Extracellular matrix remodeling precedes atrial fibrillation: Results of the PREDICT-AF trial.

BACKGROUND: To which extent atrial remodeling occurs before atrial fibrillation (AF) is unknown. OBJECTIVE: The PREventive left atrial appenDage resection for the predICtion of fuTure Atrial Fibrillation (PREDICT-AF) study investigated such subclinical remodeling, which may be used for risk stratification and AF prevention. METHODS: Patients (N = 150) without a history of AF with a CHA2DS2-VASc score of ≥2 at an increased risk of developing AF were included. The left atrial appendage was excised and blood samples were collected during elective cardiothoracic surgery for biomarker discovery. Participants were followed for 2 years with Holter monitoring to determine any atrial tachyarrhythmia after a 50-day blanking period. RESULTS: Eighteen patients (12%) developed incident AF, which was associated with increased tissue gene expression of collagen I (COL1A1), collagen III (COL3A1), and collagen VIII (COL8A2), tenascin-C (TNC), thrombospondin-2 (THBS2), and biglycan (BGN). Furthermore, the fibroblast activating endothelin-1 (EDN1) and sodium voltage-gated channel ß subunit 2 (SCN2B) were associated with incident AF whereas the Kir2.1 channel (KCNJ2) tended to downregulate. The plasma levels of COL8A2 and TNC correlated with tissue expression and predicted incident AF. A gene panel including tissue KCNJ2, COL1A1, COL8A2, and EDN1 outperformed clinical prediction models in discriminating incident AF. CONCLUSION: The PREDICT-AF study demonstrates that atrial remodeling occurs long before incident AF and implies future potential for early patient identification and therapies to prevent AF (ClinicalTrials.gov identifier NCT03130985).

Association Between Immigration Status and Acute Stroke Care: A Retrospective Study.

Background and Purpose- Immigrants to high-income countries have a lower incidence of stroke compared with long-term residents; however, little is known about the care and outcomes of stroke in immigrants. Methods- We used linked clinical and administrative data to conduct a retrospective cohort study of adults seen in the emergency department or hospitalized with ischemic stroke or transient ischemic attack between July 1, 2003, and April 1, 2013, and included in the provincial stroke registry. We ascertained immigration status using immigration records and compared processes of stroke care delivery between immigrants (defined as those immigrating after 1985) and long-term residents. In the subgroup with ischemic stroke, we calculated inverse probability treatment weight (IPTW)-adjusted risk ratios for disability on discharge (modified Rankin Scale score of 3 to 5), accounting for demographic characteristics and comorbid conditions to compare outcomes between immigrants and long-term residents. Results- We included 34 987 patients with ischemic stroke or transient ischemic attack, of whom 2649 (7.6%) were immigrants. Immigrants were younger than long-term residents at the time of stroke/transient ischemic attack (median age 67 years versus 76 years; P<0.001). In the subgroup with ischemic stroke, there were no differences in stroke care delivery, except that a higher proportion of immigrants received thrombolysis than long-term residents (21.2% versus 15.5%; P<0.001). Immigrants with ischemic stroke had a higher adjusted risk of being disabled on discharge (adjusted risk ratio, 1.18; 95% CI, 1.13-1.22) compared to long-term residents. Conclusions- Stroke care is similar in Canadian immigrants and long-term residents. Future research is needed to confirm the observed association between immigration status and disability after stroke and to identify factors underlying the association.

The Belgian experience with concomitant surgical ablation of atrial fibrillation: a multi-centre prospective registry.

