Implantable Devices Research Articles

Long-term prognosis and predictors of death in chronic Chagas cardiomyopathy in women and men

Abstract Background Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of heart failure (HF) in Latin America and carries high morbidity and mortality. Previous studies showed conflicting results in epidemiological and clinical evidence of a gender-associated risk of death in patients with HF due to CCC. Purpose This study analysed the long-term prognosis and the main predictors of death in women and men with HF due to CCC. Methods From March 2009 to January 2023, we followed a cohort of outpatients with HF due to CCC. Specific serological tests diagnosed Chagas disease. Baseline data included clinical characteristics and echocardiographic findings. Statistical analyses were performed using the Kaplan-Meier (K-M) method to analyse time-to-event data and Cox proportional hazards methods to search for predictors of death. Results We studied 739 patients, with a mean age of 57.0 ± 12.1 years, 387 (52%) male. Women had a higher mean age (58.4 ± 11.7 vs. 55.8 ± 12.3 years; p=0.001), had a higher mean baseline left ventricular ejection fraction (LVEF) (44.3±14.5 % vs. 37.0±14.5%; p<0.001) and a smaller left ventricular diastolic diameter (LVDD) (56.8±8.9 vs. 62.5±9.4 mm; p<0.001). Over a median follow-up period of 10 years, 213 (56%) men and 169 (44%) women died (K-M: log-rank p=0.043; Figure). Men received more beta-blocker therapy (52.4% vs. 47.6%; p=0.040) and had a higher prevalence of chronic kidney disease (CKD) (p=0.003) and stroke (p=0.007). HFpEF was more prevalent in women and HFrEF in men (p<0.001). Device implantation and transplant were similar between women and men. Cox regression analysis for death adjusted for age, sex, myocardial infarction, diabetes, CKD, stroke, atrial fibrillation (AF), and LVEF showed LVEF (HR= 0.98;95%CL:0.97-0.98), age (HR=1.03;95%CL1.02-1.04) and CKD (HR= 1.32;95%CL:1.10-1.64) as the main predictors of death. In men, the main predictors were age (HR=1.02;95%CL:1.01-1.04), CKD (HR=1.409;95%CL:1.07-1.86), and LVEF (HR=0.98;95%CL:0.97-0.99), and in women AF (HR=1.41;95%CL:1.03-1.91), age (HR=1.03;95%CL:1.01-1.04), and LVEF (HR=0.97;95%CL:0.96 -0.98). Conclusion women had a better prognosis than men, but gender was not an independent predictor of death. Prevention of comorbidities, especially CKD in men and AF in women, and higher beta-blocker therapy can significantly reduce the death rate in women and men with HF from CCC.

Assessing the impact of implantable loop recorder placement on anxiety level

Abstract Background Anxiety is a prolonged state of apprehension or worry that can be an independent predictor of cardiovascular events, associated with a 48% increased risk of cardiac death. About one-third of patients with arrhythmias present with high anxiety levels, and subsequently worse quality of life. In our experience of patient care, many patients feel anxious about the possibility of an arrhythmia that could lead to their demise, especially if their symptoms are undiagnosed. Purpose Our project aims to explore the change in patients’ anxiety levels following implantable loop recorder (ILR) placement. Methods This is a survey-based observational study that was performed in an outpatient clinic and hospital using validated General Anxiety Disorder-7 (GAD-7) questionnaires. Individuals who met indications to undergo ILR implantation including palpitations, syncope, subclinical atrial fibrillation, and cryptogenic stroke underwent baseline assessment of anxiety prior to implantation. Individuals had repeat assessments at 6 weeks and 12 weeks post-implantation to evaluate the effect of ILR placement. Results Our study included 50 individuals. Out of the initial subjects, 10/25 females and 11/25 males were lost to follow-up. The average initial GAD-7 score was 3.3 (Range 0, 15), average 6-week score was 1.6 (Range 0, 14), and average 12-week score was 0.9 (Range 0, 10). Total decrease in GAD-7 score after 6 weeks of having ILR was 50%. Total decrease in GAD-7 score after 12 weeks of ILR was statistically significant at 73% (P=0.03). Females showed greater improvement of GAD-7 scores in comparison to males at 6 weeks (67% vs 36%) and 12 weeks (81% vs 66%). Conclusion Studies have suggested an overall decreased level of anxiety in patients receiving implantable devices that have the potential to treat arrhythmias such as implantable cardiac defibrillators and pacemakers. Our results suggest that the benefit may extend to implantable devices that seek to provide further diagnostic information and aid in the prognostication of disease burden. As seen in our study population, GAD-7 scores showed dramatic improvement with greater percentage in female than male population. After the placement of loop recorders, many patients experience a sense of security with having a device that monitors them. Our study is the first to address the association between ILR and anxiety. Future studies evaluating this association would help increase the power of the study.Figure 1:Bar graph of GAD-7 Scores

