Left Ventricular Assist Device Implantation Research Articles

Right ventricular failure following left ventricular assist device implantation

Abstract Background Left ventricular assist device (LVAD) therapy is a lifesaving option for patients with medical therapy-refractory advanced heart failure.(1) Right ventricular failure (RVF) is a cause of major morbidity and mortality after LVAD implantation.(2,3) Our objective was to get the outcomes and predictors of RVF in adult patients undergoing LVAD implantation. Methods This retrospective study enrolled 73 adult patients with LVAD (Heart Mate III) implantation, of them 24(32.9%) patients had RVF after LVAD implantation. Results The patients with RVF had statistically significant more frequencies of acute kidney injyry (p<0.001), new need for dialysis(p<0.001), RVAD insertion (p<0.001), total mortality (p=0.012) and on-VAD mortality(p=0.018) with prolonged ICU stay (p<0.001) compared to the non-RVF group respectively. The pre-LVAD pulmonary vascular resistance(PVR) ≥3 WU (OR:2.4, 95%CI: 1.52-7.38, p=0.04) and diastolic pulmonary gradient(DPG) ≥ 7 mmHg (OR:6.4,95%CI: 5.49-18.6, p<0.001) were the independent predictors of RVF after LVAD implantation. Cox proportional regression analysis revealed that RVF was associated with increased risk of death (HR:3.12,95%CI:1.42-6.85, p=0.005). Conclusion Early RVF post-LVAD carries significant risks of mortality and multiple morbidities. Concomitant BiVAD implantation needs to be considered in patients with elevated DPG and PVR to avoid post-LVAD RVF.The significant variables of patients.Kaplan-Meier curves of the 2 groups.

Elevated cancer biomarkers in patients with severe heart failure could be a potential predictor of mortality during LVAD support

Abstract Introduction Owing to increasing numbers of heart failure patients a search for new biomarkers predicting prognosis is desirable. Background The purpose of this study was to analyze levels of cancer biomarkers in patients with severe heart failure before or after left ventricular assist device (LVAD) implantation and estimate its impact on survival during LVAD support. Methods We retrospectively analyzed data of all consecutive 168 LVAD recipients (92.8%- male, mean age 53.3 years ( median - 56.6, SD 12.0 ), median INTERMACS profile- 3.0, ischemic etiology of heart failure- 52.4%, 41.0% post CRT-D and 54.8% post ICD implantation, 36.9 post IABP, 5.4% post ECMO%, 11.9% post CABG and 8.9% post other cardiac surgery before LVAD implantation) implanted with continuous-flow LVAD (59.5%-HeartMate3, 35.1%- HeartWare, 5.4%-Heart Mate II) in our institution within years 2009-2023. Among comorbidities 63% of patients had atrial fibrillation or flutter, 41.6%- diabetes, 37.5%- arterial hypertension, 48.8%-renal failure, 7.1% pulmonary obstructive disease, 56.5% had pulmonary hypertension with mean pulmonary artery pressure above 25 mm Hg in right heart catheterization and 47% of patients had a history of cardiac arrest or sustained ventricular arrythmia before LVAD implantation. The overall mortality was 44.0 %. 31% patients were transplanted during LVAD support and in 4 patients (2.3%) LVAD was explanted or deactivated. Patient were followed to death, heart transplantation, LVAD explantation or the end of observation in our institution. Mean time of LVAD support was 885 days (1-2570). 23% of patients had right ventricular failure (RVF) early post LVAD implantation while 7.7% had late form of RVF. Results Serum concentrations of cancer biomarkers: carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, carbohydrate antigen(CA)-125 and alpha fetoprotein (AFP) taken before (56 patients -33.3%) or after (24 patients-14.3%) LVAD implantation were analyzed. Mean values, rate of abnormal results and correlation of abnormal results of CEA, CA19-9, CA-125, AFP with mortality during LVAD support were depicted in Table 1. No statistically significant correlations were found between levels of abovementioned cancer biomarkers and mortality though a trend towards increased mortality could be observed for abnormal results of CEA and Ca 19-9 taken before LVAD implantation. No malignant neoplasms were found in all analyzed patients except of one in whom a recurrence of lymphoma was found 2 months after LVAD implantation. Conclusions Patients with severe heart failure before and after LVAD implantation may present abnormal values of cancer biomarkers despite no found neoplasms. Our observation suggests that elevated cancer biomarker levels could predict mortality in heart failure patients after LVAD implantation. Further research is needed to confirm this thesis and investigate mechanisms of this phenomenon.

