Death In High-risk Patients Research Articles

Prediction of nonsustained ventricular tachycardia development by the analysis of premature ventricular complex-related intervals on 24-hour rhythm monitoring and testing a novel index

Abstract Introduction Ventricular tachycardia (VT) and ventricular fibrillation (VF) are life- threatening arrhythmias, with non-sustained ventricular tachycardia (NSVT) serving as a potential precursor. Identifying individuals at risk of NSVT is crucial for effective management and prevention of sudden cardiac death in high-risk patients. In daily clinical practice, premature ventricular complex (PVC) and sometimes NSVT are frequently detected on 24-hour ambulatory rhythm monitoring. Purpose In this study, we aimed to predict the development of NSVT by analyzing PVC morphology and intervals in 24- hour ambulatory rhythm monitorings. Methods A retrospective analysis of 24-hour ambulatory rhythm monitoring recordings from 2018 to 2023 was conducted. Inclusion criteria required clear measurement of PVC intervals, at least 100 PVC in the recording, and two preceding normal QRS beats. NSVT diagnosis was based on four consecutive PVC lasting <30 s and a rate >100/min. Various PVC-related parameters were analyzed, and new variables were derived. Statistical analysis included Mann-Whitney U tests and ROC analysis. Results The study included 202 patients, revealing significant differences in several VES temporal variables between groups with only PVC (Group I) and PVC with NSVT (Group II). Notably, Age-Adjusted Sum of Intervals Index (AASI Index-(100 x [(Tp-to- QRSvpa)+(coupling time)+(Qtc1)]/age), long coupling times, extended Tp-to-QRSvpaintervals, and prolonged Tpe-vpa intervals were associated with NSVT development. Age played a pivotal role in predicting NSVT when integrated into a specific variable AASI index. The optimal cut-off value was 4.21, with 84% sensitivity and specificity. Conclusion The study suggests that ventricular arrhythmias may be predicted using temporal parameters of PVC, especially when age is included as a modifier. The AASI index calculated on a PVC and preceeding two normal beats on 24-hour ambulatory rhythm monitoring seems to be promising parameter. These findings hold potential for future development of artificial intelligence-based algorithms for use in any PVC to identify at-risk patient groups, provided larger datasets are utilized to refine predictive models.Variables included in the analysis for cDefinitions of variables and ROC curve

Characteristics and outcomes of patients treated with sotrovimab to prevent progression to severe COVID-19 in Belgium

ABSTRACT Objective Sotrovimab, a dual-action, engineered human monoclonal antibody, has been demonstrated to significantly reduce the risk of hospitalisation and death in high-risk patients with COVID-19. Here, we describe the real-world use of, and outcomes from, sotrovimab treatment in Belgium during the Delta and Omicron waves among patients with COVID-19 at high risk of developing severe disease. Methods This was a multicentric, single-arm observational cohort study of non-hospitalised patients receiving outpatient sotrovimab treatment between 1 November 2021 and 2 August 2022 at nine hospitals in Belgium. The primary outcomes were all-cause and COVID-19-related hospitalisations and all-cause deaths during the 29-day acute follow-up period from first administration of sotrovimab. Results A total of 634 patients were included (63.4% aged < 65 years; 50.3% male). A high proportion (67.7%; n = 429/634) of patients were immunocompromised, with 36.9% (n = 234/634) actively treated for malignancy. During the 29-day acute period, 12.5% (n = 79/634) of sotrovimab-treated patients were hospitalised due to any cause (median duration 4 days; median time to hospitalisation 14 days) and 1.1% (n = 7/634) died due to any cause. The proportion of sotrovimab-treated patients experiencing COVID-19-related hospitalisation was highest during the Delta predominance and Delta/BA.1 codominance (both 6.3%) periods. During the BA.1 predominance, BA.1/BA.2 codominance and BA.2/BA.5 codominance periods, COVID-19-related hospitalisations were consistently low (all ≤2.7%). Conclusion This study indicated low rates of COVID-19-related hospitalisations and all-cause deaths in sotrovimab-treated patients in Belgium, including during Omicron subvariant periods, despite over two-thirds of the study population being immunocompromised.

