The management of cardiac implantable electronic device lead perforations: a multicentre study.

AIMS: Lead perforation is a rare, well-known complication of cardiac implantable electronic device (CIED) implants, whose management is mostly not evidence-based. Main management strategies include conservative approach based on clinical and lead function follow-up vs. routine invasive lead revision approach. This study compared the complications of both strategies by composite endpoint, including recurrent perforation-related symptoms, recurrent pericardial effusion (PEf), lead dysfunction, and device infection during 12 month follow-up. METHODS AND RESULTS: Multicentre retrospective analysis, inquiring data from imaging studies, device interrogation, pericardiocentesis, and clinical charts of patients with suspected perforating leads between 2007 and 2014 in five hospitals. All cases were reviewed by electrophysiologist and defined as definite perforations by suggestive symptoms along with lead perforation on imaging, bloody PEf on pericardiocentesis shortly after implant, or right ventricular (RV) lead non-capture along with diaphragmatic stimulation upon bipolar pacing. Clinical outcomes associated with both management approaches were compared, with respect to the composite endpoint. The study included 48 definitive perforation cases: 22 managed conservatively and 26 via lead revision. Conservative management was associated with an increased composite endpoint compared with lead revision (8/22 vs. 1/26; P = 0.007). The dominant complication among the conservative cohort was appearance of cardiac tamponade during follow-up; 5/6 occurring in cases which presented with no or only mild PEf and were treated by antiplatelets/coagulants during or shortly after CIED implantation. CONCLUSION: A conservative management of CIED lead perforation is associated with increased complications compared with early lead revision. Lead revision may be the preferred management particularly in patients receiving antiplatelets/coagulants.

Electrocardiographic Predictors of Morbidity and Mortality in Patients With Acute Myocarditis: The Importance of QRS-T Angle.

BACKGROUND: Acute myocarditis carries a variable prognosis. We evaluated the morbidity and mortality rates in patients with acute myocarditis and admission electrocardiographic predictors of outcome. METHODS AND RESULTS: Patients admitted to a tertiary hospital with a clinical diagnosis of acute myocarditis were evaluated; 193 patients were included. Median follow-up was 5.7 years, 82% were male, and overal median age was 30 years (range 21-39). The most common clinical presentations were chest pain (77%) and fever (53%). The 30-day survival rate was 98.9%. Overall survival during follow-up was 94.3%. The most common abnormalities observed on electrocardiography were T-wave changes (36%) and ST-segment changes (32%). Less frequent changes included abnormal T-wave axis (>105° or < -15°; 16%), abnormal QRS axis (12%), QTc >460 ms (11%), and QRS interval ≥120 ms (5%). Wide QRS-T angle (≥100°) was demonstrated in 13% of the patients and was associated with an increased mortality rate compared with patients with a narrow QRS-T angle (20% vs 4%; P = .007). The rate of heart failure among patients with a wide QRS-T angle was significantly higher (36% vs 10%; P = .001). Cox regression analysis demonstrated that a wide QRS-T angle (≥100°) was a significant independent predictor of heart failure (hazard ratio [HR] 3.20, 95% confidence interval [CI] 1.35-7.59; P < .01) and of the combined end point of death or heart failure (HR 2.56, 95% CI 1.14-5.75; P < .05). CONCLUSIONS: QRS-T angle is a predictor of increased morbidity and mortality in acute myocarditis.

Clinical research: remote magnetic navigation vs. manually controlled catheter ablation of right ventricular outflow tract arrhythmias: a retrospective study.