Background: The Belgian 'National Institute for Health and Disability Insurance (RIZIV-INAMI)' requested prospective collection of data on all ablations in Belgium to determine the outcomes of surgical ablation of atrial fibrillation (AF) during concomitant cardiac surgery.Methods: 890 patients undergoing concomitant ablation for AF between 2011 and 2016 were prospectively followed. Freedom from AF with and without anti-arrhythmic drugs was calculated for 817 patients with follow-up beyond the 3-month blanking period and for 574 patients with sufficient rhythm-related follow-up consisting of at least one Holter registration or a skipped Holter due to AF being evident on ECG. Besides preoperative AF type, concomitant procedure and ablation, potential covariates were entered into uni- and multivariable regression models to determine predictors of outcome.Results: The overall freedom from AF beyond 3 months was 69.9% (571/817) and without anti-arrhythmic drugs at last follow-up 51.0% (417/817), respectively, 61.3% (352/574) and 44.4% (255/574) for patients with sufficient rhythm-related follow-up. Using a Kaplan-Meier estimate, freedom from AF was 89.3%, 74.9% and 59%, without antiarrhythmic drugs 74.4%, 47.8% and 32.3% at 6, 12 and 24 months, respectively. In-hospital mortality was 1.7% (15/890) and the overall survival was 95.0% at 1 year and 92.3% at 2 years. Preoperative left atrial diameter and AF type were significant predictive factors of freedom from AF in a multivariable analysis.Conclusion: Analysis of the Belgian national registry shows that concomitant surgical ablation of atrial fibrillation is safe, achieves favourable freedom from AF and, therefore, deserves to be performed in accordance to the guidelines.

Thoracoscopic vs. catheter ablation for atrial fibrillation: long-term follow-up of the FAST randomized trial.

AIMS: Our objectives were to compare effectiveness and long-term prognosis after epicardial thoracoscopic atrial fibrillation (AF) ablation vs. endocardial catheter ablation, in patients with prior failed catheter ablation or high risk of failure. METHODS AND RESULTS: Patients were randomized to thoracoscopic or catheter ablation, consisting of pulmonary vein isolation with optional additional lines (2007-2010). Patients were reassessed in 2016/2017, and those without documented AF recurrence underwent 7-day ambulatory electrocardiography. The primary rhythm outcome was recurrence of any atrial arrhythmia lasting >30 s. The primary clinical endpoint was a composite of death, myocardial infarction, or cerebrovascular event, analysed with adjusted Cox proportional hazard ratios (HRs). One hundred and 24 patients were randomized with 34% persistent AF and mean age 56 years. Arrhythmia recurrence was common at mean follow-up of 7.0 years, but substantially lower with thoracoscopic ablation: 34/61 (56%) compared with 55/63 (87%) with catheter ablation [adjusted HR 0.40, 95% confidence interval (CI) 0.25-0.64; P < 0.001]. Additional ablation procedures were performed in 8 patients (13%) compared with 31 (49%), respectively (P < 0.001). Eleven patients (19%) were on anti-arrhythmic drugs at end of follow-up with thoracoscopy vs. 24 (39%) with catheter ablation (P = 0.012). There was no difference in the composite clinical outcome: 9 patients (15%) in the thoracoscopy arm vs. 10 patients (16%) with catheter ablation (HR 1.11, 95% CI 0.40-3.10; P = 0.84). Pacemaker implantation was required in 6 patients (10%) undergoing thoracoscopy and 3 (5%) in the catheter group (P = 0.27). CONCLUSION: Thoracoscopic AF ablation demonstrated more consistent maintenance of sinus rhythm than catheter ablation, with similar long-term clinical event rates.

Evaluación del comportamiento cardíaco mediante una metodología diagnóstica basada en sistemas dinámicos en 16 horas / Evaluation of the cardiac behaviour with a diagnostic methodology sustained in dynamical systems in 16 hours

Antecedentes: Con conceptos provenientes de la teoría de sistemas dinámicos y la geometría fractal, se ha logrado caracterizar el comportamiento de la dinámica cardíaca, dando resultados objetivos y estableciendo distinciones entre estados de normalidad y enfermedad. Objetivo: Aplicar una ley matemática exponencial de la dinámica cardíaca, inscrita en el contexto de los sistemas dinámicos y la geometría fractal, para evidenciar su utilidad diagnóstica en 16 horas. Materiales y métodos: Fueron empleados 200 Holters y registros electrocardiográficos continuos, entre normales y con diferentes alteraciones cardíacas. Se simuló una secuencia de frecuencias cardíacas en 16 y 21 horas, con la cual se construyó el atractor de cada dinámica. También se calculó la dimensión fractal y la ocupación de los atractores en el espacio fractal. Se estableció el diagnóstico físico-matemático en 16 y 21 horas y la subsecuente validación estadística. Resultados: Fueron obtenidos valores en la rejilla Kp entre 44 y 198 para estados patológicos y entre 221 y 377 para estados de normalidad en 16 horas, la sensibilidad y especificidad fue del 100% y el coeficiente Kappa de 1. Conclusión: Se logró diferenciar de manera adecuada estados normales de patológicos mediante la ley exponencial aplicada en registros de 16 horas