Preclinical assessment of transcatheter-delivered expandable endoluminal polymeric graft fabricated by electrospinning of microfiber

Abstract Background Matrix fabricated from electrospinning of micro fibre of polyester is porous and permeable to blood, facilitates cell infiltration and late resorption of the biodegradable material. This biomaterial opens an avenue of research in recreating a novel and favourable endoluminal lining in diseased vessel. Previous preclinical work has shown that implants in aorta of rodents generate layers of endoluminal elastin. In humans, one of the most impervious arteries to atherosclerosis is the intra-thoracic artery; therefore, an attempt to induce similar structures with an implantable device was made. Methods For this study, novel tissue-engineered vascular grafts (T-TEVGs) were used in a preclinical rabbit iliac artery model. It was made of resorbable polyester biomaterial processed into fibrous tubular conduits. These T-TEVGs were implanted percutaneously. In total, twelve T-TEVGs in iliac arteries of nine rabbits were implanted. Follow-up were conducted on five rabbits with eight T-TEVGs at three months, two rabbits with two T-TEVGs at six months, and two rabbits with two T-TEVGs at twelve months. At follow-up, percutaneous optical coherence tomography (OCT) was performed, and OCT-derived luminal vessel wall dimensions and fractional flow reserve (OFR) derived from OCT were assessed. Results The overall pooled analysis at different timepoints on follow-up, documented an average MLA of 1.74±0.48mm2, average of proximal and distal reference area of 4.55±0.99 mm2, average area stenosis of 61±12%, and mean OFR value of 0.96±0.03 (OFR ranging from 0.89 to 0.99). There was a moderate positive correlation between minimum lumen area and OFR (r=0.590, p< 0.01). There was a strong negative correlation between percentage area stenosis and OFR (r= - 0.846, p< 0.01). At no timepoint in follow-up and in every vessel analysed, OFR value was lower than 0.89, suggesting that none of these vessels exhibited flow-limiting narrowing. Our study has a few limitations. 1) The preclinical model is a non-atherosclerotic rabbit; 2) There was no barotrauma prior to the implantation of the device; 3) Limited sample size, short and medium follow-up duration, and pooling of assessment at different timepoints. Conclusion The current study shows the durability and favourable hemodynamics of this bioresorbable fibrillated scaffold at short and medium term follow-up, supporting the potential utility of T-TEVEGs for peripheral human artery revascularisation. Long-term follow-ups are mandatory to confirm the durability of these results. Histopathology of this preclinical model should confirm the endoluminal elastin as previously documented in rodents (rats) and will be presented at the time of the congress.

