Significant Ventricular Arrhythmias Research Articles

Adverse myocardial and vascular side effects of immune checkpoint inhibitors: a prospective multimodal cardiovascular assessment.

Immune checkpoint inhibitors (ICIs) can induce cardiovascular toxicities. To prospectively assess the incidence of major cardiovascular events (MACE) on ICIs in solid cancer patients: myocarditis, pericarditis, acute coronary syndrome, heart failure, high-degree conduction abnormalities or sustained ventricular arrhythmias, or cardiovascular death at 6weeks (early MACE), including asymptomatic clinical changes by an independent adjudication committee using current recommended diagnostic criteria. The secondary objective was the incidence of the above-mentioned events adding atrial fibrillation (AF) at 6months (late MACE). Participants underwent pre-ICIs and repeated multimodality cardiac imaging (echocardiogram, cardiac magnetic resonance (CMR)), serum biomarkers (ultrasensitive troponin I), and rhythm surveillance (ambulatory ECG monitoring) at 6weeks and 6months. Forty-nine patients (38 (77.6%) male; mean age 64.3 (SD 11.0) years old) were included (June 2020-December 2021). Early MACE were observed in 9 (18.4%) patients at mean 40.1 (SD 5.9) days, with heart failure (HF) in 5 (10.2%), ventricular arrhythmias, or new conduction disorders in 4 (8.2%) patients. History of AF (HR 4.49 (CI 1.11-18.14), P = 0.035) predicted early MACE. At 6months follow-up, 18 MACE were observed in 15/49 (31%) patients, with 6 (12.2%) HF events, 5 (10.2%) significant ventricular arrhythmias, or conduction disorders, and 4 (8.2%) AF. There was a significant decline in LVEF (P < 0.001) in patients with no MACE (P = 0.003) or HF (P = 0.0028). Higher creatinine at inclusion (HR 0.99 [0.98-1.00], P = 0.006) predicted HF on multivariate analysis. There were no significant T1 or T2 mapping changes in our study cohort on repeated CMR. Cardiotoxicity on ICIs is more frequent than previously described when using a thorough detection strategy, consisting mainly in HF and asymptomatic rhythm disorders.

A novel pulsed field ablation system using linear and spiral ablation catheters can create large and durable endocardial and epicardial ventricular lesions in vivo.

We investigated the preclinical safety and efficacy of ventricular pulsed field ablation (PFA) using a family of novel, 6-/8-Fr, linear, and spiral PFA/mapping catheters (CRC EP, Inc). QRS-gated, bipolar PFA (>2.0 kV) was performed in 10 healthy swine. Altogether, 20 endocardial and epicardial right and left ventricular applications were delivered. The catheters were inserted through an 8.5-Fr steerable introducer. The intensity of skeletal muscle activation was quantified using an accelerometer. Lesions were assessed by pre- versus post-PFA electrogram analysis, pacing threshold, 3D voltage mapping, necropsy, and histology. The swine rete mirabile, liver and kidneys were examined for embolic events. All applications were single-shot (56 ± 18 s) without catheter repositioning. Minimal microbubbling was observed without significant skeletal muscle stimulation (mean acceleration 0.05 m/s2) or ventricular tachyarrhythmias. There was significant reduction in post- versus pre-PFA electrogram amplitude (0.5 ± 0.2 mV versus 3.2 ± 0.9 mV, P < 0.001) with a marked increase in pacing threshold (>20 mA versus 7.5 ± 2.9 mA, P < 0.001). All lesions were large and durable up to 28 days, measuring 32 ± 5 mm (length), 27 ± 8 mm (width), and 8 ± 3 mm (depth) using the spiral catheters and 43 ± 1 mm (length), 7 ± 1 mm (width), and 8 ± 1 mm (depth) using the linear catheters. Despite higher waveform voltages and prolonged applications, no thermal effects were detected at necropsy/histology. Moreover, gross and microscopic examinations revealed no evidence of thromboembolism, vascular or collateral injury. A novel, QRS-gated PFA system using linear and spiral PFA catheters is capable of creating large and durable ventricular lesions in vivo without significant microbubbling, ventricular arrhythmias or thromboembolism.

Cardiac response to water activities in children with Long QT syndrome type 1

Background Swimming is a genotype-specific trigger in long QT syndrome type 1 (LQT1). Objective To examine the autonomic response to water activities in children and adolescents with LQT1. Methods In this cross-sectional study, LQT1 patients were age and sex matched to one healthy control subject. Electrocardiograms (ECGs) were recorded during face immersion (FI), swimming, diving, and whole-body submersion (WBS). Heart rate (HR) and heart rate variability (HRV) was measured. The high frequency (HF) component of HRV was interpreted to reflect parasympathetic activity, while the low frequency (LF) component was interpreted as reflecting the combined influence of sympathetic and parasympathetic activity on autonomic nervous modulation of the heart. Results Fifteen LQT1 patients (aged 7–19 years, all on beta-blocker therapy) and fifteen age and sex matched non-medicated controls were included. No significant ventricular arrhythmias were observed in the LQT1 population during the water activities. Out of these 15 matched pairs, 12 pairs managed to complete FI and WBS for more than 10 seconds and were subsequently included in HR and HRV analyses. In response to FI, the LQT1 group experienced a drop in HR of 48 bpm, compared to 67 bpm in the control group (p = 0.006). In response to WBS, HR decreased by 48 bpm in the LQT1 group and 70 bpm in the control group (p = 0.007). A significantly lower PTOT (p &lt; 0.001) and HF (p = 0.011) component was observed before, during and after FI in LQT1 patients compared with the controls. Before, during and after WBS, a significantly lower total power (p &lt; 0.001), LF (p = 0.002) and HF (p = 0.006) component was observed in the LQT1 patients. Conclusion A significantly lower HR decrease in response to water activities was observed in LQT1 subjects on beta-blocker therapy, compared to matched non-medicated controls. The data suggests an impaired parasympathetic response in LQT1 children and adolescents. An aberrant autonomic nervous system (ANS) response may cause an autonomic imbalance in this patient group.