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

Effect of disabling biventricular pacing in patients with left ventricular assist device and cardiac resynchronization therapy

Abstract Introduction Taking into account the mechanism of the left ventricular assist device (LVAD) function, the cardiac resynchronization therapy (CRT) seems to be unnecessary and, according to the current reports, the left ventricular lead (LVL) should be disabled. However, observation of the patients suggests that deactivation of the left ventricle (LV) pacing leads to deterioration of the patients condition and progression of the heart failure (HF) symptoms. Purpose The study aimed to determine differences in survival of the patients with LVAD and maintained or disabled CRT, including patients subjected to heart transplantation, as well differences in left and right ventricle function, kidneys and liver condition, NTproBNP value, subjective exercise tolerance and frequency of HF exacerbation before and after CRT deactivation. Methods The study group involved 55 patients with LVAD and CRT devices, including 11 patients with disabled LV pacing. The statistical analysis concerned the comparison of groups with and without biventricular stimulation as well results within the group with disabled LVL before and after its deactivation. Analyzed data included laboratory results, echocardiographic parameters, number of HF exacerbation episodes and exercise tolerance by NYHA classification. Results Total CRT period did not differ in group with maintained and disabled CRT [24 (12-36)months vs. 30 IQR(12-48)months respectively; p=0,74]. The median period of CRT deactivation was 30 IQR(12-48) months after LVAD implantation. Time from LVAD implantation to heart transplantation differed significantly between patients with and without CRT [20 IQR(9-32)months vs. 49,5 IQR(46,5-62)months respectively; p=0,003]. LV disabling was connected with a significant increase of NTproBNP [3072 IQR(2287-6636) pg/ml vs. 2133 IQR(1618-3437) pg/ml before LVL deactivation; p=0,009), without an aggravation of the exercise intolerance by NYHA classification (p=0,11) or total number of HF exacerbation episodes (p=0,72). Lack of LV pacing was not related to change of concentration of creatinine (p=0,13), AST (p=0,89, ALT (p=0,5), bilirubin (p=0,06) and albumin (p=0,69) before and after LV deactivation. Comparison of echocardiographic parameters with and without CRT did not demonstrate significant differences in LV ejection fraction (p=0,37), LV end-diastolic diameter (p=0,33), TAPSE (p=0,72) and tricuspid regurgitation degree (p=0,39). Death-free survival from LVAD implantation has not differed in patients with and without CRT(p=0,08), similarly like death-free survival from heart transplantation (p=0,56), however with tendency to better outcome of patients with CRT till 12 months after the heart transplant. Conclusion CRT does not improve general health condition as well death-free survival in LVAD recipients, including patients subjected to heart transplantation, however with tendency to better outcome of patients with CRT till 12 months after the heart transplant.Death-free surival after LVADDeath-free survival after transplant

Predictors of Right vEntricular Failure aftER LVAD implantation: PREFER LVAD study