Use of Imaging-guided Decongestion for Reducing Heart Failure Readmission and Death in High-risk Patients: A Multi-site Randomized Trial of a Nurse-led Strategy at the Point of Care

BackgroundNurse-led disease management programs (DMPs) decrease readmission after acute decompensated heart failure (HF). We sought whether readmissions could be further reduced by lung ultrasound (LUS)-guided decongestion before discharge and during DMP. Methods and ResultsOf 290 patients hospitalized with acute decompensated HF, 122 at high risk for readmission or mortality were randomized to receive usual care (UC) (n = 64) or UC plus intervention (DMP-Plus) (n = 58), comprising LUS-guided management before discharge and during at-home follow-up. Residual congestion was identified by ≥10 B-lines detected in 8 lung zones. The outcomes included a composite of readmission and/or mortality at 30 and 90 days, and 90-day HF readmission. Residual congestion was detected equally among the patient groups. The 30-day composite outcome occurred in 28% DMP-plus patients and 22% UC patients (odd ratio [OR], 1.36; 95% confidence interval [CI], 0.59–3.1; P = .5) and the 90-day HF readmission outcome occurred in 22% and 31%, respectively (odds ratio, 0.63; 95% CI, 0.28–1.43; P = .3). Residual congestion, identified at predischarge LUS examination in high-risk patients, was associated with early (<14-day) HF readmission (relative risk, 1.19; 95% CI, 1.06–1.32; P = .002) and multiple (≥2) readmissions over 90 days of follow-up (relative risk, 1.09; 95% CI, 1.01–1.16; P = .012), independent of demographics and comorbidities. ConclusionsReadmission in patients with incomplete decongestion before discharge occurs within the first 2 weeks. However, our DMP-plus strategy did not improve the primary outcome.

SGLT2 inhibitors and risk reduction for mortality in high-risk patients: a meta-analysis of randomized controlled trials

Background: The aim of this paper is to assess the impact of sodium-glucose cotransporters-2 (SGLT2) inhibitors on all-cause and cardiovascular (CV) death in high-risk patients and compare the efficacy of empagliflozin and dapagliflozin. Methods: PubMed was queried from inception to the last week of September 2023 for randomized controlled trials that compared SGLT2 inhibitors’ empagliflozin or dapagliflozin with placebo and included patients with heart failure (HF), type 2 diabetes mellitus (T2DM), or chronic kidney disease (CKD). The outcome of interest was CV death or all-cause death. Hazard ratios (HR) with 95% confidence intervals (CI) were pooled using a random effect model, and forest plots were created to analyze the results visually. A chi-square test was performed to assess subgroup differences between empagliflozin and dapagliflozin. Results: Eight trials (N=55,818) were included in our analysis, namely EMPA-REG, EMPEROR-Reduced, EMPEROR-Preserved, EMPA-KIDNEY, DECLARE-TIMI, DAPA-HF, DELIVER and DAPA-CKD. Pooled analysis demonstrated that compared to placebo, SGLT2 inhibition reduced the risk of CV death (SGLT2i arm = 1405 events, 29,089 total patients; placebo arm = 1515 events, 26,729 total patients; HR: 0.85; 95%CI: 0.79-0.93, p&lt;0.001) and all-cause death (SGLT2i arm = 2,491 events, 29,062 total patients; placebo arm= 2,625 events, 26,729 total patients; HR: 0.86; 95% CI 0.79-0.95, p=0.002) in high-risk patients identified as having either T2DM, HF, or CKD. No differences were observed in the effect of empagliflozin and dapagliflozin on CV death (HRempagliflozin: 0.81; 95% CI 0.68-0.97, HRdapagliflozin: 0.88; 0.82-0.95, p=0.39) and all-cause death (HRempagliflozin: 0.86; 95% CI 0.73-1.02, HRdapagliflozin: 0.87; 0.78-0.97, p=0.94). Conclusions: SGLT2 inhibitors reduce the risk of all-cause and CV death in high-risk patients. Notably, there were no discernible differences in the benefits of empagliflozin and dapagliflozin on these outcomes.

