A systematic review and meta-analysis of the efficacy and safety of Mavacamten therapy in international cohort of 524 patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a first-in-class cardiac myosin inhibitor, targets the main underlying pathology of HCM. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Mavacamten in patients with HCM. PRISMA flow chart was utilized using PubMed, SCOPUS, and Cochrane databases for all up-to-date studies using pre-defined keywords. Pre-specified efficacy outcomes comprised several parameters, including an improvement in peak oxygen consumption (pVO2) and ≥ 1 NYHA class, the need for septal reduction therapy (SRT), change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ), changes in biochemical markers and LVEF, along with peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Safety outcomes included morbidity and serious adverse events. This systematic review included five studies, four RCTs and one non-randomized control trial comprised a total of 524 (Mavacamten [273, 54.3%] vs placebo [230, 45.7%] adult (≥ 18 years) patients with a mean age of 56 years. The study. comprised patients with Caucasian and Chinese ethnicity and patients with obstructive (oHCM) and non-obstructive (nHCM) HCM. Most baseline characteristics were similar between the treatment and placebo groups. Mavacamten showed a statistically significant increase in the frequency of the primary composite endpoint (RR = 1.92, 95% CI [1.28, 2.88]), ≥ 1 NYHA class improvement (RR = 2.10, 95% CI [1.66, 2.67]), a significant decrease in LVEF, peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Mavacamten also showed a significant reduction in SRT rates (RR = 0.29, 95% CI [0.21, 0.40], p < 0.00001), KCCQ clinical summary scores (MD = 8.08, 95% CI [4.80, 11.37], P < 0.00001) troponin levels and N-terminal pro-B-type natriuretic peptide levels. However, there was no statistically significant difference between Mavacamten and placebo regarding the change from baseline peak oxygen consumption. Mavacamten use resulted in a small increase in adverse events but no statistically significant increment in serious adverse events. Our study showed that Mavacamten is a safe and effective treatment option for Caucasian and Chinese patients with HCM on the short-term. Further research is needed to explore the long-term safety and efficacy of Mavacamten with HCM. In addition, adequately powered studies including patients with nHCM is needed to ascertain befits of Mavacamten in those patients.

Quantitative metrics of the LV trabeculated layer by cardiac CT and cardiac MRI in patients with suspected noncompaction cardiomyopathy.

OBJECTIVES: To compare cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) for the quantitative assessment of the left ventricular (LV) trabeculated layer in patients with suspected noncompaction cardiomyopathy (NCCM). MATERIALS AND METHODS: Subjects with LV excessive trabeculation who underwent both CMR and CCT imaging as part of the prospective international multicenter NONCOMPACT clinical study were included. For each subject, short-axis CCT and CMR slices were matched. Four quantitative metrics were estimated: 1D noncompacted-to-compacted ratio (NCC), trabecular-to-myocardial area ratio (TMA), trabecular-to-endocardial cavity area ratio (TCA), and trabecular-to-myocardial volume ratio (TMV). In 20 subjects, end-diastolic and mid-diastolic CCT images were compared for the quantification of the trabeculated layer. Relationships between the metrics were investigated using linear regression models and Bland-Altman analyses. RESULTS: Forty-eight subjects (49.9 ± 12.8 years; 28 female) were included in this study. NCC was moderately correlated (r = 0.62), TMA and TMV were strongly correlated (r = 0.78 and 0.78), and TCA had excellent correlation (r = 0.92) between CMR and CCT, with an underestimation bias from CCT of 0.3 units, and 5.1, 4.8, and 5.4 percent-points for the 4 metrics, respectively. TMA, TCA, and TMV had excellent correlations (r = 0.93, 0.96, 0.94) and low biases (- 3.8, 0.8, - 3.8 percent-points) between the end-diastolic and mid-diastolic CCT images. CONCLUSIONS: TMA, TCA, and TMV metrics of the LV trabeculated layer in patients with suspected NCCM demonstrated high concordance between CCT and CMR images. TMA and TCA were highly reproducible and demonstrated minimal differences between mid-diastolic and end-diastolic CCT images. CLINICAL RELEVANCE STATEMENT: The results indicate similarity of CCT to CMR for quantifying the LV trabeculated layer, and the small differences in quantification between end-diastole and mid-diastole demonstrate the potential for quantifying the LV trabeculated layer from clinically performed coronary CT angiograms. KEY POINTS: • Data on cardiac CT for quantifying the left ventricular trabeculated layer are limited. • Cardiac CT yielded highly reproducible metrics of the left ventricular trabeculated layer that correlated well with metrics defined by cardiac MR. • Cardiac CT appears to be equivalent to cardiac MR for the quantification of the left ventricular trabeculated layer.

