Associations Between Biomarkers of Myocardial Injury and Systemic Inflammation and Risk of Incident Ventricular Arrhythmia.

BACKGROUND: Cardiac troponins (cTns) and biomarkers of inflammation are elevated in heart failure (HF) and predict cardiovascular risk. Whether these biomarkers associate with risk of ventricular arrhythmias (VAs) is unclear. OBJECTIVES: This study sought to assess whether cTnT, growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations are associated with incident VA. METHODS: In a prospective, observational study of patients treated with implantable cardioverter-defibrillator, cTnT, GDF-15, IL-6, and CRP were measured at baseline and after 1.4 ± 0.5 years and were associated with implantable cardioverter-defibrillator-detected incident VA, HF hospitalizations, and mortality. RESULTS: This study included 489 patients aged 66 ± 12 years and 83% were men. Median concentrations of cTnT were 15 (Q1-Q3: 9-25) ng/L at inclusion, and higher concentrations were associated with higher age, male sex, diabetes mellitus, coronary artery disease, and HF. During 3.1 ± 0.7 years of follow-up, 137 patients (28%) had ≥1 VA. cTnT concentrations were associated with an increased VA risk (per log-unit, HR: 1.63; 95% CI: 1.31-2.01; P < 0.001), also after adjustment for age, sex, body mass index, coronary artery disease, HF, renal function, and left ventricular ejection fraction (P < 0.001). GDF-15, IL-6, and CRP concentrations were not associated with incident VA, but all (including cTnT) were associated with HF hospitalization and mortality. Changes in cTnT, GDF-15, IL-6, and CRP from baseline to 1.4 years were not associated with subsequent VA. CONCLUSIONS: Higher concentrations of cTnT, GDF-15, IL-6, and CRP associate with HF hospitalization and death, but only cTnT predict incident VA. These findings suggest that myocardial injury rather than inflammation may play a pathophysiological role in VA and sudden cardiac death.

One-year mortality and causes of death after stereotactic radiation therapy for refractory ventricular arrhythmias: A systematic review and pooled analysis.

Patients treated with cardiac stereotactic body radiation therapy (radioablation) for refractory ventricular arrhythmias are patients with advanced structural heart disease and significant comorbidities. However, data regarding 1-year mortality after the procedure are scarce. This systematic review and pooled analysis aimed at determining 1-year mortality after cardiac radioablation for refractory ventricular arrhythmias and investigating leading causes of death in this population. MEDLINE/EMBASE databases were searched up to January 2023 for studies including patients undergoing cardiac radioablation for the treatment of refractory ventricular arrhythmias. Quality of included trials was assessed using the NIH Tool for Case Series Studies (PROSPERO CRD42022379713). A total of 1,151 references were retrieved and evaluated for relevance. Data were extracted from 16 studies, with a total of 157 patients undergoing cardiac radioablation for refractory ventricular arrhythmias. Pooled 1-year mortality was 32 % (95 %CI: 23-41), with almost half of the deaths occurring within three months after treatment. Among the 157 patients, 46 died within the year following cardiac radioablation. Worsening heart failure appeared to be the leading cause of death (52 %), although non-cardiac mortality remained substantial (41 %) in this population. Age≥70yo was associated with a significantly higher 12-month all-cause mortality (p<0.022). Neither target volume size nor radiotherapy device appeared to be associated with 1-year mortality (p = 0.465 and p = 0.199, respectively). About one-third of patients undergoing cardiac stereotactic body radiation therapy for refractory ventricular arrhythmias die within the first year after the procedure. Worsening heart failure appears to be the leading cause of death in this population.

Pacemaker-Related Factors and Outcomes of Fontan Patients　- Impact of Paced QRS Duration.