Background: With concepts derived from dynamical systems theory and fractal geometry, it has been possible to characterize the behavior of the cardiac dynamics, giving objective results and estabishing distinctions between states of normality and disease. Objective: To apply an exponential mathematical law of cardiac dynamics, inscribed in the context of dynamical systems and fractal geometry, to demonstrate its diagnostic utility in the context of a reduction in the evaluation time, originally of 21 hours. Materials and methods: There were used 200 Holters and cotinuous electrocardiographic records, between normal and with different cardiac alterations. A sequence of heart rates was simulated in 16 and 21 hours, with which the attractor of each dynamic was constructed. There were also calculated the fractal dimension and the occupation of the attractors in the fractal space. The physical-mathematical diagnosis was establishd at 16 and 21 hours, and the staqtistical validation was performed. Results: Values obtained in the Kp grid were between 44 y 198 for pathological sttes, and between 221 and 377 for normal states in 16 hours. The sensitivity and specificity was 100% and the Kappa coefficient was 1. Conclusion: It was possible to differentiate adequately normal states of pathological by means fo the exponential law applied in registers of 16 hours

The analysis of the parameters of 24-hr ECG Holter monitoring in patients with blood neoplasms undergoing high-dose chemotherapy and stem cell transplantation.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a widely used procedure in the treatment of malignant diseases, including blood neoplasms and has increased survival in hematological diseases. The aim of the study was to analyze parameters of 24-hr ECG monitoring in patients with selected blood neoplasms in whom the procedure of hematopoietic stem cell transplantation was performed. METHODS: The study group consisted of 64 adults diagnosed with hematologic cancer qualified for HSCT with the previous high dose chemotherapy (HDC). In all patients 24-hr Holter monitoring was carried out twice. First examination took place prior to the HSCT procedure, and the second after finishing the procedure of HSCT. RESULTS: The minimal and mean heart rate (HR min and HR max) from 24-hr ECG recording was statistically significantly higher after the transplantation in comparison with the first test. The number of premature ventricular complexes (PVCs) was higher in the test after HSCT. In the second examination there was significantly higher percentage of premature ventricular complexes, incidents of tachycardia, and Mobitz type 1 second degree atrioventricular block. In regression analysis, in a group of patients with blood neoplasms after HSCT and HDC, administration of cyclophosphamide, fludarabine and total body irradiation were independent risk factors for electrocardiographic abnormalities in 24-hr Holter monitoring, that is, the increase in HR min, HR mean and PVCs. CONCLUSION: In patients with blood neoplasms undergoing HSCT more electrocardiographic abnormalities may be found after this procedure in comparison with the 24-hr Holter monitoring before transplantation.

The Impact of First Procedure Success Rate on the Economics of Atrial Fibrillation Ablation.

OBJECTIVES: The purpose of this study was to compare health care costs associated with repeat ablation of atrial fibrillation (AF) with health care costs associated with a successful first procedure. BACKGROUND: Catheter ablation has become established as a rhythm control strategy for symptomatic paroxysmal and persistent AF. The economic impact of ablation is not completely understood, and it may be affected by repeat procedures performed for recurrent AF. METHODS: The source of data was the MarketScan (Truven Health, Ann Arbor, Michigan) administrative claims dataset from April 2008 to March 2013, including U.S. patients with private and Medicare supplemental insurance. Patients who underwent an outpatient atrial ablation procedure and a diagnosis of AF were identified. Total health care cost was calculated for 1 year before and after the ablation. Patients were categorized as having undergone a repeat ablation if an additional ablation was performed in the following year. RESULTS: Of 12,027 patients included in the study, repeat ablation was performed in 2,066 (17.2%) within 1 year. Patients with repeat ablation had higher rates of emergency department visits (43.4% vs. 32.2%; < 0.001) and subsequent hospitalization (35.6% vs. 21.5%; p < 0.001), after excluding hospitalizations for the repeat procedure. Total medical cost was higher for patients with repeat ablation ($52,821 vs. $13,412; p < 0.001), and it remained 46% higher even after excluding the cost associated with additional ablations ($19,621 vs. $13,412; p < 0.001). CONCLUSIONS: Health care costs are significantly higher for patients with a repeat ablation for AF than for patients with only a single ablation procedure, even though both groups have similar baseline characteristics. The increased costs persist even after excluding the cost of the repeat ablation itself. These results emphasize the economic benefit of procedural success in AF ablation.