SGLT2 inhibitors and risk reduction for mortality in high-risk patients: a meta-analysis of randomized controlled trials

Background: The aim of this paper is to assess the impact of sodium-glucose cotransporters-2 (SGLT2) inhibitors on all-cause and cardiovascular (CV) death in high-risk patients and compare the efficacy of empagliflozin and dapagliflozin. Methods: PubMed was queried from inception to the last week of September 2023 for randomized controlled trials that compared SGLT2 inhibitors’ empagliflozin or dapagliflozin with placebo and included patients with heart failure (HF), type 2 diabetes mellitus (T2DM), or chronic kidney disease (CKD). The outcome of interest was CV death or all-cause death. Hazard ratios (HR) with 95% confidence intervals (CI) were pooled using a random effect model, and forest plots were created to analyze the results visually. A chi-square test was performed to assess subgroup differences between empagliflozin and dapagliflozin. Results: Eight trials (N=55,818) were included in our analysis, namely EMPA-REG, EMPEROR-Reduced, EMPEROR-Preserved, EMPA-KIDNEY, DECLARE-TIMI, DAPA-HF, DELIVER and DAPA-CKD. Pooled analysis demonstrated that compared to placebo, SGLT2 inhibition reduced the risk of CV death (SGLT2i arm = 1405 events, 29,089 total patients; placebo arm = 1515 events, 26,729 total patients; HR: 0.85; 95%CI: 0.79-0.93, p&lt;0.001) and all-cause death (SGLT2i arm = 2,491 events, 29,062 total patients; placebo arm= 2,625 events, 26,729 total patients; HR: 0.86; 95% CI 0.79-0.95, p=0.002) in high-risk patients identified as having either T2DM, HF, or CKD. No differences were observed in the effect of empagliflozin and dapagliflozin on CV death (HRempagliflozin: 0.81; 95% CI 0.68-0.97, HRdapagliflozin: 0.88; 0.82-0.95, p=0.39) and all-cause death (HRempagliflozin: 0.86; 95% CI 0.73-1.02, HRdapagliflozin: 0.87; 0.78-0.97, p=0.94). Conclusions: SGLT2 inhibitors reduce the risk of all-cause and CV death in high-risk patients. Notably, there were no discernible differences in the benefits of empagliflozin and dapagliflozin on these outcomes.

SGLT2 inhibitors and risk reduction for mortality in high-risk patients: a meta-analysis of randomized controlled trials

Background: The aim of this paper is to assess the impact of sodium-glucose cotransporters-2 (SGLT2) inhibitors on all-cause and cardiovascular (CV) death in high-risk patients and compare the efficacy of empagliflozin and dapagliflozin. Methods: PubMed was queried from inception to the last week of September 2023 for randomized controlled trials that compared SGLT2 inhibitors’ empagliflozin or dapagliflozin with placebo and included patients with heart failure (HF), type 2 diabetes mellitus (T2DM), or chronic kidney disease (CKD). The outcome of interest was CV death or all-cause death. Hazard ratios (HR) with 95% confidence intervals (CI) were pooled using a random effect model, and forest plots were created to analyze the results visually. A chi-square test was performed to assess subgroup differences between empagliflozin and dapagliflozin. Results: Eight trials (N=55,818) were included in our analysis, namely EMPA-REG, EMPEROR-Reduced, EMPEROR-Preserved, EMPA-KIDNEY, DECLARE-TIMI, DAPA-HF, DELIVER and DAPA-CKD. Pooled analysis demonstrated that compared to placebo, SGLT2 inhibition reduced the risk of CV death (SGLT2i arm = 1405 events, 29,089 total patients; placebo arm = 1515 events, 26,729 total patients; HR: 0.85; 95%CI: 0.79-0.93, p&lt;0.001) and all-cause death (SGLT2i arm = 2,491 events, 29,062 total patients; placebo arm= 2,625 events, 26,729 total patients; HR: 0.86; 95% CI 0.79-0.95, p=0.002) in high-risk patients identified as having either T2DM, HF, or CKD. No differences were observed in the effect of empagliflozin and dapagliflozin on CV death (HRempagliflozin: 0.81; 95% CI 0.68-0.97, HRdapagliflozin: 0.88; 0.82-0.95, p=0.39) and all-cause death (HRempagliflozin: 0.86; 95% CI 0.73-1.02, HRdapagliflozin: 0.87; 0.78-0.97, p=0.94). Conclusions: SGLT2 inhibitors reduce the risk of all-cause and CV death in high-risk patients. Notably, there were no discernible differences in the benefits of empagliflozin and dapagliflozin on these outcomes.