BACKGROUND: Permanent pacemaker (PPM) implantation has been identified as a risk factor for morbidity and mortality after Fontan operation. This study investigated the factors associated with outcomes in patients with Fontan physiology who underwent PPM implantation. METHODS AND RESULTS: We retrospectively reviewed 508 patients who underwent Fontan surgery at Asan Medical Center between September 1992 and August 2022. Of these patients, 37 (7.3%) received PPM implantation. Five patients were excluded, leaving 32 patients, of whom 11 were categorized into the poor outcome group. Poor outcomes comprised death, heart transplantation, and "Fontan failure". Clinical, Fontan procedure-related, and PPM-related factors were compared between the poor and good outcome groups. Ventricular morphology, Fontan procedure-associated factors, pacing mode, high ventricular pacing rate, and time from first arrhythmia to PPM implantation did not differ significantly between the 2 groups. However, the poor outcome group exhibited a significantly longer mean paced QRS duration (P=0.044). Receiver operating characteristic curve analysis revealed a paced QRS duration cut-off value of 153 ms with an area under the curve of 0.73 (P=0.035). CONCLUSIONS: A longer paced QRS duration was associated with poor outcomes, indicating its potential to predict adverse outcomes among Fontan patients.

Relationship between impaired repolarization parameters and poor cardiovascular clinical outcomes in patients with potentially serious coronary artery anomalies.

BACKGROUND: Congenital coronary artery anomalies (CCAAs) have the potential for life-threatening complications, including malignant ventricular arrhythmias and sudden cardiac death (SCD). In this study, we aimed to evaluate the relationship between impaired repolarization parameters and poor cardiovascular clinical outcomes in patients with potentially serious CCAAs. METHODS: This retrospective study included 85 potentially serious CCAA patients (mean age: 54.7 ± 13.6 years; male:44) who were diagnosed with conventional and coronary computed tomography angiography (CCTA). All patients underwent transthoracic echocardiography and 12-lead surface electrocardiography. Cardiac events were defined as sustained ventricular tachycardia or fibrillation, syncope, cardiac arrest and SCD. RESULTS: The presence of interarterial course (IAC) was confirmed by CCTA in 37 (43.5%) patients. During a median follow-up time of 24 (18-50) months, a total of 11 (12.9%) patients experienced cardiac events. The presence of IAC was significantly more frequent and Tp-e interval, Tp-e/QTc ratio and frontal QRS/T angle (fQRSTa) were significantly greater in patients with poor clinical outcomes. Moreover, the presence of IAC, high Tp-e/QTc ratio and high fQRSTa were found to be independent predictors of poor clinical outcomes and decreased long-term cardiac event-free survival in these patients. A net reclassification index was +1.0 for the Tp-e/QTc ratio and +1.3 for fQRSTa which were confirmable for additional predictability of these repolarization abnormalities. CONCLUSION: Impaired repolarization parameters, including wider fQRSTa, prolonged Tp-e interval, and increased Tp-e/QTc ratio, and IAC may be associated with poor cardiovascular clinical outcomes in potentially serious CCAA patients.

QTc, Tp-e Interval and Tp-e/QTc Ratio in Patients with Hypocalcemia-case Control Study

Abstract Background: To the best of our knowledge, there are studies related to QT and QTc interval in patients with hypocalcemia, but there are no studies evaluating T wave peak and end interval (Tp-e interval), Tp-e/QT and Tp-e/QTc ratios used to evaluate cardiac arrhythmia risk and ventricular repolarization changes rates. Objectives: Therefore, we aimed to investigate whether there is a change in Tp-e interval, Tp-e/QT and Tp-e/QTc ratios in patients with hypocalcemia. Methods: Retrospectively, 29 patients with hypocalcemia in the emergency department were included in the study. Twenty-nine patients with similar age and sex distribution were included in the study as the control group. All patients underwent 12-lead electrocardiography (ECG). In addition to routine measurements, Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were measured on ECG. The study data were grouped as patients with and without hypocalcemia. Results: The mean age of the patients was 66.24 ± 4.95 years. QTc interval, Tp-e interval and Tp-e/QTc values were found to be significantly higher in patients with hypocalcemia (p <0.001 for each). QTc interval, Tp-e interval and Tp-e/QTc ratio showed a significant negative correlation with calcium levels. Conclusion: Tp-e interval and Tp-e/QTc ratios are significantly increased in patients with hypocalcemia compared to those without hypocalcemia and this can be used more effectively in the follow-up of cardiac fatal arrhythmias.

