Growth/differentiation factor-15 (GDF-15) as a predictor of serious arrhythmic events in patients with nonischemic dilated cardiomyopathy.

INTRODUCTION: Cardiac biomarkers have been proposed as a new tool to improve risk stratification of serious arrhythmic events in patients with heart failure (HF) beyond estimates of left ventricular ejection fraction. Growth differentiation factor (GDF)-15, a stress-induced cytokine, has been found to correlate with markers of myocardial fibrosis and adverse clinical outcomes, but its role as a predictor of arrhythmic events in patients with nonischemic HF is uncertain. METHODS AND RESULTS: A prospective observational study was conducted in 148 nonischemic patients with HF who underwent comprehensive clinical and laboratory evaluation, including measurement of serum GDF-15. The study endpoints were serious arrhythmic events (which included appropriate implantable cardioverter-defibrillator therapy and sudden cardiac death) and all-cause mortality. Mean age of the cohort was 54.8 ± 12.7 years, and mean left ventricular ejection fraction (LVEF) was 27.4% ± 7.5%. During a mean follow-up time of 42 months, arrhythmic events occurred in 28 patients (19%), and 40 patients (27%) died. An increase in serum GDF-15 (log-transformed) correlated linearly with a higher risk of serious arrhythmic events (HR 1.14, 95% CI 1.01-1.28, p = 0.03) even after adjustment for other potential clinical predictors (HR 1.16, 95% CI 1.02-1.32, p = 0.02). GDF-15 was also strongly and independently associated with all-cause mortality (HR 1.17, 1.05-1.31, p = 0.004). CONCLUSION: In this cohort of nonischemic HF patients on optimized medical treatment, serum GDF-15 levels were independently associated with major arrhythmic events and overall mortality. This biomarker may add prognostic information to better stratify the risk of sudden death in this particular population.

Effect of caffeine on ventricular arrhythmia: a systematic review and meta-analysis of experimental and clinical studies.

AIMS: The relationship between caffeine consumption and the occurrence of arrhythmias remains controversial. Despite this lack of scientific evidence, counselling to reduce caffeine consumption is still widely advised in clinical practice. We conducted a systematical review and meta-analysis of interventional studies of the caffeine effects on ventricular arrhythmias. METHODS AND RESULTS: The search was performed on Pubmed, Embase, and Cochrane database, and terms related to coffee, caffeine, and cardiac arrhythmias were used. Methodological quality was assessed based on The Cochrane Collaboration recommendations and the ARRIVE guidelines. There were 2016 citations retrieved on the initial research. After full-text assessment, seven human and two animal studies were included in the meta-analysis. In animal studies, the main outcome reported was the ventricular fibrillation threshold. We observed a significant mean difference of -2.15 mA (95% CI -3.43 to -0.87; I(2) 0.0%, P for heterogeneity = 0.37). The main outcome evaluated in human studies was the rate of ventricular premature beats (VPBs). The overall relative risk for occurrence of VPBs in 24 h attributed to caffeine exposure was 1.00 (95% CI 0.94-1.06; I(2) 13.5%, P for heterogeneity = 0.32). Sensitivity analysis for caffeine dose, different designs, and subject profile was performed and no major differences were observed. CONCLUSION: Our meta-analysis demonstrates that data from human interventional studies do not show a significant effect of caffeine consumption on the occurrence of VBPs. The effects observed in animal studies are most probably the result of very high caffeine doses that are not regularly consumed in a daily basis by humans.

Sudden cardiac death in Brazil: study based on physicians' perceptions of the public health care system.