Subjective and objective survival prediction in mechanically ventilated critically ill patients: a prospective cohort study

BackgroundICU risk assessment tools, routinely used for predicting population outcomes, are not recommended for evaluating individual risk. The state of health of single patients is mostly subjectively assessed to inform relatives and presumably to decide on treatment decisions. However, little is known how subjective and objective survival estimates compare.MethodsWe performed a prospective cohort study in mechanically ventilated critically ill patients across five European centres, assessed 62 objective markers and asked the clinical staff to subjectively estimate the probability of surviving 28 days.ResultsWithin the 961 included patients, we identified 27 single objective predictors for 28-day survival (73.8%) and pooled them into predictive groups. While patient characteristics and treatment models performed poorly, the disease and biomarker models had a moderate discriminative performance for predicting 28-day survival, which improved for predicting 1-year survival. Subjective estimates of nurses (c-statistic [95% CI] 0.74 [0.70–0.78]), junior physicians (0.78 [0.74–0.81]) and attending physicians (0.75 [0.72–0.79]) discriminated survivors from non-survivors at least as good as the combination of all objective predictors (c-statistic: 0.67–0.72). Unexpectedly, subjective estimates were insufficiently calibrated, overestimating death in high-risk patients by about 20% in absolute terms. Combining subjective and objective measures refined discrimination and reduced the overestimation of death.ConclusionsSubjective survival estimates are simple, cheap and similarly discriminative as objective models; however, they overestimate death risking that live-saving therapies are withheld. Therefore, subjective survival estimates of individual patients should be compared with objective tools and interpreted with caution if not agreeing.Trial registration ISRCTN ISRCTN59376582, retrospectively registered October 31st 2013.

Ventricular tachyarrhythmia treatment and prevention by subthreshold stimulation with stretchable epicardial multichannel electrode array

The implantable cardioverter-defibrillator (ICD) is an effective method to prevent sudden cardiac death in high-risk patients. However, the transvenous lead is incompatible with large-area electrophysiological mapping and cannot accommodate selective multichannel precision stimulations. Moreover, it involves high-energy shocks, resulting in pain, myocardial damage, and recurrences of ventricular tachyarrhythmia (VTA). We present a method for VTA treatment based on subthreshold electrical stimulations using a stretchable epicardial multichannel electrode array, which does not disturb the normal contraction or electrical propagation of the ventricle. In rabbit models with myocardial infarction, the infarction was detected by mapping intracardiac electrograms with the stretchable epicardial multichannel electrode array. Then, VTAs could be terminated by sequential electrical stimuli from the epicardial multichannel electrode array beginning with low-energy subthreshold stimulations. Last, we used these subthreshold stimulations to prevent the occurrence of additional VTAs. The proposed protocol using the stretchable epicardial multichannel electrode array provides opportunities toward the development of innovative methods for painless ICD therapy.

Catheter Ablation for Ventricular Arrhythmias in Hypertrophic Cardiomyopathy.

Implantable cardioverter-defibrillators are the mainstay of therapy for prevention of sudden cardiac death in high-risk patients with hypertrophic cardiomyopathy (HCM). Catheter ablation is a useful option for patients with recurrent, drug refractory monomorphic ventricular tachycardia (VT), and device therapy. Compared with other nonischemic substrates, there are limited data on the role and outcomes of catheter ablation in HCM. The challenges of VT ablation in HCM patients include deep intramural and epicardial substrates, suboptimal power delivery, and higher recurrence due to progression of disease. Patient selection, using cardiac MRI scar localization, and optimizing ablation techniques can improve outcomes in these patients.

185 Identification of At-Risk Patients in a Statewide EMS “Naloxone Leave Behind” Program

Naloxone Leave Behind (NLB) programs are an effective intervention Emergency Medical Services (EMS) can utilize to expand access to naloxone and reduce opioid overdose deaths in high-risk patients with opioid use disorder (OUD). Identification of “At-Risk” persons, patients who experience an opioid-related overdose or have indicators of OUD, is critical for successful program implementation. While many EMS systems have implemented NLB programs, few have reported on program success or areas for improvement.