Clinical outcomes of implantable cardioverter-defibrillator therapy in noncompaction cardiomyopathy: a systematic review and meta-analysis.

A subgroup of patients with noncompaction cardiomyopathy (NCCM) is at increased risk of ventricular arrhythmias and sudden cardiac death (SCD). In selected patients with NCCM, implantable cardioverter-defibrillator (ICD) therapy could be advantageous for preventing SCD. Currently, there is no complete overview of outcome and complications after ICD therapy in patients with NCCM. This study sought to present an overview using pooled data of currently available studies. Embase, MEDLINE, Web of Science, and Cochrane databases were searched and returned 915 studies. After a thorough examination, 12 studies on outcome and complications after ICD therapy in patients with NCCM were included. There were 275 patients (mean age 38.6 years; 47% women) with NCCM and ICD implantation. Most of the patients received an ICD for primary prevention (66%). Pooled analysis demonstrates that the appropriate ICD intervention rate was 11.95 per 100 person-years and the inappropriate ICD intervention rate was 4.8 per 100 person-years. The cardiac mortality rate was 2.37 per 100 person-years. ICD-related complications occurred in 10% of the patients, including lead malfunction and revision (4%), lead displacement (3%), infection (2%), and pneumothorax (2%). Patients with NCCM who are at increased risk of SCD may significantly benefit from ICD therapy, with a high appropriate ICD therapy rate of 11.95 per 100 person-years and a low cardiac mortality rate of 2.37 per 100 person-years. Inappropriate therapy rate of 4.8 per 100 person-years and ICD-related complications were not infrequent and may lead to patient morbidity.

Left ventricular assist device implantation and clinical outcomes in the Netherlands.

BACKGROUND: Left ventricular assist device (LVAD) therapy is an established treatment for advanced heart failure with reduced ejection fraction. We evaluated the characteristics and clinical outcomes of patients implanted with an LVAD in the Netherlands. METHODS: Patients implanted with an LVAD in the Netherlands between 2016 and 2020 were included in the analysis. Baseline characteristics entered into this registry, as well as clinical outcomes (death on device, heart transplantation) and major adverse events (device dysfunction, major bleeding, major infection and cerebrovascular event), were evaluated. RESULTS: A total of 430 patients were implanted with an LVAD; mean age was 55 ± 13 years and 27% were female. The initial device strategy was bridge to transplant (BTT) in 50%, destination therapy (DT) in 29% and bridge to decision (BTD) in the remaining 21%. After a follow-up of 17 months, 97 (23%) patients had died during active LVAD support. Survival was 83% at 1 year, 76% at 2 years and 54% at 5 years. Patients implanted with an LVAD as a BTT had better outcomes compared with DT at all time points (1 year 86% vs 72%, 2 years 83% vs 59% and 5 years 58% vs 33%). Major adverse events were frequently observed, most often major infection, major bleeding and cerebrovascular events (0.84, 0.33 and 0.09 per patient-year at risk, respectively) and were similar across device strategies. Patients supported with HeartMate 3 had a lower incidence of major adverse events. CONCLUSIONS: Long-term survival on durable LVAD support in the Netherlands is over 50% after 5 years. Major adverse events, especially infection and bleeding, are still frequently observed, but decreasing with the contemporary use of HeartMate 3 LVAD.

State-of-the art review: Noncompaction cardiomyopathy in pediatric patients.

