Ventricular Assist Device Implantation Research Articles

Proteomics-based computational modelling of myocardial metabolism for personalized phenotyping and outcome prediction in advanced heart failure

Abstract Background Perturbations of myocardial metabolism and energy depletion are well-established hallmarks of heart failure (HF), yet methods for their systematic assessment remain limited in humans [1]. Computational modelling of the heart of individual patients represents an emerging precision medicine approach for personalized diagnosis of specific disease mechanisms and tailored clinical decision-making [2,3]. Purpose To determine the ability of computational modelling of patient-specific myocardial metabolism to assess individual bioenergetic phenotypes and their prognostic implications in HF. Methods Based on proteomics-derived enzyme intensity profiles in cardiac biopsies, we recently developed a computational model of myocardial metabolism capturing all pathways along energy-delivering substrates are processed to generate ATP [4]. Using this framework, we studied the individual energetic state in 17 sex-matched nonfailing controls and 48 patients with advanced HF (LVEF 20±10%, 72.9% non-ischemic aetiology, 52.1% females, 29.8% diabetics) undergoing heart transplantation (n=25) or ventricular assist device (VAD) implantation (n=23). The bioenergetic impact of alterations in substrate availability and myocardial workload were simulated, and the model’s ability to predict myocardial reverse remodelling after VAD implantation was assessed. Results Compared to controls, HF patients had a reduced ATP production capacity (p<0.01), although there was considerable interindividual variance, ranging from severely decreased to normal values. While overall oxygen consumption was lower in failing hearts, the amount of ATP generated per mole of oxygen did not differ (p=0.16). Maximum uptake capacity of fatty acids, glucose, and amino acids was comparable. By contrast, maximum uptake capacity of ketone bodies and lactate was reduced in the failing heart (p for both <0.05). There was a shift from fatty acid to glucose utilization in most HF patients, depending on substrate availability and myocardial workload. The ratio of fatty acid to glucose oxidation distinguished patients with LVEF recovery >10% after VAD implantation (C-index 0.93, p<0.01; Picture 1B) and correlated significantly with improvement in post-operative LVEF (r=0.67, p<0.01). ATP production capacity was not associated with reverse remodelling after VAD implantation. Conclusions Computational modelling identified a subset of advanced HF patients with preserved myocardial metabolism despite a similar degree of systolic dysfunction. Myocardial substrate preference but not ATP production capacity was associated with myocardial recovery after VAD implantation, which suggests a potential for substrate manipulation as a therapeutic approach in those with deranged fuel use. Computational assessment of myocardial metabolism in HF may improve understanding of disease heterogeneity, individual risk stratification, and guidance of personalized clinical decision-making in the future.

Ventricular assist devices as bridge to heart transplantation: minimally invasive approach with axial pumps vs sternotomy approach with centrifugal pumps: short term results

Abstract Introduction Microaxial flow ventricular assist devices (VADs) with hybrid approach could provide an advantage over centrifugal flow VADs with surgical implantation via median sternotomy as bridge to heart transplantation. Purpose We aimed to compare short-term results in intensive cardiac care unit between both groups. Methods Single-center retrospective registry comparing patients supported with microaxial flow VADs with hybrid approach (Impella 5.0 or 5.5) and surgical centrifugal flow VADs (biventricular or left univentricular CentriMag) as bridge to heart transplantation. Results Including 12 patients (January 2020-March 2022), 7 patients in hybrid approach group (2 patients with Impella 5.0-16,7% and 5 patients with Impella 5.5-41,7%) and 5 pacientes in sternotomy approach group (33.3% biventricular support and 8.3% left ventricular support). In first 48 hours after VAD implantation, worsening of renal function was greater in sternotomy approach group (Cr 2.23±0.88, 1.07±0.58;p=0.021) and there was a trend toward lower hemoglobin values (7.72±0.19, 8.9±1.35;p =0.059), with no differences in other analyzed variables (Table). A trend toward earlier respiratory weaning was observed in hybrid approach group (median 12 vs 48 hours,p=0.067). Sternotomy approach group required more frequent use of continuous renal replacement therapy (60% vs 0%,p=0.045). There were statistically non-significant differences in need for blood products or surgical reinterventions, although percentage of red blood cells transfused in first 48 hours after VAD implantation were lower in hybrid approach group than sternotomy approach group (median 4 (1.5-8) versus 8(2.5-13.5) in sternotomy approach group, p=0.309). The most common complication in sternotomy approach group was tamponade (80%- 4 patients versus 0 patients in hybrid approach) and in hybrid approach group access-related infections (28.57%, 2 patients). Ten patients received a transplant, one died for non-cardiovascular cause, and another underwent the implantation of long term VAD as bridge to transplantation. There were no differences in time from assistance implantation to heart transplantation. The most common complication after heart transplantation was primary graft failure in both groups (40%,2 patients) with no differences in mortality. Conclusions Microxial flow VADs with hybrid approach provide adequate support, with less need for continuous renal replacement therapy and shorter duration of mechanical ventilation after VAD implantation to admission in intensive cardiac care unit, a trend towards lower rates of reintervention due to bleeding was observed. The advantages of minimally invasive approach could increase its use as bridge to heart transplantation compared to VADs with sternotomy approach although small sample size may negatively influence the failure to reach statistical significance, and more studies are necessary to validate our preliminary experience.Variables analyzed 48 hours of admission

