Cardiac Arrest in a Young Woman: A Near Miss Diagnosis.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare channelopathy involving cardiac calcium metabolism that often shows up at an early age with misleading clinical symptoms such as emotion or exercise-related syncope with a normal resting ECG, however, if misdiagnosed, CPVT can lead to cardiac arrest in children or young adults. We describe the case of a 27-year-old woman with several misdiagnosed syncopal episodes leading to out-of-hospital cardiac arrest (OHCA). Her previous medical history, combined with automatic external defibrillator records (AED) and clinical data, strongly suggested the diagnosis of CPVT. Thus beta blocker therapy was immediately started and targeted genetic test undertaken, revealing a previously unreported heterozygous variant in the ryanodine receptor-2 (RYR2) gene.

The role of atrial sensing for new-onset atrial arrhythmias diagnosis and management in single-chamber implantable cardioverter-defibrillator recipients: Results from the THINGS registry.

INTRODUCTION: Atrial tachycardia/fibrillation (AT/AF) episodes are common in implantable cardioverter-defibrillator (ICD) recipients and can be undetected by standard single-chamber devices. This study aims to explore whether a single-lead ICD with an atrial dipole (ICD DX; BIOTRONIK SE & Co, Berlin, Germany) could improve the AT/AF diagnosis and management as compared to standard ICD (ICD VR). METHODS AND RESULTS: We selected patients without AT/AF history from the THINGS registry which included consecutive patients implanted with ICD for standard indications. The ICD VR and the ICD DX groups included 236 (62.8%) and 140 (37.2%) patients, respectively, and had no significant differences in baseline characteristics. During a median follow-up of 27 months, there were 7 AT/AF diagnoses in the ICD VR and 18 in the ICD DX group. The 2-year incidence of AT/AF diagnosis was 3.6% (95% confidence interval [CI]: 1.6%-9.6%) for the ICD VR and 11.4% (95% CI: 6.8%-18.9%) for the ICD DX group (adjusted hazard ratio [HR]: 3.85 [95% CI: 1.58-9.41]; P = .003). Initiation of oral anticoagulation (OAC) due to AT/AF diagnosis was reported in 15 patients. The 2-year incidence of OAC onset was 3.6% (95% CI: 1.6%-7.8%) for the ICD VR and 6.3% (95% CI: 3.0%-12.7%) for ICD DX group (adjusted HR: 1.99 [95% CI: 0.72-5.56]; P = .184). CONCLUSION: We observed that atrial sensing capability in single-chamber ICD patients without evidence of atrial arrhythmias at implant is associated with a greater likelihood of detecting AT/AF episodes. The management of these diagnosed arrhythmias often led to clinical interventions, mainly represented by initiation of OAC therapy.

Catecholaminergic Polymorphic Ventricular Tachycardia: Challenges During Resuscitation and Post-Cardiac Arrest Care.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare channelopathy involving cardiac calcium metabolism that often shows up at an early age with misleading clinical symptoms, such as emotion- or exercise-related syncope with a normal resting electrocardiogram. In addition, it might be the underlying cause of sudden cardiac arrest in children or young adults. The particular pathophysiology of CPVT makes it particularly challenging for both resuscitation and the subsequent intensive care management after return of spontaneous circulation (ROSC). CASE REPORT: We describe a case of sudden cardiac arrest in an 11-year-old girl affected by CPVT, with a particular focus on the most challenging aspects of resuscitation and intensive care management in light of other experiences found in the literature. A warning about the prodysrythmicity of mild hypothermia induced in the context of post-ROSC targeted temperature management in this particular population of patients and its possible physiopathological basis are discussed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: CPVT is a rare but potentially lethal cause of stress-related syncope and sudden cardiac arrest in children and young adults. The diagnosis of CPVT requires a high level of suspicion and an interdisciplinary approach, including some adjustments during resuscitation and post-cardiac arrest care.

Thorax Percutaneous Approach for Epicardial Ventricular Ablation in a Patient with Electrical Storm.