Holter monitoring in neuromuscular disorders: frequency and importance in clinical management

Abstract Introduction Cardiac involvement is a common manifestation in a variety of neuromuscular disorders (NMD) and initial cardiac manifestations in these patients are often asymptomatic. Hence, regular 24h-Holter monitoring is recommended to identify conduction disturbances and rhythm disturbances. Purpose In this study, we aimed to assess abnormal findings in 24h-Holter monitoring to screen for conduction disturbances and arrhythmias in patients with NMD and evaluate its impact in patients’ treatment. Methods A retrospective single-centre study was conducted including all adult patients with NMD who received a 24h-Holter from January 2013 to September 2023. Results A total of 76 patients with NMD were included, 39 (51.3%) were male, and mean age was 46,3 ± 11,5 years. Most patients were asymptomatic. A total of 220 Holter recording was analysed. An average of 2,9 ± 1,6 Holter recordings per patient was performed. Abnormal Holter results were found in 47 (61,8%) patients, and mainly consisted of conduction disorders such as atrioventricular block in 31 (65,9%) patients. Other abnormalities included atrial fibrillation/flutter in 6 (12,8%) patients, supraventricular tachycardia in 4 (8,5%) patients, and non-sustained ventricular tachycardia in 6 (12,8) patients. Out of the group of the patients with abnormal Holter findings, ten patients had direct clinical treatment consequences, namely implantation of cardiac electronic devices or initiation of anticoagulation therapy. Conclusion In this study, holter findings resulted in relevant clinical treatment consequences in 10 out of 76 patients (13,2%). These results suggest that 24h-Holter monitoring may improve routine cardiac screening in patients with NMD.

Right ventricular to pulmonary artery coupling credicts poor outcomes after interatrial shunting in heart failure

Abstract Background Left atrial decompression is under investigation for heart failure (HF) with the potential to improve symptoms and potentially clinical outcomes. However, heterogeneous outcomes have been observed in randomized controlled studies. Purpose This study aimed to explore whether right ventricular (RV) -pulmonary artery (PA) coupling, as assessed from the tricuspid annular plane systolic excursion (TAPSE) /systolic PA pressure ratio, can be useful in predicting outcomes after implantation of the interatrial shunting device. Methods A total of 106 HF patients, n=62 with reduced ejection fraction (HFrEF), n=44 with preserved ejection fraction (HFpEF), were prospectively enrolled in the PRELIEVE registry with the Atrial Flow Regulator (AFR) implantation. Serious adverse events included cardiovascular mortality and HF worsening (W). Results Serious adverse events (SAEs) occurred in a total of 19 (18%) patients. There were no differences in baseline comorbidities, KCCQ scores, the 6-minute walking distance between patients with and without SAEs (Table). Patients with SAEs showed higher systolic pulmonary arterial pressure, NT-proBNP, serum creatinine and lower TAPSE/PASP ratio. Incidence of SAEs was higher in patients within the first TAPSE/PASP vs the third tertile (59% vs 12%, p=0.026), respectively. A TAPSE/PASP of <0.55 was identified to bear the most optimal sensitivity to predict the event (AUC=0.683, CI95% (0.533-0.833). Conclusion The reduced TAPSE/PASP ratio was associated with higher rates of serious adverse events in patients with heart failure undergoing controlled inter-atrial shunting. The hypothesis generating finding that reduced RV-PA coupling may identify potential clinical non-responders to left atrial decompression should be further prospectively validated.

Do patients maintain improvement in physical capacity achieved after hybrid telerehabilitation implemented as part of managed care after acute myocardial infarction program at one-year follow-up?

Abstract Background Managed Care after Acute Myocardial Infarction (MC-AMI) is a one-year comprehensive care program dedicated to patients with acute coronary syndrome introduced in Poland. It includes acute intervention, complex revascularization, implantation of cardiovascular electronic devices (in case of indications), rehabilitation or hybrid rehabilitation (HTR) and scheduled outpatient follow-up. HTR is a unique component of MC-AMI program. Purpose The purpose of this study was to evaluate whether the effect of improving physical capacity achieved after 5-week HTR was maintained during one-year follow-up. Methods The study enrolled 84 patients (90% males, aged 57.5 ± 10.2 years, LVEF 54,6 ± 6.8%) who underwent a 5-week HTR based on Nordic walking training and completed the entire one-year MC-AMI program. Unless there were contraindications, HTR began no later than 14 days after discharge from the hospital and consisted of an initial phase (1 week) conducted in an outpatient center and 4 weeks of telemonitored exercise training at home, five times weekly. Exercise capacity was assessed by comparing the exercise test results at baseline (before HTR), immediately after HTR and at the end of one-year MC-AMI program. Results HTR resulted in significant improvement in workload [METS] and workload duration in exercise test. This valuable effects were maintained after one-year follow-up. All results are presented in Table 1 and Figure 1. Conclusion The improvement in physical capacity achieved after 5-week of the hybrid telerehabilitation was maintained in patients who completed MC-AMI program in one-year follow-up.