ABLE-SCORE: a simplified risk score for major adverse cardiovascular outcomes in patients with left ventricular noncompaction

Abstract Background Left ventricular noncompaction (LVNC) is a heterogeneous entity with life-threatening complications and variable prognosis [1,2]. However, there are limited prediction models available to identify individuals at high risk of adverse outcomes, and the current risk score in LVNC is comparatively complex for clinical practice [3,4]. Purpose To develop and validate a simplified risk score to predict major adverse cardiovascular events (MACE) in LVNC. Methods This multicenter longitudinal cohort study consecutively enrolled morphologically diagnosed LVNC patients between January 2009 and December 2020 at a single national-level medical center (derivation cohort n=300; internal validation cohort n=129), and between January 2014 and December 2022 at two national-level medical centers (external validation cohort n=95). The derivation/internal validation cohorts and the multicenter external validation cohort were followed annually until December 2022 and December 2023, respectively. MACE was defined as a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, cardiac resynchronization therapy, malignant ventricular arrhythmia, and thromboembolism. A simplified risk score, the ABLE-SCORE, was developed based on independent risk factors for MACE in the multivariable Cox regression predictive model, and underwent both internal and external validation to confirm its discrimination (Harrell’s C-index), calibration (calibration plots), and clinical applicability (decision curve analysis). Results A total of 524 LVNC patients (43.5 ± 16.6 years, 65.8% male) were included in the study. At the end of the follow-up, 97 (32.3%), 38 (29.5%), and 20 (21.1%) individuals in the derivation, internal validation, and external validation cohort experienced at least one endpoint of MACE. The ABLE-SCORE was established using four easily accessible clinical variables: age at diagnosis, N-terminal pro-brain natriuretic peptide levels, left atrium enlargement and left ventricular ejection fraction≤40% measured by echocardiography. The risk score showed excellent performance in discrimination, with Harrell’s C-index of 0.821 (95%CI 0.772-0.869), 0.786 (95%CI 0.703-0.869), and 0.750 (95%CI 0.644-0.856) in the derivation, internal validation, and external validation cohort, respectively. Calibration plots of the three datasets suggested accurate agreement between the predicted and observed 5-year risk of MACE in LVNC. According to decision curve analysis, the ABLE-SCORE displayed greater net benefit than the currently existing risk score for MACE in LVNC [3], indicating its strength in clinical applicability. Conclusions Derived from readily available laboratory and echocardiographic variables, a simplified and efficient risk score for MACE was developed and validated using a large LVNC cohort, making it a reliable and convenient tool for the risk stratification and clinical management of patients with LVNC.Development of the ABLE-SCOREValidation of the ABLE-SCORE

Impact of digoxin on gastrointestinal bleeding following left ventricular assist device implantation: a systematic review and meta-analysis

Abstract Introduction Gastrointestinal bleeding (GIB) is a common complication post Left Ventricular Assist Device (LVAD) implantation for patients with advanced heart failure. Recent observational evidence suggested a potential association of digoxin use and GIB reduction post LVAD; however, the proposed benefit remains uncertain. Therefore, we conducted a systematic review and meta-analysis to assess the impact of digoxin use on GIB post LVAD. Methods We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for the studies published in English exploring GIB with chronic digoxin use following LVAD implantation, till 15/01/2024. Two independent reviewers assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data. The primary outcome was all-cause GIB associated with digoxin use in comparison to non-digoxin use. Heterogeneity was assessed using Q test and I2, with I2 > 50% indicating marked heterogeneity. Results A total of three peer-reviewed observational studies (n= 14277) were included in the analysis of the primary outcome. More than 50% of patients received ACE inhibitors/angiotensin receptor blockers. Digoxin use post LVAD was associated with similar GIB incidence in comparison to non-digoxin use (Odds Ratio [OR]= 0.61; 95% CI, 0.33-1.14, I2= 81%, P=0.12), as shown in Figure 1. Interestingly, one study of 199 recipients of LVAD reported significantly lower gastrointestinal angiodysplasia-induced GIB with digoxin use (3% versus 13%, P=0.039). Conclusion Among patients with advanced HF requiring LVAD implantation, the use of digoxin demonstrated similar effectiveness of GIB prevention compared to non-digoxin use. Future studies needed to explore the potential use of digoxin for gastrointestinal angiodysplasia-induced GIB.Figure 1.Forest plot of gastrointestina

Prevalence, mechanisms and prognostic impact of dynamic mitral regurgitation unmasked by handgrip exercise in patients with hypokinetic non-dilated and dilated cardiomyopathy

