Ischemic Cardiomyopathy Research Articles

Nationwide trends in utilization and safety of ventricular arrythmia ablation in patients with hypertrophic cardiomyopathy

Abstract Background Catheter ablation for ventricular arrhythmias, including ventricular tachycardia (VT) and premature ventricular complexes (PVC) is increasingly utilized across the nation, while data on its safety in Hypertrophic Cardiomyopathy (HCM) patients is sparse. Purpose To analyze the nationwide trends in utilization and complications of inpatient ventricular arrhythmia ablations in patients with HCM. Methods This study is a retrospective analysis of hospitalizations, in HCM patients 18 years of age and older, who underwent an inpatient VA ablation in the U.S., between 2016 and 2020. We drew data from the National Inpatient Sample (NIS) database. Patients without HCM undergoing the CA for VA were used as controls. Baseline sociodemographic and clinical data, procedural complications, mortality and length of stay were analyzed. Multivariable analysis was performed to identify independent predictors of procedural complications. Results Among a weighted total of 2880 patients hospitalized between 2016 and 2020, who underwent VA ablations, the median age was 67 years (IQR 56-74), 60% were male, and 73% were white. The HCM group had similar age distribution but more women (64.5% vs 33.6%, p<0.001) and more African Americans (13.2% vs. 7.3%, p=0.03). The non-HCM cohort had significantly higher rates of prior myocardial infarction (22% vs 12.4%, p=0.026), ischemic cardiomyopathy (30.1% vs 0.8%, p<0.001), heart failure (70.5% vs 39.7%, p<0.001), and peripheral vascular disease (PVD, 42.9% vs 18.2%, p<0.001). This was reflected in higher Deyo Comorbidity Index in the non-HCM cohort (score of ≥ 2 in 66.6% vs 43%, p<0.001). Overall, the real-world peri-procedural complication rate in the entire cohort was 15.3%, including 6.4% hemorrhagic, 4.5% pericardial, and 2.3% vascular complications. There was a trend for lower complication rate in the HCM group (9.9% vs. 16.7%, p = 0.08). The in-hospital mortality didn’t defer (1.7% vs. 4.2%, p=0.28) and the length of stay was shorter in the HCM group (3.5 vs. 6.4 days, p < 0.001). Multivariable logistic regression analysis showed obesity (OR 2.06; 95%CI: 1.59 - 2.67; p<0.001) and PVD (OR 2.19; 95%CI: 1.34-3.53; p=0.001) to be independent predictors of complications while HCM was not (OR 0.76, 95% CI 0.51-1.14, p = 0.195). Conclusion Real-world data from a nationwide inpatient database shows comparable safety for VA ablation in HCM patients with similar mortality and lower length of stay, compared to non-HCM patients.

Heart failure hospitalization reduction and long-term safety with remote pulmonary artery pressure monitoring: results of the CardioMEMS HF System OUS Post-Market Study

Abstract Background Heart failure (HF) is increasing in prevalence and is responsible for frequent hospitalization and readmissions, despite current guideline recommended therapies. Hemodynamic guided HF management using frequently remotely obtained pulmonary artery (PA) pressure information using a permanently implanted PA sensor (CardioMEMSTM HF System, Abbott) consistently reduced HF hospitalizations (HFH) in multiple healthcare settings. The safety and efficacy of the CardioMEMS HF System has been shown previously in several clinical studies, which reported significant reductions in HFH compared to a control (CHAMPION: 33%, 18M; GUIDE-HF: 28%, 1 yr; and MONITOR-HF: 44%, 1 yr) and longitudinally (MEMS-HF: 62%, 1 yr; and CardioMEMS US PAS: 57%, 1 yr) across varying health systems. Purpose The CardioMEMS HF System OUS Post-Market Study (COAST) aimed to evaluate the safety and effectiveness of hemodynamic guided HF management in patients with NYHA Class III HF in varying health systems across Europe and Australia. Methods COAST is a prospective, multi-centre, open-label clinical trial that consented 321 patients at 38 European and Australian centres. The primary endpoint is a combination of safety (freedom from DSRCs and freedom from pressure sensor failure at 2 years after implant) and efficacy endpoints (annualized HFH rate at 1-year vs the HFH rate in the year prior to enrolment). In this analysis we report these primary results of the study. Results Out of 321 consented patients, 17 subjects were withdrawn before implant, while the PA sensor was implanted successfully in 299 out of 304 patients who underwent the procedure (98.3% success rate). Seventy-three percent (73%) of the patients were male, the mean age was 68.4±11.7 years with ischemic cardiomyopathy in 45.4%. At baseline, all patients had NYHA Class III symptoms and an average EQ-5D-5L VAS score of 60.0±21.6. After 2 years follow-up there was 100% freedom from DSRCs and 99.7% freedom from pressure sensor failure. The annualized HFH rate after 1 year decreased by 69%, from 1.586 (pre-implant) to 0.488 (post-implant) (p<0.0001). The patient’s quality of life (EQ-5D-5L VAS) increased 8.1 units (68.2 ± 20.1, p=0.0008). Conclusion The COAST Study demonstrated that hemodynamic-guided remote HF management using PA pressure information is both safe and effective, with consistent implant safety and low risk for long-term sensor failure. At 1 year post implant, HFH were significantly reduced and quality of life improved. These results are also consistent with long-term clinical follow-up (2 yr) in other geographies with no late-stage adverse events or adverse events from sensor implant, demonstrating the generalizability of this type of hemodynamic-guided HF management.