Noncompaction cardiomyopathy (NCCM) is a disease characterized by hypertrabeculation, commonly hypothesized due to an arrest in compaction during fetal development. In 2006, NCCM was classified as a distinct form of cardiomyopathy (CMP) by the American Heart Association. NCCM in childhood is more frequently familial than when diagnosed in adulthood and is associated with other congenital heart diseases (CHDs), other genetic CMPs, and neuromuscular diseases (NMDs). It is yet a rare cardiac diseased with an estimated incidence of 0.12 per 100.000 in children up to 10 years of age. Diagnosing NCCM can be challenging due to non-uniform diagnostic criteria, unawareness, presumed other CMPs, and presence of CHD. Therefore, the incidence of NCCM in children might be an underestimation. Nonetheless, NCCM is the third most common cardiomyopathy in childhood and is associated with heart failure, arrhythmias, and/or thromboembolic events. This state-of-the-art review provides an overview on pediatric NCCM. In addition, we discuss the natural history, epidemiology, genetics, clinical presentation, outcome, and therapeutic options of NCCM in pediatric patients, including fetuses, neonates, infants, and children. Furthermore, we provide a simple classification of different forms of the disease. Finally, the differences between the pediatric population and the adult population are described.

Intermittent levosimendan infusion in ambulatory patients with end-stage heart failure: a systematic review and meta-analysis of 984 patients.

We sought to synthesize the available evidence regarding safety and efficacy of intermittent levosimendan (LEVO) infusions in ambulatory patients with end-stage heart failure (HF). Safety and efficacy of ambulatory intermittent LEVO infusion in patients with end-stage HF are yet not established. We systematically searched MEDLINE, EMBASE, SCOPUS, Web of Science, and Cochrane databases, from inception to January 30, 2021 for studies reporting outcome of adult ambulatory patients with end-stage HF treated with intermittent LEVO infusion. Fifteen studies (8 randomized and 7 observational) comprised 984 patients (LEVO [N = 727] and controls [N = 257]) met the inclusion criteria. LEVO was associated with improved New York Heart Association (NYHA) functional class (weighted mean difference [WMD] -1.04, 95%CI: -1.70 to -0.38, p < 0.001, 5 studies, I2 = 93%), improved left ventricular (LV) ejection fraction (WMD 4.0%, 95%CI: 2.8% to 5.3%, p < 0.001, 6 studies, I2 = 9%), and reduced BNP levels (WMD -549 pg/mL, 95%CI -866 to -233, p < 0001, 3 studies, I2 = 66%). All-cause death was not different (RR 0.65, 95%CI: 0.38 to 1.093, p = 0.10, 6 studies, I2 = 0), but cardiovascular death was lower on LEVO (RR 0.34, 95%CI: 0.13 to 0.87, p = 0.02, 3 studies, I2 = 0) compared to controls. Furthermore, health-related quality of life (HRQoL) was improved alongside with reduced LV size following LEVO infusions. Major adverse events were not different between LEVO and placebo. In conclusion, intermittent LEVO infusions in ambulatory patients with end-stage HF is associated with less frequent cardiovascular death alongside with improved NYHA class, quality of life, BNP levels, and LV function. However, the current evidence is limited by heterogeneous and relatively small studies.

Right ventricular functional assessment by 2D multi-plane echocardiography prior to left ventricular assist device implantation.

OBJECTIVES: Right ventricular (RV) failure post left ventricular assist device (LVAD) implantation is associated with increased morbidity and mortality. A novel RV multi-plane imaging method using two-dimensional echocardiography and electronic plane rotation (MPE) was used to quantify RV function prior to LVAD implantation and to identify potential added value in this patient population. METHODS: In twenty-five end-stage heart failure patients (age 58.9 ± 6.8 years, 76% male), systolic function of four different RV walls (lateral, anterior, inferior and inferior coronal) were evaluated from one focussed apical view using MPE. RESULTS: Feasibility of tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (RV-S') measurements were high (84-100%), with lower TAPSE values measured in the inferior (14.2 ± 4.6 mm) and inferior coronal (12.3 ± 5.0 mm) walls compared to the lateral (16.3 ± 4.5 mm) and anterior walls (16.0 ± 4.5 mm). RV wall longitudinal strain (RV-LS) measurement was most feasible in the lateral wall (80%; mean: -12.1 ± 4.2%). TAPSE and RV-LS values were significantly reduced in patients compared to matched healthy individuals (p = <0.001). Seven (28%) patients who developed moderate to severe RV failure (RVF) early post-implant (≤30 days) had lower pre-implant values across all multi-plane parameters compared to those without significant post-implant RVF, notably four-wall averaged TAPSE (11.1 ± 3.4 mm vs 15.9 ± 4.0 mm; p = 0.02). CONCLUSION: 2D MPE was highly feasible for RV wall quantification pre-LVAD surgery, detecting differences in regional wall function. This novel method comprehensively quantifies RV wall function and could complement current pre-LVAD screening protocols.