Abstract Background Recent studies suggest that mitral regurgitation (MR) is a dynamic condition influenced by global and regional left ventricular (LV) remodeling as well as mitral valvular deformation. Exercise testing plays a substantial role in assessing the hemodynamic relevance of MR and is recommended by current guidelines. Handgrip exercise may serve as alternative exercise intervention to bicycle exercise, as it is easy to perform even bedside. However, there are no data yet, on the prevalence, mechanisms and prognostic impact of dynamic MR in patients with dilated cardiomyopathy using isometric exercise testing. Aims We aimed to assess the prevalence, hemodynamic consequences, and prognostic impact of exercise-induced changes in MR in patients with hypokinetic non-dilated and dilated cardiomyopathy. Methods Patients with hypokinetic non-dilated and dilated cardiomyopathy and at least mild MR who underwent handgrip echocardiography at the University Hospital Duesseldorf between January 2018 and September 2021 were enrolled.Patients were followed-up for one year to assess clinical outcomes. We assessed all-cause mortality, HF-associated hospitalizations, MV surgery, transcatheter edge-to-edge repair (TEER), left ventricular assist device implantation and heart transplantation during follow-up. Results Fifty-eight patients were included (mean age 70±15 years; 41% female; mean LVEF 37±10%). At rest, 28 patients (48%) presented with mild MR, and 30 patients (52%) had moderate MR. Fifteen patients (26%) with non-severe MR at rest, developed dynamic severe MR during handgrip exercise. Patients with dynamic severe MR had advanced MR at rest, larger left atrial dimensions, and increased mitral annulus diameter (all p<0.01). During exercise, LVEDVi, LVESVi and parameters of local left ventricular remodeling (tenting height, tenting area) were increased in patients with dynamic severe MR compared to those with non-severe MR (all p<0.05). During one-year follow-up, there was no difference regarding all-cause mortality and HF hospitalizations in patients with dynamic severe MR and non-severe MR (Log-rank test Chi2 0.262; p=0.609)(Figure 1). However, patients with dynamic severe MR more often underwent mitral valve surgery/intervention than patients with non-severe MR (Log-rank test Chi2 29.41; p<0.001)(Figure 1). Conclusion Our results demonstrate that the evaluation of non-ischemic MR only at rest underestimates the full severity of the lesion. Handgrip exercise unmasks severe MR in every fourth patient with non-severe MR at rest. These data may have implications for therapeutic decision-making in symptomatic patients with hypokinetic non-dilated and dilated cardiomyopathy and non-severe MR at rest. TEER might present an effective treatment option to improve clinical outcomes in patients with non-ischemic cardiomyopathy and non-severe MR at rest but dynamic severe MR during exercise.Figure 1

Prognostic implications of right and left atrial strain in diabetes mellitus without coronary artery diseases

Abstract Background 2D- speckle-tracking echocardiography (2D-STE) has recently be used to assess subclinical myocardial dysfunction, however its utility in diabetes mellitus (DM) has been specifically focusing on the longitudinal systolic function of the left ventricle (LV). Aim To assess the prognostic relation between left (LA) and right (RA) systolic and diastolic strain parameters with clinical outcome in patients with DM. Methods Of the initial 1721 diabetic patients screened for this study only 502 consecutive patients with DM were eligible and retrospectively enrolled, and 2D-STE strain parameters assessed on the 2D-TTE images. All patients were prospectively followed for development of new outcome/cardiac events which included hospitalization for acute HF, CVS-related death, new onset AF/AFI, stroke, heart transplantation, or need for ventricular assist device implantation. The 2D-STE analysis was used to measure the peak LA (longitudinal, radial and circumferential) and RA (longitudinal) strain. The long-term outcomes were evaluated for all-cause CVS outcomes and recurrent hospitalization. Results For the 502 eligible patients [mean age:58±4; 58 % male sex], 221 reached the combined endpoint. Mean follow-up was 1.1±0.6years. Both LA and RA strain parameters were significantly impaired compared to normal standard references (p<.0001), the RA was more impaired than LA strain parameters. The best performance parameters predictive of CVS (combined outcomes) events were for LA>RA systolic and diastolic strain, global RA systolic and diastolic strain (AUC: 0.74 and 70) and global LA longitudinal systolic and diastolic strain (AUC: 0.86 and 0.77). The strongest association between the degree of atrial myocardial mechanical dysfunction and risk of cardiovascular events was more evident for LA strain (free wall > global strain) and lesser extend to RA strain. More myocardial mechanical strain impairments were demonstrated in those with higher left atrial volume index (LAVI), NYHA ≥II class, significantly impaired diastolic function, lower strain values (LA, LV, RV), and tricuspid annular plane systolic excursion (TAPSE), p<.001). The LA (free wall) strain impairment was the independent predictors of combined outcome (including survival) after multiple adjustments using different models. Conclusion Patients with DM, LA strain parameters are stronger predictors of outcome than RA and other conventional parameters and should be included for regular clinical screening DM patients as these parameters provide a stronger prognostic stratification.

Ringlike late gadolinium enhancement: prevalence, association with cardiac phenotype, and patient outcome in an unselected cohort referred for cardiovascular magnetic resonance imaging