A mcgyvering way to left bundle branch area pacing : using the treadmill test machine ECG system and modified V1 / V6 leads connected to the pacing system analyser for left bundle branch area pacing

Abstract Background Left bundle branch area pacing (LBBaP) is a novel pacing modality which provides physiological synchronisation of both the ventricles. However, its use and adoption requires the presence of a standardised electrophysiological (EP) system with 12 lead ECG to show left bundle branch area capture. Purpose The aim of the study was to assess the feasibility and outcomes of using the conventional treadmill test (TMT) machine 12 lead ECG system and modified V1 and V6 leads connected to the pacing system analyser (PSA) to demonstrate conduction system capture during left bundle branch area pacing (LBBaP). Methods LBBaP was attempted by a single operator in a mixed cohort of patients at peripheral hospitals lacking the standardised EP system. The presence of LBB area capture was tested with the aid of the 12 lead ECG system connected to the standard TMT machine (1). Conduction system capture was also assessed using modified V1 and V6 leads connected to the PSA for measurement of V6 left ventricular activation time (LVAT)(2) . The baseline clinical, procedural, pacing, electrocardiographic parameters, echocardiographic response (> 10% improvement in ejection fraction {EF}) and clinical response to LBBaP were assessed. Results LBBaP was attempted in 19 patients and was successful in 18 patients (94.7%). Patient characteristics include age 66.7 +/- 11.47 years, female 47.37%, male 52.63%, ischaemic cardiomyopathy 10.52% and non-ischaemic cardiomyopathy 5.26% .The mean baseline EF and QRS duration was 45%+/-14% and 130.18 +/-10.45 milliseconds(ms) respectively. LBBaP threshold was 0.59 +/-0.168 volts and R wave amplitude was 12+/-3.5 millimetres , which remained stable during the mean follow up of 15.9 +/-13.67 months. The mean fluoroscopic duration was 11.57 +/-2.58 minutes and procedural time was 108.78+/-29.20 minutes. LBBaP resulted in impressive narrowing of the QRS duration to 102.39 +/-10.55 ms (p<0.001) with LVAT of 68.94 +/-9.94 ms. LVEF improved in the patients with cardiomyopathy from 33.4 +/- 5.77 % to 48.2+/-12.37 % (p=0.028) .Clinical and echocardiographic response was noted in 87.5% of patients with cardiomyopathy. Conclusion The 12 lead ECG system with the standardised TMT machine in conjunction with the modified V1 and V6 leads connected to the PSA is a feasible alternative to the EP system to perform successful left bundle branch area pacing.ECG leads connected during LBBapClinical profile of patients

Clinical phenotyping and treatment response in patients with chronic heart failure: a latent class analysis from a Japanese multicentre registry

Abstract Background There are diversities of pathophysiology and co-morbidities in patients with chronic heart failure (HF), irrespective of left ventricular ejection fraction (LVEF). Therefore, the identification of subgroups with different outcomes and treatment response patterns may help to tailor strategies to each individual HF patient. Purpose We sought to identify phenogroups of patients with different prognosis and response to medical therapies in patients with chronic HF. Methods A total of 1565 patients with a broad spectrum of LVEF in a prospective multicentre registry of patients with chronic HF were enrolled between January 2020 and December 2023. Latent class analysis was performed in each subgroup using 80 features including patients’ demographics, laboratory, and echocardiographic data. The optimal number of phenogroups was determined using the first minimum of the Bayesian information criterion. The primary outcome was a composite of all-cause death and hospitalisation due to worsening HF. Results The analysis subclassified patients into six phenogroups. Patients in phenogroup A (young non-ischaemic cardiomyopathy, n = 242, 15.5%) were the youngest and had lower LVEF and lowest prevalence of coronary artery disease (CAD) and other comorbidities. Phenogroup B (atrial fibrillation [AF] and small left atrium, n = 282, 18.0%) had higher proportion of AF but smaller left atrium volume. Phenogroup C (ischaemic cardiomyopathy, n = 204, 13.0%) had the highest proportion of CAD and lower LVEF. Phenogroup D (classical HF with preserved ejection fraction [HFpEF], n =308, 19.7%) had the highest age, proportion of female, LVEF and thickness of LV wall. Phenogroup E (elderly and AF , n = 235, 15.0%) had higher age, the highest proportion of AF and largest left atrium volume. Phenogroup F (biventricular failure and multiple comorbidities, n = 294, 18.8%) had the highest proportion of co-morbidities and the lowest LVEF, right ventricular systolic function and renal function. During a median follow-up period of 538 (interquartile range 286-701) days, the incidence of the primary outcome significantly differed among the phenogroups (P < 0.001, Figure 1). Regarding treatment response for renin-angiotensin system blockers and beta blockers, there were no significant associations between the use of renin-angiotensin system blockers and the risk of the primary outcome among the phenogroups whereas the use of beta-blockers was significantly associated with increased risk of the primary outcome in patients classified to phenogroup D (classical HFpEF) (hazard ratio 1.83 95% confidence interval 1.05-3.19) among the phenogroups (Figure 2). Conclusion We identified six phenogroups with distinct clinical outcomes in patients with chronic HF, and the use of beta-blockers might have unfavorable effect in the classical HFpEF phenogroup. This phenotyping provides novel risk stratification and may aid in clinical decision making.Clinical outcomes among the phenogroupsTreatment effect among the phenogroups

Outcomes of intra-aortic balloon pump in patients with advanced heart failure and cardiogenic shock undergoing heart transplantation

Abstract Background Intra-aortic balloon pump (IABP) is generally used as a short-term device to maintain adequate organ perfusion in patients with cardiogenic shock (CS). However, whether IABP improves clinical outcomes as a bridge therapy for heart transplant (HTx) remains controversial. Purpose Evaluate the survival rate 30 days after heart transplant (HTx) in patients with advanced heart failure (HF) and CS using IABP pre transplant compared to non-IABP group. Methods We retrospectively analyzed consecutive patients with advanced HF and CS, admitted in the cardiac intensive care unit (ICU) of a tertiary university center, between 2009 and 2020, who underwent HTx. Study group included patients submitted to IABP implantation before HTx, and a non-IABP group submitted to HTx without left ventricular mechanical support. Propensity Score Matching was used to pair the groups according to relevant clinical covariates. The primary outcome of survival rate 30 days after HTx was estimated by the Kaplan-Meier method. Results 326 were enrolled, 199 in IABP group and 127 in non-IABP group. For non-IABP and IABP group, respectively, the most frequent etiology was Chagas disease (29,9% and 47,2%, p=0,006) followed by idiopathic cardiomyopathy and ischemic cardiomyopathy, the majority of patients were male (63% and 61,3%, p=0,760), the mean age was 46,9 ± 14,4 and 46,5 ± 12 years (p=0,791) and mean left ventricular ejection fraction was 25,9 ± 9,5% and 23,5 ± 5,9% (p=0,010). The Simplified Acute Physiology Score 3 (SAPS 3) at ICU admission was compared in both groups, which was 36,8% ± 17,8% in non-IABP group and 32,6% ± 18,6% in IABP group (p=0,042). At 30 days after HTx, there was no statistical difference in overall survival (p=0,459) between the groups (IABP: 18,1% mortality; non-IABP: 14,2% mortality). Survival rate after HTx was also similar in patients with Chagas disease compared to the other etiologies in both study groups (IABP group: p=0,221; non-IABP group: p=0,421). Conclusion In patients with advanced HF and CS submitted to HTx, the survival rate 30 days after HTx was equivalent in the IABP and non-IABP groups. In patients with Chagas disease the survival was also similar compared to other etiologies in both groups.Characteristics according to groupsKaplan-Meier survival estimates