Reassessment of clinical variables in cardiac resynchronization defibrillator patients at the time of first replacement: Death after replacement of CRT (DARC) score.

INTRODUCTION: Cardiac resynchronization defibrillator (CRT-D) as primary prevention is known to reduce mortality. At the time of replacement, higher age and comorbidities may attenuate the benefit of implantable cardioverter-defibrillator (ICD) therapy. The purpose of this study was to evaluate the progression of comorbidities after implantation and their association with mortality following CRT-D generator replacement. In addition, a risk score was developed to identify patients at high risk for mortality after replacement. METHODS AND RESULTS: We identified patients implanted with a primary prevention CRT-D (n = 648) who subsequently underwent elective generator replacement (n = 218) from two prospective ICD registries. The cohort consisted of 218 patients (median age: 70 years, male gender: 73%, mean left ventricular ejection fraction [LVEF]: 36 ± 11% at replacement). Median follow-up after the replacement was 4.2 years during which 64 patients (29%) died and 11 patients (5%) received appropriate ICD shocks. An increase in comorbidities was observed in 77 patients (35%). The 5-year mortality rate was 41% in patients with ≥2 comorbidities at the time of replacement. A risk score incorporating age, gender, LVEF, atrial fibrillation, anemia, chronic kidney disease, and history of appropriate ICD shocks at time of replacement accurately predicted 5-year mortality (C-statistic 0.829). Patients with a risk score of greater than 2.5 had excess mortality at 5-year postreplacement compared with patients with a risk score less than 1.5 (57% vs. 6%; p < .001). CONCLUSION: A simple risk score accurately predicts 5-year mortality after replacement in CRT-D patients, as patients with a risk score of greater than 2.5 are at high risk of dying despite ICD protection.

Clinical implementation of coronary computed tomography angiography for routine detection of cardiac allograft vasculopathy in heart transplant patients.

Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease that affects long-term outcomes in heart transplant (HTx) patients. We prospectively evaluated the feasibility of coronary computed tomography angiography (CCTA) for the detection of CAV during clinical implementation at our center. All consecutive HTx patients >4 years post-transplant were actively converted from myocardial perfusion imaging to CCTA for the annual assessment of CAV. Between February 2018 and May 2019, 129/172 (75%) HTx patients underwent a CCTA. Renal impairment (n = 21/43) was the most frequent reason for patients could not undergo CCTA. CCTA image quality was good-excellent in 118/129 (92%) patients, and the radiation dose was 2.1 (1.6-2.8) mSv. CCTA showed obstructive CAV in 19/129 (15%) patients. Thirteen (10%) patients underwent additional tests, of which 8 patients underwent coronary revascularization within 90 days of CCTA. After 1 year, 3 additional coronary angiograms were performed, resulting in one revascularization in a patient with known severe CAV who developed ventricular tachycardia. One myocardial infarction after coronary stenting and 2 non-cardiac deaths were observed. CCTA can be successfully implemented for routine detection of CAV with good image quality and low radiation dose. CCTA allows CAV evaluation with the limited need for additional invasive testing.

The Effectiveness of Levosimendan on Veno-Arterial Extracorporeal Membrane Oxygenation Management and Outcome: A Systematic Review and Meta-Analysis.

OBJECTIVES: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides a temporary support system for patients with cardiogenic shock refractory to conventional medical therapies. It has been reported that levosimendan may facilitate VA-ECMO weaning and improve survival. The primary objective of this review was to examine the effect of levosimendan use on VA-ECMO weaning and mortality in critically ill patients on VA-ECMO. DESIGN: MEDLINE, EMBASE, and CENTRAL were searched. A pair of reviewers identified eligible clinical trials. Two reviewers extracted data and independently assessed the risk of bias. A random-effect model was used to combine data. The primary outcome was the success of weaning from VA-ECMO. MEASUREMENTS AND MAIN RESULTS: Seven studies of observational design, including a total of 630 patients, were selected in the final analysis. The sample size ranged from ten-to-240 patients, with a mean age between 53 and 65 years, and more than half of them underwent cardiac surgeries. The VA-ECMO durations varied between four and 11.6 days. Overall, levosimendan use was significantly associated with successful weaning compared with control (odds ratio [OR] 2.89, 95% CI, 1.53-5.46; poverall effect = 0.001); I2 = 49%). For survival, six studies (n = 617) were included in the meta-analysis involving 326 patients in the levosimendan group and 291 in the comparator group. Pooled results showed a significantly higher survival rate in the levosimendan group (OR 0.46, 95% CI, 0.30-0.71; poverall effect = 0.0004; I2 = 20%). CONCLUSIONS: Levosimendan therapy was significantly associated with successful weaning and survival benefit in patients with cardiogenic or postcardiotomy shock needing VA-ECMO support for severe cardiocirculatory compromise. To date, there is limited literature and absence of evidence from randomized trials addressing the use of levosimendan in VA-ECMO weaning. This study may be considered a hypothesis-generating research for randomized controlled trials to confirm its findings.