Abstract 17652: Association Between Ventricular Arrhythmias and Myocardial Fibrosis in Patients With Chagas Disease Without Known Cardiomyopathy

Introduction: Chagas disease (CD) is an important cause of cardiomyopathy, arrhythmias and sudden death. The presence of myocardial fibrosis detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) in these patients has been correlated with an increased prevalence of ventricular arrhythmias. The incidence of ventricular arrhythmias in patients with CD without established cardiomyopathy has not been well described. Hypothesis: We aim to evaluate if there is an association between LGE on CMR and incidence of ventricular arrhythmias in patients with CD but without cardiomyopathy. Methods: Patients treated at a Chagas disease center of excellence were retrospectively analyzed for ambulatory rhythm monitoring (Holter and/or 14-day patch monitor) and CMR data. Significant ventricular arrhythmias were defined as either a PVC burden &gt;/=1% or non-sustained ventricular tachycardia (NSVT) ≥4 beats. A Fisher exact test was used to compare categorical variables. Results: There were 191 patients treated between 12/2014 and 8/2022 available for analysis. Of these, 46 patients with CD and no prior history of cardiomyopathy received both ambulatory rhythm monitoring and CMR. There were 16 male and 30 female patients with average age of 52.2 ± 11.5 years, and LV ejection fraction of 58.8% ± 14.2%. Of the 46 patients, 15 (32.6%) were found to have LGE on cMRI while 31 (67.4%) had no evidence of LGE. Within the patients with LGE, 8/15 (53.3%) were found to have significant ventricular arrhythmias. Of the patients without LGE, only 7/31 (22.6%) were determined to have significant ventricular arrhythmias (p = 0.038). Conclusions: These data suggest that for patients with CD without cardiomyopathy, the presence of LGE on CMR is independently associated with incident ventricular arrhythmias detected on ambulatory rhythm monitoring. Whether these findings indicate increased risk of sudden cardiac death requires further study.

Abstract 17328: A Case of Reversible Severe Systolic Cardiomyopathy; Thinking Outside the Box

Introduction: Non-ischemic systolic cardiomyopathy is associated with significant morbidity and mortality. Prompt evaluation and timely removal of the potential insult may lead to reverse remodeling and recovery of the left ventricular (LV) systolic function. Case: A 39-year-old female with BMI 40 presented with dyspnea and bilateral lower extremity edema. Vital signs significant for mild tachycardia and hypertension. ECG showed sinus tachycardia. Physical exam revealed bibasilar crackles and 3+ pitting edema of the lower extremities. Laboratory significant for NTpro BNP 563 pg/dL and TSH &lt;0.005 IU/mL with a free T4 of 2.73 ng/dL. Chest x-ray showed pulmonary vascular congestion. Echocardiogram showed severely reduced LV systolic function with ejection fraction (EF) of 27%, global LV hypokinesis and diastolic LV diameter of 6.85 cm. No significant atrial or ventricular arrhythmias noted on Telemetry. A CT angiography of the coronary arteries showed no evidence of calcification or obstructive coronary disease. Additional labs revealed severely elevated TSH receptor antibody and thyroid stimulating immunoglobulin. Diffuse thyroid enlargement noted on ultrasound. Patient was diagnosed with Grave’s disease (GD) with Burch-Wartofsky score of 30 indicating an impending thyroid storm. She was treated with Metoprolol and Methimazole. She underwent intravenous diuresis and was started on guideline-directed medical therapy for systolic cardiomyopathy. In follow-up after 6 months, her TSH had normalized. On repeat imaging, her LVEF improved to &gt; 50% with diastolic LV diameter of 5.6 cm. Discussion: This patient was diagnosed with non-ischemic dilated systolic cardiomyopathy due to severe hyperthyroidism from GD. Thyrotoxicosis-induced systolic cardiomyopathy occurs in about 1% of patients with GD and is associated with increased morbidity and mortality. Excess thyroid hormones in thyrotoxicosis can affect multiple regulatory and structural genes of cardiac myocytes resulting in abnormal intracellular calcium regulation and impaired LV systolic and diastolic function. Our experience is consistent with literature demonstrating the importance of timely diagnosis and treatment of this reversible cause of systolic cardiomyopathy.

Incidence of cardiac events in on-pump elective surgical interventions on the aorta and heart valves

Aim. To determine the incidence and predictors of cardiovascular events in onpump cardiac operations in modern practice.Material and methods. The study included 200 patients who underwent various elective cardiac surgical interventions. Cardiovascular events (CVEs) were determined within 30 days from the operation, according to medical records and autopsy protocols. We identified major CVEs (cardiovascular death, stroke, myocardial infarction) and minor CVEs (angina pectoris, significant ventricular arrhythmias, atrial fibrillation or flutter episodes, AV conduction disorders, etc.). A comprehensive preoperative examination was performed, including an extended echocardiography protocol and coronary angiography.Results. In 101 patients (50,05%), various CVEs were identified: 4,0% had major CVEs and 46,05% had minor CVEs and various non-cardiac complications, while perioperative mortality was 2,0%. Most ischemic CVEs, as well as most intracardiac conduction disorders, were registered during the first 3 days after surgery. In contrast, episodes of atrial fibrillation/flutter occurred 2-7 days after the intervention. There were following preoperative examination parameters with the highest prognostic value: history of heart failure, age &gt;65 years, history of myocardial infarction, occlusion of at least one coronary artery, and diabetes.Conclusion. The data obtained indicate the high efficiency of current surgical and anesthetic technologies, which lead to relatively low risk of severe and fatal events. The parameters of the preoperative examination, which determine the increased risk of intervention, are highlighted.