The MADIT-ICD benefit risk score for Japanese patients -from Nippon Storm study-

Abstract Background Implantable cardioverter-defibrillators (ICDs) play a crucial role in preventing sudden death due to lethal arrhythmias such as ventricular tachycardia and ventricular fibrillation. However, like any medical intervention, ICD implantation is not without its complications. It is essential to carefully consider the risks and benefits, and appropriately stratify the risk of sudden death in order to make informed decisions. In 2020, the MADIT-ICD benefit risk score was proposed to utilize personalized integrated assessment of the competing risk of lethal arrhythmias vs. non-arrhythmic mortality in implantable cardioverter-defibrillator (ICD) candidates. Purpose To evaluate the risk stratification of using the MADIT-ICD benefit risk score in Japanese patients. Methods We analyzed the data of 451 patients, enrolled in the Nippon Storm Study, with left ventricular ejection fraction (LVEF) ≤35% who underwent ICD implantation for primary prophylaxis of sudden cardiac death (men, 78%; age, 65±12 years; LVEF, 25±6.4%; cardiac resynchronization therapy, 73%; ischemic cardiomyopathy (ICM), 33%). Results A total of 336 patients were enrolled iln this study. The MADIT-ICD benefit risk scores, except systolic blood pressure, was calculated (Figure 1). These patients were classified into 3 groups (Lowest, Intermediate, Highest). There were no significant differences between the three groups in all-cause mortality, cardiovascular death, non-arrhythmic death, and appropriate ICD therapy (Figure 2). The multivariate analysis demonstrated that LVEF ≤25% was significantly associated with all-cause mortality, cardiovascular death, non-arrhythmic death (p=0.0487, 0.0150, 0.0387). Conclusion The MADIT-ICD benefit risk score may not be appropriate to risk stratification in Japanese patients using ICD for primary prophylaxis.Figure 1Figure 2

Dual-chamber CRT-D using ICD lead implantation in the LBBAP position

Abstract Background Interest in conduction system pacing (CSP) has increased in recent years. For left bundle branch area pacing (LBBAP), 4F and 6F pacing leads have been shown to be effective and safe. No information is available on the potential use of ICD leads for LBBAP. Aim The objective of the study was to demonstrate the feasibility of implanting an ICD lead in the LBBAP position to reduce the number of leads for CRT-D therapy. Patients and Methods We implanted the 7F ICD lead in the LBBAP position through a new 10F CSP delivery sheath in ten consecutive patients. Periprocedural data, QRS morphology and degree of QRS reduction were analyzed. Results Ten consecutive patients (one female) aged 69.5±9.2 years were treated with the above-mentioned method. Eight patients had ischemic cardiomyopathy and two patients had nonischemic cardiomyopathy. All patients had a CRT-D indication. Eight patients had a wide QRS complex with complete LBB and a QRS complex of 184.8±25.8 ms. Two patients had a narrow QRS complex but first-degree AV block with a PR interval greater than 240 ms. Left ventricular ejection fraction was 31.8±8.6%. Operative and fluoroscopy times were 103.6±30.3 minutes and 10.5±6.1 minutes, respectively. On average, 1.7 ± 0.6 screwing attempts were required per patient. The intraprocedural LBBAP threshold was 0.78±0.6V/1.0ms, the impedance was 530.8±86.5 ohm, and the R-wave amplitude was 9±3.3mV. The unipolar paced QRS complex was 123.6±15.9ms, the bipolar paced QRS complex was 129.5±12.8ms, and the bipolar paced QRS complex on the next day was 133.3±11.7. The mean duration from stimulus to R-wave peak in lead V6 was 82.9 ± 19.7 ms. The R-wave interpeak interval between leads V6 and V1 was 43.4 ± 9.7 ms. All but one patient received an effective defibrillation threshold test at 30J (n=8) and 36J (n=1). One patient was not tested during the procedure due to high risk. Conclusion This first-in-human study of ICD lead implantation in the LBBAP position demonstrated its feasibility and efficacy in achieving conduction system stimulation. This approach may lead to a reduction in the number of leads implanted for cardiac resynchronization therapy. Figure 1. A- RAO view, angiography of the RV for verification of the TVA-summit. B- LAO view, angiography from the CSP- sheath after reaching final position of the LBBAP lead (right sided interventricular septum - yellow dotted line). C – 12 lead ECG (speed 50mm/sec) demonstrating paced and native QRS complexes. D – Fluoroscopy in RAO view, final result. E – Fluoroscopy in LAO view, final result. F – Transthoracic echocardiography the next day (4Ch view) demonstrates optimal LBBAP lead position.. RAO – right anterior oblique; LAO – left anterior oblique; TVA – tricuspid valve anulus; CSP – conduction system pacing; LBBAP – left bundle branch area pacing.Figure 1.