Chemotherapy-Induced Arrhythmia - Underrecognized and Undertreated.

Cancer is one of the leading causes of death worldwide. Chemotherapy-induced arrhythmia is a potential complication of treatment that confers increased morbidity and mortality. The relationship between chemotherapeutic agents and arrhythmias is poorly established. Atrial fibrillation, ventricular ectopic beats, and prolonged QTc are the most common arrhythmias suffered by cancer patients undergoing chemotherapy. The treatment of atrial fibrillation in cancer is complicated by complex drug-drug interactions and a lack of evidence guiding practice. Furthermore, the normal risk assessment scores utilized in the decision-making for anticoagulation in the normal population are not validated in the cancer population. Multiple agents are implicated in prolonging the QTc, and this can often have adverse consequences for both the patient and the treatment of their cancer. This can manifest as torsades de pointes and sudden cardiac death. It is advised that, during treatment, oncologists should have close liaison with cardio-oncologists to ensure optimum patient management.

QT interval prolongation and the risk of malignant ventricular dysrhythmia and/or cardiac arrest: Systematic search and narrative review of risk related to the magnitude of QT interval length.

Prolongation of the QTc interval is associated with an increased risk of malignant ventricular dysrhythmias, such as ventricular tachycardia (VT), and sudden cardiac death. The quantifiable risk rates of adverse dysrhythmic outcome in relation to specific QTc interval length are not known. We conducted a literature review on the topic of QT interval prolongation in adult patients and the associated risk of malignant dysrhythmic event. We specifically formulated our literature search and subsequent literature review to address the following question: Can the clinician identify specific QTc intervals at which a specific quantifiable risk of malignant dysrhythmic event (malignant ventricular dysrhythmia and/or cardiac arrest) occurs in an undifferentiated adult patient population? In the literature search, we identified 701 studies; upon review using specific, pre-determined inclusion criteria, we identified 16 articles for inclusion in the review. From this literature, we were unable to answer the question in a quantifiable manner and only noted that the risk of malignant dysrhythmic event increases with progressively longer QTc interval. The current literature on this topic is inadequate to answer this important question due to heterogenous study methodology, patient populations, endpoints, and periods of observation. Additional prospective research is required on this topic, aimed at addressing the important issue of specific, quantifiable risk and its relation to degree of prolongation of the QTc interval.

Causes of Cardiovascular Hospitalization and Death in Patients With Transthyretin Amyloid Cardiomyopathy (from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial [ATTR-ACT]).

In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis significantly reduced mortality and cardiovascular (CV)-related hospitalizations compared with placebo in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This analysis aimed to assess the causes of CV-related death and hospitalization in ATTR-ACT to provide further insight into the progression of ATTR-CM and efficacy of tafamidis. ATTR-ACT was an international, double-blind, placebo-controlled, and randomized study. Patients with hereditary or wild-type ATTR-CM were randomized to tafamidis (n = 264) or placebo (n = 177) for 30 months. The independent Endpoint Adjudication Committee determined whether certain investigator-reported events met the definition of disease-related efficacy endpoints using predefined criteria. Cause-specific reasons for CV-related deaths (heart failure [HF], arrhythmia, myocardial infarction, sudden death, stroke, and other CV causes) and hospitalizations (HF, arrhythmia, myocardial infarction, transient ischemic attack/stroke, and other CV causes) were assessed. Total CV-related deaths was 53 (20.1%) with tafamidis and 50 (28.2%) with placebo, with HF (15.5% tafamidis, 22.6% placebo), followed by sudden death (2.7% tafamidis, 5.1% placebo), the most common causes. The number of patients with a CV-related hospitalization was 138 (52.3%) with tafamidis and 107 (60.5%) with placebo; with HF the most common cause (43.2% tafamidis, 50.3% placebo). All predefined causes of CV-related death or hospitalization were less frequent with tafamidis than placebo. In conclusion, these data provide further insight into CV disease progression in patients with ATTR-CM, with HF the most common adjudicated cause of CV-related hospitalization or death in ATTR-ACT. Clinical trial registration ClinicalTrials.gov: NCT01994889.