Abatacept for immune checkpoint inhibitor associated myocarditis (ATRIUM): Phase 3, investigator-initiated, randomized, placebo-controlled study to evaluate the efficacy and safety of abatacept compared to placebo in hospitalized patients with immune checkpoint inhibitor associated myocarditis.

TPS2680 Background: Patients with myocarditis secondary to treatment with an immune checkpoint inhibitor (ICI) represent a poor prognosis population with a critical unmet clinical need. Data have shown that the rate of major adverse cardiac events (MACE) with ICI myocarditis despite administration of corticosteroids ranges from 25-50%. Abatacept is a selective co-stimulation modulator that inhibits T cell activation by binding to CD80 and CD86, thereby blocking its interaction with CD28. In preclinical animal models of ICI myocarditis, the administration of abatacept led to a reduction in cardiac immune activation and an increase in survival. Methods: The abatacept for immune checkpoint inhibitor associated myocarditis (ATRIUM) trial is designed as a phase 3, investigator-initiated, randomized, placebo-controlled study to evaluate the efficacy and safety of abatacept compared to placebo in hospitalized participants with ICI associated myocarditis. Hospitalized participants diagnosed with ICI-related myocarditis, as defined by the International Cardio-Oncology Society, ≥ 18, with serum evidence of ongoing myocardial injury (troponin ≥5 times the upper limit normal), and treated, or with intent to treat, with 1000 mg of solumedrol/day are eligible. In the randomized protocol, participants receive either abatacept (10 mg/kg) or placebo given IV followed by study drug infusion/placebo again at 24 hours and on day 14. Of note, there is an optional 4th dose on day 28. The primary aim is to test whether abatacept, as compared to placebo, is associated with a reduction in MACE among participants hospitalized with myocarditis secondary to an ICI. The primary outcome, MACE, is a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrhythmias, significant bradyarrhythmias, or incident heart failure. Each component of the primary composite end point will be evaluated individually as a secondary endpoint, as are troponin levels, rates of deep venous thrombosis and pulmonary embolism, and incidence rates of treatment-related adverse events. Exploratory outcomes focus on cancer outcomes, healthcare utilization, quality of life, and correlative studies. Recently, the trial has been amended to allow eligible participants who have achieved an ATRIUM primary end-point prior to randomization to be eligible for inclusion in the RESCUE arm of the protocol where they will be given open-label Abatacept on day 1, 2, 14, with optional dose at 28. The study is open at 20 sites across the US with a plan for a total of 50 locations across US and Canada. This study is recruiting at time of submission. Target enrollment is 390 patients. Clinical trial information: NCT05335928 .

PO-04-223 ASSOCIATION BETWEEN ANTIPARASITIC TREATMENT AND VENTRICULAR ARRYTHMIAS IN PATIENTS WITH CHAGAS DISEASE

Benznidazole and Nifurtimox are the two currently available antiparasitic treatments available for Chagas disease (CD), an important cause of cardiomyopathy and arrhythmias. There are limited data available describing impact of antiparasitic treatment on arrhythmia outcomes. Compare the incidence of ventricular arrhythmias in Chagas patients treated with anti-parasitic medication versus those who did not receive treatment. Patients treated at a Chagas disease center of excellence were retrospectively analyzed for ambulatory rhythm monitoring data (Holter and 14-day patch monitor). Patients with implantable cardiac devices were excluded. Significant ventricular arrhythmias were defined as either a PVC burden >/=1% or non-sustained ventricular tachycardia (NSVT) ≥4 beats. Patients were analyzed based on CD treatment: Benznidazole, Nifurtimox, or no treatment. Patients with incomplete treatment courses were excluded from analysis. A Fisher exact test was used to compare categorical variables. There were 191 patients with CD between 12/2014 and 8/2022 available for analysis, of whom 66 patients underwent ambulatory rhythm monitoring. Of these, 20 were male and 46 were female with an average age of 55.3 ± 12.6 years, and ejection fraction of 56.7 ± 10.5%. Of the 66 patients, 42 (63.6%) received treatment, 22 (33.3%) had no treatment, and 2 (3.0%) received incomplete treatment for CD. Among patients that received treatment for CD, 11/42 (26.2%) had significant ventricular arrhythmias on ambulatory rhythm monitoring. In comparison, among patients who did not receive CD treatment, 12/22 (54.5%) had significant ventricular arrhythmias (p = 0.031). No significant difference in the number of ventricular arrhythmias was observed between the Benznidazole (7/29, 24.1%) and Nifurtimox (4/12, 33.3%) treatment groups. These data demonstrate that treatment of CD is associated with a reduction in ventricular arrhythmias on ambulatory rhythm monitoring. Further studies are needed to determine if CD treatment can lead to reduced incidence of sudden death.