Single center experience of internal jugular vein as alternative access for implantation of a wireless pulmonary artery pressure sensor

Abstract This single-center study delves into the novel use of the internal jugular vein (IJ) as an alternative access pathway for the implantation of the CardioMEMS device, a wireless pulmonary artery pressure sensor. This approach is compared to the conventional femoral vein access in terms of procedural times, contrast volume, and patient outcomes. The study spans five years, from 2018 to 2023, evaluating the efficacy and safety of IJ access for CardioMEMS implantation. The analysis revealed a tendency towards shorter procedural times and reduced contrast volume with IJ access, although statistical significance was not reached due to the small sample size. Notably, IJ access provided a quicker needle-to-door time, suggesting benefits such as improved patient throughput and potentially shorter hospital stays, which are pivotal in a healthcare landscape that prioritizes efficiency and cost-effectiveness. In conclusion, this investigation offers initial evidence that IJ vein access is a feasible and potentially superior alternative for CardioMEMS device implantation. While the findings are preliminary due to the study's limited scale, they pave the way for future larger-scale, multicenter studies. Such research could confirm the benefits of IJ access and possibly influence clinical practices, enhancing the management of heart failure patients.

Efficacy and safety of the Aria pulmonary endovascular device in pulmonary hypertension

Abstract Background and aims A common feature of various forms of pulmonary hypertension (PH) is progressive decline of pulmonary arterial compliance (CPA), which correlates with reduced survival. In this acute study, we evaluated feasibility, safety and hemodynamic performance of the Aria pulmonary endovascular device in patients with PH associated with left heart disease (PH-LHD) and chronic lung disease (PH-CLD). Methods 8 patients with PH-LHD and 10 patients with PH-CLD were included in this study. The device was placed in the main pulmonary artery via the right femoral vein and was connected by a catheter to a gas-filled reservoir outside the body. During systole, gas shifts from the balloon to the reservoir, leading to deflation of the balloon. In diastole, the gas returns from the reservoir to the balloon, leading to balloon inflation and enhancing diastolic blood flow to the distal pulmonary capillary bed. Hemodynamics were assessed at baseline, and again with device off, device on and device off. The primary safety endpoint was the incidence of serious adverse events through 30 days after the procedure. Results No complications or investigational device-related serious adverse events occurred. Device activation in PH-LHD and PH-CLD patients decreased pulmonary arterial pulse pressure by 5.6±4.2mmHg (-12%; p=0.003) and 4.2±2.2mmHg (-11%; p<0.001), increased CPA by 0.4±0.2mL/mmHg (+23%; p=0.004) and 0.4±0.3mL/mmHg (+25%; p=0.001), and increased RV-PV coupling by 0.24±0.18 (+40%; p=0.012) and 0.11±0.07 (+21%; p=0.001), respectively. Conclusions Temporary implantation of the Aria endovascular device was feasible and safe. Device activation resulted in acute improvement of CPA and RV-PV coupling.Figure

Extracellular volume analysis on cardiac computed tomography is useful to predict prognosis after cardiac resynchronization therapy