Targeted potassium levels to decrease arrhythmia burden in high risk patients with cardiovascular diseases (POTCAST): Study protocol for a randomized controlled trial

Low plasma potassium (p-K) is associated with increased risk of malignant arrhythmia and observational studies indicate protective effects of p-K in the upper reference level. However, randomized clinical studies are needed to document whether actively increasing p-K to high-normal levels is possible and safe and improves cardiovascular outcomes. To investigate if increased p-K reduces the risk of malignant arrhythmia and all-cause death in high-risk patients with a cardiovascular disease treated with an implantable cardioverter defibrillator (ICD) for primary or secondary preventive causes. Secondly, to investigate whether high-normal p-K levels can be safely reached and maintained using already available medications and potassium-rich dietary guidance. This is a prospective, randomized, and open-labelled study enrolling patient at high-risk of malignant arrhythmias. According to sample size calculations, 1,000 patients will be randomized 1:1 to either an investigational regiment that aims to increase and maintain p-K at high-normal levels (4.5-5.0 mmol/L) or to usual standard of care and followed for an expected four years. The trial will run until a total of 291 events have occurred providing an α=0.05 and 1-β=0.80. The composite primary endpoint includes ventricular tachycardia >125 bpm lasting >30 seconds, any appropriate ICD-therapy, and all-cause mortality. At present, 739 patients have been randomized. We present the rationale for the design of the POTCAST trial. The inclusion was initiated 2019 and is expected to be finished 2022. The study will show if easily available treatments to increase p-K may be a new treatment modality to protect against malignant arrythmias.

Here’s what we know about FDA-authorized COVID-19 antivirals

Here’s what we know about FDA-authorized COVID-19 antivirals

Long-Term clinical outcomes of subcutaneous implantable defibrillator therapy in patients with heart failure and reduced ejection fraction: a single center experience

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): P. JACON consultant: Boston Scientific France Introduction The implantable cardioverter defibrillator (ICD) is the most effective therapy for prevention of sudden cardiac death in high-risk patients with heart failure and reduced ejection fraction (HFrEF). The subcutaneous implantable cardioverter defibrillator (S-ICD) has been considered as a comparable and relatively safer alternative to transvenous ICD in patients (pts) without pacing indication. Purpose Our aim was to assess the clinical "real-life" outcomes of S-ICD in patients with HFrEF and primary or secondary prevention, over a long-term follow-up (FU) period after S-ICD implantation. Methods All pts with HFrEF (left ventricular ejection fraction ≤35%) implanted with a S-ICD and a FU above 6 months were included in a cross-sectional monocentric study. Pts were followed by remote monitoring. Results 88 pts were included (52 ± 12.8 years old, male 87.5%). Indications were: primary 92% and secondary 8% prevention (ischemic cardiopathy 46%; dilated 46%; hypertrophic 5%; congenital 2%; valvular 1%). The mean left ventricular ejection fraction was 27%. 9 pts had a previous transvenous ICD implanted, but required revision because of infection or lead defects. The mean FU period was 33 ± 18 months with a mortality rate of 10% (S-ICD-related death secondary to inappropriate (inap) shocks for one patient). 5 pts underwent S-ICD system extraction after a mean FU period of 30 ± 21 months. Reasons were infectious complication (1 pt), pacing indication (2 pts) and S-ICD lead dysfunction (2 pts). Extraction after heart transplant was performed in 4 pts. During FU, 18 pts (20.5%) experienced at least one therapy: 8 pts (9%) with appropriate (ap) (3.3% per year) and 11 pts (12%) with inap shocks (4.36% per year). A total number of 24 ap shocks have been observed (3 ± 4 ap shocks per patient, several shocks for 3 pts), the first shock occurred after a mean FU period of 24 ± 14 months. 2 pts were referred to VT ablation and no recurrence of events was observed after medical therapy modification for the other pts. For the 11 pts with inap shocks, time to the first event was 19 ± 20 months. Reasons were: supraventricular arrhythmias (18%), T wave (36%) and noise (54%) oversensing. There was 1.8 ± 1.6 shock per patient with several shocks for 4 pts. Among pts with inap shocks, 2 pts required S-ICD system extraction, 1 pt died, while reprogramming and medical therapy options were efficient in other pts. Conclusion In pts with HFrEF at high risk of sudden cardiac death, S-ICD has proven to be effective in treating ventricular arrhythmias. However, more investigations must be conducted to explain the real-life high rate of inappropriate therapies. Abstract Figure. Survival-free from therapies curve

Study of the effect of Occlutech Atrial Flow Regulator on symptoms, hemodynamics, and echocardiographic parameters in advanced pulmonary arterial hypertension.