Cardiopulmonary examinations of athletes returning to high-intensity sport activity following SARS-CoV-2 infection

After SARS-CoV-2 infection, strict recommendations for return-to-sport were published. However, data are insufficient about the long-term effects on athletic performance. After suffering SARS-CoV-2 infection, and returning to maximal-intensity trainings, control examinations were performed with vita-maxima cardiopulmonary exercise testing (CPET). From various sports, 165 asymptomatic elite athletes (male: 122, age: 20y (IQR: 17-24y), training:16 h/w (IQR: 12–20 h/w), follow-up:93.5 days (IQR: 66.8–130.0 days) were examined. During CPET examinations, athletes achieved 94.7 ± 4.3% of maximal heart rate, 50.9 ± 6.0 mL/kg/min maximal oxygen uptake (V̇O2max), and 143.7 ± 30.4L/min maximal ventilation. Exercise induced arrhythmias (n = 7), significant horizontal/descending ST-depression (n = 3), ischemic heart disease (n = 1), hypertension (n = 7), slightly elevated pulmonary pressure (n = 2), and training-related hs-Troponin-T increase (n = 1) were revealed. Self-controlled CPET comparisons were performed in 62 athletes: due to intensive re-building training, exercise time, V̇O2max and ventilation increased compared to pre-COVID-19 results. However, exercise capacity decreased in 6 athletes. Further 18 athletes with ongoing minor long post-COVID symptoms, pathological ECG (ischemic ST-T changes, and arrhythmias) or laboratory findings (hsTroponin-T elevation) were controlled. Previous SARS-CoV-2-related myocarditis (n = 1), ischaemic heart disease (n = 1), anomalous coronary artery origin (n = 1), significant ventricular (n = 2) or atrial (n = 1) arrhythmias were diagnosed. Three months after SARS-CoV-2 infection, most of the athletes had satisfactory fitness levels. Some cases with SARS-CoV-2 related or not related pathologies requiring further examinations, treatment, or follow-up were revealed.

Arrhythmogenic cardiomyopathy is under-recognized in end-stage pediatric heart failure: A 36-year single-center experience.

Although ventricular failure is a late finding in adults with AC, we hypothesize that this is a presenting symptom in pediatric heart failure patients who undergo HT and that their ventricular arrhythmia burden could differentiate AC from other cardiomyopathies. We performed a single-center retrospective cohort study reviewing 457 consecutive pediatric (≤18 years) HT recipients at our institution. Explanted hearts were examined to establish the primary diagnosis, based on pathologic findings. Demographic and clinical variables were compared between AC versus non-HCM cardiomyopathy cases. Forty-five percent (n= 205/457) had non-HCM cardiomyopathies as the underlying primary diagnosis. Ten cases (10/205=4.9%) were diagnosed with AC. All 10 had biventricular disease. In 8/10 patients (80%), AC diagnosis was unrecognized pre-HT. Compared with non-AC cardiomyopathies, the AC group was older at diagnosis (9.3 years vs. 4.3 years, p= .012) and transplant (11.1 years vs. 6.5 years, p= .010), had more ventricular arrhythmias (80.0% vs 32.8%, p= .003), and required more anti-arrhythmic use (80.0% vs 32.3%, p= .001). Genetic testing yielded causative pathogenic variants in all tested individuals (n= 5/5, 100%). AC is often an unrecognized cardiomyopathy pretransplant in children who undergo HT. Pediatric non-HCM phenotypes with heart failure who have a significant ventricular arrhythmia burden should be investigated for AC.

The impact of midazolam used in cataract surgery sedation on frontal QRS-T angle.

Midazolam is one of the most commonly used drugs in procedures requiring sedoanalgesia. It affects the myocardium's ventricular depolarization and repolarization. Previous studies examining the arrhythmogenic effects of midazolam yielded conclusive results. These studies are based on QT and Tp -e distances. The frontal QRS-T angle (f-[QRS-T]a) is a new electro cardiac parameter that shows the heterogeneity of ventricular electrical activity. This study aims to examine the effect of midazolam on f-(QRS- T)a and other depolarization-repolarization parameters in patients who have had cataract surgery. The study included 177 patients administered midazolam as a sedoanalgesia during cataract surgery. The sedative effect was evaluated 2-3minutes after a 0.05 mg/kg dose of midazolam was given. Sedation was assessed again by giving 0.5mg every 2-3minutes until the desired level of sedation was achieved. 12-lead electrocardiogram (ECG) recordings of all patients were taken just before and immediately after surgery. ECGs were used to calculate the QT interval, QTc interval, Tp -e interval, Tp -e/QT, Tp -e/ QTc ratios and f-(QRS-T)a. After cataract surgery, f-(QRS-T)a was unchanged compared to presurgery (29.14 ± 4.52 vs. 29.18 ± 5.39, p= 0.852). In addition, no significant change in QT(351.32 ± 21.98 vs. 351.94 ± 22.44, p= 0.091), QTc (384.05 ± 24.52 vs. 385.19 ± 26.12, p= 0.819), Tp -e interval (93.12 ± 9.60 vs. 94.44 ± 8.82, p= 0.179) and Tp -e/QT (0.27 ± 0.02 vs. 0.28 ± 0.03, p= 0.664), Tp -e/ QTc ratios (0.28 ± 0.02 vs. 0.29 ± 0.03, p= 0.655) was observed after surgery when compared to presurgery values. Significant ventricular and supraventricular arrhythmias were not observed in any patient during the operation. Midazolam did not affect f -(QRS-T) with classical repolarization parameters in patients who underwent cataract surgery, according to this study. Midazolam has been found to be safe for the heart in sedoanalgesia. These results show that sedation with midazolam can be performed without electrocardiogram monitoring.