Demographic and Clinical Characteristics to Predict Paroxysmal Atrial Fibrillation: Insights from an Implantable Loop Recorder Population.

BACKGROUND: There is growing interest in detecting paroxysmal atrial fibrillation (PAF) to identify patients at high risk of thromboembolic stroke. The implantable loop recorder (ILR) is emerging as a powerful new tool in the diagnosis of PAF. Widespread implantation has significant cost implications and their use must be targeted at those patients at most risk. METHODS: We retrospectively studied a population of 200 adult patients who underwent ILR implantation for the investigation of syncope or palpitations. Clinical data, baseline electrocardiogram (ECG) characteristics, and echocardiographic data were collected. All ECGs and electrograms (EGMs) were scrutinized by two blinded investigators. PAF incidence was defined as episodes lasting >30 seconds on EGMs recorded in ILR memory. RESULTS: Our ILR population consists of 200 patients, 111 (56%) male, with a mean age of 61.4 years (range 19-95). PAF was detected in 42 patients. The following factors were significant predictors of PAF by multivariate logistic regression analysis: cigarette smoking (odds ratio [OR] = 3.73, 95% confidence interval [CI] = 1.40-10.24, P = 0.009) and incomplete right bundle branch block (IRBBB; OR = 9.04, 95% CI = 2.51-34.64, P = 0.00088). Significant differences included incidence of IRBBB (P = 0.012), cigarette smoking (P = 0.026), hypercholesterolemia (P = 0.015), age (P = 0.002), estimated glomerular filtration rate (P = 0.031), left atrial volume (P = 0.019), and PR interval (P = 0.031). The PAF group had significantly higher CHA2 DS2 -VASc scores (P = 0.01). CONCLUSIONS: Our study reports predictive factors for PAF in an ILR population. We suggest that cigarette smoking and IRBBB are independently associated with paroxysmal AF in patients presenting with palpitations or syncope.

Ventricular tachycardias in patients with pulmonary hypertension: an underestimated prevalence? A prospective clinical study.

BACKGROUND: Sudden cardiac death (SCD) accounts for approximately 30 % in patients with pulmonary arterial hypertension (PAH). The exact circumference for SCD in this patient population is still unclear. Malignant cardiac arrhythmias are reported to be rarely present. There are no systematic data concerning long-term electrocardiographic (ECG) recording in patients with PAH. OBJECTIVES: We sought to investigate the rate of potentially relevant arrhythmias in patients with pulmonary hypertension (PH). METHODS: Consecutive patients without diagnosis of known cardiac arrhythmias followed in our outpatient clinic for PH were enrolled in the study. All patients underwent a 72-h Holter ECG. Clinical data, 6-min walk distance, laboratory values, and echocardiography were collected/performed. RESULTS: Ninety-two consecutive patients (New York Heart Association class (NYHA) III/IV: 65.2 %/5.4 %, PH Group 1: 35.9 %, Group 3: 10.9 %, Group 4: 28.3 %, Group 5: 2.2 %) were investigated. Relevant arrhythmias were newly detected in 17 patients: non-sustained ventricular tachycardia (n = 12), intermittent second-degree heart block (n = 1), intermittent third-degree heart block (n= 3), and atrial flutter (n = 1). Echocardiographic systolic pulmonary pressure and diameter of the right heart were elevated in patients with relevant arrhythmias. Right heart catheterization revealed higher pulmonary vascular resistance (672 vs. 542 dyn · s · cm(-5), p = 0.247) and lower cardiac index (2.46 vs. 2.82 l/min/m(2), p = 0.184). CONCLUSIONS: Ventricular tachycardias occur more often in PH patients than previously reported. However, the prognostic relevance of non-sustained ventricular tachycardias in this cohort remains unclear. As a large number of PH patients die from SCD, closer monitoring, e.g., using implantable event recorders, might be useful to identify patients at high risk.