Management of Arrhythmias After Heart Transplant: Current State and Considerations for Future Research.

Orthotropic heart transplantation remains the most effective therapy for patients with end-stage heart failure, with a median survival of ≈13 years. Yet, a number of complications are observed after orthotropic heart transplantation, including atrial and ventricular arrhythmias. Several factors contribute to arrhythmias, such as autonomic denervation, effect of the surgical technique, acute and chronic rejection, and transplant vasculopathy among others. To minimize risk of future arrhythmias, the bicaval technique and minimizing ischemic time are current surgical standards. Sinus node dysfunction is the most common indication for early (within 30 days) pacemaker implantation, whereas atrioventricular block incidence increases as time from transplant increases. Atrial fibrillation can occur in the first few weeks following transplantation but is uncommon in the long term unless secondary to a precipitant such as acute rejection. The most common atrial arrhythmias are atrial flutters, which are mainly typical, but atypical circuits can be observed such as those that involve the remnant donor atrium in regions immediately adjacent to the atrioatrial anastomosis suture line. Choosing the appropriate pharmacological therapy requires careful consideration due to the potential interaction with immunosuppressive agents. Despite historical concerns, adenosine is effective and safe at reduced doses if administered under cardiac monitoring. Catheter ablation has emerged as an effective treatment strategy for symptomatic supraventricular tachycardias, including ablation of atypical flutter circuits. Cardiac allograft vasculopathy is an important risk factor for sudden cardiac death, yet the role of prophylactic implantable cardioverter-defibrillator implant for sudden death prevention is unclear. Current indications for implantable cardioverter-defibrillator implantation are as in the nontransplant population. A number of questions for future research are posed.

Prognostic Value of Nonischemic Ringlike Left Ventricular Scar in Patients With Apparently Idiopathic Nonsustained Ventricular Arrhythmias.

BACKGROUND: Left ventricular (LV) scar on late gadolinium enhancement (LGE) cardiac magnetic resonance has been correlated with life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). We investigated the prognostic significance of a specific LV-LGE phenotype characterized by a ringlike pattern of fibrosis. METHODS: A total of 686 patients with apparently idiopathic nonsustained VA underwent contrast-enhanced cardiac magnetic resonance. A ringlike pattern of LV scar was defined as LV subepicardial/midmyocardial LGE involving at least 3 contiguous segments in the same short-axis slice. The end point of the study was time to the composite outcome of all-cause death, resuscitated cardiac arrest because of ventricular fibrillation or hemodynamically unstable ventricular tachycardia and appropriate implantable cardioverter defibrillator therapy. RESULTS: A total of 28 patients (4%) had a ringlike pattern of scar (group A), 78 (11%) had a non-ringlike pattern (group B), and 580 (85%) had normal cardiac magnetic resonance with no LGE (group C). Group A patients were younger compared with groups B and C (median age, 40 vs 52 vs 45 years; P<0.01), more frequently men (96% vs 82% vs 55%; P<0.01), with a higher prevalence of family history of sudden cardiac death or cardiomyopathy (39% vs 14% vs 6%; P<0.01) and more frequent history of unexplained syncope (18% vs 9% vs 3%; P<0.01). All patients in group A showed VA with a right bundle-branch block morphology versus 69% in group B and 21% in group C (P<0.01). Multifocal VAs were observed in 46% of group A patients compared with 26% of group B and 4% of group C (P<0.01). After a median follow-up of 61 months (range, 34-84 months), the composite outcome occurred in 14 patients (50.0%) in group A versus 15 (19.0%) in group B and 2 (0.3%) in group C (P<0.01). After multivariable adjustment, the presence of LGE with ringlike pattern remained independently associated with increased risk of the composite end point (hazard ratio, 68.98 [95% CI, 14.67-324.39], P<0.01). CONCLUSIONS: In patients with apparently idiopathic nonsustained VA, nonischemic LV scar with a ringlike pattern is associated with malignant arrhythmic events.