Development and Validation of Predictive Model-HASBLAD Score-For Major Adverse Cardiovascular Events During Perioperative Period of Non-cardiac Surgery: A Single Center Experience in China.

BackgroundMajor adverse cardiovascular events (MACEs) represent a significant reason of morbidity and mortality in non-cardiac surgery during perioperative period. The prevention of perioperative MACEs has always been one of the hotspots in the research field. Current existing models have not been validated in Chinese population, and have become increasingly unable to adapt to current clinical needs.ObjectivesTo establish and validate several simple bedside tools for predicting MACEs during perioperative period of non-cardiac surgery in Chinese hospitalized patients.DesignWe used a nested case-control study to establish our prediction models. A nomogram along with a risk score were developed using logistic regression analysis. An internal cohort was used to evaluate the performance of discrimination and calibration of these predictive models including the revised cardiac risk index (RCRI) score recommended by current guidelines.SettingPeking University Third Hospital between January 2010 and December 2020.PatientsTwo hundred and fifty three patients with MACEs and 1,012 patients without were included in the training set from January 2010 to December 2019 while 38,897 patients were included in the validation set from January 2020 and December 2020, of whom 112 patients had MACEs.Main Outcome MeasuresThe MACEs included the composite outcomes of cardiac death, non-fatal myocardial infarction, non-fatal congestive cardiac failure or hemodynamically significant ventricular arrhythmia, and Takotsubo cardiomyopathy.ResultsSeven predictors, including Hemoglobin, CARDIAC diseases, Aspartate aminotransferase (AST), high Blood pressure, Leukocyte count, general Anesthesia, and Diabetes mellitus (HASBLAD), were selected in the final model. The nomogram and HASBLAD score all achieved satisfactory prediction performance in the training set (C statistic, 0.781 vs. 0.768) and the validation set (C statistic, 0.865 vs. 0.843). Good calibration was observed for the probability of MACEs in the training set and the validation set. The two predictive models both had excellent discrimination that performed better than RCRI in the validation set (C statistic, 0.660, P < 0.05 vs. nomogram and HASBLAD score).ConclusionThe nomogram and HASBLAD score could be useful bedside tools for predicting perioperative MACEs of non-cardiac surgery in Chinese hospitalized patients.

The benefits of the earlier use of sacubitril/valsartan in de novo heart failure with reduced ejection fraction patients.

AimsWe evaluated the clinical outcomes and trajectory of cardiac reverse remodelling according to the timing of sacubitril/valsartan (Sac/Val) use in patients with heart failure (HF) with reduced ejection fraction (HFrEF).Methods and resultsPatients with de novo HFrEF who used Sac/Val between June 2017 and October 2019 were retrospectively enrolled. Patients were grouped into the earlier use group (initiation of Sac/Val < 3 months after the first HFrEF diagnosis) and the later use group (initiation of Sac/Val ≥ 3 months after the first HFrEF diagnosis). Primary outcome was a composite of HF hospitalization and cardiac death. Secondary outcomes were HF hospitalization, cardiac death, all‐cause death, significant ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation), and echocardiographic evidence of cardiac reverse remodelling including left ventricular ejection fraction (LVEF) change during follow‐up. Among 115 enrolled patients, 67 were classified in the earlier use group, and 48 were classified in the later use group. Mean period of HFrEF diagnosis to Sac/Val use was 52.1 ± 14.3 days in the earlier use group, and 201.8 ± 127.3 days in the later use group. During the median follow‐up of 721 days, primary outcome occurred in 21 patients (18.3%). The earlier use group experienced significantly fewer primary outcome than the later use group (10.4% vs. 29.2%, P = 0.010). The Kaplan–Meier survival curve showed better event‐free survival in the earlier use group than in the later use group (log rank = 0.017). There were no significant differences in cardiac death, all‐cause death, and ventricular arrhythmia between two groups (1.5% vs. 2.1%, P = 0.811; 1.5% vs. 4.2%, P = 0.375; 3.0% vs. 0%, P = 0.227, respectively). Despite a significantly lower baseline LVEF in the earlier use group (21.3 ± 6.4% vs. 24.8 ± 7.9%, P = 0.012), an early prominent increase of LVEF was noted before 6 months (35.2 ± 11.9% vs. 27.8 ± 8.8%, P = 0.007). A delayed improvement of LVEF in the later use group resulted in similar LVEF at last follow‐up in both groups (40.7 ± 13.4% vs. 39.4 ± 10.9%, P = 0.686). Although the trajectory of left ventricular remodelling showed similar pattern in two groups, left atrial (LA) reverse remodelling was less prominent in the later use group during the follow‐up period (final LA volume index: 43.6 ± 14.3 mL/m2 vs. 55.2 ± 17.1 mL/m2, P = 0.011).ConclusionsEarlier use of Sac/Val was related with better clinical outcome and earlier left ventricular reverse remodelling. Remodelling of LA was less prominent in the later use group implying delayed response in diastolic function.

Assessment of Exercise Function in Children and Young Adults with Hypertrophic Cardiomyopathy and Correlation with Transthoracic Echocardiographic Parameters.