Optimal sized balloon atrial septostomy improves hemodynamics in advanced pulmonary arterial hypertension. Occlutech Atrial Flow Regulator is designed to provide an atrial septal fenestration diameter titrated according to the age and right atrial pressures. This observational study analyzed symptoms, exercise distance, oxygen saturations, hemodynamics and echocardiographic parameters after Atrial Flow Regulator implantation in patients with syncope or right-heart failure. Patients with high-risk predictors of mortality during septostomy were scrutinized. Thirty-nine patients (9 children) with syncope (34/39) or right-heart failure (27/39) underwent Atrial Flow Regulator implantation without procedural complications. Six-minute walk distance increased from 310 ± 158.2 to 376.4 ± 182.6 m, none developed syncope. Oxygen saturations reduced from 96.4 ± 6.4% to 92 ± 4.9% at rest and further to 80.3 ± 5.9% on exercise. Right atrial pressures reduced from 9.4 ± 5 (2–27) mmHg to 6.9 ± 2.6 (1–12) mmHg, while cardiac index increased from 2.4 ± 0.8 (0.98–4.3) to 3 ± 1 (1.1–5.3) L/min/m2 and systemic oxygen transport increased from 546.1 ± 157.9 (256.2–910.5) to 637.2 ± 191.1 (301.3–1020.2) ml/min. Echocardiographic improvement included significant reduction of pericardial effusion and inferior caval congestion at a median follow-up of 37 months. Overall survival improved except two early and one late deaths in high-risk patients. Five of seven patients with advanced disease and key hemodynamic predictors of mortality survived. Acute hemodynamic benefits in pulmonary arterial hypertension after Atrial Flow Regulator were improved cardiac output, systemic oxygen transport, and reduced right atrial pressures. Improvement of symptoms especially syncope, exercise duration, and right ventricular systolic function as well as device patency were sustained on mid-term follow-up. Implantation was safe in all including young children without procedural complications. Mortality was noted only in patients who had high-risk predictors and patients at advanced stage of the disease.

Abstract 15961: Multicenter Prospective Prevention of Sudden Death in High Risk Patients Utilizing Enhanced ACC/AHA Risk Model

Introduction: Strategies for reliable selection of high-risk hypertrophic cardiomyopathy (HCM) patients for prevention of sudden cardiac death (SCD) with implantable cardioverter-defibrillators (ICDs) continue to be debated. Objective: Assess the sensitivity of sudden death risk strategies in predicting SCD events (appropriate ICD shocks, sudden death or out of hospital cardiac arrest) among a large multicenter cohort of high-risk HCM patients. Methods: Observational longitudinal study from 6-HCM centers in North America and Europe to determine outcomes in consecutive HCM patients considered high risk for sudden death based on an enhanced ACC/AHA (U.S./Canada) guidelines-based risk factor algorithm with primary prevention ICD placement. ESC risk score was retrospectively calculated in this cohort and compared to ACC/AHA risk factor method for predicting SCD events. Results: Of 1185 patients with primary prevention ICDs implanted based on ≥ 1 major risk marker, 162 (14%) experienced device therapy terminating VT/VF episodes at 49 ± 18 years of age and 4.6 ± 4.2 years after device implant. Within the 6 HCM centers, only 28 other patients not implanted with ICD died suddenly or had resuscitated cardiac arrests, including 19 (68%) with risk-markers who declined ICDs. Of these 190 high risk patients with SCD or SCD events, 67 (35%) had ESC risk-scores scores ≥6%/5-years, considered sufficient to recommend a prophylactic ICD, while 83 (44%) had low risk scores (&lt;4%/5-years) that likely would have excluded an ICD recommendation. Compared to enhanced ACC/AHA risk factors, the ESC risk-score was less sensitive than ACC/AHA (35% vs. 95%, p&lt;0.01), consistent with identifying fewer high-risk patients with events. Conclusion: In this large multicenter study of high-risk HCM patients, an enhanced ACC/AHA risk factor strategy was superior to the ESC risk score in identifying patients at greatest risk for SCD events.