Aims: Remote magnetic navigation (RMN) is an alternative to manual catheter control (MCC) radiofrequency ablation of right ventricular outflow tract (RVOT) arrhythmias. The data to support RMN approach is limited. We aimed to investigate the clinical and procedural outcomes in a cohort of patients undergoing RVOT premature ventricular complex/ventricular tachycardia (PVCs/VT) ablation procedures using RMN vs. MCC. Methods and results: Data was collected from two centres. Eighty-nine consecutive RVOT PVCs/VT ablation procedures were performed in 75 patients; RMN: 42 procedures and MCC: 47 procedures. CARTOXPTM or CARTO3 (Biosense Webster) was used for endocardial mapping in 19/42 (45%) in RMN group and 28/47 (60%) in MCC group; EnSiteTM NavXTM (St. Jude Medical) was used in the rest of the cohort. Stereotaxis platform (Stereotaxis Inc., St. Louis, MO, USA) was used for RMN approach. Procedural time was 113 ± 53 min in the RMN group and 115 ± 69 min in MCC (P = 0.90). Total fluoroscopic time was 10.9 ± 5.8 vs. 20.5 ± 13.8 (P < 0.05) and total ablation energy application time 7.0 ± 4.7 vs 11.9 ± 16 (P = 0.67) accordingly. There were two complications in RMN group and five in MCC (P = 0.43). Acute procedural success rate was 80% in RMN vs. 74% in MCC group (P = 0.46). After a median follow-up of 25 months (interquartile range 13-34), the success rate remained 55% in the RMN group and 53% in MCC (P = 0.96). Conclusion: Right ventricular outflow tract arrhythmia ablations were performed using half of fluoroscopic times with Stereotaxis platform RMN compared to manual approach. Acute and chronic success rates as well as complication rates were not significantly different.

Variable clinical expression of a novel FLNC truncating variant in a large family.

BACKGROUND: Variants in Filamin-C (FLNC) have been associated with various hereditary cardiomyopathies. Recent literature reports a prevalence of sudden cardiac death (SCD) of 13-25% among carriers of truncating-variants, with mean age of 42±15 years for first SCD event. This study reports two familial cases of SCD and the results of cascade screening of their large family. METHODS: Molecular-autopsy of the SCD victims revealed a novel truncating-variant in the FLNC gene (chr 7:128496880 [hg19]; NM_001458.5; c.7467_7474del; p.(Ser2490fs)). We screened thirty-two family members following genetic counseling, and variant carriers underwent a comprehensive workup followed by consultation with a cardiologist with expertise in the genetics of cardiac diseases. RESULTS: Seventeen variant carriers were identified: ages between 9 and 85 (mean 47±26). Fifteen underwent clinical evaluation. To date, none of the identified carriers has had major adverse events. In evaluated patients, ECG showed right-axis deviation in 60% (n = 9). Holter recorded frequent premature ventricular contractions (PVCs) (991±2030 per 24 h) in 33% (n = 5) with 4 patients having polymorphic PVC morphology. Three carriers had echocardiographic evidence of mild left-ventricular (LV) systolic dysfunction and another with mild LV dilatation. Cardiac magnetic-resonance (CMR) exhibited late­gadolinium-enhancement in 10 out of 11 exams, mainly in the mid-myocardium and sub-epicardium, frequently involving the septum and the inferior-lateral wall. CONCLUSION: This large FLNC truncating variant carrier family exhibits high cardiomyopathy penetrance, best diagnosed by CMR, with variable clinical expressions. These findings present a challenge in SCD prevention management and underscoring the imperative for better risk stratification measures.

Incidence and Predictors for Recurrence of Ventricular Arrhythmia Presenting During Acute Myocarditis: A Multicenter Study.

BACKGROUND: Management of acute myocarditis (AM) patients experiencing ventricular arrhythmia (VA) during acute illness is controversial, especially regarding early implantable cardioverter-defibrillator (ICD) implantation. OBJECTIVES: The purpose of this study was to evaluate the prevalence of and find predictors for long-term sustained VA recurrence and overall mortality among AM patients with VA. METHODS: This was a multicenter retrospective analysis of AM patients (verified by cardiac magnetic resonance imaging or myocardial biopsy) with documented VA during the acute illness ("initial VA"). Patients with history of myocardial infarction, heart failure, or VA were excluded. The study endpoint was a composite of sustained VA and overall mortality during follow-up. RESULTS: The study included 69 AM patients with initial VA: sustained monomorphic ventricular tachycardia (MMVT) (n = 25), sustained polymorphic ventricular tachycardia (VT)/ventricular fibrillation (n = 13), and nonsustained VT (n = 31). Age was 44 ± 13 years, and 23 of 69 (33.3%) were women. During median follow-up of 5.5 years, 27 of 69 (39%) patients reached the composite endpoint including sustained VA (n = 24) and death (n = 11). Initial MMVT, predischarge left ventricular dysfunction (left ventricular ejection fraction <50%), and anteroseptal delayed enhancement on cardiac magnetic resonance imaging were significantly associated with the composite endpoint. On multivariable analysis, initial MMVT (HR: 5.17; 95% CI: 1.81-14.6; P = 0.001) and predischarge LV dysfunction (HR: 4.57; 95% CI: 1.83-11.5; P = 0.005) were independently associated with the composite endpoint. Using these 2 predictors, we could delineate subgroups with low (∼4%), medium (∼42%), and high (∼82%) 10-year incidence of composite endpoint. CONCLUSIONS: AM patients presenting with VA have high incidence of sustained VA recurrence and mortality posthospitalization. Initial MMVT and predischarge LV dysfunction are independently associated with VA recurrence and mortality. Implantable cardioverter-defibrillator implantation may be considered in such high-risk patients.