Exercise function is well characterized in adults with hypertrophic cardiomyopathy (HCM); however, there is a paucity of data in children and young adults with HCM. Here we sought tocharacterize exercise function in young people with HCM, understand limitations in exercise function by correlating exercise function parameters with echocardiogram parameters and identify prognostic value of exercise parameters. We performed aretrospective, single-center cohort study characterizing exercise function in patients < 26years old with HCM undergoing cardiopulmonary exercise testing (CPET). Patients with syndromic HCM or submaximal effort were excluded. We compared exercise function in this cohort to population normal values and measured changes in exercise function over time. We correlated exercise function parameters with echocardiographic parameters and investigated the relationship between exercise test parameters and a clinical composite outcome comprised of significant ventricular arrhythmia, death, or heart transplantation. We identified 229 CPETs performed by 117 patients (mean age at time of first CPET 15.6 ± 3.2years). Mean %-predicted peak VO2, O2 pulse, and peak heart rate were statistically significantly depressed compared to population normal values and exercise function gradually worsened over time. Abnormal exercise testing correlated closely with echocardiographic indices of diastolic dysfunction. There was a trend toward increased incidence of poor clinical outcome in patients with abnormal exercise function.While adverse clinical outcomes were rare, normal exercise function appears to be a marker of low risk for adverse clinical outcomes in this population.

568 Echocardiography and impedance cardiography as determinants of successful slow Levosimendan infusion in patients with acute advanced heart failure

Abstract Aims Despite new therapeutic options, patients with heart failure (HF) still progress to advanced stage. Among new therapeutic options, Levosimendan was recently approved in order to treat patients hospitalized for acute decompensated heart failure (ADHF) with severe systolic dysfunction. The pharmacological effects of Levosimendan consist of inotropy, vasodilatation, and cardioprotection through the increase of calcium sensitivity. These effects should be monitored with echocardiography and in particular with speckle tracking and tri-dimensional echocardiography which appear to be useful in LV systolic function detection and monitoring. In this study we aim to evaluate the effect of slow infusion of Levosimendan on the non-invasive measurement of cardiac output, the speckle tracking parameters and the tri-dimensional echocardiography measurements in advanced ADHF patients. Methods and results This is a prospective observational study evaluating Levosimendan efficacy through advanced echocardiography. We enrolled 11 patients with diagnosis of ADHF who respect the recent ESC criteria of ‘advanced heart failure’. Patients underwent to blood sample examination to measure electrolytes, creatinine, and NTproBNP. Patients underwent to advanced echocardiography examination (performed for each patient pre- and post-Levosimendan infusion) with tri-dimensional echocardiography and global longitudinal strain assessment. Furthermore patients underwent to non-invasive cardiac output and cardiac index collection through impedance cardiography pre- and post-Levosimendan infusion. All patients were followed for 30 days after discharge for all cause of mortality and HF re-hospitalization. A total of 11 patients affected by advanced ADHF were included in this study. Mean age was 73.8 ± 4.7 years. 72.7% (n 8) patients were men. 81.9% (n 9) of patients recognize ischaemic heart disease as HF etiology. At admission mean systolic arterial pressure was 100 ± 17 mmHg, mean NTproBNP was 24 445 ± 12 194 pg/ml and mean serum creatinine was 1.55 ± 0.84 mg/dl. At tri-dimensional echocardiography mean LV ejection fraction (LVEF) was 19.7 ± 5.7% and at bi-dimensional echocardiography mean tricuspid anular plane systolic excursion (TAPSE) and pulmonary arterial systolic pressure (PASP) were, respectively, 12.5 ± 2.7 mm and 48 ± 16 mmHg. Mean LV global longitudinal strain (GLS) was −3.0 ± 1.8. Mean furosemide in-hospital infusion was 306 ± 102 mg/die and mean urine output 1436 ± 496 ml. None developed significant ventricular or supraventricular arrhythmias. All patients were treated with betablockers during infusion. At 30 days of follow-up two patients died and 1 patient was re-hospitalized. Evaluating the differences among our variables pre- and post-Levosimendan infusion, we found that NTproBNP was significantly reduced post-Levosimendan infusion (P = 0.01). Among ICG non-invasive measurement, we found significant differences in stroke volume (SV) and cardiac output (CO) in terms of significant improvement (P = 0.001 for both). Analysing tri-dimensional echocardiography variables, we observed a significant improvement of LVEF (P = 0.003), SV (P = 0.03) and 3-D LV GLS (P = 0.002). Furthermore, we observed a significant reduction in end-systolic volume (ESV) post-Levosimendan infusion (P = 0.02). Among bi-dimensional echocardiography measurements, there was a significant reduction in end-diastolic diameter of right ventricle (EDDRV) and in B-lines count (respectively, P = 0.02 and P = 0.002). Moreover, we observed a significant improvement in TAPSE (P = 0.003) and in LV GLS (P = 0.004). Conclusions Our study showed that slow Levosimendan infusion (12.5 mg at velocity of 0.05–1 mcg/kg/min) without bolus could be considered in advanced ADHF patients to improve cardiac performance without severe adverse events. ICG and echocardiography in-hospital evaluation seemed to be necessary to understand treatment success and patients status improvement as well as cardiac function benefit.

Catheter ablation of atrial fibrillation results in significant QTc prolongation in the postoperative period.