Accuracy of endocardial abnormal electrogram characterization using a 17-AHA-segmental late boundary and voltage-dependent sensitivity annotation for ventricular tachycardia ablation

Abstract Background Substrate-based catheter ablation of ventricular tachycardia (VT) has become the mainstay therapy for patients with scar-related VT. Correct identification and timing of abnormal near-field EGMs and discerning it from far-field EGMs, is key for procedural success. The novel CARTO™ Late Activation Mapping (LAM) module provides fast and accurate annotation of near-field EGMs including late abnormal ventricular activation. For the algorithm to succeed, a late boundary (LB) annotation line should be positioned immediately behind the normal near-field EGM, however, since the timing of normal local near-field activation varies greatly throughout the endocardium, there is currently no consensus for the optimal LB positioning. We hypothesized that 17-AHA segmental annotation of the endocardial LB followed by scar-dependent sensitivity settings, will improve the accuracy of the near-field EGM characterization. Purpose To evaluate the accuracy of endocardial abnormal EGM characterization using a 17-AHA-segmental late boundary and voltage-dependent sensitivity annotation as compared to conventional mid-QRS LB positioning. Methods Five high-resolution substrate voltage maps were obtained from 5 patients (80% male, 68±7 years old, 80% ischemic cardiomyopathy) that underwent a catheter-based ablation for scar-related VT. A personalized CT-derived anatomical reconstruction of the 17-segment AHA model was co-registered offline with the electroanatomic voltage map, using ADAS3D software. Per segment, individual LB timings were set at the highest sensitivity. A gold standard annotation map was created by two independent experts after manual scrutiny of individual EGMs. Next, the expert map was compared to automatic maps created from segmental LB and mid-QRS LB positions at normal, high, highest or mixed (normal/high or normal/highest) sensitivities, focusing on EGM voltage and activation accuracy. Results A mean of 2041±1028 points per map were analyzed. Correct correlation of EGM annotation was found on average in 91% (activation) and 81% (voltage) for all segmental LB positioned maps (segLB), and in 83% (activation) and 77% (voltage) for all mid-QRS LB positioned maps (mid-QRSLB). The highest correlation with expert map for both activation and voltage annotation was found in the mixed sensitivity normal/highest map with segmental LB positioning (activation 98%, voltage 88%). The correlation on activation was significantly superior in the segLB map when compared to the normal sensitivity maps (p=0.0008 for mid-QRSLB and p=0.02 for segLB). For correlation on voltage, the segLBmap with mixed sensitivity was significantly superior compared to three mid-QRSLB maps at normal (p=0.04), high and highest (p=0.01) sensitivity. Conclusion Individualized, 17-AHA-segmental late boundary and voltage-dependent sensitivity annotation provides a possible accurate and clinically-relevant framework for substrate assessment. Prospective validation is needed.

3D target definition and initial results from the electroanatomic substrate-guided stereotactic ablative radiotherapy for refractory ventricular tachycardia (ELSTAR-VT)

Abstract Background/introduction Noninvasive stereotactic radiotherapy (STAR) is an emerging transmural ablative therapy for refractory ventricular tachycardia (VT). Delineation of the arrhythmogenic gross target volume (GTV) relies on electrical (exit and isthmus) VT characteristics and anatomical scar detailing. 17-AHA segmental approaches or eyeballing techniques are adopted to transfer the GTV to the treatment planning CT. An individualized 3D GTV delineated with ADAS3D based on the areas of interest of each modality could lead to a smaller GTV compared to 17-AHA segmental approaches. Purpose We investigated whether our workflow using ADAS3D for the delineating of the GTV renders smaller GTV compared to 17-AHA segmental approaches whilst remaining effective for VT treatment during follow-up. Methods We targeted 3D-personalized GTV with STAR in patients with refractory VT in structural heart disease. Electroanatomical detailing was achieved by combining high-resolution invasive and noninvasive (ECG imaging during noninvasive programmed stimulation) mapping, combined with wall thickness analyses by cardiac CT. After coregistration in ADAS3D, a 3D DICOM-radiation therapy file including the delineated target volume was generated and transferred into the free-breathing and respiration-corrected 4D CT scan. Standard STAR using a single-fraction of 20-25 Gy was applied. We compared conventional (17-AHA segmental approaches) versus 3D-based GTV demarcation, and assessed VT burden and procedural safety. Results From January 2023 to February 2024 STAR was successfully performed in three patients (all male, mean age 73±1 years, two ischemic cardiomyopathy, one laminopathy) with persistent VT despite ≥2 catheter-based (endocardial/epicardial) ablation procedures. The 3D-derived GTVs showed a statistical trend towards smaller volumes compared to conventional segmental delineation (11±4 versus 21±3 cm3, p=0.07). VT burden and ICD therapy was reduced by 100% over 9 patients-months (8-week blanking period). No acute or subacute adverse events occurred. One patient died of progressive heart failure. Conclusion 3D-individualized target volume annotation may hold promise for effective and safe STAR employment.ELSTAR workflow

Stereotactic arrhythmia radioablation - A systematic review and meta-analysis of the prospective clinical studies

Abstract Background Stereotactic arrhythmia radioablation (STAR) is increasingly being evaluated in prospective studies as a new promising treatment option for patients with therapy-refractory ventricular tachycardia (VT). In STAR, the VT substrate is noninvasively treated with a high dose of radiotherapy. Recently, several single-arm prospective studies evaluating the clinical outcomes of STAR were published. Considering that the evidence base consists mainly of retrospective case series, we conducted a systematic review and meta-analysis to synthesize the prospective data on outcomes of STAR. Purpose To perform a systematic review and meta-analysis of prospective studies evaluating clinical outcomes of STAR for VT. Methods This study was registered in PROSPERO and adhered to the PRISMA reporting guidelines. Full-text studies describing prospective studies evaluating the safety and efficacy of STAR for VT were included in this study. Records published until August 2023 were retrieved from OVID MEDLINE, OVID Embase, Web of Science Core Collection, the Cochrane Central Register of Controlled Trials, and Google Scholar search engine (top 200 hits), deduplicated, and screened for eligibility. Abstract screening, full-text screening, data extraction and quality assessment were performed by two reviewers independently. Endpoints were defined as treatment related CTCAE grade ≥3 adverse events within 90 days after treatment, overall survival (OS), time to VT recurrence, and recurrence-free survival. Rates of patients achieving pre-defined 50%, 75% and 95% VT burden reduction thresholds were summarised. Random-effects generalized linear mixed-effects models and inverse variance models were used for the meta-analysis. Results 1861 records were identified, 987 were screened, and 10 full-text manuscripts published between 2019 and 2023 describing the results of STAR in 82 patients were included in this study. The majority were male (n=72; 88%), between 45 and 85 years old, and suffered from ischaemic cardiomyopathy (n=51; 62%). Median left ventricular ejection fraction ranged from 21 to 38% between studies. 20 patients did not undergo a prior catheter ablation for VT. All patients were treated with a single dose of 25 Gy and median planned target volume ranged from 45 to 198 cc between studies. Pooled 12-month OS rate was 0.73, and the proportion of patients experiencing grade ≥3 adverse events within 90 days after STAR was 0.11 (Figure 1). Reduction in VT burden is shown in Table 1. Although these were not pooled because of large heterogeneity in VT reduction time frame definitions, it can be appreciated that most of the patients experienced a reduction in VT burden. Conclusion The increasing evidence from prospective studies on STAR shows acceptable 12-month OS in a population of patients with advanced heart failure and refractory VT. Moreover, there is a modest rate of high-grade adverse events and most patients experience a reduction in VT burden.