Safety and feasibility of hemodynamic pulmonary artery pressure monitoring using the CardioMEMS device in LVAD management.

BACKGROUND: There is a clinical need for additional remote tools to improve left ventricular assist device (LVAD) patient management. The aim of this pilot concept study was to assess the safety and feasibility of optimizing patient management with add-on remote hemodynamic monitoring using the CardioMEMS in LVAD patients during different treatment stages. METHODS: Ten consecutive patients accepted and clinically ready for (semi-) elective HeartMate 3 LVAD surgery were included. All patients received a CardioMEMS to optimize filling pressure before surgery. Patients were categorized into those with normal mean pulmonary artery pressure (mPAP) (≤25 mmHg, n = 4) or elevated mPAP (>25 mmHg, n = 6), and compared to a historical cohort (n = 20). Endpoints were CardioMEMS device safety and a combined endpoint of all-cause mortality, acute kidney injury, renal replacement therapy and/or right ventricular failure at 1-year follow-up. Additionally, we investigated hospital-free survival and improvement in quality of life (QoL) and exercise tolerance. RESULTS: No safety issues or signal interferences were observed. The combined endpoint occurred in 60% of historical controls, 0% in normal and 83% in elevated mPAP group. Post-discharge, the hospital-free survival was significantly better, and the QoL improved more in the normal compared to the elevated mPAP group. CONCLUSION: Remote hemodynamic monitoring in LVAD patients is safe and feasible with the CardioMEMS, which could be used to identify patients at elevated risk of complications as well as optimize patient management remotely during the out-patient phase with less frequent hospitalizations. Larger pivotal studies are warranted to test the hypothesis generated from this concept study.

Uncertainties and challenges in surgical and transcatheter tricuspid valve therapy: a state-of-the-art expert review.

Tricuspid regurgitation (TR) is a frequent and complex problem, commonly combined with left-sided heart disease, such as mitral regurgitation. Significant TR is associated with increased mortality if left untreated or recurrent after therapy. Tricuspid regurgitation was historically often disregarded and remained undertreated. Surgery is currently the only Class I Guideline recommended therapy for TR, in the form of annuloplasty, leaflet repair, or valve replacement. As growing experience of transcatheter therapy in structural heart disease, many dedicated transcatheter tricuspid repair or replacement devices, which mimic well-established surgical techniques, are currently under development. Nevertheless, many aspects of TR are little understood, including the disease process, surgical or interventional risk stratification, and predictors of successful therapy. The optimal treatment timing and the choice of proper surgical or interventional technique for significant TR remain to be elucidated. In this context, we aim to highlight the current evidence, underline major controversial issues in this field and present a future roadmap for TR therapy.

Impact of Continuous Flow Left Ventricular Assist Device Therapy on Chronic Kidney Disease: A Longitudinal Multicenter Study.