BackgroundThe corrected QT interval (QTc) is a measure of ventricular repolarization time, and a prolonged QTc increases risk for malignant ventricular arrhythmias. Pulmonary vein isolation (PVI) may increase QTc but its effects have not been well studied.ObjectiveDetermine the incidence, risk factors, and outcomes of patients presenting for PVI in sinus and atrial fibrillation with postoperative QTc prolongation in a large cohort.MethodsWe performed a single-center retrospective study of consecutive atrial fibrillation ablations. QTc durations using Bazett correction were obtained from electrocardiograms at different postoperative intervals and compared to preoperative QTc. We studied clinical outcomes including clinically significant ventricular arrhythmia and death. A multivariable model was used to identify factors associated with clinically significant QTc prolongation, defined as ΔQTc ≥60 ms or new QTc duration ≥500 ms.ResultsA total of 352 PVIs were included in this study. We observed a statistically significant increase in mean QTc compared to baseline (446.3 ± 37.8 ms) on postoperative day (POD)0 (471.7 ± 38.2 ms, P < .001) and at POD1 (456.5 ± 35.0 ms, P < .001). There was no significant difference at 1 month (452.4 ± 33.5 ms, P = .39) and 3 months (447.3 ± 40.0 ms, P = .78). Sixty-six patients (19.2%) developed ΔQTc ≥60 ms or QTc ≥500 ms on POD0, with 4.1% persisting past 90 days. Female sex (odds ratio [OR] = 1.82, 95% confidence interval [CI] =1.01–3.29, P = .047) and history of coronary artery disease (OR = 2.16, 95% CI = 1.03–4.55, P = .042) were independently predictive of QTc prolongation ≥500 ms or ΔQTc ≥60 ms. There were no episodes of clinically significant ventricular arrhythmia or death attributable to arrhythmia.ConclusionQTc duration increased significantly immediately post-PVI and returned to baseline by 1 month. PVI did not provoke significant ventricular arrhythmias in our cohort.

Sex Differences in Patients With Suspected Cardiac Sarcoidosis Assessed by Cardiovascular Magnetic Resonance Imaging.

Background: There are few data on sex differences in suspected cardiac sarcoidosis. Methods: Consecutive patients with histologically proven sarcoidosis and suspected cardiac involvement were studied. We investigated sex differences in presenting features, cardiac involvement, and the long-term incidence of a primary composite end point of all-cause death or significant ventricular arrhythmia and secondary end points of all-cause death and significant ventricular arrhythmia. Results: Among 324 patients, 163 (50.3%) were female and 161 (49.7%) were male patients. Female patients had a greater prevalence of chest pain (37.4% versus 23.6%; P=0.010) and palpitations (39.3% versus 26.1%; P=0.016) than male patients but not dyspnea, presyncope, syncope, or arrhythmias at presentation. Female patients had a lower prevalence of late gadolinium enhancement on cardiovascular magnetic resonance imaging (20.2% versus 35.4%; P=0.003) and less often met criteria for a clinical diagnosis of cardiac sarcoidosis (Heart Rhythm Society consensus criteria, 22.7% versus 36.0%; P=0.012 and 2016 Japanese Circulation Society guideline criteria, 8.0% versus 19.3%; P=0.005), indicating lesser cardiac involvement. However, the long-term incidence of all-cause death or significant ventricular arrhythmia was not different between female and male patients (23.2% versus 23.2%; P=0.46). Among the secondary end points, the incidence of all-cause death was not different between female and male patients (20.7% versus 14.3%; P=0.51), while female patients had a lower incidence of significant ventricular arrhythmia compared with male patients (4.3% versus 13.0%; P=0.022). On multivariable analyses, sex was not associated with the primary end point (hazard ratio for female patients, 1.36 [95% CI, 0.77–2.43]; P=0.29). Conclusions: We observed distinct sex differences in patients with suspected cardiac sarcoidosis. A paradox was identified wherein female patients had a greater prevalence of chest pain and palpitations than male patients, but lesser cardiac involvement, and a similar long-term incidence of all-cause death or significant ventricular arrhythmia.

ARRHYTHMIC PHENOTYPE OF NON-COMPACTION CARDIOMYOPATHY

Purpose . To evaluate the genotype-phenotype association in Belarusian patients with non-compaction cardiomyopathy (NCCM) and clinically significant ventricular arrhythmias. Materials and methods . The study included 170 unrelated patients with NCCM prospectively observed in the RSPC “Cardiology” for 36 months. [6; 42,0], who underwent 24-hour Holter ECG monitoring for 12 months after entering the study. The median age of patients was 42 [18; 69] years, men – 63,2%. The arrhythmic phenotype of NCСM was diagnosed by the presence of unexplained syncope; nonsustained ventricular tachycardia, the presence of ≥ 500 ventricular premature beats (VPB) per day. The diagnosis of NCCM was established on the basis of the following criteria: 1) Echocardiography of the Jenny criteria; 2) CMR of the S. Petersen and A. Jaquier criteria. The mutations search in the coding sequences of 174 genes was performed in 30 unrelated patients with NCCM using next generation sequencing (NGS). Results . In 76 out of 170 (44,7%) patients, clinically significant arrhythmias were the leading manifestation of the disease. Nonsustained VT was recorded in 54 (71,1%) patients, sustained VT – in 11 (14,5%) patients, VPB more than 500 per day – in 50 (65,8%). During the follow-up period (median follow-up of 36 months), devices (ICD/CRT-D) were implanted in 16 (21,1%). NGS sequencing revealed 40 changes in the nucleotide sequence (5 pathogenic mutations, 30 variants with uncertain significance (VUS), 5 new substitutions) in 27 genes in 26 (86,7%) probands with the arrhythmic phenotype NCCM. The proportion of mutations in sarcomeric proteins genes of was 26,9%, and in ion channel proteins genes was 23,1%. Nucleotide changes in genes encoding structural proteins accounted for 11,5%. In 38,5% of cases, not one, but two or more rare mutations were detected, and in 30,8%, amino acid changes affected proteins of different functional classes. Conclusions . In the group of patients with the arrhythmic NCCM phenotype, the proportion of individuals with genes mutations associated with various cardiomyopathies was 86,7% and was significantly higher than reported in patients with NCCM generally (59%). The frequency of multiple mutations was also higher (38,5%) in this cohort. The genetic characteristics of patients, along with their clinical characteristics, are markers of a high risk of developing life-threatening arrhythmias and can be additionally used for predicting adverse events in patients with NCCM, as well as for early diagnosis of the disease in their relatives.