Abstract Background The identification of a non-ischemic ringlike enhancement in the left ventricular (LV) myocardium by cardiac magnetic resonance imaging (CMR) has emerged as a significant biomarker associated with arrhythmogenic cardiomyopathy (CMP) and adverse patient outcomes. Recently, the term "scarring CMP" has been also proposed to encompass various conditions characterized by a high burden of non-ischemic, often ring-like, myocardial scarring, including both genetic and acquired etiologies. Purpose To systematically evaluate CMR phenotypic traits and etiologic backgrounds in patients with ringlike enhancement and to assess the burden of adverse outcomes during follow-up (FU). Methods This is a single-center, retrospective analysis of prospectively enrolled patients undergoing CMR (from 2002 to 2024). Ringlike late gadolinium enhancement (LGE) was defined as continuous enhancement in three or more adjacent segments based on the AHA 17 segment model. Patients records were reviewed for etiologic classification and FU assessment. Results Among 23.472 patients, 19.696 (84%) underwent LGE assessment. In 152 patients (0.77%; 73% male; mean age 48.5 ± 17 years) a ringlike LGE was identified. The mean number of LV segments with LGE was 10 ± 3. Right ventricular (RV) LGE was present in 23% of subjects. LV fatty metaplasia was detected in 22%. Infero-lateral segments were most frequently affected. CMR showed the following morpho-functional features: LV dilatation (53%), LV hypokinesia (69%), LV hypertrophy (10.5%), LV non-compaction (11%), RV dilation (26%), and RV ejection fraction < 40% (21%). Phenotypic classification according to 2023 ESC guidelines identified dilated CMP phenotype (43%), non-dilated LV CMP phenotype (39%), predominant arrhythmogenic right ventricular phenotype (6%), hypertrophic phenotype (7%). 5% of cases remained unclassified, all of them showing LV dilated non-hypokinetic phenotype. Genetic analysis was performed in 101 patients (66%). Etiologic classification revealed non-desmosomal gene related CMP (24%), desmosomal gene related CMP (8%), inflammatory CMP (16%), genetic neuromuscular diseases (5%), congenital metabolic errors (3%), familiar gene elusive CMP (2%) and unknown etiology (45%). Notably, only 17% of patients classified as having inflammatory CMP and 66% of those with unknown etiology underwent genetic testing, with negative results. The median follow-up duration was 3 (IQR: 1-7) years. All-cause mortality occurred in 10.5% of patients, while 17% experienced sustained ventricular tachycardia, appropriate implantable cardioverter-defibrillator therapies, or sudden cardiac death. Heart transplantation or left ventricular assist device implantation was required in 8% of cases. Conclusion Ringlike LGE is a rare, non-disease-specific feature that can be found in different morpho-functional CMP phenotypes. It is associated with frequent genetic-determined etiology and high burden of arrhythmic and non-arrhythmic outcomes.

Genotype predicts heart failure independent of left ventricular ejection fraction and NT-proBNP levels in hypertrophic cardiomyopathy

Abstract Background/Introduction Hypertrophic cardiomyopathy (HCM) is a myocardial disease associated with progression to heart failure. In around 40% of cases, the disease is caused by variants in genes encoding sarcomere proteins. Purpose To evaluate the role of genotype in predicting heart failure (HF) outcomes. Methods In this observational single-centre cohort study, consecutive patients with HCM were assessed for heart failure clinically stratified by genetic status into genotype-elusive which included those with no significant variants (G-) or variants of unknown significance (VUS) and genotype-positive (G+) with pathogenic/likely pathogenic (LP/P) variants. Heart failure endpoint was defined as left ventricular assist device implantation, heart transplantation or heart-failure-related death. The incidence of HF endpoint was compared between genotypes during follow-up using a time-to-event analysis. Results 474 patients (50.9 ±14.5 years, 67.3 males) with HCM (25% with left ventricular (LV) outflow obstruction) were followed for 10.9 years (IQR 5.1-13.5). G+ LP/P patients (201/474 (42.4%)) were younger (45.8. ±14.0 years) compared to G- (225/474 (47.5%), 55.2 ±13.4 years) and VUS (48/474 (10.1%), 52.0 ± 15 years); 29/474 (6.1%) reached the heart failure endpoint. The incidence of heart failure endpoints was 12.4% (25/201) in the G+ LP/P group compared to 1.5% (4/273) in the gene elusive group. A multivariate Cox proportional hazards model including NT-proBNP and LV ejection fraction (LVEF) and genetic status showed that G+ LP/P was associated with increased risk of heart failure outcomes (HR: 5.11, 95% CI: 1.43–18.25, p=0.012). Every 100-unit rise in NT-proBNP was associated with a 41% increase in risk (HR: 1.41, 95% CI: 1.20–1.66, p<0.0001). A one-unit (1%) reduction in LVEF correlated with a 10% increase in heart failure risk (HR: -0.90, 95% CI: 0.87–0.93, p<0.0001). Conclusion(s) Genetic status is a predictor of heart failure outcomes independent of LVEF and NT-proBNP levels in HCM. This underscores the importance of genetic testing in the clinical management of HCM.

Organ perfusion pressure: a significant predictor of outcomes in cardiogenic shock