Comparison of transvenous vs subcutaneous defibrillator therapy in patients with cardiac arrhythmia syndromes and genetic cardiomyopathies

BackgroundInherited arrhythmia syndromes and genetic cardiomyopathies attribute in a significant proportion to sudden cardiac death. Implantable cardioverter defibrillators (ICDs) are the cornerstone in the prevention of sudden death in high-risk patients. However, ICD therapy is also associated with high rates of inappropriate shocks and/or device-related complications especially in young patients. ObjectiveTo determine the outcome of high-risk patients with inherited arrhythmia syndromes and genetic cardiomyopathies comparing two defibrillator technologies. MethodBetween 2010 and 2018, 183 consecutive patients from two large German tertiary care centers were enrolled in the study. The majority of patients (83%) had either cardiac channelopathies or idiopathic ventricular fibrillation without cardiac structural abnormalities, while the remaining 17% had a genetic cardiomyopathy (HCM/ARVC). Eighty-six patients (47%) received a transvenous ICD (TV-ICD), while a subcutaneous ICD (S-ICD) was implanted in another 97 patients (53%). ResultsDuring a mean follow-up of 4.3 years, 30 patients had an appropriate ICD therapy (annual rate 3.8%). Fifteen patients experienced an inappropriate shock (annual rate 1.9%). Lead failure occurred in 17 (9%) patients and was less frequent in the S-ICD group (OR 0.48, 95%CI 0.38–0.62). Adverse defibrillator events, defined as a composite of inappropriate shocks and lead failure requiring surgical revision were significantly lower in the S-ICD group as compared to the TV-ICD group (OR 0.55, 95%CI 0.41–0.72). There was a non-significant trend towards lower appropriate shocks in the S-ICD group, that in combination with all-cause shocks yielded in a significantly higher freedom of any shock in the S-ICD group (RR 39%, p = 0.003). No deaths occurred during follow-up. ConclusionThe present data favor the use of the subcutaneous ICD for patients with inherited arrhythmia syndromes and genetic cardiomyopathies who do not need anti-bradycardia pacing.

Microvolt T-wave alternans at the end of surgery is associated with postoperative mortality in cardiac surgery patients

Microvolt T-wave alternans (MTWA), which reflects electrical dispersion of repolarization, is known to be associated with arrhythmia or sudden cardiac death in high risk patients. In this study we investigated the relationship between MTWA and postoperative mortality in 330 cardiac surgery patients. Electrocardiogram, official national data and electric chart were analysed to provide in-hospital and mid-term outcome. MTWA at the end of surgery was significantly associated with in-hospital mortality in both univariate analysis (OR = 27.378, 95% CI 5.616–133.466, p < 0.001) and multivariate analysis (OR = 59.225, 95% CI 6.061–578.748, p < 0.001). Cox proportional hazards model revealed MTWA at the end of surgery was independently associated with mid-term mortality (HR = 4.337, 95% CI 1.594–11.795). The area under the curve of the model evaluating MTWA at the end of surgery was 0.764 (95% CI, 0.715–0.809) and it increased to 0.929 (95% CI, 0.896–0.954) when combined with the EuroSCORE II. MTWA positive at the end of surgery had a 60-fold increase in in-hospital mortality and a 4-fold increase in mid-term mortality. Moreover, MTWA at the end of surgery could predict in-hospital mortality and this predictability is more robust when combined with the EuroSCORE II.

Enhanced American College of Cardiology/American Heart Association Strategy for Prevention of Sudden Cardiac Death in High-Risk Patients With Hypertrophic Cardiomyopathy