Abstract Introduction The use of left ventricular assist devices (LVAD) is increasing both as bridge-to-transplantation or destination therapy, considering the lack of heart donors for transplantation in advanced heart failure (AHF) population. Right ventricular post-implantation failure, major bleedings and infective events remain the principal adverse events in LVAD carriers, thus an accurate selection of candidates is needed. Purpose To identify between clinical, laboratory, standard and advanced (Speckle Tracking, STE) echocardiography, and right heart catheterization (RHC) indices, the best predictors of outcome after LVAD implantation. Materials and Methods We screened in our third-level center 30 patients with AHF, followed up from May 2013 to February 2022, for the assessment of LVAD implantation suitability. They all underwent a complete cardiological history collection, electrocardiography, standard and STE left ventricular (LV) and left atrial (LA) size and function assessment. Regarding the right ventricle, SIENA score parameters, including RV sphericity index, RV free wall longitudinal strain (LS), right ventricular fractional area change (RVFAC), and 3D ejection fraction were used for exclude RV disfunction. RHC was performed on the same day of echocardiography. Follow-up was conducted at 1, 3, 6, 9 and 12 months repeating all the assessments, for the occurrence of RV failure, all-causes mortality, hemorrhagic events and re-hospitalization for heart failure. With a univariate and multivariate statistical analysis, we went to test among all the parameters the possible predictors of outcome. Results The final population consists of 29 patients (93% male, mean age of 63±11 years), in NYHA class III or IV and a severe reduction of left ventricular (LV) ejection fraction (EF), in whom arterial hypertension and smoking, present or previous, were present in 58% and 65% of cases, respectively. The population was divided into two groups according to the occurrence of at least one cardiovascular event. 11 major events were recorded: including 4 hemorrhagic events, 3 all-causes mortality and 4 hospital admission for HF. No RV failure occurred in the first 12 months of follow-up. No differences were identified between the two groups in terms of echocardiographic indices and RV function, including RVFAC or RV-FWLS. At univariate analysis (see Table 1), the only parameter able to predict major CV events was central venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) ratio, obtained by RHC, an index of balance between right and left heart filling pressure. Conclusions A careful application of SIENA score indices before LVAD implantation can significantly reduce the incidence of post-operative RV failure, as in our small population. Our results also confirmed the paramount role of RHC in the diagnostic work up of AHF.

CMR predictors of acute right heart failure after LVAD implantation

Abstract Background Acute right heart failure (RHF) is one of the most dangerous complications after placement of left ventricular assisted device (LVAD), having a significant impact on prognosis, and is estimated to be around 3 to 35%. Even though right ventricular evaluation with hemodynamical and echocardiographic measurements is a key aspect prior to LVAD implantation, prediction of RHF remains a challenge in daily clinical practice. Purpose To identify cardiac magnetic resonance (CMR) predictors of RHF after LVAD placement. Methods We retrospectively enrolled patients referred to our centre for implantation who also underwent CMR scan prior to LVAD implantation. Acute RHF was defined according to Mechanical Circulatory Support Academy Research Consortium (MRC ARC) criteria. Baseline characteristics, preoperative laboratory, echocardiographic, right heart catheterization (RHC) and CMR parameters were obtained. Patients were divided into two groups based on the development of acute RHF. The variables showing significant differences between the two groups were analysed with the receiver operating characteristic (ROC) curves to find the best cut-offs and then combined into a risk score. Results We enrolled 54 patients who underwent continuous-centrifugal flow LVAD implantation from 2013 to 2021 in whom a CMR within median time of 30 days pre-implantation was available. Four patients were excluded due to low quality images. Among the final cohort of 50 patients, 15 (28%) developed acute RHF. Patients who developed RHF showed worse INTERMACS class, worse renal and liver function, higher central venous pressure at RHC, worse TAPSE at echocardiography and overall smaller left ventricles at the CMR analysis when compared to those who had not acute RHF. No CMR derived right ventricle parameters nor moderate to severe tricuspid regurgitation at echocardiography were different among the two groups. We found that CMR-derived LV mass indexed < 65 g/m2, left ventricular end diastolic diameter (LVEDD) < 70 mm, and LV eccentricity index >1,12 were independent predictors of acute RHF. A CMR-derived score with these three parameters was built (1 point for each). This CMR score has shown to be an independent predictor of acute RHF at multivariate analysis with an odds ratio of 7,084 (CI 95%1.614-37.734) when corrected for other clinical and instrumental predictors of acute RHF. Conclusions Our study proposes a simple scoring system based on three CMR- derived parameters (LVEDD, LV mass indexed and LV eccentricity index) to screen for acute RHF prior LVAD implantation. This score shows promise to be an independent predictor of acute RHF, even when adjusted for clinical, echocardiographic, and haemodynamic parameters. Our model is built on CMR measurement of the LV, showing how patients with smaller ventricles and a left displacement of the interventricular septum (expressed with a higher LV eccentricity index) are at higher risk of developing acute RHF.ROC curves