Abstract Background Cardiogenic shock (CS) is an ominous condition with a high mortality rate. The diagnosis of CS relies upon signs and/or symptoms of end-organ hypoperfusion. However, the combination of hypoperfusion and systemic congestion poses a serious risk and significantly increases mortality rates in critically ill patients. Purpose This study evaluated organ perfusion pressure (OPP), calculated as mean arterial pressure (MAP) minus central venous pressure (CVP), as a predictor of outcomes in CS. Methods All consecutive patients with CS related to acute myocardial infarction (AMI-CS) or acutely decompensated heart failure (ADHF-CS) enrolled in the multicenter Altshock-2 registry between January 2020 and November 2023 were selected. Only patients with both OPP and primary endpoint data available were included in the analysis. The primary outcome was in-hospital all-cause mortality. Results 316 patients fulfilled the inclusion criteria (mean age: 64±13 years, 62 [20%] females, mean left ventricular ejection fraction: 24%±10%, mean MAP: 71±16 mmHg, mean CVP: 12±6 mmHg). Mean OPP was 59.1±17.3 mmHg. In-hospital all-cause death occurred in 117 (37%) patients. In univariable analysis, higher OPP was associated with a significantly lower risk of in-hospital all-cause death both as a continuous variable (HR 0.981 per mmHg [95%CI 0.969-0.993], p-value=0.003) and dichotomized (HR 0.522 [95%CI 0.354-0.770], p-value=0.001) according to the optimal cut-off value of 59.5 mmHg identified by receiver operating characteristic curve analysis (specificity 66.4%, sensitivity 53.8%, area under the curve 0.61). OPP greater than 59.5 mmHg predicted significantly reduced risk of in-hospital all-cause death among ADHF-CS patients (HR 0.315 [95%CI 0.151-0.660], p-value=0.002), but not among AMI-CS patients (HR 0.628 [95%CI 0.392-1.007], p-value=0.054). After multivariable adjustment for significant clinical data available at first bedside assessment, namely age and Sequential Organ Failure Assessment score, higher OPP still predicted significantly lower risk of in-hospital all-cause death (HR 0.984 [95%CI 0.972-0.996], p-value=0.010). In univariable analysis, OPP was also associated with significantly increased long-term overall survival (p-value<0.001), but not with worsening renal function at 24 hours after CS onset, in-hospital length of stay or the composite of left ventricular assist device implantation or heart transplantation. Conclusions In this multicenter, observational, prospective study of patients hospitalized for CS, higher OPP on admission was associated with a significantly reduced risk of in-hospital all-cause death.

What is the true normal: comparison of different equations for estimating peak oxygen uptake for outcome prediction in heart failure

Abstract Background and Objectives One of the strongest prognostic parameters obtained during Cardiopulmonary exercise testing (CPET) in patients with heart failure (HF) is the peak oxygen uptake (pVO2), as a standalone or as a percentage of the predicted peak oxygen uptake (ppVO2) reached. However, traditional standards by which ppVO2 is calculated have limitations, having been derived from small cohorts, lacking portability and poorly represented by women. Thus, we aim to compare the FRIEND Registry equation to previously used methods of calculating ppVO2 as it relates to prognostic value imparted by the percentage of ppVO2 (%ppVO2) reached during CPET and portability to the Portuguese HF population. Methods Single centre retrospective study of patients with HF with LVEF < 50% who underwent CPET between 2015-2021. Patients who did not reach RER≥ 1.05 were excluded from our analysis. All tests were evaluated and ventilatory thresholds determined by 3 independent, experienced operators. ppVO2 was calculated according to 1) the Wasserman equation; 2) the Wasserman equation using ideal body weight; 3) the Neder equation, 4) the SHIP equation and 5) the FRIEND equation. Our primary endpoint was a composite of CV death, urgent transplant or left ventricular assist device implantation and HF hospitalization. Results We included 238 patients (mean age 59 ± 11 years, 83% males). The HF aetiology was mostly ischemic in nature (68%), with LVEF of 34 ± 9% and median NTproBNP of 776 (2566 – 2342) pg/mL. Most patients (67%) were in class NYHA I-II and with high prevalence of GDMT (93% ACEi/ARB; 97% beta-blockers and 64% on MRA). Mean BMI in this group was 27.3 ± 4.7 kg/min. Patients performed CPET on a treadmill with a protocol adjusted to their predicted exercise capacity. Mean pVO2 was 18.1 ± 6.2mL/kg/min, corresponding to a median %ppVO2 that ranges from 51 ± 16% to 71 ± 22%, depending on the equation that is used. Mean VE/VCO2 Slope was 42 ± 13 and 48 % (n = 98) of patients showed exercise oscillatory ventilation (EOV). Mean ppVO2 as per the FRIEND and Wasserman equations was 18.9 ± 6.6 and 21.2 ± 4.5 mL/kg/min, with no statistically significant difference between both. %ppVO2 as calculated through all equations was an independent predictor of prognosis on multivariate analysis adjusted for LVEF, NTproBNP and VE/VCO2 Slope (p < 0.001 for values derived from all equations). However, the FRIEND and Wasserman equations showed a slight advantage over the remaining 2 equations, with higher AUC on ROC curve analysis (see figure). Conclusions In our population of Portuguese patients with HF, both the FRIEND registry and Wasserman equations for predicting pVO2 yielded strong prognostic power. However, these equations provide different absolute predicted VO2 values for the same patients and thus should not be used interchangeably. Standardisation of the type ppVO2 equation used should be recommended by local scientific societies.

Comparison between invasive cardiac output and left ventricular assist device flow parameter.