Genotype-phenotype association in patients with arrhythmic variant of non-compaction cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Purpose. To evaluate the genotype-phenotype association in Belarusian patients with non-compaction cardiomyopathy (NCCM) and clinically significant ventricular arrhythmias. Methods. The study included 170 unrelated pts with NCCM prospectively observed in the RSPC "Cardiology", who underwent 24-hour Holter ECG monitoring for 12 months after entering the study. The median follow-up was 36 months [6; 152,0]. The median age of pts was 42 [18; 69] years, men – 63,2%. The arrhythmic phenotype of NCСM was diagnosed by the presence of unexplained syncope; nonsustained ventricular tachycardia, defined as ≥3 consecutive ventricular contractions lasting &amp;lt;30 seconds with a frequency of ≥120 bpm; the presence of ≥ 500 ventricular premature beats (VPB) per day. The diagnosis of NCCM was established on the basis of the following criteria: 1) Echocardiography of the R. Jenni criteria; 2) CMR of the S. Petersen and A. Jaquier criteria. The mutations search in the coding sequences of 174 genes was performed in 30 unrelated pts with NCCM using next generation sequencing (NGS). Results. In 76 out of 170 (44,7%) pts, clinically significant arrhythmias were the leading manifestation of the disease. Nonsustained VT was recorded in 54 (71,1%) pts, sustained VT – in 15 (19,7%) pts, VPB more than 500 per day – in 50 (65,8%), chronic AF with episodes of nonsustained VT was noted in 34 (44,7%) pts. During the follow-up period (median follow-up of 36 months), devices (ICD/CRT-D) were implanted in 15 (19,7%) pts, appropriate shocks were observed in two of them; three pts died, among which SCD occurred in one patient with CRT-D therapy, which was ineffective in stopping sustained VT. NGS sequencing revealed 40 changes in the nucleotide sequence (5 pathogenic mutations, 30 variants with uncertain significance (VUS), 5 new substitutions) in 27 genes in 26 (86,7%) probands. The proportion of mutations in sarcomeric proteins genes was 26,9%, and in ion channel proteins genes was 23,1%. Nucleotide changes in genes encoding structural proteins accounted for 11,5%. In 38,5% of cases, not one, but two or more rare mutations were detected, and in 30,8% – amino acid replacements were found in proteins of different functional classes. Conclusions. The frequency of multiple mutations was higher (38,5%) in the group of pts with the arrhythmic NCCM phenotype. In the group of pts with implantable devices (ICD/CRT-D), mutations in the genes of sarcomeric proteins were observed more often. The genetic characteristics of pts, along with their clinical characteristics, are markers of a high risk of developing life-threatening arrhythmias and can be additionally used for predicting adverse events in pts with NCCM, as well as for early diagnosis of the disease in their relatives.

Identification and prognostication of the substrate of ventricular arrhythmia with cardiac magnetic resonance (CMR) imaging in patients with normal echocardiography

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Self Introduction Malignant ventricular arrhythmia contributes to approximately half of the sudden cardiac deaths. In common practice, echocardiography is used to identify structural heart diseases that are the most frequent substrate of VA. Identification and prognostication of structural heart diseases are very important as they are the main determinant of poor prognosis of ventricular arrhythmia. Purpose : The objective of this study is to determine whether cardiac magnetic resonance (CMR) may identify structural heart disease (SHD) in patients with ventricular arrhythmia who had no pathology observed on echocardiography. Methods : A total of 864 consecutive patients were enrolled in this single-center prospective study with significant ventricular arrhythmia. VA was characterized as &amp;gt;1000 ventricular ectopic beats per 24 hours, non-sustained ventricular arrhythmia, sustained ventricular arrhythmia, and no pathological lesion on echocardiography. The primary endpoint was the detection of SHD with CMR. Secondary endpoints were a composite of CMR detection of SHD and abnormal findings not specific for a definite SHD diagnosis. Results : CMR studies were used to diagnose SHD in 212 patients (24.5%) and abnormal findings not specific for a definite SHD diagnosis in 153 patients (17.7%). Myocarditis (n = 84) was the more frequent disease, followed by arrhythmogenic cardiomyopathy (n = 51), ischemic heart disease (n = 32), dilated cardiomyopathy (n = 17), hypertrophic cardiomyopathy (n = 12), congenital cardiac disease (n = 08), left ventricle noncompaction (n = 5), and pericarditis (n = 3). The strongest univariate and multivariate predictors of SHD on CMR images were chest pain (odds ratios [OR]: 2.5 and 2.33, respectively) and sustained ventricular tachycardia (ORs: 2.62 and 2.21, respectively). Conclusion : Our study concludes that SHD was able to be identified on CMR imaging in a significant number of patients with malignant VA and completely normal echocardiography. Chest pain and sustained ventricular tachycardia were the two strongest predictors of positive CMR imaging results. Abstract Figure. Distribution of different SHD