Describing Clinically Significant Arrhythmias in Postoperative Vascular Surgery Patients.

BACKGROUND: The American Heart Association guidelines instruct use of postoperative telemetry (POT) should be reserved for patients undergoing cardiac procedures and/or those with ischemic cardiac symptoms, but acknowledge that major vascular procedures deserve unique consideration. Telemetry remains a limited resource in many hospitals; however, it has been poorly defined which vascular patients have greatest need for POT. The purpose of this study is to define the rates of postoperative arrhythmias (POAs) after major vascular operations using the Society for Vascular Surgery Vascular Quality Initiative (VQI) registry, identify independent predictors of POA, and determine the effect of POA on mortality to guide the use of POT in vascular patients. METHODS: A retrospective cohort study was performed using the following VQI modules: open abdominal aortic aneurysm repair (oAAA), complex endovascular aneurysm repair (EVAR) (thoracic endovascular aortic repair [TEVAR]/c-EVAR), EVAR, suprainguinal bypass (SIB), and infrainguinal bypass (IIB). POA was defined in the VQI as a new rhythm disturbance requiring treatment with medication or cardioversion. The incidence of POA, preoperative risk factors, and demographics were determined for each procedure. RESULTS: A total of 121,652 procedures were identified with an overall POA event rate of 5.1% (n = 6,265). Procedure-specific event rates for POA among VQI registries are as follows: oAAA 14.4%, TEVAR/c-EVAR 8.5%, EVAR 2.7%, SIB 6.2%, and IIB 3.8%. Across all procedure types, POA was associated with emergent operations and increased procedure time. Procedure-specific multivariable regression revealed additional independent preoperative intraoperative factors associated with POA that were unique with each procedure. Across all procedural groups, the presence of POA was associated with increased rates of clinical myocardial infarction and decreased survival on Kaplan-Meier analysis. CONCLUSIONS: Rates of POA in patients undergoing vascular procedures appear higher than previously reported, and POA is associated with decreased survival. Our study elucidated patient- and procedure-specific predictor factors associated with POA that can be used to inform the use of POT.

Effect of metoprolol tartrate tablets and recombinant human B-type natriuretic peptide on the sudden cardiac death and malignant arrhythmias in patients with acute myocardial infarction and heart failure.

To explore the effect of metoprolol tartrate tablets and recombinant human natriuretic peptide B (NPPB) on sudden cardiac death and malignant arrhythmias in patients with acute myocardial infarction and patients with heart failure (AMI-HF). A total of 105 AMI-HF patients treatedfrom January 2020 and June 2021 were enrolled and divided into Group I (n=53) and Group II (n=52). Both groups received conventional treatment, and Group II was additionally treated with metoprolol tartrate tablets and NPPB. The clinical observation indicators of the two groups of patients were compared. Group II had better left ventricular end diastolic diameter (LVEDd), left ventricular end systolic diameter (LVESD) and left ventricular ejection fraction (LVEF) (p<0.05). The standard deviation of NN (R-R) interval (SDNN), mean NN (R-R), root mean square of continuous difference (RMSSD) and the percentage of difference between adjacent RR intervals >50ms (pNN50) increased after treatment, with more increase in the Group II (p<0.05). Group II obtained significantly lower levels of B type natriuretic peptide (BNP),N terminal pro B type natriuretic peptide (NT-ProBNP), interleukin (IL)-6 and hs-CRP in contrast to Group I (p<0.05). Markedly higher total response rates were observed in Group II (p<0.05). The combination of metoprolol tartrate tablets and NPPB is effective in treating AMI-HF.