Evaluate the correlation between left ventricular assist device flow parameter and invasive cardiac output measurements. We retrospectively evaluated right heart catheterization examinations performed in left ventricular assist device patients from 2 tertiary medical centers. We evaluated the correlation between cardiac output measurement methods (indirect Fick and thermodilution) and pump flow parameter using linear regression, agreement was graphically displayed using Bland-Altman plot technique. Clinical, echocardiographic, pump and haemodynamic parameters were compared between patients with and without discordance, defined as at least 20% difference between measurements. The study population consisted of 102 patients (median age 58 [51-64], 86% males, 17 ± 12 months post left ventricular assist device implantation) with a total of 544 measurement compared. Discordance between measurements were present in 102 of 226 (45%) comparisons between indirect Fick and pump flow and in 72 of 161 (48%) between thermodilution and pump flow. A comparison of indirect Fick and left ventricular assist device exhibited a statistical correlation of R = 0.751, and that of thermodilution and left ventricular assist device of R = 0.789. Parameters associated with the presence of discordance between cardiac output measurements included a higher rate of aortic valve opening, lower indirect Fick and higher thermodilution cardiac output. After excluding the lowest tertile of indirect Fick cardiac output values, the correlation between measurements improved (thermodilution: R = 0.879 and indirect Fick: R = 0.843, p < 0.001). The current left ventricular assist device flow parameter provides an estimation of cardiac output that correlates well with indirect Fick and exhibits the strongest correlation with thermodilution. This correlation was stronger after excluding lower cardiac output values.

Effects of atrial fibrillation ablation on arrhythmia burden and ventricular function in end-stage heart failure: Lessons from CASTLE-HTx.

The CASTLE-HTx trial showed the benefit of atrial fibrillation (AF) ablation compared to medical therapy in decreasing mortality, need for left ventricular assist device implantation or heart transplantation (HTx) in patients with end-stage heart failure (HF). Herein we describe the effects of catheter ablation on AF burden, arrhythmia recurrences, and ventricular function in end-stage HF. The CASTLE-HTx protocol randomized 194 patients in end-stage HF with AF to catheter ablation and medical therapy or medical therapy alone. AF burden, left ventricular ejection fraction (LVEF), and type of AF were assessed at baseline and at each follow-up visit. Overall, 97 patients received ablation; 66 patients (68%) underwent pulmonary vein isolation (PVI) and 31 patients (32%) were treated with PVI and additional ablation. Electroanatomic mapping showed the extent of left atrial low voltage (cardiomyopathy) >10% in 31 (31.9%) patients. At 12 months post-ablation, persistent AF was present in 31/89 patients (34.8%), which was significantly less frequent compared to baseline (p = 0.0001). Median AF burden reduction was 36.3 (interquartile range 13.6-63.3) percentage points at 12 months and LVEF improved from 29.2 ± 6.2% to 39.1 ± 8.3% (p < 0.001) following ablation. AF burden reduction <50% was significantly associated with LVEF improvement ≥5% at 12 months after ablation (p = 0.017). Atrial fibrillation ablation in end-stage HF leads to a substantial decrease in AF burden, a regression from persistent to paroxysmal AF and notably improved LVEF. Favourable ablation outcomes were observed in patients regardless of the presence or absence of signs indicating left atrial cardiomyopathy.

Left ventricular unloading to facilitate ventricular remodelling in heart failure: A narrative review of mechanical circulatory support.

Heart failure represents a dynamic clinical challenge with the continuous rise of a multi-morbid and ageing population. Yet, the evolving nature of mechanical circulatory support offers a variety of means to manage candidates who might benefit from such interventions. This narrative review focuses on the role of the main mechanical circulatory support devices, such as ventricular assist device, extracorporeal membrane oxygenation, Impella and TandemHeart, in the physiological process of ventricular unloading and remodelling in heart failure, highlighting their characteristics, mechanism and clinical outcomes. The outcome measures described include physiological changes (i.e., stroke volume or preload and afterload), intracardiac pressure (i.e., end-diastolic pressure) and extracardiac pressure (i.e., pulmonary capillary wedge pressure). Overall, all the above mechanical circulatory support strategies can facilitate the unloading of the ventricular failure through different mechanisms, which subsequently affects the ventricular remodelling process. These physiological changes start immediately after ventricular assist device implantation. The devices are indicated in different but overlapping populations and operate in distinctive ways; yet, they have evidenced performance to a favourable standard to improve cardiac function in heart failure, although this proved variable for different devices, and further high-quality trials are vital to assess their clinical outcomes further. Both Impella and TandemHeart are indicated mainly in cardiogenic shock and high-risk percutaneous coronary intervention patients; at the time the literature was evaluated, both devices were found to yield a significant improvement in haemodynamics but not in survival. Nevertheless, the choice of device strategy should be based on individual patient factors, including indication, to optimize clinical outcomes.

Patient selection for left ventricular assist device implantation. The main problems

To analyze the experience of Chazov National Medical Research Center of Cardiology in patient selection for left ventricular assist device (LVAD) implantation. 901 patients, whose documents were sent to Chazov National Medical Research Center of Cardiology from regional medical and prophylactic institutions, were screened as selection for LVAD implantation. Firstly, all patients underwent transthoracic echocardiography performed according to the extended protocol with a comprehensive assessment of the left and right ventricle size and function. Patients who underwent the screening procedure underwent further examination including both laboratory and instrumental diagnostic methods. In addition, the polyclinic database of patients diagnosed with chronic heart failure (CHF) and dilated cardiomyopathy was also analyzed. Among 901 screened patients 7.9% were suitable candidates for LVAD implantation and only 23 (2.6%) patients underwent surgery. Among those not eligible for surgery: 208 (29%) patients were not on optimal medical therapy, 15% of patients had indications for other surgical treatment of CHF, 12% of patients had severe right ventricular failure, 9.8% had severe comorbidities, 6.8% of patients refused surgery. The main problems of selection for LVAD implantation were: low awareness of doctors about the introduction of new treatment methods, poor quality of transthoracic echocardiography, a large percentage of patients not receiving basic therapy for CHF, untimely referral of patients for other types of surgical treatment.

