Postoperative bridging anticoagulation and left ventricular assist system thrombosis.

Reduced emphasis on early postoperative bridging anticoagulation is one explanation for the increased incidence of HeartMate II (HM II) pump thrombosis. We conducted a single-center analysis of initial postoperative anticoagulation practices and their impact on the incidence of HM II pump thrombosis. Data was collected on 105 patients undergoing primary HM II implant from 2009 to 2014. A parenteral bridge was defined as use of parenteral anticoagulation prior to attainment of an international normalized ratio ≥ 2 on warfarin. A parenteral bridge was further characterized as early if initiated ≤ 3 days of implant and therapeutic if a manufacturer-specified goal partial thromboplastin time (PTT) was achieved during each of the first 3 days of administration. Pump thrombosis was "suspected" based upon suggestive clinical parameters leading to hospital admission with parenteral anticoagulant administration and "confirmed" by direct visualization of thrombus in the device. A majority of patients (70%) were treated with an initial parenteral bridge, which was started within 3 days of device implantation in 68% of cases. Therapeutic PTT levels were achieved in 52% of patients treated with a parenteral bridge. Patients who were bridged had lower Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles (p = 0.039) and longer intensive care unit stay (p = 0.005). Pump thrombosis was suspected in 25% and confirmed in 13% of patients within 6 months of implant. Point estimates of pump thrombosis incidence demonstrated a lower event rate at 6 months in patients who received a therapeutic bridge (15.8%, 95% CI 6.3-29.1% for suspected; 7.9%, 95% CI 2.0-19.3% for confirmed) compared to those who did not receive a therapeutic bridge (29.9%, CI 19.3-41.1% for suspected; 16.4%, 95% CI 8.7-26.3% for confirmed). This trend was not sustained at 12 and 24 months. Cumulative incidence analyses showed no significant difference in the overall incidence of pump thrombosis between patients who did and did not receive a parenteral bridge. In patients undergoing HM II implantation, the use of initial postoperative parenteral bridging anticoagulation is common but frequently sub-therapeutic. Use of a parenteral bridge reaching therapeutic targets may decrease the 6-month but not the overall incidence of pump thrombosis.

Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-γ in patients with triglyceride deposit cardiomyovasculopathy.

Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, "Triglyceride deposit cardiomyovasculopathy (TGCV)". Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5' splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules' lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients' passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG is defective, the marked up-regulation of PPARγ and related genes may lead to increased uptake of LCFAs, the substrates for TG synthesis. This potentially vicious cycle of LCFAs could explain the massive accumulation of TG and severe clinical course for this rare disease.

Pressure-dimension index and left ventricular sphericity index following HeartMate II and HeartMate 3 implantation.

AIMS: This study aimed to compare the changes in the left ventricle (LV) and right ventricle (RV) geometry and performance after the implantation of HeartMate II (HMII) and HeartMate 3 (HM3). In addition, we investigated whether the echocardiographic parameters LV sphericity index (LVSI) and the novel pressure-dimension index (PDI) can predict post-operative right ventricular failure (RVF). METHODS AND RESULTS: Between 2012 and 2020, 46 patients [HMII (n = 22) and HM3 (n = 24)] met the study's criteria and had echocardiography tests pre-operatively, 6 and 12 months post-operatively. The LVSI and PDI were calculated together with the standard LV and RV echocardiographic parameters. The mean follow-up was 24 ± 7 months. In both groups, the LV end-diastolic diameter (LVEDD) significantly decreased 12 months post-operatively compared with the pre-operative values (HMII: 6.4 ± 1.4 cm vs. 5.7 ± 0.9 cm, P = 0.040; HM3: 6.7 ± 1.3 cm vs. 5.5 ± 0.9 cm, P < 0.01, respectively). RV function 12 months post-operatively was better in the HM3 group than in the HMII group, as indicated by a significantly higher RV fractional area change (RVFAC) in the HM3 group than in the HMII group 12 months post-operatively (35 ± 12% vs. 26 ± 16%, P = 0.039), significantly higher tricuspid annular plane systolic excursion (TAPSE) in the HM3 group 12 months post-operatively compared with the HMII group (13.9 ± 1.9 mm vs. 12.0 ± 2.1 mm, P = 0.002), and the tissue Doppler estimated tricuspid annular systolic velocity (TASV) was also significantly higher in the HM3 group 12 months post-operatively compared with the HMII group (11.5 ± 2.7 mm/s vs. 9.9 ± 1.5 mm/s, P = 0.020). The LVSI value was significantly higher 12 months post-operatively in the HMII group than in the HM3 group (1.2 ± 0.4 vs. 0.8 ± 0.2, P = 0.001, respectively), indicating worse geometric changes. The PDI decreased 12 months post-operatively in the HM3-group compared with the baseline (3.4 ± 1.4 mmHg/cm2 vs. 2.0 ± 0.8 mmHg/cm2, P < 0.001). In the univariate and multivariate analyses, only the pre-operative PDI was a predictor of post-operative RVF [odds ratio: 3.84 (95% CI: 1.53-18.16, P = 0.022)]. The area under the curve for pre-operative PDI was 0.912. The 2 year survival was significantly better in the HM3 group (log-rank, P = 0.042). CONCLUSIONS: The design of HM3 offered better geometrical preservation of the LV and enabled normal PDI values, leading to improved RV function, as indicated by better RVFAC, TAPSE, and TASV values. The use of pre-operative PDI as an additional tool for established risk scores might offer a better pre-operative predictor of RVF.