Subxiphoid puncture is considered the standard approach for epicardial ablation of ventricular arrhythmia, but in some cases this access is impracticable due to the patient's anatomy. We describe the case of a patient with electrical storm and abnormal subdiaphragmatic anatomy that precluded the usual subxiphoid approach. In this patient the pericardial space was gained through a direct thorax puncture at the fifth intercostals space close to the mammary line. The tools and technique utilized in this case were similar to what is usually used for traditional subxiphoid puncture. The thorax percutaneous puncture was successfully carried out without complication.

Left Ventricular Reverse Remodeling Elicited by a Quadripolar Lead: Results from the Multicenter Per4mer Study.

BACKGROUND: To understand the impact of a quadripolar left ventricular (LV) lead on reverse remodeling and phrenic nerve stimulation (PNS) in congestive heart failure patients treated by cardiac resynchronization therapy at 8-month follow-up (FU). METHODS: One hundred and fifty-eight patients received an LV Medtronic Performa lead (Medtronic Inc., Minneapolis, MN, USA) and were reevaluated at FU by echocardiography and measurement of electrical parameters. RESULTS: A targeted LV lead placement was achieved in 140 (89%) patients. Super responders and responders were 76 (50%) and 26 (18%), respectively, at FU; seven (4%) died and 13 (8%) were hospitalized for any cause. Nonischemic etiology was the only independent predictor of reverse remodeling. The configurations available only with the Performa leads reduced PNS occurrence at 8 V@0.4 ms from 43 (27%) to 14 (9%) of patients at implantation, and from 44 (28%) to 19 (12%) at last FU, compared to configurations available with bipolar leads. Patients with detectable PNS had >10/16 pacing configurations with a PNS safety margin >2 V both at implantation and at FU. During FU 16 (10%) patients had an adverse event possibly related to the lead or to modification of the underlying heart disease but 99% of these events were fixed by reprogramming of the pacing vector. CONCLUSIONS: Performa Lead enables an increased capability to achieve a targeted lead positioning in the broad clinical scenario of large- and small-volume implanting centers, with a relevant impact on the occurrence of reverse remodeling compared to literature data. The enhanced management of PNS resulted in a dislodgement rate of only 1%.

Cardiovascular safety of testosterone replacement therapy in men: an updated systematic review and meta-analysis.

INTRODUCTION: The cardiovascular (CV) safety of testosterone (T) replacement therapy (TRT) is still conflicting. Recent data suggested a TRT-related increased risk of atrial fibrillation (AF). The aim of this study was to systematic review and meta-analyze CV risk related to TRT as derived from placebo controlled randomized trials (RCTs). AREAS COVERED: An extensive Medline, Embase, and Cochrane search was performed. All placebo-controlled RCTs reporting data on TRT-related CV safety were considered. To better analyze the role of T on AF, population-based studies investigating the relationship between endogenous circulating T levels and AF incidence were also included and analyzed. EXPERT OPINION: Out of 3.615, 106 studies were considered, including 8.126 subjects treated with TRT and 7.310 patients allocated to placebo. No difference between TRT and placebo was observed when major adverse CV events were considered. Whereas the incidence of non-fatal arrhythmias and AF was increased in the only trial considering CV safety as the primary endpoint, this was not confirmed when all other studies were considered (MH-OR 1.61[0.84;3.08] and 1.44[0.46;4.46]). Similarly, no relationship between endogenous T levels and AF incidence was observed after the adjustment for confounders Available data confirm that TRT is safe and it is not related to an increased CV risk.

[Conduction disorders after transcatheter aortic valve implantation: incidence, characteristics, and clinical management]. / I disturbi di conduzione dopo impianto transcatetere di protesi aortica: incidenza, caratteristiche e gestione clinica.