Prospective assessment of risk factors for appropriate ICD intervention in patients with ischemic cardiomyopathy: results of PARCADIA trial

Abstract Background There is still a big unmet need for better risk stratification tools to identify patients at high risk for sudden cardiac death in the era of primary prevention ICD therapy. Scar burden on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging may be a risk marker for the prediction of ventricular arrhythmia in post-myocardial infarction (MI) patients. Purpose The aim of the PARCADIA trial was to assess whether scar characteristics, determined via LGE-CMR, or other baseline risk markers are associated with appropriate ICD therapy. Methods In this prospective, multi-center, clinical trial, we enrolled post-MI patients with an indication for de novo primary prevention ICD. Main exclusion criteria were indication for cardiac resynchronization therapy and NYHA class IV. Prior to the ICD implantation, LGE-CMR was performed to analyze the amount of scar tissue (LGE core mass + grey zone mass) and LV function / volumes. A 24h Holter recording was performed to collect information on potential triggers like premature ventricular beats (PVB) and sympathetic-vagal balance based on heart rate variability (HRV). Follow-ups were performed in-office every 6 months, including remote monitoring. Appropriate ICD therapy was used as primary endpoint and adjudicated by a clinical event committee. Results 199 patients were enrolled at 5 investigational sites in Europe. Patients mean age was 64.3 years, with a mean LVEF of 27.7 %, timing from the index MI was 9.1 years, and 42.7% received a primary PCI on index MI. After a median follow-up duration of 47.7 months, 23.1% of patients received appropriate ICD therapy. In 135 patients (67.8%), quality of LGE-CMR was sufficient for detailed analysis. The mean LGE core mass (20.5 vs. 19,7 g) and grey zone mass (10.5 vs. 11.4 g) was not different in patients with or without appropriate ICD therapy, also not when corrected for LV mass. However, LVEF (28.5 vs. 32.9 %) was lower, while diastolic myocardial mass (141 vs. 125 g), and end-diastolic volume (265.0 vs. 226.7 ml) were significantly higher in patients with appropriate ICD therapy. On 24h Holter the mean PVB burden (3695 vs. 1643 beats), and non-sustained ventricular tachycardia (12 vs. 0.9), were higher in patients with appropriate ICD therapy, while the HRV (96.1 vs. 113.1 SDNN) was lower. In univariate analysis the variables LVEF, timing to index MI, primary PCI on index MI, PVB burden and HRV appeared to be predictors for appropriate ICD intervention, while in multivariate analysis LVEF and PVB burden remained predictive. Conclusion In post-MI patients with appropriate ICD therapy, scar burden was not different from patients without appropriate ICD therapy. Only LVEF and PVB burden were independent predictors of increased arrhythmogenicity. Improved CMR analysis on scar characteristics (conduction channels) to identify potential arrhythmogenic regions might be the topic for future research.

Blood urea monitoring in heart failure patients - an important predictor of mortality

Abstract Background Recent ESC position statement regarding worsening renal failure recommends the use of blood urea monitoring of patients with heart failure with reduced ejection fraction (HFrEF). Although both serum creatinine and blood urea nitrogen are markers for renal dysfunction, blood urea nitrogen levels are also affected by reabsorption in the renal tubules, a process modulated by renin-angiotensin-aldosterone activity, sympathetic nervous activity and arginine-vasopressin activity. Thus, neurohormonal activity is reflected in the BUN/creatinine ratio (bUCR) which effectively ‘normalizes’ BUN for the degree of renal dysfunction, as measured by the creatinine level. Previous studies have demonstrated increased mortality at bUCR >100mmol/l. however, most of the prognostic data has come from patients admitted with acute heart failure. The use of bUCR in patients with chronic HFrHF receiving intensive titration of guideline directed medical therapy (GDMT) has not been studied. Purpose To identify the extent of blood urea monitoring in primary care in HFrEF and whether bUCR remains a significant prognostic indicator despite intensive GDMT. Methods We analysed the electronic health records of all patients referred to the Heart Failure Nurse Service (HFNS) in an NHS population approx. 400,000 in 2022. Inclusion criteria consists of patients with symptomatic heart failure NYHA II-IV with echocardiogram demonstrating HFrEF. Patients were segregated into two cohorts, with a urea/creatinine ratio greater or less than 100mmol/l and analysed. Results Data from 338 patients [mean age 72.3 ± 15.6 years; 218 (64.5%) males; 143 (42.3%) ischaemic cardiomyopathy; 141 (41.7%) AF; 49 (14.5%)] were analysed. Of these, 112 (33.1%) had chronic kidney disease (CKD) with eGFR <60 ml/min/1.73m2 at the time of HF diagnosis and 181 (53.6%) had CKD on discharge from the HFNS. During follow-up, 132 (39%) had further admission with HF and 76 (22.5%) died. Sixty-eight (20.1%) patients did not have blood urea checked despite the availability of serum creatinine. While an eGFR < 60 ml/min/1.73m2 at discharge was associated with a twofold increased risk of death (OR 2.4, 95% CI 1.1-5.3, p=0.029), a bUCR > 100mmol/l at discharge was associated with a four-times greater risk of death (OR 4.2, 95% CI 2.2-7.9, p <0.001). Conclusion Blood urea/creatinine ratio is an important predictor of outcome and can be utilised to help identify at-risk patients with HFrEF despite intensive GDMT.Survival from diagnosis bUCR

Ischemic Stroke Induced by an Electric Shock in a Patient with Ischemic Cardiomyopathy: An Unusual Association of Events

Electrocution is a well-known accident that can lead to a highly variable clinical presentation, including cardiac and neurological complications. Some studies have shown that electric shock contributes to arterial ischemia; either through vasospasm or by inducing thrombotic reactions. Here, we present a 66-year-old male patient with unrecognized cardiac disease who developed brachio-facial paresis related to ischemic stroke immediately after being electrocuted with domestic electricity.