Comparative analysis of multi-organ failure trajectories reflected by the MELD-3.0 following heart transplantation and heartmate 3 implantation

Abstract Background Multi-organ failure (MOF) frequently complicates advanced heart failure (HF), substantially impacting patient prognosis. The Model of End-Stage Liver Disease 3.0 (MELD-3.0) scale, encompassing liver and kidney function parameters, is a valuable tool for assessing the severity of organ dysfunction. Purpose This study aims to elucidate the trajectory of MOF in individuals undergoing either heart transplantation (HTx) or left ventricular assist device (LVAD) - HeartMate 3 implantation, utilizing the MELD-3.0 scale, over a 1-year follow-up period. Methods A comprehensive analysis was conducted, examining data from 1 month preceding to 1 year subsequent to the HTx or LVAD implantation. The MELD-3.0 score was calculated using the average values of international normalized ratio, bilirubin, creatinine, sodium, and albumin levels during this timeframe. Comparative assessments of the average MELD-3.0 scores were performed between the HTx and LVAD groups at 1 month pre-procedure, as well as at 1 week, 1 month, 3 months, 6 months, and 1 year post-procedure. Results The analysis included 107 patients undergoing HTx and 31 patients undergoing HMi, with a median age of 54 years (47-62), 85% were male. There was no difference in MELD-3.0 between HTx and LVAD patients in the pre-procedure period: 12.3 (7.3-15.9) vs 13.1 (7.7-16.6), p=0.95. There was also no difference in MELD-3.0 at 1 week and 1 month post-procedure. However, in the 3rd month, the difference gained statistical significance: 7.3 (4.6-9.4) vs 13.8 (11.5-19.7), p<0.01 and continued to be significant in the next follow-ups: 12-month 5.4 (3.1-10.2) vs 11.1 (6.7—15.1), p<0.01, comparing respectively HTx vs LVAD. In both groups of patients, a significant decrease in MELD-3.0 score from 3-month follow-up when compared to 1 month preceding the procedure was observed. Within 12 months post-procedure, 30 patients (22%) died (19 in HTx group and 11 in LVAD group), 8 LVAD patients (26%) had HTx. Conclusion The utilization of the MELD-3.0 scale reveals significant differences in the trajectory of multi-organ failure between HTx and LVAD patients. Both forms of advanced HF therapy result in an improvement of liver and kidney condition, while HTx patients' benefits are larger and last longer, highlighting the distinct impacts of this intervention on organ function.MELD 3.0 score in time

Reversibility of precapillary pulmonary hypertension and outcomes after heart transplantation bridged with left ventricular assist devices: insight from the UNOS