Transcatheter aortic valve implantation may be complicated by the development of conduction disturbances, including left bundle branch block and high-grade atrioventricular blocks, especially in patients with predisposing risk factors, such as pre-existing right bundle branch block. Permanent pacemaker implantation is a procedure with potential short- and long-term complications, and it should be reserved to patients with appropriate indications. Electrophysiological testing and/or prolonged ambulatory ECG monitoring are valuable tools for stratifying the risk of pacemaker implantation. However, the management of new-onset conduction disorders is not always straightforward, and there are different approaches depending on the center's attitude. Therefore, the purpose of this review is to define clinical management based on current evidence, while awaiting data from randomized trials.

Inappropriate therapies in modern implantable cardioverter-defibrillators: A propensity score-matched comparison between single- and dual-chamber discriminators in single-chamber devices THe sINGle lead Study (THINGS Study).

BACKGROUND: In patients with implantable cardioverter-defibrillators (ICDs), inappropriate therapies (ITs) are often caused by supraventricular tachyarrhythmias (SVTs). OBJECTIVE: We aimed to estimate the incidence of IT in modern single-lead ICDs. METHODS: The THINGS study enrolled patients with single-lead ICDs with 2 SVT discrimination modalities: dual chamber (DC) with an atrial floating dipole or single chamber (SC) with morphology criterion. All devices were programmed with 2-zone therapy: ventricular tachycardia (VT) zone from 170 beats/min with ≥15 seconds (≥36 beats) detection time and SVT discriminators; and ventricular fibrillation (VF) zone from 214 beats/min with ≥7 seconds (≥24 beats) detection time. The primary end point was the first occurrence of IT, adjudicated by an independent board. RESULTS: A total of 526 patients (median age, 66 years; 83% male), 183 (34.8%) with DC and 343 (65.2%) with SC discrimination, were observed for a median of 2.2 years. The incidence rate of IT was 4.2% (95% confidence interval [CI], 2.7%-6.4%) at 1 year and 7.1% (95% CI, 5.0%-9.9%) at 2 years. Younger age (adjusted hazard ratio, 0.97; 95% CI, 0.95-0.99; P = .013) and history of atrial fibrillation (adjusted hazard ratio, 2.67; 95% CI, 1.30-5.46; P = .007) were significantly associated with increased IT risk. In a propensity score-matched comparison, DC discrimination showed a trend toward reduced IT rates compared with SC discrimination in the VT zone (1-year incidence, 1.8% vs 3.5%; P = .105). CONCLUSION: High-rate VF cutoff and prolonged detection time programming resulted in a low IT rate in single-lead ICD patients with modern SVT discriminators. A trend favoring the DC system was observed in the VT zone.

TeleNEwCARe: An Italian case-control telegenetics study in patients with Hereditary NEuromuscular and CARdiac diseases.

Telemedicine provides healthcare services remotely and represents a fundamental resource for the management of rare and fragile patients. Tele-health implementation is a main objective of the European Reference Networks (ERNs) mission to accelerate diagnosis for rare diseases. TeleNewCARe is a pilot case-control project which evaluates the efficacy and satisfaction of telegenetics for neuromuscular and cardiac adult patients, compared to face-to-face genetic counselling. The virtual sessions were co-hosted by a medical geneticist and a neurologist/cardiologist. Specific questionnaires (Clinical Genetics Satisfaction Questionnaire (CGS), Telemedicine Satisfaction Questionnaire (TSQ) and a Satisfaction Questionnaire for medical geneticists) were used to assess the effectiveness and fulfilment of telecounselling, both for patients and health care providers. Satisfaction expressed for telegenetics did not significantly differ from face-to-face counselling. The virtually enrolled patients declared they had the possibility to relate confidentially with the specialists, to share information and to be informed in an exhaustive way about their disease. Almost all patients declared themselves willing to reuse the telecounselling in the future. The multidisciplinary care was perceived as a significant added value. No overt technical problems were reported although the need for digital skills and tools can limit patients' compliance. Our experience supports telegenetics as a valid alternative to traditional genetic counselling in cardiac and neuromuscular patients. This innovative approach facilitates multidisciplinary care, grants a periodical follow up, without forcing patients to discomfortable travelling, and allows to maintain expert care. This result meets the ERNs needs to reduce patients' burden to access and monitor their healthcare.