BACKGROUND: There are no available statistical data about sudden cardiac death in Brazil. Therefore, this study has been conducted to evaluate the incidence of sudden cardiac death in our population and its implications. METHODS: The research methodology was based on Thurstone's Law of Comparative Judgment, whose premise is that the more an A stimulus differs from a B stimulus, the greater will be the number of people who will perceive this difference. This technique allows an estimation of actual occurrences from subjective perceptions, when compared to official statistics. Data were collected through telephone interviews conducted with Primary and Secondary Care physicians of the Public Health Service in the Metropolitan Area of São Paulo (MASP). RESULTS: In the period from October 19, 2009, to October 28, 2009, 196 interviews were conducted. The incidence of 21,270 cases of sudden cardiac death per year was estimated by linear regression analysis of the physicians' responses and data from the Mortality Information System of the Brazilian Ministry of Health, with the following correlation and determination coefficients: r = 0.98 and r(2) = 0.95 (95% confidence interval 0.8-1.0, P < 0.05). The lack of waiting list for specialized care and socioadministrative problems were considered the main barriers to tertiary care access. CONCLUSIONS: The incidence of sudden cardiac death in the MASP is high, and it was estimated as being higher than all other causes of deaths; the extrapolation technique based on the physicians' perceptions was validated; and the most important bureaucratic barriers to patient referral to tertiary care have been identified. (PACE 2012; 35:1326-1331).

Cardiopulmonary exercise testing may not predict appropriate implantable cardioverter defibrillator therapies in heart failure patients.

Background: The prognostic value of cardiopulmonary exercise testing (CPET) variables for major cardiovascular events in patients with heart failure (HF) is widely established. However, the prognostic value of these variables as predictors of appropriate implantable cardioverter-defibrillator (ICD) therapies has not been sufficiently well addressed. This study aimed to evaluate CPET variables such as peak oxygen uptake (VO2 peak), relationship between change in minute ventilation (VE) and carbon dioxide output (VCO2) during incremental exercise (VE/VCO2 slope) and exercise-related periodic breathing (EPB) as appropriate ICD therapy predictors in HF patients.Methods: We retrospectively assessed 61 HF patients who underwent CPET and had ICD implanted for primary prevention. Patients were followed for 767 ± 601 days. Primary outcome was appropriate ICD-delivered therapy, either anti-tachycardia pacing (ATP) or shock.Results: The sample consisted mostly of male patients (65.6%), with severe ventricular dysfunction (mean left ventricular ejection fraction (LVEF) 27 ± 6%). The primary outcome occurred in 20 patients (32%). There were no significant differences in VO2 peak (17.7 ± 4.1 and 16.9 ± 4.5 mL/kg/min), VE/VCO2 slope (39.7 ± 8.4 and 39.6 ± 10.2) or EPB prevalence (20% and 19.5%) in patients with or without appropriate ICD therapy. According to Cox regression analysis, none of the CPET variables were significant predictors of appropriate ICD therapy.Conclusions: In this cohort study of HF patients, CPET variables did not predict appropriate ICD therapies. Further studies with large number of patients are warranted to address this issue.

Short-term Effects of High-Dose Caffeine on Cardiac Arrhythmias in Patients With Heart Failure: A Randomized Clinical Trial.