Long-term outcomes of arrhythmia and distinct electrophysiological features in congenitally corrected transposition of the great arteries in an Asian cohort.

Congenitally corrected transposition of the great arteries (ccTGA) is associated with various types of arrhythmia, including supraventricular tachycardia (SVT) and complete atrioventricular block (cAVB). Our study aims to characterize the arrhythmia burden, associated risk factors, arrhythmia mechanisms, and the long-term follow-up results in patients with ccTGA in a large Asian cohort. METHODS: We enrolled 104 patients (43 women and 61 men) diagnosed with ccTGA at our institution. The mean age at last follow-up was 20.8 years. RESULTS: For 40 patients (38%) with tachyarrhythmia, paroxysmal SVT (PSVT) and atrial arrhythmia were observed in 17 (16%) and 27 (26%) patients, respectively, with 4 patients (4%) having both types of SVT. The 20-year and 30-year SVT-free survival rates were 68% and 54%, respectively. Seven patients (7%) developed cAVB: 2 (2%) developed spontaneously, and the other 5 (5%) was surgically complicated (surgical risk of cAVB: 7%, all associated with ventricular septal defect repair surgery). PSVT was mostly associated with accessory pathways (5/9) but also related to twin atrioventricular nodal reentry tachycardia (3/9) and atrioventricular nodal reentry tachycardia (1/9). Most of the accessory pathways were located at tricuspid valve (9/10). Catheter ablation successfully eliminated all PSVT substrates (10/10) and most of the atrial arrhythmia substrates (3/5), with low recurrence rate. CONCLUSIONS: The arrhythmia burden in patients with ccTGA is high and increases over time. However, cAVB incidence was relatively low and kept stationary in this Asian cohort. The mechanisms of SVT are complicated and can be controlled through catheter ablation.

The effect of revascularization on mortality and risk of ventricular arrhythmia in patients with ischemic cardiomyopathy.

BACKGROUND: There is clear evidence that patients with prior myocardial infarction and a reduced ejection fraction benefit from implantation of a cardioverter-defibrillator (ICD). It is unclear whether this benefit is altered by whether or not revascularization is performed prior to ICD implantation. METHODS: This was a retrospective cohort study following patients who underwent ICD implantation from 2002 to 2014. Patients with ischemic cardiomyopathy and either primary or secondary prevention ICDs were selected for inclusion. Using the electronic medical record, cardiac catheterization data, revascularization status (percutaneous coronary intervention or coronary bypass surgery) were recorded. The outcomes were mortality and ventricular arrhythmia. RESULTS: There were 606 patients included in the analysis. The mean age was 66.3 ± 10.1 years, 11.9% were women, and the mean LVEF was 30.5 ± 12.0, 58.9% had a primary indication for ICD, 82.0% of the cohort had undergone coronary catheterization prior to ICD implantation. In the overall cohort, there were fewer mortality and ventricular arrhythmia events in patients who had undergone prior revascularization. In patients who had an ICD for secondary prevention, revascularization was associated with a decrease in mortality (HR 0.46, 95% CI (0.24, 0.85) p = 0.015), and a trend towards fewer ventricular arrhythmia (HR 0.62, 95% CI (0.38, 1.00) p = 0.051). There was no association between death or ventricular arrhythmia with revascularization in patients with primary prevention ICDs. CONCLUSION: Revascularization may be beneficial in preventing recurrent ventricular arrhythmia, and should be considered as adjunctive therapy to ICD implantation to improve cardiovascular outcomes.