Abstract Background Left-ventricular (LV) extracellular volume (ECV) (LVECV) is often evaluated on magnetic resonance imaging (MRI), and the value is well correlated with biopsy-identified myocardial fibrosis. Recently, mechanical development has been achieved, and ECV analysis on cardiac computed tomography (CCT) has been eligible using the latest software, and the ECV on CCT is well correlated with the ECV on MRI. Cardiac resynchronization therapy (CRT) has been usually performed in cases with severe heart failure, but almost 30 percent of them are non-responders. Therefore, the indicators to predict non-responders to cardiac resynchronization therapy (CRT) have been sought in advance. Purpose The purpose of this study is to reveal the utility of LVECV on CCT for the prediction of patient prognosis in the candidates of cardiac resynchronization therapy (CRT) who have low LV function. Methods We analyzed 53 patients (30 males, 65 ± 14 years old) with heart failure who underwent CCT, including late phase scan, using 320-row detector CT (Aquilion One or Aquilion One ViSion Edition, Cannon Medical Systems) or 256-row detector CT (Revolution CT Apex, GE Healthcare), before the implantation of a CRT device from December 2008 to January 2024. The primary outcomes were defined as cardiac death, hospitalization due to HF, and fatal arrhythmia after CRT implantation. CRT responders were defined as the patients whose LV endo-systolic volume was decreased by 15% or more on transthoracic echocardiography. Results Twenty-two patients (42%) had primary outcomes (10 cardiac death, 7 fatal arrhythmia, 5 hospitalization due to HF). LVECV was lower in CRT responder (n = 23) than the others (n = 25) (35 ± 6.3% vs 41 ± 6.8%, P = 0.006). LVECV was higher in the patients with primary outcomes (n = 22) than the others (n = 31) (35 ± 5.0% vs 41 ± 7.8%, P = 0.019). Based on the receiver-operating characteristics curve analysis, the best cut-off of LVECV for predicting primary outcomes was 44.03% (B). In the survival analysis using the Cox proportional hazard model, LVECV on CCT was a significant predictor of primary outcomes (HR, 1.07; 95% CI, 1.13-1.01; P = 0.012). On Kaplan-Meier analysis, the higher LVECV group (≥ 44.03%) had a significantly greater number of primary outcomes than the others (P = 0.010) (C). Conclusion LVECV on CCT may be useful for predicting responders of CRT and prognosis after CRT implantation.ROC curve and Kaplan-Meier analysis

Long-term outcomes of cardiogenic shock survivors: a contemporary retrospective analysis from a tertiary center

Abstract Background Cardiogenic shock (CS) is a complex syndrome that still portends a dismal short-term prognosis. However, in patients that survive the initial admission and are later discharged, the long-term prognosis remains ill-characterized. Aim We aimed to describe the long-term morbidity and mortality outcomes of patients surviving the index admission for CS. Methods Retrospective analysis of all consecutive patients admitted to a cardiac intensive care unit (CICU) between December 2016 and December 2022 with a diagnosis of CS. All etiologies were included and further categorized as: acute myocardial infarction (AMI-CS), acute-on-chronic heart failure (HF-CS) and secondary causes [(S-CS): myocarditis, arrhythmic storm, acute pulmonary embolism, among others]. Our primary endpoint was defined as all-cause death, conditional to being discharged alive. Secondary endpoints comprised heart transplant, durable left ventricular assist device (LVAD) implantation, implantable cardioverter-defibrillator (ICD) insertion and hospital readmission during follow-up. Results A total of 208 patients were included [median age 68 years (IQR 57-80), 66% males, mean Charlson comorbidity index 4±3], of whom 52% (n=108) had AMI-CS, 27% (n=56) HF-CS and 21% (n=44) S-CS. During the index admission, mean SAPS II score was 49±18 and most patients were in SCAI-C (66%, n=137) stage. Organ support in the form of invasive mechanical ventilation, renal replacement therapy or temporary mechanical circulatory assist devices was necessary in 62% (n=129), 27% (n=56) and 26% (n=55) of patients, respectively. 53% of patients (n=110) survived the index admission [median CICU length of stay 8 (IQR 3-15) days; median hospital length of stay 13 (IQR 4-25) days]. At discharge, mean left ventricular ejection fraction was 38±16% and 28% (n=26) of patients underwent ICD implantation. Median follow-up after discharge was 679 (IQR 373-1056) days, with 4 (4%) patients lost to follow-up. Overall mortality was 22% (n=24) and was numerically higher for AMI-CS when compared to HF-CS and S-CS (9% vs 7% vs 6% respectively, p=0.640). Secondary endpoint analysis showed that 10% (n=11) had a heart transplant, 2% (n=2) received a durable LVAD, 9% (n=10) received an ICD and 26% (n=28) were re-hospitalized during that period. Conclusions Although the long-term mortality of patients discharged alive after the index admission for CS is not overwhelming, one in every four will be readmitted and a small proportion will be eligible for advanced heart failure therapies. Healthcare strategies to improve the morbidity and mortality of many CS survivors should be devised.