Mode and Characteristics of Arrhythmia Initiation in Idiopathic Ventricular Fibrillation: A THESIS Substudy.

BACKGROUND: There is limited information on the mode of arrhythmia initiation in idiopathic ventricular fibrillation (IVF). A non-pause-dependent mechanism has been suggested to be the rule. OBJECTIVES: The aim of this study was to assess the mode and characteristics of initiation of polymorphic ventricular tachycardia (PVT) in patients with short or long-coupled PVT/IVF included in THESIS (THerapy Efficacy in Short or long-coupled idiopathic ventricular fibrillation: an International Survey), a multicenter study involving 287 IVF patients treated with drugs or radiofrequency ablation. METHODS: We reviewed the initiation of 410 episodes of ≥1 PVT triplet in 180 patients (58.3% females; age 39.6 ± 13.6 years) with IVF. The incidence of pause-dependency arrhythmia initiation (prolongation by >20 ms of the preceding cycle length) was assessed. RESULTS: Most arrhythmias (n = 295; 72%) occurred during baseline supraventricular rhythm without ambient premature ventricular complexes (PVCs), whereas 106 (25.9%) occurred during baseline rhythm including PVCs. Nine (2.2%) arrhythmias occurred during atrial/ventricular pacing and were excluded from further analysis. Mode of PVT initiation was pause-dependent in 45 (15.6%) and 64 (60.4%) of instances in the first and second settings, respectively, for a total of 109 of 401 (27.2%). More than one type of pause-dependent and/or non-pause-dependent initiation (mean: 2.6) occurred in 94.4% of patients with ≥4 events. Coupling intervals of initiating PVCs were <350 ms, 350-500 ms, and >500 ms in 76.6%, 20.72%, and 2.7% of arrhythmia initiations, respectively. CONCLUSIONS: Pause-dependent initiation occurred in more than a quarter of arrhythmic episodes in IVF patients. PVCs having long (between 350 and 500 ms) and very long (>500 ms) coupling intervals were observed at the initiation of nearly a quarter of PVT episodes.

Acute viral myocarditis: current concepts in diagnosis and treatment.

Acute myocarditis is one of the most challenging diseases to diagnose and treat in cardiology. The true incidence of the disease is unknown. Viral infection is the most common etiology. Modern techniques have improved the ability to diagnose specific viral pathogens in the myocardium. Currently, parvovirus B19 and adenoviruses are most frequently identified in endomyocardial biopsies. Most patients will recover without sequelae, but a subset of patients will progress to chronic inflammatory and dilated cardiomyopathy. The pathogenesis includes direct viral myocardial damage as well as autoimmune reaction against cardiac epitopes. The clinical manifestations of acute myocarditis vary widely--from asymptomatic changes on electrocardiogram to fulminant heart failure, arrhythmias and sudden cardiac death. Magnetic resonance imaging is emerging as an important tool for the diagnosis and follow-up of patients, and for guidance of endomyocardial biopsy. In the setting of acute myocarditis endomyocardial biopsy is required for the evaluation of patients with a clinical scenario suggestive of giant cell myocarditis and of those who deteriorate despite supportive treatment. Treatment of acute myocarditis is still mainly supportive, except for giant cell myocarditis where immunotherapy has been shown to improve survival. Immunotherapy and specific antiviral treatment have yet to demonstrate definitive clinical efficacy in ongoing clinical trials. This review will focus on the clinical manifestations, the diagnostic approach to the patient with clinically suspected acute myocarditis, and an evidence-based treatment strategy for the acute and chronic form of the disease.