Incidence of acute cellular and antibody mediated rejection in heart transplantation from a tertiary care center

Abstract Background Heart transplant greatly increases the survival in patients with end stage heart failure. However, cardiologists and cardiothoracic surgeons face difficulty in detecting rejection at times. Post-cardiac transplant surveillance biopsy remains the gold standard for diagnosing rejection and therapeutic intervention. Purpose The objective is to report our experience of monitoring rejection by endomyocardial biopsy (EMB). Methods The index study is an ambispective one where we evaluated all the patients who underwent heart transplant at our center from 1994 to 2021. Results Heart transplant were carried out in 72 patients within a period of 28 years, with majority being done after 2016. The patients mean age was 31.6 years (10-59 years). The commonest indication was dilated cardiomyopathy (67%) followed by ischemic cardiomyopathy (2.5%), congenital heart disease (7%) and other miscellaneous causes (5%). The mean age of donors was 31.8 years (14-55 years). Eight of the 72 patients died without any post cardiac transplant endomyocardial biopsy. The remaining 64 patients underwent cumulatively a total of 271 endomyocardial biopsy procedures. Majority of endomyocaridal biopsies contained three cores (range 1-7). First EMB procedure was performed in 17 (26.6%) patients within first seven days, 35(53.1%) within the second week and 12(20.3%) after 14 days. Histologically rejection was identified in 42 (66%) patients. Thirty-nine (61%) had only acute cellular rejection (ACR), one (1.6%) had only antibody mediated rejection (AMR) and two (3.1%) had mixed ACR and AMR. These 42 patients with rejection had a total of 90 (33.2%) episodes of ACR detected in 271 endomyocardial biopsies. Out of 90 ACR, 44 (48.9%) occurred in less than six months; seventeen (18.9% of 90 ACR) episodes occurred between six and 12 months and 29 (32.2%) after one year. The mean of presentation of first ACR episode was 36 weeks (range 5 days to 3.6 years). There were 172 endomyocardial procedures within one year of transplantation of which 61 (35%) showed rejection. Ninety-nine endomyocardial procedures were performed one year of transplantation of which 29 (29%) showed rejection. Most common grade in both the time period was ACR grade 1R (International Society for Heart and Lung Transplantation (ISHLT) 2004) (72.1% in ≤1 year and 65.5% in >1 year) followed by 2R and 3R. Thirty-eight (90.4%) of 42 patients expired in less than five years since transplantation. Two (4.8%) patients survived between five to ten years post transplantation and two (4.8%) survived more than ten years. The longest cardiac transplant recipient had completed 23 years since cardiac transplant and is alive till date. Conclusions EMB being the gold standard for cardiac allograft rejection, the cardiac pathologists need to be aware of the various grades of rejection including mixed rejection.Acute cellular rejection (ISHLT 2004)

Ablation of right ventricular endocavitary arrhythmias

Abstract Background The right ventricular moderator band-papillary muscle (RV MB-PM) complex has a rich subendocardial network of purkinje fibers which can lead to ventricular arrhythmias (VA)1. Catheter ablation of such arrhythmias is procedurally challenging and there remains limited studies on long-term procedural success. Purpose We aimed to systematically study RV MB-PM complex VA. Methods A single center retrospective study from January 2013 to December 2023 identified 3249 patients who underwent VA ablation. The RV MB-PM complex was targeted in 47 patients. Acute success was defined as suppression of the targeted VA >=30 minutes post ablation. Long-term success was defined as the absence of symptoms, total PVC burden <5% or improvement in EF in patients presenting with isolated PVCs and as freedom from appropriate ICD therapy in patients presenting with malignant PVCs inducing VF, sustained VT or VT storm. Results Mean age was 51.9 ± 16.7 years and 64% were male. 40 (85%) patients had VA targeted from the MB and 7 (15%) from the PM complex (2 anterior, 2 inferior and 3 septal PM). 34 (72%) had no underlying structural heart disease, 3 (6%) ischemic cardiomyopathy and 10 (21%) non-ischemic cardiomyopathy. No patient had delayed gadolinium enhancement in the RV MB-PM complex. VA were inducible in 42 (89%) of patients and activation mapping was used in 9 (19%), pace mapping in 5 (11%) and a combination of activation and pace mapping used in 33 (70%) patients. Intracardiac echocardiography was used in all cases. Pre-QRS duration was 34.0 ± 10.4 ms. Radiofrequency ablation was used in 37 (78.7%) cases, cryotherapy in 4 (8.51%) cases and a combination of the 2 energy sources in 6 (12.8%) cases. In all cases, acute peri-procedural success was achieved. 24 (51.1%) patients presented with isolated PVCs and were followed up for 4.72 ± 3.55 years after their index procedure. 3 patients underwent repeat catheter ablation targeting the same PVC focus but all patients had long term success with a PVC burden of 16.1 ± 12.5% prior to ablation and 2.40 ± 2.44% at last follow-up. 16 patients underwent ablation for recurrent ICD shocks after initially presenting with PVC induced VF. Patients were followed up for 3.22 ± 2.09 years and 14 (88%) patients remained free from ICD therapy. 7 patients had MB ablation for sustained VT and were followed up for 4.06 ± 3.77 years. 5 (71%) patients remained free from ICD therapy. A purkinje potential was seen in 8% (2/24) cases of isolated PVCs and in 39% (9/23) cases of PVC induced VF or VT (p=0.13). Conclusions RV MB-PM VA commonly present with malignant VF and a purkinje potential is more likely to be seen in these cases suggesting different VA mechanisms to isolated PVCs and catheter ablation is an effective long-term strategy.