IMPORTANCE: The presumed proarrhythmic action of caffeine is controversial. Few studies have assessed the effect of high doses of caffeine in patients with heart failure due to left ventricular systolic dysfunction at high risk for ventricular arrhythmias. OBJECTIVE: To compare the effect of high-dose caffeine or placebo on the frequency of supraventricular and ventricular arrhythmias, both at rest and during a symptom-limited exercise test. DESIGN, SETTING, AND PARTICIPANTS: Double-blinded randomized clinical trial with a crossover design conducted at the heart failure and cardiac transplant clinic of a tertiary-care university hospital. The trial included patients with chronic heart failure with moderate-to-severe systolic dysfunction (left ventricular ejection fraction <45%) and New York Heart Association functional class I to III between March 5, 2013, and October 2, 2015. INTERVENTIONS: Caffeine (100 mg) or lactose capsules, in addition to 5 doses of 100 mL decaffeinated coffee at 1-hour intervals, for a total of 500 mg of caffeine or placebo during a 5-hour protocol. After a 1-week washout period, the protocol was repeated. MAIN OUTCOMES AND MEASURES: Number and percentage of ventricular and supraventricular premature beats assessed by continuous electrocardiographic monitoring. RESULTS: We enrolled 51 patients (37 [74%] male; mean [SD] age, 60.6 [10.9] years) with predominantly moderate-to-severe left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 29% [7%]); 31 [61%] had an implantable cardioverter-defibrillator device. No significant differences between the caffeine and placebo groups were observed in the number of ventricular (185 vs 239 beats, respectively; P = .47) and supraventricular premature beats (6 vs 6 beats, respectively; P = .44), as well as in couplets, bigeminal cycles, or nonsustained tachycardia during continuous electrocardiographic monitoring. Exercise test-derived variables, such as ventricular and supraventricular premature beats, duration of exercise, estimated peak oxygen consumption, and heart rate, were not influenced by caffeine ingestion. We observed no increases in ventricular premature beats (91 vs 223 vs 207 beats, respectively) in patients with higher levels of plasma caffeine concentration compared with lower plasma levels (P = .91) or with the placebo group (P = .74). CONCLUSIONS AND RELEVANCE: Acute ingestion of high doses of caffeine did not induce arrhythmias in patients with systolic heart failure and at high risk for ventricular arrhythmias. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02045992.

Intrinsic sinus and atrioventricular node electrophysiologic adaptations in endurance athletes.

OBJECTIVES: In the present study, we evaluated sinus and atrioventricular (AV) node electrophysiology of endurance athletes and untrained individuals before and after autonomic pharmacologic blockade. BACKGROUND: Endurance athletes present a higher prevalence of sinus bradycardia and AV conduction abnormalities, as compared with untrained individuals. Previous data from our laboratory suggest that nonautonomic factors may be responsible for the longer AV node refractory period found in well-trained athletes. METHODS: Six aerobically trained male athletes and six healthy male individuals with similar ages and normal rest electrocardiograms were studied. Maximal oxygen uptake (O(2)max) was measured by cardiopulmonary testing. The sinus cycle length (SCL), AV conduction intervals, sinus node recovery time (SNRT), Wenckebach cycle (WC) and anterograde effective refractory period (ERP) of the AV node were evaluated by invasive electrophysiologic studies at baseline, after intravenous atropine (0.04 mg/kg) and after addition of intravenous propranolol (0.2 mg/kg). RESULTS: Athletes had a significantly higher O(2)max as compared with untrained individuals. The SCL was longer in athletes at baseline, after atropine and after the addition of propranolol for double-autonomic blockade. The mean maximal SNRT/SCL was longer in athletes after atropine and after propranolol. The WC and anterograde ERP of the AV node were longer in athletes at baseline, after atropine and after propranolol. CONCLUSIONS: Under double-pharmacologic blockade, we demonstrated that sinus automaticity and AV node conduction changes of endurance athletes are related to intrinsic physiology and not to autonomic influences.

Cost-effectiveness of cardiac resynchronization therapy in patients with heart failure: the perspective of a middle-income country's public health system.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms and survival in patients with heart failure (HF). However, the devices used to deliver it are costly and can impose a significant burden to the relatively constrained health budgets of middle-income countries such as Brazil. METHODS: A Markov model was constructed, representing the follow-up of a hypothetical cohort of HF patients, with a 20-year time horizon. Input data were based on information from a Brazilian cohort of 316 HF patients, as well as meta-analyses of data on devices' effectiveness and risks. Stochastic and probabilistic sensitivity analyses were performed for all important variables in the model. Costs were expressed as International Dollars (Int$), by application of current purchasing power parity conversion rate. RESULTS: In the base-case analysis, the incremental cost-effectiveness ratio (ICER) of CRT over medical therapy was Int$ 15,723 per quality-adjusted life years (QALYs) gained. For CRT combined with an implantable cardioverter-defibrillator (ICD), ICER was Int$ 36,940/QALY over ICD alone, and Int$ 84,345/QALY over CRT alone. Sensitivity analyses showed that the model was generally robust, though susceptible to the cost of the devices, their impact on HF mortality, and battery longevity. CONCLUSIONS: CRT is cost-effective for HF patients in the Brazilian public health system scenario. In patients eligible for CRT, upgrade to CRT+ICD has an ICER above the World Health Organization willingness-to-pay threshold of three times the nation's Gross Domestic Product per Capita (Int$ 31,689 for Brazil). However, for ICD eligible patients, upgrade to CRT+ICD is marginally cost-effective.