Abstract Background In light of the updated lowered threshold for diagnosing pulmonary hypertension (PH), the reversibility of precapillary PH with left ventricular assist device (LVAD) and the associated post heart transplantation (HT) outcomes remain unclear. Purpose and methods Using data from the United Network for Organ Sharing database, we aimed to investigate predictors of persistent precapillary PH in HT recipients bridged with LVAD, and examine the interrelated post-HT survival, using the updated pulmonary vascular resistance (PVR) cutoff of >2 WU for precapillary PH. Results Among 2169 HT recipients bridged with LVAD, 1299 had PVR>2 at baseline; 551 (42.4%) of whom normalized their PVR≤2 and 748 (57.6%) remained with elevated PVR>2 after LVAD implantation. Female sex (adjusted odds ratio [aOR] 2.22, 95% confidence interval [CI]:1.61-3.07, p<0.001) and inotropes-treatment at-listing (aOR 1.31, 95% CI: 1.03-1.66, p=0.028) were associated with persistently elevated PVR post LVAD. Conversely, longer duration of LVAD support (aOR 0.74, 95% CI: 0.65-.84, p<0.001) and use of HeartMate 2 (aOR 0.74, CI: 0.59-0. 93, p=0.011) were protective against persistently elevated PVR post-LVAD. Persistently elevated PVR >2 post-LVAD was associated with increased risk of death compared to those who normalized their PVR (adjusted hazard ratio [aHR] 1.26, 95% CI: 1.01-1.57, p=0.037). However, normalized PVR post-LVAD group had comparable survival to those with PVR≤2 at baseline (aHR 0.76, 95% CI: 0.57-1.02, p=0.07). Conclusions Many HT recipients bridged with LVAD remain with PVR>2 post-LVAD implantation, which is associated with increased risk of death post-HT compared to patients with normalized PVR post-LVAD.

Association of gut microbiota imbalance with risk of postoperative infections in patients with left ventricular assist device

Abstract Background Infections are the most common complications following left ventricular assist device (LVAD) implantation and associated with adverse events. Gut microbial imbalance may predispose to mucosal colonization with pathogens, resulting in a risk of subsequent serious infections. However, it remains unclear whether gut microbiota imbalance is associated with postoperative infections in patients with LVAD. Purpose The aim of this study was to investigate whether gut microbiota imbalance was associated with postoperative infections in patients with LVAD. Methods We prospectively examined 22 consecutive LVAD patients who were admitted to a university hospital for routine check-ups and had stool cultures taken between March 2022 and December 2023. All patients had no signs of infection. The patients were divided into two groups according to positive (normal bacterial flora and other bacteria including Streptococcus viridans, Klebsiella, or Extended-spectrum β-lactamase Escherichia coli; n = 7) and negative (normal bacterial flora only; n = 15) for stool culture. The primary outcome was serious infection requiring hospitalisation treated with intravenous antimicrobial agents. Results Patients were predominantly male (68%) and the median age was 49 (interquartile range [IQR] 29-58) years. There were no significant differences in age, sex, primary aetiology of heart failure, type of LVAD devices, time on LVAD support, the history of infection, or antibiotics use within six months between the groups. During a median follow-up period of 316 days (IQR 242-559), the primary outcome occurred in seven patients (32%), including four hospitalisation for driveline infections, two pneumoniae and bacterial bloodstream infections, and one lung abscess and bacterial bloodstream infection. Kaplan–Meier analysis showed that the adverse events more frequently occurred in LVAD patients with positive for stool culture (P = 0.010) (Figure). A multivariable Cox regression analysis showed that positive for stool culture was independently associated with an increased subsequent risk of the primary outcome (hazard ratio 6.99, 95% confidence interval 1.17-41.7, P = 0.033), even after adjustments for age, male, body mass index, diabetes, INTERMACS profile, mechanical circulatory support, serum creatinine, serum albumin, and white blood cell count, which are known to be strong determinants of worse clinical outcomes in patients with LVAD. Conclusions In patients with LVAD, gut microbial imbalance was associated with subsequent serious infections. These findings suggest that the screening of stool culture might be useful for early identification of high-risk patients for infectious complication after LVAD implantation.