ABLE-SCORE, a simplified risk score for major adverse cardiovascular outcomes in left ventricular hypertrabeculation: a multicenter longitudinal cohort study.

Left ventricular hypertrabeculation (LVHT) is a heterogeneous entity with life-threatening complications and variable prognosis. However, there are limited prediction models available to identify individuals at high risk of adverse outcomes, and the current risk score in LVHT is comparatively complex for clinical practice. This study aimed to develop and validate a simplified risk score to predict major adverse cardiovascular events (MACE) in LVHT. This multicenter longitudinal cohort study consecutively enrolled morphologically diagnosed LVHT patients between January 2009 and December 2020 at Fuwai Hospital (derivation cohort, n = 300; internal validation cohort, n = 129), and between January 2014 and December 2022 at two national-level medical centers (external validation cohort, n = 95). The derivation/internal validation cohorts and the external validation cohort were followed annually until December 2022 and December 2023, respectively. MACE was defined as a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, cardiac resynchronization therapy, malignant ventricular arrhythmia, and thromboembolism. A simplified risk score, the ABLE-SCORE, was developed based on independent risk factors in the multivariable Cox regression predictive model for MACE, and underwent both internal and external validations to confirm its discrimination, calibration, and clinical applicability. A total of 524 LVHT patients (43.5 ± 16.6years, 65.8% male) were included in the study. The ABLE-SCORE was established using four easily accessible clinical variables: age at diagnosis, N-terminal pro-brain natriuretic peptide levels, left atrium enlargement, and left ventricular ejection fraction ≤ 40% measured by echocardiography. The risk score showed excellent performance in discrimination, with Harrell's C-index of 0.821 [95% confidence interval (CI), 0.772-0.869], 0.786 (95%CI, 0.703-0.869), and 0.750 (95%CI, 0.644-0.856) in the derivation, internal validation, and external validation cohort, respectively. Calibration plots of the three datasets suggested accurate agreement between the predicted and observed 5-year risk of MACE in LVHT. According to decision curve analysis, the ABLE-SCORE displayed greater net benefits than the existing risk score for LVHT, indicating its strength in clinical applicability. A simplified and efficient risk score for MACE was developed and validated using a large LVHT cohort, making it a reliable and convenient tool for the risk stratification and clinical management of patients with LVHT.

Potential of plasma biomarkers for heart failure prediction, management, and prognosis: A multiomics perspective.

Heart failure (HF) remains a major global health challenge, and more effective and comprehensive plasma biomarkers are needed to effectively treat HF patients. Multiomics studies have shown that DNA fragments, noncoding RNAs, proteins, and metabolites may be potential plasma biomarkers for HF. However, comprehensive reviews that focus on research on plasma biomarkers for HF from an omics perspective are lacking. This review summarizes the applications of various omics approaches in the exploration of biomarkers related to the risk assessment, diagnosis, subtype classification, medical management, and prognosis prediction of HF. Moreover, as heart transplantation and left ventricular assistant device (LVAD) implantation are terminal therapies for end-stage HF patients, this review also discusses the role of cell-free DNA as a biomarker for cardiac transplant rejection and omics studies of plasma biomarkers in patients who respond to LVAD therapy. Our findings suggest that future omics research on HF biomarkers should employ integrated multiomics methods and expand the sample size to increase the robustness of the results and that the identified biomarkers should be further validated in large cohorts.

Anti-factor Xa and activated partial thromboplastin time strategies for unfractionated heparin dosing after HeartMate 3 left ventricular assist device implantation.

No clear guidelines exist for perioperative anticoagulation management after durable left ventricular assist device insertion. In this study, we sought to compare outcomes between anti-factor Xa (FXa) and activated partial thromboplastin time (aPTT) in monitoring unfractionated heparin (UFH) dosing after HeartMate 3 (HM3) insertion. This is a single-center retrospective review of patients who received UFH after HM3 insertion between 01/2020-12/2022. Post-operative UFH dose was titrated by aPTT goal 45-60 sec (n = 53) or FXa goal 0.1-0.2 U/mL (n = 59). Baseline differences between cohorts were balanced by inverse probability treatment weighting. At baseline, unadjusted FXa patients were more likely to be white (47.5% vs. 35.8%, p < 0.001), INTERMACS 1-2 (69.5% vs. 47.2%, p = 0.013), have history of coronary artery disease (66.1% vs. 43.4%, p = 0.026), and lower eGFR (54.1 vs. 63.7 mL/min/1.73 m2, p = 0.029) compared to the aPTT group. After adjusting for several bleeding/thrombosis risk factors, 97.5% of FXa and 91.0% of aPTT patients reached therapeutic levels with comparable UFH duration and maximum dose. Moreover, in-hospital mortality (2.5% vs. 3.1%, p = 0.842), major bleeding events (4.2% vs. 9.2%, p = 0.360), and thromboembolic events (21.8% vs. 10.1%, p = 0.151) remained without significant differences between FXa and aPTT cohorts. There was a high degree of variability in FXa (r2 = 0.20) and aPTT (r2 = 0.22) values for any given UFH dose. No differences in frequency of bleeding or thromboembolic events were observed in this study between FXa versus aPTT cohorts after HM3 implantation. More longitudinal studies are warranted to determine whether or not one assay is superior to the other.