Strategies for reliable selection of high-risk patients with hypertrophic cardiomyopathy (HCM) for prevention of sudden cardiac death (SCD) with implantable cardioverter/defibrillators (ICDs) are incompletely resolved. To assess the reliability of SCD prediction methods leading to prophylactic ICD recommendations to reduce the number of SCDs occurring in patients with HCM. In this observational longitudinal study, 2094 predominantly adult patients with HCM consecutively evaluated over 17 years in a large HCM clinical center were studied. All patients underwent prospective ICD decision making relying on individual major risk markers derived from the HCM literature and an enhanced American College of Cardiology/American Heart Association (ACC/AHA) guidelines-based risk factor algorithm with complete clinical outcome follow-up. Data were collected from June 2017 to February 2018, and data were analyzed from February to July 2018. Arrhythmic SCD or appropriate ICD intervention for ventricular tachycardia or ventricular fibrillation. Of the 2094 study patients, 1313 (62.7%) were male, and the mean (SD) age was 51 (17) years. Of 527 patients with primary prevention ICDs implanted based on 1 or more major risk markers, 82 (15.6%) experienced device therapy-terminated ventricular tachycardia or ventricular fibrillation episodes, which exceeded the 5 HCM-related SCDs occurring among 1567 patients without ICDs (0.3%), including 2 who declined device therapy, by 49-fold (95% CI, 20-119; P = .001). Cumulative 5-year probability of an appropriate ICD intervention was 10.5% (95% CI, 8.0-13.5). The enhanced ACC/AHA clinical risk factor strategy was highly sensitive for predicting SCD events (range, 87%-95%) but less specific for identifying patients without SCD events (78%). The C statistic calculated for enhanced ACC/AHA guidelines was 0.81 (95% CI, 0.77-0.85), demonstrating good discrimination between patients who did or did not experience an SCD event. Compared with enhanced ACC/AHA risk factors, the European Society of Cardiology risk score retrospectively applied to the study patients was much less sensitive than the ACC/AHA criteria (34% [95% CI, 22-44] vs 95% [95% CI, 89-99]), consistent with recognizing fewer high-risk patients. A systematic enhanced ACC/AHA guideline and practice-based risk factor strategy prospectively predicted SCD events in nearly all at-risk patients with HCM, resulting in prophylactically implanted ICDs that prevented many catastrophic arrhythmic events in this at-risk population.

Intravenous arsenic trioxide and all-trans retinoic acid as front-line therapy for low-risk acute promyelocytic leukemia

ABSTRACTIntroduction: The outcome of acute promyelocytic leukemia (APL) has drastically improved following the identification of the PML-RARA oncogene as a key player in the pathogenesis of APL, and the subsequent introduction of all-trans retinoic acid (ATRA) as a therapeutic agent.Areas covered: Randomized trials have recently demonstrated the efficacy of arsenic trioxide (ATO) in combination with ATRA for the front-line treatment of standard and medium risk APL patients. This chemotherapy-free combination is associated with a decreased cumulative rate of relapse, prolonged overall survival, and reduced early death rate.Expert commentary: The most challenging issue in the management of APL remains the significant rate of early deaths in high-risk patients. The ongoing studies will clarify the possible role of ATO in this setting in combination with ATRA and other agents. The aim of this review is to report data of efficacy and safety of intravenous ATO in newly diagnosed patients and discuss on its potential role as a new standard of care for APL patients.

Asian Subpopulations May Exhibit Greater Cardiovascular Benefit from Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A Meta-Analysis of Cardiovascular Outcome Trials.

BackgroundBased on reported results of three large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), we aimed to investigate the overall effect of GLP-1 RAs on major adverse cardiovascular events (MACEs) and to identify subpopulations exhibiting the greatest cardiovascular (CV) benefit.MethodsThree CVOTs reporting effects of long-acting GLP-1 RAs were included: LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide once weekly). In all studies, the primary endpoint was three-point MACE, comprising CV death, non-fatal myocardial infarction, and non-fatal stroke. Overall effect estimates were calculated as hazard ratios and 95% confidence intervals (CIs) using the random-effects model; subgroup analyses reported in the original studies were similarly analyzed.ResultsOverall, statistically significant risk reductions in MACE and CV death were observed. Subgroup analysis indicated a significant racial difference with respect to CV benefit (P for interaction <0.001), and more substantial risk reductions were observed in subjects of African origin (relative risk [RR], 0.78; 95% CI, 0.60 to 0.99) and in Asians (RR, 0.35; 95% CI, 0.09 to 1.32). However, post hoc analysis (Bonferroni method) revealed that only Asians exhibited a significantly greater CV benefit from treatment, compared with white subjects (P<0.0001).ConclusionLong-acting GLP-1 RAs reduced risks of MACE and CV deaths in high-risk patients with type 2 diabetes mellitus. Our findings of a particularly effective reduction in CV events with GLP-1 RA in Asian populations merits further exploration and dedicated trials in specific populations.