SCN5A mutation is associated with a higher Shanghai Score in patients with type 1 Brugada ECG pattern.

AIMS: Brugada syndrome (BrS) is an inherited arrhythmic disease characterized by a coved ST-segment elevation in the right precordial electrocardiogram leads (type 1 ECG pattern) and is associated with a risk of malignant ventricular arrhythmias and sudden cardiac death. In order to assess the predictive value of the Shanghai Score System for the presence of a SCN5A mutation in clinical practice, we studied a cohort of 125 patients with spontaneous or fever/drug-induced BrS type 1 ECG pattern, variably associated with symptoms and a positive family history. METHODS: The Shanghai Score System items were collected for each patient and PR and QRS complex intervals were measured. Patients were genotyped through a next-generation sequencing (NGS) custom panel for the presence of SCN5A mutations and the common SCN5A polymorphism (H558R). RESULTS: The total Shanghai Score was higher in SCN5A+ patients than in SCN5A- patients. The 81% of SCN5A+ patients and the 100% of patients with a SCN5A truncating variant exhibit a spontaneous type 1 ECG pattern. A significant increase in PR (P = 0.006) and QRS (P = 0.02) was detected in the SCN5A+ group. The presence of the common H558R polymorphism did not significantly correlate with any of the items of the Shanghai Score, nor with the total score of the system. CONCLUSION: Data from our study suggest the usefulness of Shanghai Score collection in clinical practice in order to maximize genetic test appropriateness. Our data further highlight SCN5A mutations as a cause of conduction impairment in BrS patients.

Catheter Ablation of Well Tolerated Ventricular Tachycardia in Patients With Structural Heart Disease and Without Automatic Defibrillator Implantation: Long Term Follow-up.

The occurrence of a sustained monomorphic ventricular tachycardias (SMVT) in patients with underlying structural heart disease (SHD) is considered related to poor prognosis. The purpose of our work was to evaluate if these patients could benefit from radiofrequency (RF) ablation, and the defibrillator (ICD) implantation could be deferred during follow-up. We reviewed consecutive patients with well-tolerated SMVT, SHD and left ventricular ejection fraction over 30%. These patients were treated by RF ablation and were discharged without ICD. The primary outcome was a composite of all-cause death and recurrence of SMVT; the secondary outcome was death from all causes. Sixty-two patients were selected. After a median follow-up of 38.8 months, the primary outcome occurred in 24 (38.7%) and the secondary in 11 (17.7%) patients. The annual mortality rate was 4.3% and no patient died from sudden death. RF ablation as a first-choice therapy seems to represent an effective and beneficial therapeutic approach.

[Is it time to implement Cardiac Arrest Centers in Italy? The integrated experience in the decade 2009-2019 between metropolitan area and Maggiore Hospital of Bologna]. / È il momento per implementare i Centri per l'Arresto Cardiaco in Italia? L'esperienza integrata nel decennio 2009-2019 tra area metropolitana ed Ospedale Maggiore di Bologna.

Cardiac arrest (CA) is the third cause of death in Europe. This paper highlights the various treatments for the prevention and early management of CA and provides an overview of available evidence on the CA center concept. The experience of Maggiore Hospital of Bologna, Italy over the last 11 years is also outlined along with the treatments applied to patients with CA and their impact on improving outcomes. The new concept of the "Systems Saving Lives" approach is presented as a potential way for implementing Italian healthcare systems involved in the management of CA patients. Finally, the future perspective of implementation of CA centers in Italy is also described encouraging the healthcare professionals involved in the treatment of CA patients to consider a multidisciplinary approach (including a cardiologist, emergency physician, neurologist, physiatrist, radiologist, and intensivist).