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.

High incidence of malignant arrhythmias and heart failure in patients with RBM20-associated cardiomyopathy: a multicenter cohort study and review of the literature

Abstract Background Patients with RBM20 cardiomyopathy commonly experience malignant arrhythmias, sudden cardiac death (SCD), and progressive heart failure (HF). Objective The aim of this study is to investigate genotype-phenotype correlations, clinical outcomes and causes of death in patients with RBM20-associated cardiomyopathy in a multicenter cohort, combined with an overview of the current literature. Methods This international, multicenter cohort included all patients with cardiomyopathy who had a pathogenic (P) or likely pathogenic (LP) RBM20 variant. For survival and regression analysis, we matched a control group based on sex, age, and presence of left ventricular dysfunction. Additionally, we conducted a literature search on studies investigating RBM20-associated cardiomyopathy. Results Sixty-two patients (45% male) were included in the study, with a mean age of 42 ± 15 years at presentation. Of the LP/P RBM20 variants identified, 9 were novel. Eleven variants were truncating, while the remaining variants consisted of missense and splice-site variants. Patients with a truncating variant who developed HF were on average older at the time of diagnosis compared to patients with missense variants (mean age 62 ± 9 vs. 45 ± 14; p=0.01). After a median follow-up duration of 5.0 [1.0 – 10.5] years, 21 (34%) patients reached the composite endpoint of ventricular arrhythmias (VA), implantable cardioverter-defibrillator therapy, heart transplantation (HTx), left ventricular assist device (LVAD) implantation, or cardiovascular death. Of these, 19 (31%) patients experienced malignant VA (mean age 45 ± 15 years, 63% males). Males were at higher risk for the composite endpoint (log-rank p= 0.02), particularly for VA (log-rank p=0.007). The literature review analyzed 34 studies with a total of 678 patients, of whom 53% were male. In these studies, 123 (24%) patients experienced a VA, 58 (12%) underwent HTx or were treated with LVAD, and 52 (11%) died. Conclusion In this multicenter study the patients carrying a LP/P variant in RBM20 variants had a severe phenotype, with a high incidence of VA, particularly in males. Additionally, this study presents 9 novel DNA variants, of which 8 were truncating, and were mainly observed in older individuals. Finally, we report a lower mortality rate compared to the literature, possibly due to a higher number of heart transplantations performed in our patient cohort.Survival composite endpoint for sex