National trends of left ventricular assist device therapy in Germany

Abstract Background The prevalence of advanced heart failure (HF) is increasing and prognosis remains poor. Although heart transplantation is still considered to be the gold standard for the treatment of advanced HF in selected patients, its use is limited by organ donor shortage and a growing burden of cormorbidities among potential recipients. The 2021 European Society of Cardiology (ESC) guidelines recommend consideration of long-term mechanical circulatory support with a left ventricular assist device (LVAD) in eligible patients with advanced heart failure (HF) who are refractory to medical/device therapy. Purpose The purpose of this study was to evaluate the national trends of LVAD in Germany. The main hypothesis was that LVAD therapy is still underutilized. Methods From the national database of the German Federal Statistical Office (DESTATIS), we identified all patients who underwent LVAD implantation in Germany between January 2011 and December 2022 (n = 9,232). We compared temporal trends and in-hospital outcomes. Results From 2011 to 2022, number of LVAD implantation was highest in the year 2017 (n = 914) and steadily decreased over the following years (2022: n = 617). Mean age of LVAD recipients was 56.2 years (2011-2015) and increased to 58.4 years (2020-2022). The majority of LVAD recipients are male (84,8 %), and this trend has been stable during the entire time period. In-hospital mortality after LVAD remains high, but has been decreasing (25.8% during 2011-2015 compared to 20.2% during 2020-2022). Conclusion Although LVAD is recommended in eligible patients with advanced HF, our study suggests an underutilization of LVAD in this patient population and especially in female patients.

Ventricular arrhythmia characteristics after left ventricular assist device implantation

Abstract Background Ventricular arrhythmia (VA) characteristics in patients with advanced heart failure (HF) and left ventricular assist devices (LVADs) are currently poorly studied. Methods Patients with advanced HF implanted with third-generation LVADs during 2019-2023 were enrolled, and six-month post-LVAD VA events were retrospectively analyzed. Baseline characteristics, 6-month VA events, Holter monitoring and ambulatory blood pressure were also analyzed. Post-LVAD VA events were categorized as new right bundle-branch block (RBBB) superiorly directed VA and prior VA recurrence. Results Fifty-four advanced HF patients (90.7% male, 50.0±13.7 years old) who underwent LVAD (CH-VAD: n=23; Evaheart2: n=10; Corheart6: n=21) were consecutively enrolled in this study. Twenty-two patients suffered post-LVAD VA events (15 new RBBB superiorly directed VA, 7 prior VA recurrence), and 94.4% of the patients were hemodynamically stable. A total of 46.3% of the patients presented with a 50% reduction in VA burden, and amiodarone use decreased from 25.9% to 16.7%. The nighttime mean arterial pressure (MAP) and maximum inferior venous cava (IVC) diameter had opposite predictive effects on the new RBBB VA, and the post-LVAD left ventricular ejection fraction (LVEF) was negatively correlated with the prior VA recurrence. Multivariate analysis revealed that a higher nighttime MAP/IVC ratio (OR 2.24, 95% CI 2.22-4.52; P=0.025) and a lower post-LVAD LVEF (OR 0.75, 95% CI 0.57-0.99; P=0.048) were independently related to the new RBBB superiorly directed VA and prior VA recurrence, respectively. Conclusion The overall VA burden decreased after LVAD implantation. Volume deficiency and poor post-LVAD cardiac function were associated with different VA patterns.Changes in VAs pre- and 6 monthsVA distributions of patients