[Brugada syndrome and early repolarization syndrome: similarities and differences. The lesson from case reports]. / Sindrome di Brugada e sindrome della ripolarizzazione precoce: affinità e differenze. La lezione dei casi clinici.

In subjects with cardiac arrest and aborted sudden death, the presence of an ECG pattern (spontaneous or drug-induced) suggesting a Brugada syndrome (BrS) is generally considered the proof of a BrS. We present three case reports of patients with resuscitated sudden death in whom a BrS was diagnosed, but in whom the real cause was probably an early repolarization syndrome (ERS). This distinction is not only theoretical but has also practical consequences. In fact, the arrhythmic substrate is different in the two conditions: right ventricular outflow tract in BrS, inferior ventricular wall in ERS. As a consequence, catheter ablation of the right ventricular outflow tract may be useful in BrS, whereas it is useless in ERS.

Mortality after cardioverter-defibrillator replacement: Results of the DECODE survival score index.

BACKGROUND: Device replacement is the ideal time to reassess health care goals regarding continuing implantable cardioverter-defibrillator (ICD) therapy. Only few data are available on the decision making at this time. OBJECTIVES: The goals of this study were to identify factors associated with poor prognosis at the time of ICD replacement and to develop a prognostic index able to stratify those patients at risk of dying early. METHODS: DEtect long-term COmplications after implantable cardioverter-DEfibrillator replacement (DECODE) was a prospective, single-arm, multicenter cohort study aimed at estimating long-term complications in a large population of patients who underwent ICD/cardiac resynchronization therapy - defibrillator replacement. Potential predictors of death were investigated, and all these factors were gathered into a survival score index (SUSCI). RESULTS: We included 983 consecutive patients (median age 71 years (63-78)); 750 (76%) were men, 537 (55%) had ischemic cardiomyopathy; 460 (47%) were implanted with cardiac resynchronization therapy - defibrillator. During a median follow-up period of 761 days (interquartile range 628-904 days), 114 patients (12%) died. In multivariate Cox regression analysis, New York Heart Association class III/IV, ischemic cardiomyopathy, body mass index < 26 kg/m2, insulin administration, age ≥ 75 years, history of atrial fibrillation, and hospitalization within 30 days before ICD replacement remained associated with death. The survival score index showed a good discriminatory power with a hazard ratio of 2.6 (95% confidence interval 2.2-3.1; P < .0001). The risk of death increased according to the severity of the risk profile ranging from 0% (low risk) to 47% (high risk). CONCLUSION: A simple score that includes a limited set of variables appears to be predictive of total mortality in an unselected real-world population undergoing ICD replacement. Evaluation of the patient's profile may assist in predicting vulnerability and should prompt individualized options, especially for high-risk patients.

Is electrocardiography a reliable tool for identifying patients with isthmus-dependent atrial flutter?

AIMS: To verify the reliability of the surface ECG to discriminate between cavotricuspid isthmus-dependent atrial flutter (CTI-AFL) and non-CTI-AFL. METHODS AND RESULTS: We reviewed the ECGs of 186 consecutive patients who underwent catheter ablation of AFL between January 2004 and January 2008. The ECG pattern was defined typical for CTI-AFL, if F-waves were: (i) dominantly negative in the inferior leads and positive in V1 (CCW) or (ii) dominantly positive in the inferior leads and negative in V1 (CW). At the electrophysiological study (EPS), 138 patients (74.2%) had a CTI-AFL and 48 patients (25.8%) had a non-CTI-AFL. A CTI-AFL was found not only in 90.5% of patients having a typical ECG, but also in 40% of patients having an atypical ECG. Thus, a typical AFL ECG showed a sensitivity of 0.83 and a specificity of 0.75 to predict a CTI-AFL, with a positive predictive value of 90.5% and a negative predictive value of 60%. CONCLUSION: Typical AFL ECG is a good predictor of CTI-AFL, and in this case, an ablation procedure can be recommended. On the contrary, an atypical AFL ECG does not rule out a CTI-AFL; so, even in this group of patients, an EPS should not be denied when indicated by the clinical circumstances.