Exercise stress testing recovery kinetics: the forgotten phase

Abstract Background Impaired exercise capacity is a cardinal feature of heart failure (HF). Peak oxygen uptake (pVO2) and ventilatory efficiency (VE/VCO2 slope) during exercise are well-consolidated prognostic markers in patients with HF. A previous study suggested that abnormally prolonged VO2 recovery, specifically the failure to decrease VO2 from peak exercise by 10.5 mL/kg/min at 180 seconds of the recovery phase, predicts adverse outcomes in HF. However, it is unknown to what extent the recovery of VEqCO2, a marker of ventilation/perfusion mismatch, adds prognostic value to the already existing parameters. Purpose The aim of this study was to characterize the functional and prognostic significance of VEqCO2 kinetics following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (>3 months) and stable HF with left ventricular ejection fraction (LVEF) <50% who underwent cardiopulmonary exercise testing (CPET) between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sittng passively for 2 minutes). VO2 and VEqCO2 kinetics during recovery, described as the absolute difference to peak VO2 (difVO2) and VEqCO2 (difVEqCO2), were measured at 30, 60, 120, and 180 seconds. Outcomes were assessed as a composite of cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) implantation at 1 year. Results A total of 238 patients were included (mean age 58 ± 12 years; 82% males; mean LVEF 34 ± 10%; 68% with ischemic HF; 75% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean VE/VCO2 slope 41 ± 12). During the 1-year follow-up, 19 patients met the endpoint (8 CV deaths, 8 urgent heart transplants, and 3 LVAD). ROC curve analysis showed that the best correlation between difVEqCO2 and outcomes was apparent at difVEqCO2 of 180 seconds (AUC 0.83) with a cut-off value of 1 (sensitivity 93%, specificity 58%). These patients, who had a decrease in VEqCO2 (difVEqCO2 >1) at 180 seconds, were significantly older (p=0.02), had a lower LVEF (p<0.001), and higher NYHA (p<0.001). They were at an increased risk of cardiovascular events compared to those with an increase in VEqCO2 (difVEqCO2 <1) at 180 seconds (event-free survival at 1 year 86% vs. 98%, log-rank p<0.001). In multivariate analysis, the statistical association between difVEqCO2 and outcomes remained significant, even after adjusting for difVO2 at 180 seconds (HR 4.315, CI95% (1.349-13.804), p=0.014). Conclusion Abnormal VEqCO2 kinetics in the recovery period of CPET is an easily recognizable non-invasively derived measurement that predicts outcomes in HF. VEqCO2 may complement the evaluation of VO2 and other parameters during recovery to further improve prognostic risk stratification in HF.

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.

Feasibility of hybrid telerehabilitation and telecare in heart failure patients with implanted left ventricular assist device LVAD

Abstract Background Left ventricular assist device (LVAD) implantation is increasingly used as a treatment option for patients with advanced heart failure (HF). There is a need to provide patients with LVAD with long-term care, preferably at home. The implementation of home-based telerehabilitation (HTR) and telecare offers new opportunities in this field. Purpose The purpose of this study was to assess feasibility and safety of HTR and telecare in HF patients with implanted LVAD and evaluate patients’ acceptance of and adherene to HTR. Methods The study enrolled 30 HF patients with recent implanted LVAD (21 Heart Mate III, 9 Heart Ware) (29 males, 19–67, mean 59 years) who underwent a 12-week telecare and HTR program based on walking, respiratory and resistance training, five times weekly. HTR was telemonitored with a device adjusted to register electrocardiogram (ECG) recording and to transmit data via mobile phone network to the monitoring center. The moments of automatic ECG registration were pre-set and coordinated with exercise. The influence on physical capacity was assessed by comparing changes in peak oxygen consumption (VO2 peak; [ml/kg/min]) and workload duration (t; [sec]) in cardiopulmonary exercise test. Results HTR resulted in a significant physical capacity improvement pVO2 12.5±2.9 vs 15.1±3.0 (p<0.001), and workload duration t 628±204 vs 728±222 (p<0.001) in cardiopulmonary exercise test. There were neither deaths nor adverse events during HTR. Patients accepted HTR, including the need for interactive everyday collaboration with the medical team from monitoring center. All patients completed HTR. Conclusions HTR is a feasible, safe form of rehabilitation, well accepted by patients. The adherence to HTCR was high.

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.

Preexisting pulmonary hypertension impact on in-hospital outcomes of cardiac implantable electrical device implantation