Novel Approaches for the Diagnosis of Concealed Nodo-Ventricular and His-Ventricular Pathways.

BACKGROUND: Confirming the presence and participation of concealed nodo-ventricular (cNV) or concealed His-ventricular (cHV) pathways in tachyarrhythmias is challenging. We describe novel observations to aid in diagnosing cNV or cHV pathways. METHODS: We present 7 cases of cNV and cHV pathway-mediated arrhythmias and focus on several laboratory observations: (1) differential ventricular overdrive pacing (VOD) from the base versus apex, (2) response to His refractory premature ventricular complexes, (3) paradoxical atriohisian response (shorter atriohisian interval during tachycardia than that during sinus rhythm) in long RP tachycardia, and (4) the role of adenosine to aid in the diagnosis. RESULTS: Three cases underwent differential VOD during tachycardia. All demonstrated a shorter postpacing interval minus tachycardia cycle length during basal pacing than apical pacing with one case exhibiting apical VOD results compatible with atrioventricular nodal reentrant tachycardia. Basal VOD was useful for localizing the ventricular connection in a case with cHV pathway. In 3 cases, His refractory premature ventricular complexes reset the tachycardia without conduction to the atrium, which excluded the involvement of an atrioventricular pathway or atrial tachycardia, or atrioventricular nodal reentrant tachycardia alone. One case had His refractory premature ventricular complexes followed by subsequent constant AA interval and then tachycardia termination, suggesting a bystander cNV pathway involvement. Two cNV pathway cases presented with long RP tachycardia had paradoxical atriohisian shortening of >15 ms, suggesting parallel activation of the atrium and the atrioventricular node. Adenosine terminated the tachycardia with retrograde block in 2 cases with cNV pathways but had no response on a cHV pathway. CONCLUSIONS: cNV and cHV pathways mediated tachyarrhythmias can present with variable clinical presentations. We emphasize the important role of differential VOD sites, His refractory premature ventricular complexes that reset or terminate the tachycardia without conduction to the atrium, paradoxical atriohisian response in long RP tachycardia, and the use of adenosine for diagnosing cNV and cHV pathways.

Novel RyR2 Mutation (G3118R) Is Associated With Autosomal Recessive Ventricular Fibrillation and Sudden Death: Clinical, Functional, and Computational Analysis.

Background The cardiac ryanodine receptor type 2 (RyR2) is a large homotetramer, located in the sarcoplasmic reticulum (SR), which releases Ca2+ from the SR during systole. The molecular mechanism underlying Ca2+ sensing and gating of the RyR2 channel in health and disease is only partially elucidated. Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT1) is the most prevalent syndrome caused by RyR2 mutations. Methods and Results This study involves investigation of a family with 4 cases of ventricular fibrillation and sudden death and physiological tests in HEK 293 cells and normal mode analysis (NMA) computation. We found 4 clinically affected members who were homozygous for a novel RyR2 mutation, G3118R, whereas their heterozygous relatives are asymptomatic. G3118R is located in the periphery of the protein, far from the mutation hotspot regions. HEK293 cells harboring G3118R mutation inhibited Ca2+ release in response to increasing doses of caffeine, but decreased the termination threshold for store-overload-induced Ca2+ release, thus increasing the fractional Ca2+ release in response to increasing extracellular Ca2+. NMA showed that G3118 affects RyR2 tetramer in a dose-dependent manner, whereas in the model of homozygous mutant RyR2, the highest entropic values are assigned to the pore and the central regions of the protein. Conclusions RyR2 G3118R is related to ventricular fibrillation and sudden death in recessive mode of inheritance and has an effect of gain of function on the protein. Despite a peripheral location, it has an allosteric effect on the stability of central and pore regions in a dose-effect manner.

Low serum albumin: A significant predictor of reduced survival in patients with chronic heart failure.