[Premature ventricular beats: are they always benign? Diagnostic and therapeutic aspects]. / Extrasistolia ventricolare: è sempre benigna? Aspetti diagnostici e terapeutici.

Premature ventricular complexes (PVCs) are usually benign, and commonly only severely symptomatic patients are treated. In the literature, frequent PVCs have been reported to cause ventricular dysfunction, which may improve after PVC treatment. PVCs can also worsen the prognosis in patients with structural heart disease. Catheter PVC ablation is often the treatment of choice considering the high success rates. Ventricular dysfunction due to frequent PVCs is not always easy to identify as patients can be asymptomatic and the interpretation of imaging tests may be challenging in the presence of frequent PVCs. Treatment of patients with mild ventricular dysfunction is still a matter of debate.

Congenital myopathy with hanging big toe due to homozygous myopalladin (MYPN) mutation.

BACKGROUND: Myopalladin (MYPN) is a component of the sarcomere that tethers nebulin in skeletal muscle and nebulette in cardiac muscle to alpha-actinin at the Z lines. Autosomal dominant MYPN mutations cause hypertrophic, dilated, or restrictive cardiomyopathy. Autosomal recessive MYPN mutations have been reported in only six families showing a mildly progressive nemaline or cap myopathy with cardiomyopathy in some patients. CASE PRESENTATION: A consanguineous family with congenital to adult-onset muscle weakness and hanging big toe was reported. Muscle biopsy showed minimal changes with internal nuclei, type 1 fiber predominance, and ultrastructural defects of Z line. Muscle CT imaging showed marked hypodensity of the sartorius bilaterally and MRI scattered abnormal high-intensity areas in the internal tongue muscle and in the posterior cervical muscles. Cardiac involvement was demonstrated by magnetic resonance imaging and late gadolinium enhancement. Whole exome sequencing analysis identified a homozygous loss of function single nucleotide deletion in the exon 11 of the MYPN gene in two siblings. Full-length MYPN protein was undetectable on immunoblotting, and on immunofluorescence, its localization at the Z line was missed. CONCLUSIONS: This report extends the phenotypic spectrum of recessive MYPN-related myopathies showing: (1) the two patients had hanging big toe and the oldest one developed spine and hand contractures, none of these signs observed in the previously reported patients, (2) specific ultrastructural changes consisting in Z line fragmentation, but (3) no nemaline or caps on muscle pathology.

Cardiac arrest and Brugada syndrome: Is drug-induced type 1 ECG pattern always a marker of low risk?

BACKGROUND: Patients diagnosed as affected by Brugada syndrome (BrS) on the basis of a drug-induced type 1 ECG pattern (type1) are regarded as at low risk for cardiac arrest. We tested whether this assumption matches reality. METHODS: The study population included 26 patients from our group and 217 patients from three studies published between 2002 and 2013, all of them with aborted cardiac arrest (ACA) and in whom a previously unrecognized type1 (spontaneous or drug-induced) was discovered after the event, thus leading to the diagnosis of BrS. RESULTS: Among our 26 patients, a drug-induced type1 was detected in 11 (42%) and only 1/11 showed a spontaneous pattern during follow-up; of 6 patients with syncope before ACA, 4 (67%) had only a drug-induced pattern. ICD shocks rates were similar in both spontaneous and drug-induced groups (57% and 45%). Early on, year 2002, the percentage of drug-induced type1 after ACA was much lower (14%) and has progressively increased to approximately 50%. CONCLUSIONS: If drug-induced type1 carries low arrhythmic risk, it should seldom be the only marker for BrS after an ACA. In studies on patients after an unexpected ACA, a drug-induced type1 leads to the diagnosis of BrS more often than anticipated. This contrasts with prospective studies focusing on patients already diagnosed as BrS and which consider drug-induced type1 as a marker of low risk. Contrary to current views, it is possible that not all patients with a drug-induced BrS type1 are at low risk of future events.