BACKGROUND: Many patients undergoing durable left ventricular assist device (LVAD) implantation suffer from chronic kidney disease (CKD). Therefore, we investigated the effect of LVAD support on CKD. METHODS: A retrospective multicenter cohort study, including all patients undergoing LVAD (HeartMate II (n = 330), HeartMate 3 (n = 22) and HeartWare (n = 48) implantation. In total, 227 (56.8%) patients were implanted as bridge-to-transplantation; 154 (38.5%) as destination therapy; and 19 (4.7%) as bridge-to-decision. Serum creatinine measurements were collected over a 2-year follow-up period. Patients were stratified based on CKD stage. RESULTS: Overall, 400 patients (mean age 53 ± 14 years, 75% male) were included: 186 (46.5%) patients had CKD stage 1 or 2; 93 (23.3%) had CKD stage 3a; 82 (20.5%) had CKD stage 3b; and 39 (9.8%) had CKD stage 4 or 5 prior to LVAD implantation. During a median follow-up of 179 days (IQR 28-627), 32,629 creatinine measurements were available. Improvement of kidney function was noticed in every preoperative CKD-stage group. Following this improvement, estimated glomerular filtration rates regressed to baseline values for all CKD stages. Patients showing early renal function improvement were younger and in worse preoperative condition. Moreover, survival rates were higher in patients showing early improvement (69% vs 56%, log-rank P = 0 .013). CONCLUSIONS: Renal function following LVAD implantation is characterized by improvement, steady state and subsequent deterioration. Patients who showed early renal function improvement were in worse preoperative condition, however, and had higher survival rates at 2 years of follow-up.

Emerging electromagnetic interferences between implantable cardioverter-defibrillators and left ventricular assist devices.

AIMS: To investigate the prevalence of electromagnetic interference (EMI) between left ventricular assist devices (LVADs) and implantable cardioverter-defibrillators (ICDs)/pacemakers (PMs). METHODS AND RESULTS: A retrospective single-centre study was conducted, including all patients undergoing HeartMate II (HMII) and HeartMate 3 (HM3) LVAD implantation (n = 106). Electromagnetic interference was determined by the inability to interrogate the ICD/PM. Overall, 85 (mean age 59 ± 8, 79% male) patients had an ICD/PM at the time of LVAD implantation; 46 patients with HMII and 40 patients with HM3. Among the 85 LVAD patients with an ICD's/PM's, 11 patients (13%) experienced EMI; 6 patients (15%) with an HMII and 5 patients (11%) with an HM3 (P = 0.59). Electromagnetic interference from the HMII LVADs was only present in patients with a St Jude/Abbott device; 6 of the 23 St Jude/Abbott devices. However, in the HM3 patients, EMI was mainly present in patients with Biotronik devices: 4 of the 18 with only one (1/25) patient with a Medtronic device. While initial interrogation of these devices was not successful, none of the 11 cases experienced pacing inhibition or inappropriate shocks. CONCLUSION: In summary, the prevalence of EMI between ICDs in the older and newer type of LVAD's remains rather high. While HMII patients experienced EMI with a St Jude/Abbott device (which was already known), HM3 LVAD patients experience EMI mainly with Biotronik devices. Prospective follow-up, preferably in large registries, is warranted to investigate the overall prevalence and impact of EMI in LVAD patients.

COVID-19 in solid organ transplant recipients: a single-center experience.

Solid organ transplant (SOT) recipients may be at risk for severe COVID-19. Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the effective treatment strategy for these patients is unknown. We describe our institutional experience with COVID-19 in SOT. Demographic, clinical, and treatment data were extracted from the electronic patient files. A total of 23 SOT transplant recipients suffering from COVID-19 were identified (n = 3 heart; n = 15 kidney; n = 1 kidney-after-heart; n = 3 lung, and n = 1 liver transplant recipient). The presenting symptoms were similar to nonimmunocompromised patients. Eighty-three percent (19/23) of the patients required hospitalization, but only two of these were transferred to the intensive care unit. Five patients died from COVID-19; all had high Clinical Frailty Scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only three patients were treated with chloroquine. Most patients recovered without experimental antiviral therapy. Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID-19. Pre-existent frailty is associated with death from COVID-19.

Derivation and Validation of a Novel Right-Sided Heart Failure Model After Implantation of Continuous Flow Left Ventricular Assist Devices: The EUROMACS (European Registry for Patients with Mechanical Circulatory Support) Right-Sided Heart Failure Risk Score.