In-hospital outcomes of ventricular tachycardia catheter ablation in the presence of intra-cardiac thrombus

Abstract Background Ventricular tachycardia (VT) catheter ablation in the presence of intracardiac thrombi was evaluated in very few studies. Objectives To investigate in-hospital outcomes of VT ablation in the presence of an intracardiac thrombus, in a large inpatient US registry. Methods Using the National Inpatient Sample (NIS) database, patients who underwent non-elective VT catheter ablations in the US between 2016 and 2019 were identified using ICD-10 codes. Sociodemographic, clinical data, in-hospital procedures and outcomes as well as in-hospital mortality were collected. In-hospital outcomes were compared using propensity score (PS) matching analysis with a 1:3 ratio between patients with and without intracardiac thrombus. Results A weighted total of 15,725 admissions for non-elective VT ablation were included in the study, of which 190 (1.2%) had a discharge diagnosis of intracardiac thrombus. Patients with intracardiac thrombus had a higher comorbidity burden and were more likely to have ischemic cardiomyopathy and a diagnosis of cardiac aneurysm. In PS analysis, the presence of intracardiac thrombus was significantly associated with higher rates of any in-hospital complications (42.1% vs 19.3%, P<0.009), driven by higher periprocedural cerebrovascular accident and vascular injury events. In-hospital mortality rates were not significantly different between the groups. Conclusions In patients undergoing non-elective VT ablation, intracardiac thrombus was associated with higher rates of in-hospital complications, but not higher in-hospital mortality. These findings suggest that intracardiac thrombus should not contraindicate VT ablation when deemed necessary, while efforts should be made to decrease potential complications.

Estimated plasma volume in heart failure with reduced ejection fraction: ACE inhibitors versus angiotensin receptor/neprilysin inhibitor in follow up

Abstract Background Estimated plasma volume status (ePVs) has been considered a biological surrogate for congestion and has been shown to be associated with post-discharge outcomes in patients with heart failure with reduced ejection fraction (HFrEF). The plasma volume status can be easily estimated by the index of the PVs according to the haemoglobin and haematocrit levels. Purpose The aim of the study was to examine the change in ePVs and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels during the 12-month follow up of HFrEF patients treated with ACE inhibitors (ACEi) and angiotensin receptor/neprilysin inhibitor (ARNI). Methods We included all patients treated or diagnosed with HFrEF in our hospital from May 2021 to February 2022 and prescribed with either ACEi or ARNI among complete guideline-directed medical therapy (GDMT). We used Strauss-derived Duarte formula [ePVs= (100-Hct%) ÷ Hb] to estimate PVs during the initiation of GDMT and after 12-month follow up. Results This registry-based study included 619 patients with HFrEF, out of which 278 were prescribed with ACEi (ACEi group) and 273 with ARNI (ARNI group). There were no differences between the groups regarding age (ACEi 68 vs. ARNI 67 years, p=0.09), however, ACEi group had significantly more women (30% vs. 26% of patients, p=0.02). Patients in ACEi group were more likely to have ischemic cardiomyopathy (61 vs. 49%, p<0.01), higher estimated glomerular filtration rate (72 vs. 64 L/min/1.73m², p=0.01), while patients in ARNI group were more likely to be NYHA III class (40 vs. 48%, p=0.04). Initial ePVs (4.23 for ACEi vs. 4.20 for ARNI, p=0.46), NT-proBNP levels (3357.5 for ACEi vs. 2786 for ARNI, p=0.08), and left ventricular ejection fraction (median 35% for ACEi vs. 35% for ARNI, p=0.49) did not significantly differ between the groups. After the 12-month follow up, the change in ePVs was similar between the groups (-0.22 for ACEi vs. -0.19 for ARNI, p=0.93). Reduction of NT-proBNP levels was more prominent in ACEi group (1750.5 vs. 858.5 pg/mL, p=0.01). Mortality rate did not differ between the groups during 12-month follow up (9.71% in ACEi vs. 8.42% in ARNI, p=0.60). Conclusion In HFrEF patients both ACEi and ARNI reduced ePV and NTproBNP levels during 12-month follow up. ACEi were more potent in reducing NT-proBNP levels. Despite the more prominent reduction in NT-proBNP levels, no significant difference was observed in mortality rate during follow up between the groups.

REDUCE-HF: a stronger heart go a long way

Abstract Introduction/Purpose Heart failure (HF) is a serious cardiovascular condition with a significant global health concern. The risk of heart failure rehospitalisation is high globally and locally, the 30-day HF readmission was about 32% from a local study (1). The study aims to adopt an intensive treatment strategy similar to Strong-HF trial (2) and evaluate rapid up-titration of guideline directed medical therapy (GDMT) and close follow-up will improve patients' outcomes after acute heart failure (AHF). Objectives The Reduction of Decompensation and Unnecessary Cardiac failure Emergency admissions: ambulatory Heart Failure service model (REDUCE-HF) is a non-randomised prospective study evaluating clinical outcome of patients discharged from AHF. Exclusion criteria included primary valvular disorders, end-stage renal failure and metastatic cancer. After HF discharge, eligible patients were recruited into our REDUCE-HF program irrespective of LVEF. They were subsequently managed in our ambulatory HF centre within two weeks, where intensive up-titration of GDMT and close follow-up would be proceeded. The data of our service model will be compared with our 5-year historical cohort. Primary outcome comprised of all-cause mortality and heart failure hospitalisation. Secondary outcome will be comparison of clinical and functional status at baseline and 3-month on follow up. Results Between October 2022, and December 2023, 245 patients were successfully recruited into our REDUCE-HF service model. Historical cohort of 6867 patients with primary diagnosis of acute heart failure were served as control (usual care pathway), data extracted from 2018 to 2022. Their mean age was 67.8+/-12.2 and 72.2%were male. 60% of them were HFrEF (EF<=40%) and 28% were ischaemic cardiomyopathy. The mean follow up period was 3 months. At 90 days, REDUCE-HF cohort group has shown much lower all-cause mortality than usual care group (2.5% vs 9.3%, HR 0.26, 95% CI 0.18-0.41, p<0.001). There was a much lower incidence of heart failure hospitalisation in REDUCE-HF group as compared to control (8.6% vs 13.1%, HR 0.65; 95% CI 0.55 to 0.74, p<0.01). In secondary outcome, there was significant reduction of NT-ProBNP of 45.2% (from 4229 to 2319pg/m, p<0.001), tremendous increment of 6-minute walk test (from 211 to 250m, p<0.001) and remarkable improvement of KCCQ score from 55.1 to 86.7, p<0.001. The overall LVEF was significantly increased from 39% to 44%, p<0.05. The positive outcome were attributed to good adherence to GDMT: ACEi/ARB/ARNI 91%, Betablocker 90.3%, MRA 72.4% and SGLT2i 95.5%. Conclusion The REDUCE-HF ambulatory service model has been proven effective in reducing mortality, decompensation and preventing unnecessary heart failure hospitalisation in this prospective study. By intervening proactively, this model not only enhances the quality of life but also hold promise in alleviating the burden of in-patient services on heart failure.