Lateral QRS amplitude is independently associated with outcome after cardiac resynchronization therapy: advancing patient selection?

Cardiac resynchronization therapy (CRT) is a cornerstone in the treatment of selected heart failure patients. However, a relevant proportion of patients does not show beneficial response. Identification of simple, additive, and outcome-relevant selection criteria may improve patient selection. We sought to determine whether baseline QRS amplitude is associated with outcome in CRT. Quantification of intrinsic, pre-CRT-implantation QRS amplitude in an observational multinational two-center retrospective cohort analysis (derivation cohort Zurich, n=178, 2000-2015; validation cohort Leuven, n=183, 1999-2016) with a composite endpoint of all-cause mortality, ventricular assist device implantation or heart transplantation at 5 years. Higher baseline-to-peak amplitude in lateral leads (lead I and V6) was associated with a lower risk of reaching the composite endpoint (lead I: HR 0.86 [95%CI 0.78-0.95] per mV, p=0.002, lead V6: HR 0.94 [95%CI 0.88-1.00] per mV, p=0.043). Concordance index-based comparison of quartile-, spline-, and ROC curve analysis suggested cut-off values of 6mV for lead I and 3mV for V6 for optimal discrimination of outcome. External validation confirmed the cut-off of 3mV in lead V6 as highly significant discriminator of outcome (p<0.001), associated with a risk reduction of 65%. Low QRS amplitude in lateral ECG leads is associated with higher risk of poor outcome in CRT patients. A cut-off of 3mV in lead V6 proved highly discrimitative. Further studies need to confirm the additive value of QRS amplitude in patient selection for CRT and to assess whether CRT may be made available to more patients.

Early Stroke Following Durable Left Ventricular Assist Device (LVAD) Implantation: An Analysis of The Society of Thoracic Surgeons Intermacs National Database

BackgroundStroke remains a devastating complication of durable left ventricular assist device (LVAD) therapy. This study evaluated the incidence and risk factors for early stroke within 7 days following LVAD implantation investigating both traditional pre-implant and new intraoperative variables collected by The Society of Thoracic Surgeons (STS) Intermacs National Database. MethodsSTS Intermacs was queried for patients undergoing implantation of a fully magnetically levitated centrifugal LVAD between 11/25/2020 and 6/30/2023. STS Intermacs stroke definitions were used to identify patients who suffered a stroke within the first 7 postoperative days (POD). A multivariable logistic regression model was created to generate adjusted odd ratios (OR) for variables associated with early stroke. ResultsAmong 6950 patients in the study cohort, 5.9% (413/6950) developed a stroke after a median follow-up of 11 months, with 50% (205/413) of strokes occurring within 7 days after LVAD implantation. Of the strokes occurring during POD 0-7, 70% (144/205) occurred on POD 0-2. By multivariable analysis, the following factors were associated with early stroke: older age (70 vs. 50; OR 1.4, P=0.0129), white race (OR 1.5, P=0.0078), pre-implant temporary MCS bridge (temporary LVAD only: OR 1.6, ECMO only: OR 1.7, combination of both devices: OR 3.3; P=0.0001) and presence of an unremoved left atrial clot (OR 8.0, P<0.0001). ConclusionA significant proportion of strokes occur within the first 7 days following LVAD implantation, particularly within the first 2 days. In addition to pre-implant variables, we identified modifiable intraoperative factors associated with stroke that provide an opportunity for further risk mitigation and improvement in quality of care.

Propensity score-based comparison of high-risk coronary artery bypass grafting vs. left ventricular assist device implantation in patients with coronary artery disease and advanced heart failure.

Revascularization in patients with severely reduced left ventricular function and coronary artery disease (CAD) is associated with a high perioperative risk. In this setting, implantation of a durable left ventricular assist device (LVAD) might be an alternative. We retrospectively compared the outcomes of adult patients with CAD and a left ventricular ejection fraction (LVEF) ≤ 25% who underwent coronary artery bypass grafting (CABG) vs. LVAD implantation. Propensity score (PS) matching was performed for statistical analysis, resulting in 168 pairs. In the PS-matched cohorts, the mean age was 62 years; one third had a history of myocardial infarction, 11% were resuscitated, half of the patients were on inotropic support, and 20% received preoperative mechanical circulatory support. LVAD patients required significantly longer ventilation (58 h [21, 256] vs. 16 h [9, 73], p < 0.001) and had a longer ICU stay (11d [7, 24] vs. 4d [2, 10], p ≤ 0.001) compared to CABG patients The incidence of postoperative renal replacement therapy (2 [1.2%] vs.15 [8.9%], p = 0.002) and temporary mechanical circulatory support was lower in the LVAD group (1 [0.6%] vs. 51 [30.4%], p ≤ 0.001). The in-hospital stroke rate was similar (LVAD 7 [5.4%] vs. CABG 8 [6.2%], p = 0.9). In-hospital survival, 1-year survival, and 3-year survival were 90.5% vs. 85.5% (p = 0.18), 77.4% vs. 68.9% (p = 0.10) and 69.6% vs. 45.9% (p < 0.001), for CABG and LVAD patients respectively. Patients with CAD and advanced HF demonstrate better mid-term survival if they undergo CABG rather than LVAD implantation.