Impact of pump replacement on outcome in advanced heart failure patients with left ventricular assist system.

Pump thrombosis is one of the major adverse events associated with the use of a left ventricular assist system (LVAS) in patients with advanced heart failure. We investigated the clinical implication of pump replacement because of thrombus formation. This study included 87 patients who underwent implantation of a Nipro (Toyobo) pulsatile extracorporeal LVAS intended as a bridge to transplantation and were alive more than 3 months after implantation. The pump of this device is translucent, and daily evaluation for signs of thrombus formation was performed. Pump replacement was performed for significant thrombus formation that became visible. Data collection including demographics as well as hematologic values were performed 1 day before (baseline) and 3 months after implantation, and all patients were followed for 2 years or until death. At 3 months after LVAS implantation, 41 patients (47.1%) had undergone pump replacement because of pump thrombus. Baseline body surface area <1.63 m(2) was a significant predictor of pump replacement (hazard ratio [HR] 2.15, P = 0.04). At 3 months after implantation, there was a significantly higher incidence of stroke (P < 0.05) as well as a significantly greater decrease in body weight (F = 4.92, P = 0.03) in patients who underwent pump replacement as compared to those without. The 2-year mortality after implantation was 26.4%. Multivariate Cox regression analysis showed that pump replacement within 3 months after implantation was an independent predictor of mortality (HR 2.50, P = 0.03). In conclusion, pump replacement for thrombus formation may have a strong association with worse outcome. Our results reconfirm the clinical importance of device thrombus in the management of LVAS.

Long-term evaluation of a fully magnetically levitated circulatory support device for advanced heart failure-two-year results from the HeartMate 3 CE Mark Study.

AIM: This study aimed to assess safety and outcomes of patients, 2 years after implantation with the HeartMate 3 Left Ventricular Assist System. METHODS AND RESULTS: This study included 50 adults with New York Heart Association (NYHA) class IIIB or IV symptoms or American College of Cardiology/American Heart Association stage D heart failure with an ejection fraction ≤25% and a cardiac index ≤2.2 L/min/m2 without inotropes, or inotrope-dependent with optimal medical management, or listed for heart transplant. The median duration of left ventricular assist device support was 694 days (range: 19-833 days). At baseline, cardiac index was 1.8 ±0.5 L/min/m2 , 58% of patients were receiving inotropes, and 92% were INTERMACS profiles 2-4. At 2 years, Kaplan-Meier survival was 74 ±6%, 5 (10%) patients were transplanted, and 32 patients (64%) remain with support. Adverse event rates include bleeding requiring surgery (16%), gastrointestinal bleeding (20%), driveline infection (24%), ischaemic stroke (16%), haemorrhagic stroke (8%), right heart failure (14%), and outflow graft thrombosis (2%). Notably, no haemolysis, pump thrombosis, or pump malfunction events occurred. At 2 years, 47% of patients remained in NYHA class I and 41% in NYHA class II (P <0.0001). From baseline to 2 years, the mean six-minute walk distance increased from 239 m to 347 m (P <0.0001), and the mean EQ-5D quality of life score improved from 48.2 to 70.6 (P < 0.0001). CONCLUSIONS: Two years post-HeartMate 3 implantation, results show expected and acceptable survival, enhanced haemocompatibility, improved patient functional status and quality of life. This corroborates the success of HeartMate 3 since its first-in-man implantation case in Germany. ClinicalTrials.gov: NCT02170363.

[Cardiac implantable electronic devices and health-related quality of life]. / Beitrag von kardialen elektronischen Implantaten zur gesundheitsbezogenen Lebensqualität.

Patients, scientists and healthcare providers are increasingly interested in identifying interventions that not only reduce mortality but also improve symptoms, function and health-related quality of life. Health-related quality of life is a strong, independent predictor of mortality, cardiovascular events, hospitalization and treatment costs in patients with cardiac diseases. Remote monitoring of pacemakers has a positive effect on health-related quality of life and functional capacity and is equivalent to monitoring these patients in hospitals. Implantation of an implantable cardioverter defibrillator has a major impact on mental health, with the majority of patients experiencing the fear of ICD shocks as particularly detrimental to the quality of life. Variables, such as age, gender and duration of implantation should be considered in the assessment and planning of strategies for improving the quality of life of patients with electronic implantable cardiac devices.

Screening for heart transplantation and left ventricular assist system: results from the ScrEEning for advanced Heart Failure treatment (SEE-HF) study.