BACKGROUND: Low serum albumin is common in patients with chronic heart failure (HF). HYPOTHESIS: Albumin may have an impact on clinical outcome in HF. We evaluated the effect of albumin levels on clinical outcome in a real-world cohort of patients with HF. METHODS: All patients with HF at a health maintenance organization were followed for cardiac-related hospitalizations and death. RESULTS: A total of 5779 HF patients were included in the study; mean follow-up was 576 days; median serum albumin was 4.0 g/dL (interquartile range 3.7-4.2), and 12% of the patients had hypoalbuminemia (albumin<3.5 g/dL). Low albumin was associated with increasing age, higher urea and C-reactive protein, lower sodium, hemoglobin, iron, less treatment with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, reduced right ventricular function, and pulmonary hypertension. Cox regression analysis after adjustment for significant predictors demonstrated that decreasing quartiles of albumin was significantly associated with mortality: Lowest quartile compared to highest: hazard ratio (HR) 5.74, 95% confidence interval (CI) 4.08 to 8.07, P < 0.001. Cox regression analysis of albumin as a continuous parameter using restricted cubic splines after adjustment for significant parameters demonstrated that reduced albumin levels were directly associated with increased mortality (P < 0.001 for the adjusted model). Decreasing quartiles of albumin were also a significant predictor of increased cardiac-related hospitalizations. A decrease in albumin on follow-up was an independent predictor of increased mortality by Cox regression analysis: HR 2.58, 95% CI 2.12 to 3.14, P < 0.001. CONCLUSIONS: Low albumin provides important information regarding several detrimental processes in HF and is a significant predictor of a worse outcome in these patients.

Temporal changes in electrocardiographic frontal QRS-T angle and survival in patients with heart failure.

BACKGROUND: Heart failure (HF) is associated with considerable mortality. The electrocardiographic frontal QRS-T angle is a simple parameter to measure, reflects changes in the direction of the repolarization sequence and predicts outcome in patients with HF. Data regarding temporal changes in the frontal QRS-T angle in patients with HF and its impact on outcome is limited. AIM: To evaluate temporal changes in the frontal QRS-T angle and its effect on survival in patients with HF. METHODS: Baseline and follow-up QRS-T angle were calculated from the frontal QRS and T axis of the 12-lead surface electrocardiogram. Patients were followed for survival. RESULTS: 2,929 HF patients were evaluated. Median interval between baseline ECG and follow-up ECG was 895 days, median follow-up time was 1526 days. Overall, the QRS-T angle tended to be stable, with minor changes in the angle over time. The median QRS-T angle change was +3° (IQR -19° to +30°). Overall survival during follow-up was 60%. Cox regression analysis after adjustment for significant predictors demonstrated that the QRS-T angle was an incremental predictor of increased mortality. A widening of the QRS-T angle during follow-up was independently associated with an increase in mortality, evident with an increase of the QRS-T angle difference above 0° (P<0.0001 for the adjusted model). CONCLUSION: QRS-T angle is relatively stable in patients with HF and is a powerful predictor of outcome. Widening of the QRS-T angle has predictive value and is an ominous sign.

Pacing Spikes All Over.

Ventricular safety pacing (VSP) is used to avoid cross talk by delivering ventricular stimulus shortly after an atrial-paced event if ventricular-sensed event occurs. Although VSP is a protective feature that exists for decades in different pacing devices, there are some reports of unfavorable outcomes of this algorithm. More so, health care providers sometimes face difficulties in interpreting and dealing with VSP strips. This case report discusses an important pacemaker algorithm and encourages further attention to possible pitfalls and hence avoids unnecessary interventions.

Ethnic disparity in the clinical characteristics of patients with heart failure.