BACKGROUND: The aim of the study was to derive and validate a novel risk score for early right-sided heart failure (RHF) after left ventricular assist device implantation. METHODS: The EUROMACS (European Registry for Patients with Mechanical Circulatory Support) was used to identify adult patients undergoing continuous-flow left ventricular assist device implantation with mainstream devices. Eligible patients (n=2988) were randomly divided into derivation (n=2000) and validation (n=988) cohorts. The primary outcome was early (<30 days) severe postoperative RHF, defined as receiving short- or long-term right-sided circulatory support, continuous inotropic support for ≥14 days, or nitric oxide ventilation for ≥48 hours. The secondary outcome was all-cause mortality and length of stay in the intensive care unit. Covariates found to be associated with RHF (exploratory univariate P<0.10) were entered into a multivariable logistic regression model. A risk score was then generated using the relative magnitude of the exponential regression model coefficients of independent predictors at the last step after checking for collinearity, likelihood ratio test, c index, and clinical weight at each step. RESULTS: A 9.5-point risk score incorporating 5 variables (Interagency Registry for Mechanically Assisted Circulatory Support class, use of multiple inotropes, severe right ventricular dysfunction on echocardiography, ratio of right atrial/pulmonary capillary wedge pressure, hemoglobin) was created. The mean scores in the derivation and validation cohorts were 2.7±1.9 and 2.6±2.0, respectively (P=0.32). RHF in the derivation cohort occurred in 433 patients (21.7%) after left ventricular assist device implantation and was associated with a lower 1-year (53% versus 71%; P<0.001) and 2-year (45% versus 58%; P<0.001) survival compared with patients without RHF. RHF risk ranged from 11% (low risk score 0-2) to 43.1% (high risk score >4; P<0.0001). Median intensive care unit stay was 7 days (interquartile range, 4-15 days) versus 24 days (interquartile range, 14-38 days) in patients without versus with RHF, respectively (P<0.001). The c index of the composite score was 0.70 in the derivation and 0.67 in the validation cohort. The EUROMACS-RHF risk score outperformed (P<0.0001) previously published scores and known individual echocardiographic and hemodynamic markers of RHF. CONCLUSIONS: This novel EUROMACS-RHF risk score outperformed currently known risk scores and clinical predictors of early postoperative RHF. This novel score may be useful for tailored risk-based clinical assessment and management of patients with advanced HF evaluated for ventricular assist device therapy.

Prediction of long-term (> 10 year) cardiovascular outcomes in heart transplant recipients: Value of stress technetium-99m tetrofosmin myocardial perfusion imaging.

BACKGROUND: Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) is useful in the evaluation of cardiac allograft vasculopathy (CAV) in heart transplant (HTx) recipients. The current study evaluated the long-term prognostic value of stress SPECT MPI for predicting all-cause mortality and cardiac events in HTx recipients. METHODS: The study population consisted of 166 HTx recipients (mean age 54 ± 10 years, 84% male) who underwent exercise or dobutamine stress 99mTc-tetrofosmin SPECT MPI for the assessment of CAV. An abnormal SPECT MPI was defined as the presence of a fixed or a reversible perfusion defect. Endpoints were all-cause mortality, cardiac mortality, and non-fatal myocardial infarction (MI). RESULTS: MPI abnormalities were detected in 55 patients (33%), including fixed defects in 28 patients (17%), partially reversible in 17 patients (10%), and completely reversible defects in 10 patients (6%). During a median follow-up of 12.8 years (range 0-15, mean follow-up 9.5 years), 109 (66%) patients died (all-cause mortality), of which 67 (40%) were due to cardiac causes. A total of 5 (3%) patients experienced a non-fatal MI. HTx recipients with a normal stress 99mTc-tetrofosmin SPECT MPI had a significantly better prognosis as compared with those with an abnormal study, up to 5 years after the initial test. The presence of a reversible perfusion defect was a significant predictor of all-cause mortality, cardiac mortality, and major cardiac events, during the entire follow-up period. CONCLUSIONS: Stress 99mTc-tetrofosmin SPECT MPI provides valuable prognostic information for the prediction of long-term outcome in HTx recipients. Patients with a normal stress 99mTc-tetrofosmin SPECT MPI have a significantly better prognosis as compared with those with an abnormal study, up to 5 years after initial testing.

Patient-specific evolution of renal function in chronic heart failure patients dynamically predicts clinical outcome in the Bio-SHiFT study.