The relative importance of ischaemia and scar in the genesis of ventricular arrhythmia in ischaemic cardiomyopathy

Abstract Background Ventricular arrhythmias are a leading cause of death in patients with ischaemic cardiomyopathy (ICM). Ischaemia and scar are thought to contribute to arrhythmogenesis; as scar is considered fixed, strategies to reduce ischaemia such as revascularisation are undertaken to attempt to reduce risk, despite limited evidence behind this practice. Purpose The study rationale was to understand the relative contributions of ischaemia and scar on the genesis of arrhythmia in an ICM population, by undertaking a detailed assessment of arrhythmic substrate in a highly characterised population and secondly by validating these findings in a large cohort. Methods We assessed the relationship between scar, ischaemic burden and impact of ischaemia modulation via revascularisation on the arrhythmic substrate (study 1) and major arrhythmic events (study 2). S1: Patients were eligible for enrolment if they had an LVEF≤40%, extensive coronary disease (BCIS Jeopardy Score (JS) ≥6) and were due to undergo CABG or PCI. Arrhythmic substrate was characterised by the LV activation recovery interval (ARI) dispersion recorded by electrocardiographic imaging (ECGi). Scar and ischaemic burden were assessed via stress perfusion cardiac magnetic resonance (pCMR) imaging, calculated as a percentage of total LV myocardial volume. ECGi and pCMR were repeated 3 months post revasc. S2: Arrhythmia data were collected from device interrogation reports and blinded core lab analyses performed of CMR scans and angiograms of patients enrolled in the REVIVED-BCIS2 trial. Extent of revasc (quantified by change in JS/baseline JS) was used to estimate change in ischaemic burden. The primary outcome was death or aborted sudden death. Results S1: 30 patients were recruited; age 67±10 years, 87% male, BMI 28±5. Baseline LV ARI dispersion at rest was correlated with scar burden (r=0.37, p=0.04) but not ischaemic burden (r=0.25,p=0.21). Changes in metrics are shown(Table 1). Ischaemic burden reduced after revascularisation. Delta ischaemic burden was correlated with delta LV ARI dispersion (r=0.51, p=0.007 unadjusted). S2: Data was collected on 479 patients from REVIVED-BCI2 who underwent CMR; age 69±9 yrs, 88% male, BMI 28±6, LVEF 26±8%. 237 were randomised to PCI and 242 to OMT; no difference in rates of all-cause death, CV death, aborted sudden death, appropriate device therapy or arrhythmia was identified between the groups. Scar burden was associated with death or aborted sudden death, extent of revascularisation was not(Figure 1). Conclusion In our studies, the volume of scar was strongly related to both the arrhythmic substrate and occurrence of arrhythmic events. Whilst ischaemia reduction affected the arrhythmic substrate, this did not translate to a reduction in clinical events. These findings suggest that scar burden, rather than ischaemia reduction by revascularisation, should be the focus of risk stratification and therapeutic decision making in patients with ICM.Table 1Figure 1

Acute kidney injury stage 2/3 during acute heart failure admission - clinical contributors and outcomes

Abstract Introduction Acute Heart failure (AHF) may be complicated by acute kidney injury (AKI) as a result of cardiorenal syndrome.(1) However other factors may contribute to AKI. AKI stage 2 or 3 predicts negative inpatient outcomes in the general population.(2) We have reported data in a contemporary cohort on AKI in AHF. This study looks at a larger cohort in 5 previous years to test whether those findings were consistent. Better understanding of this clinical scenario may lead to improvements in care. Aim To assess the clinical factors associated with AKI 2/3 in AHF inpatients. Methods This study used retrospective data from a single teaching hospital collected for inclusion in the UK National Heart Failure National Audit. All AHF admissions over a 5-year period, from April 2017 – April 2022 inclusive, were analysed. Renal function on admission and discharge/death were assessed. AKI stage was defined according to KDIGO guidelines based on serum creatinine levels. Electronic patient records were reviewed and the clinical course leading up to and following AKI 2/3 was reviewed. Reported mode of death was also collected. Results 3219 AHF admissions (2360 unique patients) were assessed. 257 patients died during admission (8% admission mortality, 10.9% patients). 157 (4.9%) admissions had AKI 2/3 on admission/discharge. 85 (54.1%) AKI 2/3 died during their hospital admission vs 6.1% mortality in admissions without AKI 2/3. Baseline population characteristics are summarised in Table 1. Admissions with AKI 2/3 who died were older (77.6±11.5 vs 71.5 ±15.8) and had higher rates of atrial fibrillation (48.2% vs 39.9%), diabetes (40% vs 36%), ischaemic cardiomyopathy (56.5% vs 41.7%) and LVEF <35% (38.8% vs 27.7%). The most frequent contributors to AKI 2/3 were sepsis (55, 64.7%) and congestive cardiac failure/cardiorenal syndrome (48, 56.6%). Hypotension (25, 29.4%), over-diuresis (17, 20%), radioiodine contrast (10, 11.8%) and aminoglycosides (8, 9.4%) were less common factors in development of AKI 2/3. ≥2 contributors were present in 49, 57.6%. The dominant contributor for AKI 2/3 was adjudicated to be sepsis in 33 (38.8%) of admissions, followed by cardiorenal syndrome (congestive heart failure with AKI) in 29 (34.1%), and cardiogenic shock in 7 (8.2%). AKI 2/3 contributors are summarised in Table 2. In AKI 2/3 cases who died, 35 (41.2%) involved renal specialist input; 60 (70%) involved heart failure specialist review. Conclusion AKI in AHF is associated with high inpatient mortality. Despite this, specialist renal input was uncommon. AKI 2/3 was usually multifactorial. Cardiorenal syndrome accounted for one third of cases and may not be preventable. In keeping with our findings from a smaller contemporary cohort, sepsis was the most common dominant cause of severe AKI. Prevention, early identification, and treatment of infection could reduce this risk. Awareness of the high mortality of AKI in AHF and specialist review may improve outcomes in AHF.