AIMS: The characteristics of heart failure (HF) patients of different ethnic backgrounds in Israel are unknown. The purpose of the present study was to evaluate the clinical characteristics of Arab vs. Jewish patients with chronic HF. METHODS AND RESULTS: Patients with a diagnosis of HF at a health maintenance organization in Jerusalem, Israel were evaluated. All patients were followed for cardiac-related hospitalizations and death. The study cohort included 6773 HF patients; 4991 (74%) were Jewish and 1735 (26%) were Arab. The overall prevalence of HF in the Jewish vs. Arab population was similar (women, 4.3% vs. 4.7%, respectively, P = 0.06; men, 5.3% vs. 5.2%, P = 0.61). The prevalence of HF was significantly higher in Arab subjects of younger age groups (50-70 years). Arabs developed HF on average 10 years earlier and had a significantly higher rate of diabetes and obesity. Standard of care based on prescribed medications was similar between the ethnic groups. Glucose and cholesterol levels were higher in the Arab cohort. Mortality was similar between the groups at median follow-up (576 days), with the exception of cardiovascular hospitalizations and death that were higher in Arab men. CONCLUSIONS: Arab subjects develop HF at a much younger age compared with their Jewish counterparts and have a higher prevalence of diabetes and obesity. Standard of care and clinical outcome are comparable. Implementation of prevention programmes to reduce risk factors, particularly diabetes and obesity, may help reduce the disparity between Arabs and Jews.

Impaired fasting glucose: a predictor of reduced survival in patients with heart failure.

AIMS: Glucose abnormalities are associated with heart failure (HF), are increasingly prevalent, and may have an impact on outcome. Our aim was to evaluate the effect of fasting glucose levels on clinical outcome in patients with HF. METHODS AND RESULTS: Patients with a diagnosis of HF as coded at a health maintenance organization in Jerusalem, Israel were evaluated retrospectively. Impaired fasting glucose (IFG) was defined as fasting plasma glucose levels between 100 and 125 mg/dL. All patients were followed for cardiac-related hospitalizations and death. A total of 6067 HF patients were included. Mean follow-up was 487 days; mean age 75 ± 13 years; 48% of the patients (n = 2,942) had diabetes; and 11.9% (n = 722) had IFG. Overall survival during the follow-up was 82.5%. Cox regression analysis after adjustment for significant predictors including age, gender, ischaemic heart disease, hyperlipidaemia, hypertension, body mass index, glomerular filtration rate, serum urea, sodium, and haemoglobin levels demonstrated that patients with diabetes and IFG had a very similar outcome. Both were significant predictors of reduced survival compared with 'normal' glucose levels (fasting glucose levels between 92 and 99 mg/dL) [diabetes, hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.08-1.86, P = 0.01; IFG, HR 1.55, 95% CI 1.13-2.15, P < 0.01]. Diabetes and IFG were also predictors of increased cardiac-related hospitalizations (diabetes HR 1.31, 95% CI 1.16-1.48, P < 0.001; IFG, HR 1.17, 95% CI 1.00-1.35, P < 0.05). CONCLUSIONS: Diabetes and IFG are common in patients with HF and have a similar effect on outcome including survival and cardiac hospitalizations. Glucose abnormalities including subclinical diabetes confer significant risk in patients with HF.

The effect of thyroid function on clinical outcome in patients with heart failure.

AIMS: Thyroid dysfunction is known to effect cardiac function and is a risk factor for developing heart failure (HF). Data regarding the clinical significance of thyroid-stimulating hormone (TSH) levels alone as a predictor of outcome in patients with HF is sparse. We evaluated the significance of TSH on clinical outcome in a large cohort of patients with chronic HF. METHODS AND RESULTS: Patients with a diagnosis of HF at a Health Maintenance Organization (n = 5599) were followed for cardiac-related hospitalizations and death. Median TSH levels were 2.2 mIU/L (interquartile range 1.4-3.5). We divided patients into quartiles based on TSH levels. Median follow-up time was 434 days and the overall mortality rate was 13.2%. Both a high and a low TSH level was associated with an increased mortality rate. Cox regression analysis after adjustment for other significant predictors demonstrated that the highest TSH quartile was associated with increased mortality compared with those with the lowest mortality [second quartile: TSH 1.4-2.2 mIU/L, hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.08-1.71, P = 0.01]. TSH was also an independent predictor of death and cardiac-related hospitalization. Analysis of patients not on levothyroxine treatment (78%) demonstrated that TSH was an even stronger predictor of mortality (HR 1.54, 95% CI 1.17-2.03, P = 0.002). Additional analysis based on accepted clinical cut-offs of TSH demonstrated that increasing TSH levels above normal were independently associated with increased mortality and cardiac-related hospitalizations. CONCLUSIONS: Increased TSH levels are associated with worse clinical outcome in patients with HF. Thyroid imbalance confers significant risk in HF and warrants attention.