BACKGROUND: Heart transplantation (HTx) and implantable left ventricular assist systems (LVAS) improve outcomes in advanced heart failure but may be underutilized. We hypothesized that screening can identify appropriate candidates. METHODS AND RESULTS: The ScrEEning for advanced Heart Failure treatment (SEE-HF) study was a multicentre prospective study screening patients with existing cardiac resynchronization therapy (CRT) and/or implantable cardioverter-defibrillator (ICD) for ejection fraction ≤40% and New York Heart Association (NYHA) class III-IV, and subsequently for guideline-based HTx and LVAS indication. Of 1722 (mean age 64 ± 14 years, 26% women) patients screened at eight centres in seven European countries, 121 (7.0%) were eligible and 99 (5.7%; mean age 61 ± 10 years, 19% women) patients were enrolled for detailed assessment. Twenty-six of the 99 enrolled patients (26%) were eligible for either HTx or LVAD (18 eligible for HTx; 7 eligible for LVAD; and 1 eligible for both). Eleven patients were listed for HTx and three received an LVAS. Eligible patients were 61 ± 8 years and 19% women, whereas those actually receiving intervention were 56 ± 8 years and 8% women. CONCLUSIONS: Among patients with CRT and/or ICD, a minority have NYHA class III-IV heart failure and ejection fraction ≤40%. Among these, however, more than one-quarter have an unrecognized need for HTx or LVAS. When patients are offered intervention based on screening, many decline. Discrepancies exist between clinical and patient equipoise. Clinical Trial Registration ClinicalTrials.gov Unique Identifier: NCT00894387.

Cardiac Implantable Electronic Devices in Patients With Left Ventricular Assist Systems.

Recent progress and evolution in device engineering, surgical implantation practices, and periprocedural management have advanced the promise of durable support with left ventricular assist systems (LVAS) in patients with stage D heart failure. With greater uptake of LVAS globally, a growing population of LVAS recipients have pre-existing cardiac implantable electronic devices (CIEDs). Strategies for optimal clinical management of CIEDs in patients with durable LVAS are evolving, and clinicians will increasingly face complex decisions regarding implantation, programming, deactivation, and removal of CIEDs. Traditional decision-making pathways for CIEDs may not apply to LVAS-supported patients, as few patients die of arrhythmic causes and many arrhythmias may be well tolerated. Given limited data, treatment decisions must be individualized and made collaboratively among electrophysiologists, advanced heart failure specialists, and patients and their caregivers. Large, prospective, well-conducted studies are needed to better understand the contemporary utility of CIEDs in patients with newer-generation LVAS.

Quality of life and functional capacity outcomes in the MOMENTUM 3 trial at 6 months: A call for new metrics for left ventricular assist device patients.

BACKGROUND: The Multicenter Study of MAGLEV Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) clinical trial demonstrated improved 6-month event-free survival, but a detailed analysis of health-related quality of life (HR-QOL) and functional capacity (FC) was not presented. Further, the effect of early serious adverse events (SAEs) on these metrics and on the general ability to live well while supported with a left ventricular assist system (LVAS) warrants evaluation. METHODS: FC (New York Heart Association [NYHA] and 6-minute walk test [6MWT]) and HR-QOL (European Quality of Life [EQ-5D-5L] and the Kansas City Cardiomyopathy [KCCQ]) assessments were obtained at baseline and 6 months after HeartMate 3 (HM3, n = 151; Abbott, Abbott Park, IL) or HeartMate II (HMII, n = 138; Abbott) implant as part of the MOMENTUM 3 clinical trial. Metrics were compared between devices and in those with and without events. The proportion of patients "living well on an LVAS" at 6 months, defined as alive with satisfactory FC (NYHA I/II or 6MWT > 300 meters) and HR-QOL (overall KCCQ > 50), was evaluated. RESULTS: Although the median (25th-75th percentile) patient KCCQ (change for HM3: +28 [10-46]; HMII: +29 [9-48]) and EQ-5D-5L (change for HM3: -1 [-5 to 0]; HMII: -2 [-6 to 0]) scores improved from baseline to 6 months (p < 0.05), there were no differences between devices (p > 0.05). Likewise, there was an equivalent improvement in 6MWT distance at 6 months in HM3 (+94 [1-274] meters] and HMII (+188[43-340 meters]) from baseline. In patients with SAEs (n = 188), 6MWTs increased from baseline (p < 0.001), but gains for both devices were less than those without SAE (HM3: +74 [-9 to 183] meters with SAE vs +140 [35-329] meters without SAE; HMII: +177 [47-356] meters with SAE vs +192 [23-337] meters without SAE, both p < 0.003). SAEs did not affect the 6-month HR-QOL scores. The "living well" end point was achieved in 145 HM3 (63%) and 120 HMII (68%) patients (p = 0.44). CONCLUSIONS: Gains in HR-QOL and FC were similar early after HM3 and HMII implant. 6MWT improvements were attenuated in patients experiencing SAEs, but HR-QOL metrics did not change. The development of left ventricular assist device-specific HR-QOL tools is needed to better characterize the effect of SAEs on a patient's well-being. CLINICAL TRIAL NO: MOMENTUM 3 clinical trial #NCT02224755.