis group than in the no prophylaxis group (p = 0.018); the daily maintenance dose and regularly measured area under the concentration-time curve (AUC) of mycophenolic acid did not significantly differ between groups. In conclusion, the risk of developing neutropenia was higher in HTRs receiving low-dose VGCV prophylaxis than it was in those not receiving prophylaxis, probably not attributed to dosing period and cumulative dose of VGCV until the onset of neutropenia.

Short-term outcomes of EXCOR Paediatric implantation.

OBJECTIVES: The aim of this study was to review a single institution's experience with EXCOR Paediatric implantation. METHODS: Patients <15 years old who underwent EXCOR implantation as a bridge to transplantation between 2015 and 2021 were enrolled. Major adverse events included death, cerebrovascular event resulting in sequelae, major infection (sepsis or surgical site infection requiring open sternal irrigation or device removal) and device malfunction requiring surgical treatment. RESULTS: Overall median age and weight for all 20 children at implantation were 10.8 (interquartile range, 7.9-33.2) months and 6.3 (4.6-10.2) kg. Ten patients (50%) weighed <5 kg. Primary diagnoses were dilated cardiomyopathy in 13 patients, fulminant myocarditis in 3, restrictive cardiomyopathy in 2 and congenital heart disease in 2. Two patients required biventricular assist support. The median support time was 365 (241-636) days. Six patients (30%) were supported for >20 months. One patient died. Seven patients underwent heart transplant. Heart transplant has not been performed in the last 1.5 years. Five patients were weaned from EXCOR support after native myocardial recovery, including a patient with dilated cardiomyopathy who recovered after 24 months of EXCOR support. Major complication-free survival at 6, 12 and 18 months were 79.3%, 49.6% and 38.6%, respectively. Body weight <5 kg at implantation was a risk factor for decreased major complication-free survival. CONCLUSIONS: Survival during EXCOR Paediatric support was good, but it prolonged the wait time for a heart transplant. The number of major complications increased over time and was not negligible, especially in small children.

[Beneficial Effects of the Modified Bicaval Anastomosis Technique for Orthotopic Heart Transplantation from a Size-Mismatched Donor:20-year Single Center Experience].

BACKGROUND: Size-mismatched heart transplantation( HTx) is associated with a risk of stenosis of the caval anastomosis site or low cardiac output syndrome. We developed a modified bicaval anastomosis technique( mBCAT) that achieved an adjustable caval anastomosis to compensate for the size mismatch. This study clarified clinical outcomes of HTx with mBCAT technique according to the degree of the size mismatch. METHODS AND RESULTS: This study consisted of 130 adult patients who underwent HTx with the mBCAT during a 22-year period and were followed up for at least 1 year. The cohort was divided into three groups according to the donor-to-recipient body weight ratio:<0.8, undersized group (n=19);0.8 ~1.3, size-matched group( n=89);and >1.3, oversized group( n=22). The undersized, size-matched, and oversized groups showed no significant differences in the rate of mild or worse tricuspid regurgitation on echocardiography at 1 month [ 1( 5.3%), 8( 9.0%), and 1( 4.6%), respectively;p=0.683] or the survival rate at 10 years( 100%, 96%, and 95%, respectively;p=0.452). The right heart catheter study revealed no pressure gradient across the orifices of both cavae in any patient. Additionally, the cardiac index immediately post-HTx was low in the undersized group, but improved over time in all groups, achieving the comparable value at 6 and 12 months post-HTx. CONCLUSIONS: The mBCAT prevented caval anastomosis-related complications in size-mismatched HTx and achieved excellent hemodynamics regardless of donor size.

Immunocompetent cells in durable ventricular assist device-implanted non-ischaemic dilated cardiomyopathy.

OBJECTIVE: Because the presence of immunocompetent cells in the myocardium is associated with the pathological stage and/or myocardial viability, we explored relationships between functional recovery after left ventricular assist device implantation and the distribution of immunocompetent cells in non-ischaemic dilated cardiomyopathy patients. METHODS: We reviewed 50 consecutive dilated cardiomyopathy patients implanted with HeartMate II at our institute between April 2013 and December 2018 who were treated with optimal medical therapy during left ventricular assist device support. Patients were stratified by improvement of the left ventricular ejection fraction at 6 months after implantation: ≥ 10% increase (Gr ≥ 10%), 5-10% (Gr 5-10%), and ≤ 5% (Gr ≤ 5%). T cells and macrophages were evaluated in the apical myocardium after left ventricular assist device implantation. RESULTS: During left ventricular assist device support, 12 patients underwent heart transplantation and 2 patients died. Four patients with Gr ≤ 5% were readmitted because of congestive heart failure, but none with Gr ≥ 10%. Macrophages and T cells in the left ventricular myocardium with Gr ≥ 10% were significantly more present compared to those in other groups. CONCLUSIONS: The distribution of immunocompetent cells in the left ventricular myocardium might predict myocardial viability of this pathology after implantation.

Successful bridge to recovery in a patient with fulminant giant cell myocarditis that developed from multiple autoimmune disorders including myasthenia gravis: a case report.

BACKGROUND: A recently indicated immunotherapy strategy, combined with mechanical circulatory support (MCS), seems to improve outcomes in patients with fulminant giant cell myocarditis (GCM). However, characterizing a definitive clinical outcome of this strategy remains challenging, and the autoimmunity associated with the onset of GCM remains controversial. CASE SUMMARY: A 26-year-old man with poor control of atopic dermatitis and ulcerative colitis presented with cardiogenic shock requiring MCS. He was diagnosed with fulminant GCM; hence, immunotherapy (including steroids and intravenous immunoglobulin) was administered and an extracorporeal left ventricular assist device (LVAD) was needed. As the patient complained of prominent fatigue and double vision before myocarditis onset, and acetylcholine receptor-binding antibody titres were elevated, he was diagnosed with myasthenia gravis (MG). No anti-striational antibodies known to be associated with GCM in patients with MG were found in the patient's serum. Cyclosporin-based immunosuppression under LVAD therapy led to an almost complete resolution of his muscle weakness, intermittent ptosis, and cardiac dysfunction along with the histopathological remission of GCM resulting in LVAD removal. He remained at home without recurrence of GCM and worsening symptoms of MG over the 6-month period following discharge. DISCUSSION: We describe a case of GCM with multiple autoimmune disorders, which recovered by treatment with early cyclosporin-based immunosuppressive therapy under LVAD therapy. The present case suggests the involvement of unknown anti-striational antibodies in the development of GCM in patients with MG and may provide information to guide a novel therapeutic regimen for patients with fulminant GCM requiring mechanical circulatory support.