Malignant Arrhythmias in Patients With COVID-19: Incidence, Mechanisms, and Outcomes.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) who develop cardiac injury are reported to experience higher rates of malignant cardiac arrhythmias. However, little is known about these arrhythmias-their frequency, the underlying mechanisms, and their impact on mortality. METHODS: We extracted data from a registry (NCT04358029) regarding consecutive inpatients with confirmed COVID-19 who were receiving continuous telemetric ECG monitoring and had a definitive disposition of hospital discharge or death. Between patients who died versus discharged, we compared a primary composite end point of cardiac arrest from ventricular tachycardia/fibrillation or bradyarrhythmias such as atrioventricular block. RESULTS: Among 800 patients with COVID-19 at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring, and either died (52) or were discharged (88). The median (interquartile range) age was 61 years (48-74); 73% men; and ethnicity was White in 34%. Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%. Compared with discharged patients, those who died had elevated peak troponin I levels (0.27 versus 0.02 ng/mL) and more primary end point events (17% versus 4%, P=0.01)-a difference driven by tachyarrhythmias. Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, while atrioventricular block was largely an independent primary event. CONCLUSIONS: Hospitalized patients with COVID-19 who die experience malignant cardiac arrhythmias more often than those surviving to discharge. However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04358029.

The Role of Acute Hyperglycemia on the Risk of Malignant Arrhythmia in Acute Myocardial Infarction Patients: A Study of Myocardial Damage, Ion Channel Changes and Inflammatory Factors.

BACKGROUND: acute myocardial infarction (AMI) is often followed by hyperglycemia. To date, there is no study that examine the role of myocardial damage, ion channel changes and increased inflammatory response as a pathomechanism of malignant arrhythmias due to hyperglycemia in AMI patients. The aim of this study is to determine the effect of acute hyperglycemia on the occurence of malignant arrhythmias, troponin I, VLP, echocardiographic strain, ion channel changes (CaMKII) and hsCRP. This study also aims to assess the effect of troponin I, VLP, GLS, CaMKII and hsCRP on the occurence of malignant arrhythmias in AMI patients with acute hyperglycemia. METHODS: a cross-sectional study followed by a cohort study was conducted on AMI patients treated at ICCU Cipto Mangunkusumo Hospital Jakarta during November 2018 to May 2019 period. Patients with severe infections and who had experienced malignant arrhythmias at admission were excluded from the study. The occurence of malignant arrhythmias as the main outcome of this study and CaMKII level were assessed on the fifth day of treatment. Patients who died before the fifth day of treatment due to causes other than malignant arrhythmias were excluded from analysis. The association between acute hyperglycemia with VLP and the occurence of malignant arrhythmias was analyzed through a chi-square test, whereas the differences between troponin I, GLS, CaMKII and hsCRP, based on the hyperglycemia status of the patient, were analyzed by Mann-Whitney U test. RESULTS: a total of 110 patients were included in the study. Two patients died on the third day of observation due to malignant arrhythmias. No significant relationship was found between acute hyperglycemia in AMI and malignant arrhythmias (RR = 1,38, 95%CI 0.50-3.77). There were differences of CaMKII level on day-1 and day-5 between those who were experienced malignant arrhytmia and those who were not (p-value for differences are 0,03 and 0,01, respectively. In the acute hyperglycemia group, there was difference of CaMKII day-5 levels between positive and negative VLP (p = 0.03). CONCLUSION: it was concluded that the inititial stage of AMI causes more dominant myocardial damage, as compared to metabolic factors. In the next stage of AMI, acute hyperglycemia increases ROS and the activation of ion channel changes described by CaMKII. This change results in electrophysiological remodeling of the heart, as seen in the VLP image on SA-ECG.

Cardiac involvement, morbidity and mortality in hereditary transthyretin amyloidosis because of p.Glu89Gln mutation.