Renal dysfunction is an important component of chronic heart failure (CHF), but its single assessment does not sufficiently reflect clinically silent progression of CHF prior to adverse clinical outcome. Therefore, we aimed to investigate temporal evolutions of glomerular and tubular markers in 263 stable patients with CHF, and to determine if their patient-specific evolutions during this clinically silent period can dynamically predict clinical outcome. We determined the risk of clinical outcome (composite endpoint of Heart Failure hospitalization, cardiac death, Left Ventricular Assist Device placement, and heart transplantation) in relation to marker levels, slopes and areas under their trajectories. In each patient, the trajectories were estimated using repeatedly measured glomerular markers: creatinine/estimated glomerular filtration rate (eGFR), cystatin C (CysC), and tubular markers: urinary N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule (KIM)-1, plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL). During 2.2 years of follow-up, we collected on average 8 urine and 9 plasma samples per patient. All glomerular markers predicted the endpoint (univariable hazard ratio [95% confidence interval] per 20% increase: creatinine: 1.18[1.07-1.31], CysC: 2.41[1.81-3.41], and per 20% eGFR decrease: 1.13[1.05-1.23]). Tubular markers, NAG, and KIM-1 also predicted the endpoint (NAG: 1.06[1.01-1.11] and KIM-1: 1.08[1.04-1.11]). Larger slopes were the strongest predictors (creatinine: 1.57[1.39-1.84], CysC: 1.76[1.52-2.09], eGFR: 1.59[1.37-1.90], NAG: 1.26[1.11-1.44], and KIM-1: 1.64[1.38-2.05]). Associations persisted after multivariable adjustment for clinical characteristics. Thus, during clinically silent progression of CHF, glomerular and tubular functions deteriorate, but not simultaneously. Hence, patient-specific evolutions of these renal markers dynamically predict clinical outcome in patients with CHF.

Heart re-transplantation in Eurotransplant.

Internationally 3% of the donor hearts are distributed to re-transplant patients. In Eurotransplant, only patients with a primary graft dysfunction (PGD) within 1 week after heart transplantation (HTX) are indicated for high urgency listing. The aim of this study is to provide evidence for the discussion on whether these patients should still be allocated with priority. All consecutive HTX performed in the period 1981-2015 were included. Multivariate Cox' model was built including: donor and recipient age and gender, ischaemia time, recipient diagnose, urgency status and era. The study population included 18 490 HTX, of these 463 (2.6%) were repeat transplants. The major indications for re-HTX were cardiac allograft vasculopathy (CAV) (50%), PGD (26%) and acute rejection (21%). In a multivariate model, compared with first HTX hazards ratio and 95% confidence interval for repeat HTX were 2.27 (1.83-2.82) for PGD, 2.24 (1.76-2.85) for acute rejection and 1.22 (1.00-1.48) for CAV (P < 0.0001). Outcome after cardiac re-HTX strongly depends on the indication for re-HTX with acceptable outcomes for CAV. In contrast, just 47.5% of all hearts transplanted in patients who were re-transplanted for PGD still functioned at 1-month post-transplant. Alternative options like VA-ECMO should be first offered before opting for acute re-transplantation.

First-Line Support by Intra-Aortic Balloon Pump in Non-Ischaemic Cardiogenic Shock in the Era of Modern Ventricular Assist Devices.

OBJECTIVES: Little is known about circulatory support in cardiogenic shock (CS) from other causes than the acute coronary syndrome or after cardiotomy. We evaluated the effects of first-line intra-aortic balloon pump (IABP) support in this subpopulation of CS patients. METHODS: A retrospective study was performed in 27 patients with CS from end-stage cardiomyopathy supported firstly by IABP in the years 2011-2016. RESULTS: At 24 h, lactate decreased from 3.2 (2.1-6.8) to 1.8 (1.2-2.2) mmol/L (p < 0.001). Eighteen patients (67%) defined as IABP responders were successfully bridged to either recovery (n = 7), left ventricular assist device (n = 5), or heart transplantation (n = 6). IABP failed in 9 patients (non-responders, 33%) who either died (n = 7) or needed support by extracorporeal membrane oxygenation (n = 2). At 24 h of IABP support, urinary output was higher (2,660 [1,835-4,440] vs. 1,200 [649-2,385] mL; p = 0.02) and fluid balance more negative (-1,564 [-2,673 to -1,086] vs. -500 [-930 to +240] mL; p < 0.001) in responders than non-responders. Overall survival at 1 year was 63%. CONCLUSION: In most patients, first-line support by IABP in end-stage cardiomyopathy is associated with improvement in organ perfusion and clinical stabilisation for at least 24 h allowing time for decision making on next therapies.