Experience with Holter monitoring during propranolol therapy for infantile hemangiomas.

BACKGROUND: Although adverse events in children treated with propranolol have proven rare, the appropriate methods of assessing cardiovascular risk and monitoring for toxicity when the medication is used for infantile hemangiomas remain unclear. OBJECTIVE: We sought to analyze Holter monitor reports of otherwise healthy patients on propranolol for infantile hemangiomas to determine the incidence of sustained arrhythmias and to evaluate the utility of Holter monitoring in the outpatient setting. METHODS: We retrospectively reviewed the charts of patients with infantile hemangioma who underwent 24-hour Holter monitoring after initiation or dose escalation of propranolol between 2011 and 2014. RESULTS: In all, 43 patients aged 1.8 to 36.2 months, with 44 Holter monitor reports, were included in the study. No sustained arrhythmias were revealed. The treatment plan was not altered in any patient based on the Holter monitor report. LIMITATIONS: This was a retrospective study design. CONCLUSION: Our study suggests that Holter monitoring may be unnecessary in otherwise healthy patients with infantile hemangioma older than 12 weeks who are treated with propranolol in the outpatient setting.

[Choosing wisely: the Top 5 list of the Italian Association of Hospital Cardiologists (ANMCO)]. / "Fare di più non significa fare meglio". Le proposte dell'ANMCO.

In recent years, a progressive increase in the number of medical diagnostic and interventional procedures has been observed, namely in cardiology. A significant proportion of them appear inappropriate, i.e. potentially redundant, harmful, costly, and useless. Recently, the document Medical Professionalism in the New Millennium: A Physician Charter, the American Board of Internal Medicine (ABIM) Foundation Putting the Charter into Practice program, JAMA's Less Is More and BMJ's Too Much Medicine series, and the American College of Physicians' High-Value, Cost-Conscious Care initiatives, have all begun to provide direction for physicians to address pervasive overuse in health care. In 2010, the Brody's proposal to scientific societies to indicate the five medical procedures at high inappropriateness risk inspired the widely publicized ABIM Foundation's Choosing Wisely campaign. As part of Choosing Wisely, each participating specialty society has created lists of Things Physicians and Patients Should Question that provide specific, evidence-based recommendations physicians and patients should discuss to help make wise decisions about the most appropriate individual care. In Italy, Slow Medicine launched the analogue campaign Fare di più non significa fare meglio. The Italian Association of Hospital Cardiologists (ANMCO) endorsed the initiative by recognizing the need to optimize available resources, reduce costs and avoid unnecessary cardiovascular assessments, thereby enhancing the more efficient care delivery models. An ad hoc ANMCO Working Group prepared a list of five cardiac procedures that seem inappropriate for routine use in our country and, after an internal revision procedure, these are presented here.

Are patients admitted to emergency departments with regular supraventricular tachycardia (SVT) treated appropriately?

Regular supraventricular tachycardia (SVT) is frequently encountered in clinical practice. Guidelines are available from the National Service Framework (NSF) for the treatment of patients attending emergency departments (ED) with SVT. These recommend a thyroid-function test (TFT) and arrhythmia electrocardiography (ECG), and referral to a heart-rhythm specialist on discharge. Hospital admission is rarely required. In our multicentre study, we examined the implementation of these guidelines among patients attending the ED with SVT. Only 34% of patients had specialist referrals, with an average wait of 50.3 days (the majority of delays resulted from referral requests from general practitioners). A history of previous SVT, the mode of tachycardia termination, patient age and/or comorbidities were similar for the 27 (23.5%) patients who were admitted overnight. Of these, 15 (13%) of the total 115 patients who attended ED with regular SVT were referred for Holter monitoring despite having ECGs demonstrating arrhythmia. Low referral rates, unnecessary investigations and admissions indicate a need for improvement for better patient care and to minimise healthcare costs. We have formulated a standard operating procedure, which will be available via the College of Emergency Medicine website.

What is the best pre-operative risk stratification tool for major adverse cardiac events following elective vascular surgery? A prospective observational cohort study evaluating pre-operative myocardial ischaemia monitoring and biomarker analysis.