Health-related quality of life and prognosis in cardiac sarcoidosis

Abstract Background Cardiac sarcoidosis (CS) is characterized by inflammatory myocardial disease, often leading to conduction disturbances, ventricular tachycardias, and heart failure. While factors like initial symptoms, LVEF, and troponin levels are known prognostic indicators, the impact of CS on health-related quality of life (HRQoL) is not well-understood. Additionally, limited data exists on the predictive value of FDG-PET in CS. Purpose This study aimed to assess HRQoL in CS patients and investigate its prognostic relevance concerning cardiac events. Methods Patients diagnosed with CS completed the RAND-36 general health-related questionnaire, covering eight dimensions. Clinical data were obtained from the Finnish myocardial inflammatory diseases registry. Follow-up data on cardiac events, including life-threatening ventricular tachyarrhythmias (VT/VF), heart transplant, left ventricular assist device (LVAD) implantation, pericardial tamponade, or death, were collected over 36 months. Results Of the 240 CS patients surveyed, 179 (75%) were female, with a median age of 56 [IQR 48 – 64]. CS patients reported significantly lower RAND-36 scores across all dimensions compared to the general Finnish population. Over the 3-year follow-up, 38 (16%) patients experienced cardiac-related adverse events, including VT/VF (26 cases), deaths (8 cases), heart transplants (2 cases), LVAD implantation (1 case), and pericardial tamponade (1 case). We divided CS patients into those without adverse event (N=202) and with adverse events (N=38). Interestingly, in four dimensions of PF 70.0 [50.0-90.0] vs 60.0 [33.8-80.0], p=0.019, RP 50.0 [0.0-100.0] vs 0.00 [0-56.3], p=0.002, MH 76.0 [59.0-88.0] vs 66.0 [51.0-84.0], p=0.036, and SF 75.0 [50-100] vs 62.5 [37.5-78.1], p=0.037 were significantly lower scores in the event group. Univariate Cox regression analysis (Table 1) revealed that physical functioning (PF) and role-physical (RP) dimensions, along with certain clinical factors, such as younger age, higher NYHA classification, elevated proBNP levels, lower hemoglobin levels, and the main manifestation of the disease as ventricular tachyarrhythmia, independently predicted adverse cardiac events. In the multivariate analysis, lower role-physical scores and younger age remained independent prognostic factors for adverse cardiac events. Conclusions Patients with CS demonstrated lower HRQoL compared to the general Finnish population. This study enhances our understanding of prognosis in CS and underscores the predictive value of HRQoL in identifying future adverse cardiac events, highlighting its relevance in the clinical management of these patients.

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

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.

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.

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.

The implantation of a left ventricular assist device causes changes in the aortic miRNome and proteome - an integrative analysis

Abstract Background Left ventricular assist devices (LVAD) have been widely used and accepted to treat patients with end-stage heart failure. LVAD non-physiological blood flow velocity, wall shear stress distribution, vorticity current intensity, and vorticity flow generation affect the pathophysiology of vascular changes in aortic tissue. Purpose In this study, we performed multi-omics-based analysis of the aorta to identify molecular markers that could clarify vascular remodeling during LVAD support. Methods Aortic specimens from 48 patients (pair matched samples N=96) were excised during implantation and explantation of LVAD. Small RNA-Seq screening using Next Generation Sequencing and proteomic profile using Data-Independent Acquisition mass spectroscopy were conducted. Experimental and computational approaches, proteomics and transcriptomics data, were integrated and bioinformatics analyses were performed. Results The principal component analysis of miRNome and permutational multivariate analysis of variance of proteomic profile clearly segregated samples before and after LVAD support. We identified a total of 113 differently expressed (DE) miRNAs (61 up-regulated; Padj<0.05 and log2 fold change>|0.5|) after long-term LVAD support. Proteomic analysis identified in total 93 protein significantly changed (47 increased; Padj<0.05 and log2 fold change>|0.5|). Correlation analysis identified strong association between 270 proteins and 66 DE-miRNAs (Padj<0.05 and correlation coefficient>|0.7|). Gene Set Enrichment Analysis revealed, that predicted target genes of DE-miRNAs were mainly engaged in axon guidance, regulation of actin cytoskeleton, endocytosis, and MAP signaling pathway (Padj<0.05). DE-proteins participated mainly in ECM-receptor interaction, focal adhesion, and platelet activation (Padj<0.05). Conclusion Our study presents a network-based method of integrating microRNAs and proteome data and reveals molecular signatures that reflects aortic vascular remodeling due to LVAD treatment.PCA of miRNA DESeq2PCA of protemic profile

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.