Abstract Background Preexisting pulmonary hypertension (PH) is associated with unfavorable in-hospital outcomes in cardiac as well as non-cardiac surgeries and procedures. However, its impact on cardiac implantable electronic device (CIED) implantations is not established. We investigated the extent of preexisting PH among patients undergoing CIED implantations and evaluated its effect on in-hospital outcomes. Methods Using the National Inpatient Sample (NIS) database, we identified patients who were hospitalized in the US between 2016-2019 and underwent CIED implantation with a preexisting diagnosis of PH. Patients with any CIED in-situ were excluded. Sociodemographic, clinical data, in-hospital procedures and outcomes as well as in-hospital mortality were collected. Multivariable logistic regression models were used to identify predictors of in-hospital complications. Results An estimated total of 718,980 patients underwent CIED implantation during the study period. Of them, 74,150 patients (10.3%) had preexisting PH diagnosis. Compared with non-PH patients, PH patients were older, had higher Charlson Comorbidity Index, and more often implanted with implantable cardioverter defibrillators and cardiac resynchronization therapy devices. Higher rate of total complications was observed in PH patients (14.5% versus 9.9%; P<0.001) driven mainly by respiratory complications as well as in-hospital mortality (2.3% versus 1.2%; P<0.001). Multivariable analyses confirmed PH as an independent predictor for respiratory complications, total complications and in-hospital mortality. Conclusion Preexisting PH in patients undergoing CIED implantation was associated with increased risk for respiratory complications as well as in-hospital mortality in a US nationwide, all-comer registry.

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.

Identifying at-risk patients for atrial high-rate episodes by machine learning

Abstract Background Current evidence suggests that atrial high rate episodes (AHRE)/subclinical atrial fibrillation (AF) are associated with increasing risk of clinical AF, and subsequently, ischaemic stroke and other adverse cardiovascular events. Purpose To construct a high-performance model by machine learning (ML) for the prediction of AHRE detected by a cardiac implantable electronic device (CIED) capable of atrial sensing in a European cohort. Methods We utilized data from a prospective cohort of patients with CIED. AHRE was defined as an episode lasting at least 5 minutes with atrial rate ≥ 175 beats per minute. We divided the cohort into training and internal validation cohorts in 7:3 and used 5-fold cross-validation in the training cohort to assess model performance and prevent model overfitting. Pre-selected features were imported into eight common ML algorithms to predict AHRE, including light gradient boosting machine (LightGBM), random forest (RF), logistic regression, support vector machine, multiple perceptron, eXtreme gradient boosting machine (XGBoost), Gaussian naïve Bayes, and K nearest neighbours. The importance ranking of the features was interpreted by calculating the SHapley Additive exPlanationation (SHAP) value for each feature within the optimal model. Results A total of 500 consecutive patients with CIEDs (mean age 70.2±13.3; 39.2% female) were included. Of these, 164 patients (32.8%) were found to have AHRE. Among all ML models, RF was the best performing model, which obtained the highest AUC (0.738), recall (0.673) and F1-score (0.584) in the internal validation cohort. The results of SHAP showed that antiplatelet, statin, age, white blood cell count, and cardiomyopathy were the first five important features, indicating that the RF model had good interpretability and reliability. Conclusion Our study is the first to demonstrate in a European cohort the effectiveness and feasibility of ML algorithms in predicting AHRE in patients detected by CIEDs. The best RF models require further external validation to assess generalizability to other cohorts.Figure 1Figure 2

The Utilization of Blockchain for Data Security for the Chronic Pain Physician.

The COVID-19 pandemic accelerated the surge in medical data utilization, notably impacting chronic pain management given its enormous economist cost. While the collection and use of data enhances research and care quality, data exchange risks compromising integrity and privacy, exemplified by the Change Healthcare cyberattack. Here, we review the potential of blockchain for the utilization for cybersecurity in the healthcare system with an emphasis on the field of chronic pain. Blockchain technology emerges as a potential solution, offering decentralized, secure, and immutable data management. Blockchain ensures transparency, integrity, and data privacy, which is crucial in healthcare. Smart contracts may offer automated, secure management of implantable neuromodulation devices such as spinal cord stimulators and intrathecal pumps. Blockchain's potential in pharmaceutical supply chain integrity is exemplified in preliminary efforts ensuring that the medication retrieved by the patient is indeed the intended medication. Despite limitations such as speed of transactions, blockchain presents innovative avenues for healthcare security and quality improvement, necessitating further development for widespread implementation. Blockchain's applicability is not only applicable to chronic pain management, but can be used in medicine as a whole.