Although brain natriuretic peptide has been shown to be superior to the revised cardiac risk index for risk stratification of vascular surgical patients, it remains unknown whether it is superior to alternative dynamic risk predictors, such as other pre-operative biomarkers (C-reactive protein and troponins) or myocardial ischaemia monitoring. The aim of this prospective observational study was to determine the relative clinical utility of these risk predictors for the prediction of postoperative cardiac events in elective vascular surgical patients. Only pre-operative troponin elevation (OR 56.8, 95% CI 6.5-496.0, p < 0.001) and brain natriuretic peptide above the optimal discriminatory point (OR 6.0, 95% CI 2.7-12.9, p < 0.001) were independently associated with cardiac events. Both brain natriuretic peptide and troponin risk stratification significantly improved overall net reclassification (74.6% (95% CI 51.6%-97.5%) and 38.5% (95% CI 22.4-54.6%, respectively)); however, troponin stratification decreased the correct classification of patients with cardiac complications (-59%, p < 0.001). Pre-operative brain natriuretic peptide evaluation was the only clinically useful predictor of postoperative cardiac complications.

Identification of low and high frequency ranges for heart rate variability and blood pressure variability analyses using pharmacological autonomic blockade with atropine and propranolol in swine.

Understanding autonomic nervous system functioning, which mediates behavioral and physiological responses to stress, offers great potential for assessing farm animal stress and welfare. Evaluation of heart rate variability (HRV) and blood pressure variability (BPV), using time and frequency domain analyses may provide a sensitive and reliable measure of affective states and stress-mediated changes in sympathetic and parasympathetic tones. The aim of this research was to define low (LF) and high frequency (HF) power spectral ranges using pharmacological autonomic blockade, and to examine HRV and BPV parameter changes in response to atropine and propranolol in swine. Ten, 13-week old, barrows (n=6) and gilts (n=4) underwent surgery to place an intra-cardiac electrode and a blood pressure catheter attached to a biotelemetric transmitter; pigs had a 3-week recovery period prior to data collection. Each pig was subjected to administration of 4 intravenous (i.v.) drug treatments: a control treatment, 3 mL of saline, and 3 blockade treatments; 0.1 mg/kg of atropine, 1.0 mg/kg of propranolol, and .1 mg/kg of atropine together with 1.0 mg/kg of propranolol. All treatments were delivered by injection in the jugular vein with a minimum of 48 h between individual treatments. Behavior, ECG and blood pressure data were recorded continuously for a total of 1h, from 30 min pre-injection to 30 min post-injection. For data analyses, two 512-beat intervals were selected for each treatment while the pig was lying and inactive. The first interval was selected from the pre-injection period (baseline), and the second was selected between 10 and 30 min post-injection. Time and frequency domain (power spectral density) analyses were performed on each data interval. Subsequent, LF and HF bands from the power spectral densities were defined based on general linear and regression analyses. The HRV and BPV were computed with a covariate (baseline) factorial analysis of treatment by sex interaction, and day of injection, with mixed models and Tukey's post-hoc tests. The best-fit range for LF was 0.0-0.09 Hz, and HF was 0.09-2.0 Hz (r²: 0.41 and 0.43, respectively). Propranolol and saline injections led to a greater overall total power and overall higher inter-beat interval, HF and LF power. Atropine led to a dominant sympathovagal balance of the cardiac activity in pigs. In addition, atropine led to an increase in LF power of both systolic and diastolic blood pressures in gilts suggesting vagal tone mediation of BPV. The understanding of autonomic regulation of HRV and BPV in domestic swine facilitates our ability to detect and quantify stress responses, and broadens its application in assessing farm animal welfare.

Early detection of adverse events with daily remote monitoring versus quarterly standard follow-up program in patients with CRT-D.