BACKGROUND: Hereditary transthyretin amyloidosis is a systemic infiltrative disease, caused by a mutation in the transthyretin gene. p.Glu89Gln is the most common mutation in the Balkan countries. METHODS: We evaluated the clinical manifestations, cardiac involvement, morbidity and mortality in 78 patients with p.Glu89Gln mutation, verified through a DNA analysis. Clinical assessment, electrocardiogram and echocardiography were performed at the time of diagnosis. The patients have been followed for 30 months. RESULTS: All included patients were Caucasian, 39 (50%) - men, with median age at diagnosis of 56 years (42-73), median age at onset -- 53 years (35-69), starting significantly earlier in men (4.36, P = 0.004). Cardiac and neurological involvement was found in 74 (95%) patients. Pathological ECG was present in 65 (84%) patients, infarct pattern in 43 (56%), low voltage in 24 (31%). Echocardiography revealed an infiltrative cardiomyopathy with restrictive filling in 31 (40%) and ejection fraction less than 50% in 20 (27%) patients. Twenty-two patients (28%) died: 14 (64%) because of advanced heart failure, 6 (27%) died suddenly, 2 (9%) from an ischemic stroke. The median age at death was 58.5 years (52-72). No statistically significant sex difference in survival was observed; a significant difference in survival was found for the New York Heart Association class, familial amyloidotic polyneuropathy stage, ejection fraction, filling pattern and tafamidis treatment. CONCLUSION: Cardiac involvement is common and has significant prognostic implications in the evaluated patients with p.Glu89Gln mutation. Heart failure and rhythm disturbances are the main causes of death. An earlier identification of the disease is crucial to improve prognosis.

Dissecting the Cardiac Conduction System: Is It Worthwhile?

BACKGROUND: Pathologic examination of conduction system (CS) is not routinely performed, and histologic changes are mostly reported in forensic practice. METHODS: We studied the value of dissecting the CS in a cohort of pediatric patients with unexplained sudden death or severe, inexplicable arrhythmias. Histopathologic changes present in CS components were recorded and correlated with findings noted in other cardiac structures. RESULTS: Twenty-one subjects (11 unexplained sudden deaths and 10 life-threatening arrhythmias) were identified; 18 (86%) had CS pathologic abnormalities. In 13 patients (62%), the CS findings mirrored those found in other cardiac sections (inflammation, allograft vasculopathy, vascular fibromuscular dysplasia, cardiomyopathy-related changes, and tumor/tumor-like conditions). Five cases (24%) had abnormalities restricted to CS (bundle of His [BH] with fibrotic scar and patch material following ventricular septal defect repair, inflammation, BH with fibrosis and calcifications, and intimal fibroplasia of sinoatrial node artery). CONCLUSIONS: Pathologic changes within the CS are present in a high number of pediatric patients presenting with unexplained sudden death or life-threatening arrhythmias. Frequently, the findings mirror those observed in other cardiac structures. However, in a significant number of cases (24%), the changes are restricted to CS and likely explain the patients' symptoms or cause of death, suggesting that systematic dissection of CS unveils valuable information.

Year in Review in Cardiac Electrophysiology.

In the past year, there have been numerous advances in our understanding of arrhythmia mechanisms, diagnosis, and new therapies. We have seen advances in basic cardiac electrophysiology with data suggesting that secretoneurin may be a biomarker for patients at risk of ventricular arrhythmias, and we have learned of the potential role of an NPR-C (natriuretic peptide receptor-C) in atrial fibrosis and the role of an atrial specific 2-pore potassium channel TASK-1 as a therapeutic target for atrial fibrillation. We have seen studies demonstrating the role of sensory neurons in sleep apnea-related atrial fibrillation and the association between bariatric surgery and atrial fibrillation ablation outcomes. Artificial intelligence applied to electrocardiography has yielded estimates of age, sex, and overall health. We have seen new tools for collection of patient-centered outcomes following catheter ablation. There have been significant advances in the ability to identify ventricular tachycardia termination sites through high-density mapping of deceleration zones. We have learned that right ventricular dysfunction may be a predictor of survival benefit after implantable cardioverter-defibrillator implantation in patients with nonischemic cardiomyopathy. We have seen further insights into the role of His bundle pacing on improving outcomes. As our understanding of cardiac laminopathies advances, we may have new tools to predict arrhythmic event rates in gene carriers. Finally, we have seen numerous advances in the treatment of arrhythmias in patients with congenital heart disease.