BACKGROUND: A relative high rate of clinical and device-related adverse events (AE) is generally reported in patients with implantable defibrillators for cardiac resynchronization therapy (CRT-D). Aim of this study was to compare a daily remote monitoring (RM) to a standard program of in-office visits. METHODS AND RESULTS: We retrospectively analyzed RM database and hospital files of 99 CRT-D consecutive patients who were visited in the out-patient clinic every 3-4 months; thirty-three patients were in addition controlled remotely with RM (RM group). Kaplan-Meier curves of clinical or device-related AE-free rates were obtained. During a median follow-up of 7 months, clinical AEs were: ventricular and atrial arrhythmias in 14 and 11 patients, low CRT pacing in nine, heart failure, strokes, or death in 15. Device-related AEs were: insufficient pacing/sensing performances in nine patients, lead dislodgement in five. As comparing the RM group with the remaining patients, Kaplan-Meier curves of clinical AEs diverged to significantly different rates: 23.8% (confidence interval [CI] 0.1%-47.5%) in the RM group and 48.7% (21.6-75.7%) in the remaining patients (P = 0.00002), with a hazard ratio of 0.14 (CI 0.06-0.37). Nondivergent Kaplan-Meier curves were obtained for device-related AE-free rates. CONCLUSION: CRT-D patients followed with quarterly in-office visits without a daily RM system had an 86% higher risk of delayed detection of clinical AEs, during a median follow-up of 7 months.

Use of high-frequency peak in spectral analysis of heart rate increment to improve screening of obstructive sleep apnoea.

PURPOSE: Several studies have correlated the ratio of the very low frequency power spectral density of heart rate increment (%VLFI) with obstructive sleep apnoea syndrome (OSAS). However, patients with impaired heart rate variability may exhibit large variations of heart rate increment (HRI) spectral pattern and alter the screening accuracy of the method. METHODS: To overcome this limitation, the present study uses the high-frequency increment (HFI) peak in the HRI spectrum, which corresponds to the respiratory influence on RR variations over the frequency range 0.2 to 0.4 Hz. We evaluated 288 consecutive patients referred for snoring, observed nocturnal breathing cessation and/or daytime sleepiness. Patients were classified as OSAS if their apnoea plus hypopnoea index (AHI) during polysomnography exceeded 15 events per hour. Synchronized electrocardiogram Holter monitoring allowed HRI analysis. RESULTS: Using a %VLFI threshold >2.4% for identifying the presence of OSAS, sensitivity for OSAS was 74.9%, specificity 51%, positive predictive value 54.9% and negative predictive value 71.7% (33 false negative subjects). Using threshold for %VLFI >2.4% and HFI peak position >0.4 Hz, negative predictive value increased to 78.2% while maintaining specificity at 50.6%. Among 11 subjects with %VLFI <2.4% and HFI peak >0.4 Hz, nine demonstrated moderate to severe OSAS (AHI >30). CONCLUSIONS: HFI represents a minimal physiological criterion for applying %VLFI by ensuring that heart rate variations are band frequency limited.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy diagnostic task force criteria: impact of new task force criteria.

BACKGROUND: Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) Diagnostic Task Force Criteria (TFC) proposed in 1994 are highly specific but lack sensitivity. A new international task force modified criteria to improve diagnostic yield. A comparison of diagnosis by 1994 TFC versus newly proposed criteria in 3 patient groups was conducted. METHODS AND RESULTS: In new TFC, scoring by major and minor criteria is maintained. Structural abnormalities are quantified and TFC highly specific for ARVD/C upgraded to major. Furthermore, new criteria are added: terminal activation duration of QRS > or = 55 ms, ventricular tachycardia with left bundle-branch block morphology and superior axis, and genetic criteria. Three groups were studied: (1) 105 patients with proven ARVD/C according to 1994 TFC, (2) 89 of their family members, and (3) 39 patients with probable ARVD/C (ie, 3 points by 1994 TFC). All were screened for pathogenic mutations in desmosomal genes. Three ARVD/C patients did not meet the new sharpened criteria on structural abnormalities and thereby did not fulfill new TFC. In 62 of 105 patients with proven ARVD/C, mutations were found: 58 in the gene encoding Plakophilin2 (PKP2), 3 in Desmoglein2, 3 in Desmocollin2, and 1 in Desmoplakin. Three patients had bigenic involvement. Ten additional relatives (11%) fulfilled new TFC: 9 (90%) were female, and all carried PKP2 mutations. No relatives lost diagnosis by application of new TFC. Of patients with probable ARVD/C, 25 (64%) fulfilled new TFC: 8 (40%) women and 14 (56%) carrying pathogenic mutations. CONCLUSIONS: In this first study applying new TFC to patients suspected of ARVD/C, 64% of probable ARVD/C patients and 11% of family members were additionally diagnosed. ECG criteria and pathogenic mutations especially contributed to new diagnosis. Newly proposed TFC have a major impact in increasing diagnostic yield of ARVD/C.

Influence of heavy cigarette smoking on heart rate variability and heart rate turbulence parameters.

BACKGROUND: Cigarette smoking increases the risk of cardiovascular events related with several mechanisms. The most suggested mechanism is increased activity of sympathetic nervous system. Heart rate variability (HRV) and heart rate turbulence (HRT) has been shown to be independent and powerful predictors of mortality in a specific group of cardiac patients. The goal of this study was to assess the effect of heavy cigarette smoking on cardiac autonomic function using HRV and HRT analyses. METHODS: Heavy cigarette smoking was defined as more than 20 cigarettes smoked per day. Heavy cigarette smokers, 69 subjects and nonsmokers 74 subjects (control group) were enrolled in this study. HRV and HRT analyses [turbulence onset (TO) and turbulence slope (TS)] were assessed from 24-hour Holter recordings. RESULTS: The values of TO were significantly higher in heavy cigarette smokers than control group (-1.150 +/- 4.007 vs -2.454 +/- 2.796, P = 0.025, respectively), but values of TS were not statistically different between two groups (10.352 +/- 7.670 vs 9.613 +/- 7.245, P = 0.555, respectively). Also, the number of patients who had abnormal TO was significantly higher in heavy cigarette smokers than control group (23 vs 10, P = 0.006). TO was correlated with the number of cigarettes smoked per day (r = 0.235, P = 0.004). While LF and LF/HF ratio were significantly higher, standard deviation of all NN intervals (SDNN), standard deviation of the 5-minute mean RR intervals (SDANN), root mean square of successive differences (RMSSD), and high-frequency (HF) values were significantly lower in heavy smokers. While, there was significant correlation between TO and SDNN, SDANN, RMSSD, LF, and high frequency (HF), only HF was correlated with TS. CONCLUSION: Heavy cigarette smoking has negative effect on autonomic function. HRT is an appropriate noninvasive method to evaluate the effect of cigarette on autonomic function. Simultaneous abnormal HRT and HRV values may explain increased cardiovascular event risk in heavy cigarette smokers.

Association between symptoms of depression and anxiety with heart rate variability in patients with implantable cardioverter defibrillators.

OBJECTIVE: This study investigated whether depression and anxiety symptoms are associated with measures of autonomic nervous system dysfunction in patients with implantable cardioverter defibrillators who are at high risk of cardiac rhythm disturbances. Depression and anxiety are associated with autonomic nervous system dysfunction, which may promote the risk of malignant cardiac arrhythmias. METHODS: Patients with an implantable cardioverter defibrillator (ICD) underwent ambulatory electrocardiographic (ECG) monitoring (n = 44, mean age = 62.1 +/- 9.3 years). Depression was assessed using the Beck Depression Inventory and anxiety was evaluated using the Taylor Manifest Anxiety Scale. Heart rate variability was assessed using time (RMSSD, pNN50, and SDNN) and frequency domain measures derived from 24-hour R-R intervals. Multivariate models were adjusted for age, sex, hypertension, diabetes, and smoking status. RESULTS: Defibrillator patients with elevated depression symptoms (n = 12) had significantly lower RMSSD (15.25 +/- 1.66 ms versus 24.97 +/- 2.44 ms, p = .002) and pNN50 (1.83 +/- 0.77 versus 5.61 +/- 1.04, p = .006) than defibrillator patients with low depression symptoms (n = 32). These associations remained significant after multivariate adjustment for covariates. ICD patients with high anxiety levels (n = 10) displayed lower RMSSD (p = .013), which became marginally significant when adjusting for covariates (p = .069). CONCLUSIONS: Depression and anxiety in defibrillator patients are associated with autonomic nervous system dysfunction indices of reduced parasympathetic control. Autonomic nervous system dysfunction may partially explain the association between depression and anxiety with life-threatening cardiac outcomes in vulnerable patients.