Seasonal variation of ventricular tachycardia registered in 24-hour Holter monitoring.

OBJECTIVE: To evaluate the seasonal variation of ventricular arrhythmias and its correlation with ambient temperature in patients submitted to 24-hour Holter monitoring in the city of Porto Alegre, southern Brazil. METHODS: Holter monitoring reports of 3,034 patients from 1996 to 2002 were analyzed. Ventricular tachycardia (VT) was defined as the presence of 3 or more consecutive ventricular beats, at a rate equal to or higher than 100 beats per minute. Percentage distribution of patients presenting VT by seasons and its correlation with ambient temperature were analyzed. RESULTS: Mean age was 59.2 +/- 17.4 years, with a predominance of the female sex (61.9%). Patient distribution by season of the year was: 561 (18.5%) in summer, 756 (24.9%) in fall, 843 (27.8%) in winter and 874 (28.8%) in spring. Fifty-two patients (9.3%) presented VT episodes in summer, 39 (5.2%) in autumn, 56 (6.6%) in winter and 60 (6.9%) in spring (p = 0.035). There was a 40% relative increase in the proportion of patients presenting VT during summer in comparison to winter. There was a trend of increase in the proportion of patients presenting VT with rising temperatures (r = 0.57; p = 0.052). CONCLUSION: The occurrence of VT presents seasonal variations in southern Brazil, with a higher proportion of episodes occurring in summer. There is an association trend between VT and temperature increase.

Variação sazonal de episódios de taquicardia ventricular avaliados por Holter / Seasonal variation of ventricular tachycardia registered in 24-hour Holter monitoring / Seasonal variation of ventricular tachycardia registered in 24-hour Holter monitoring

OBJETIVO: Avaliar a variação sazonal de arritmias ventriculares e sua correlação com a temperatura ambiente em pacientes submetidos à realização de Holter em Porto Alegre, Sul do Brasil. MÉTODOS: Foram avaliados os resultados de Holter de 3.034 pacientes realizados no período de 1996 a 2002. Taquicardia ventricular (TV) foi definida pela presença de três ou mais batimentos ventriculares consecutivos, em freqüência igual ou superior a 100 batimentos por minuto. Foram avaliadas a distribuição do percentual de pacientes com TV entre as estações do ano e sua correlação com a temperatura ambiente. RESULTADOS: A idade média foi 59,2 ± 17,4 anos, com predomínio do sexo feminino (61,9 por cento). A distribuição dos pacientes por estações do ano foi: verão 561 (18,5 por cento), outono 756 (24,9 por cento), inverno 843 (27,8 por cento) e primavera 874 (28,8 por cento). No verão, 52 pacientes apresentaram TV (9,3 por cento), no outono, 39 (5,2 por cento), no inverno, 56 (6,6 por cento) e, na primavera, 60 (6,9 por cento) (p = 0,035). Houve aumento relativo de 40 por cento na proporção de pacientes com TV no verão em relação ao inverno. Houve tendência de aumento da proporção de pacientes com TV com o aumento da temperatura (r = 0,57; p = 0,052). CONCLUSÃO: A ocorrência de TV apresenta variação sazonal no Sul do Brasil, com maior proporção de episódios ocorrendo durante o verão. Existe tendência de associação entre aumento da temperatura e TV.

OBJECTIVE: To evaluate the seasonal variation of ventricular arrhythmias and its correlation with ambient temperature in patients submitted to 24-hour Holter monitoring in the city of Porto Alegre, southern Brazil. METHODS: Holter monitoring reports of 3,034 patients from 1996 to 2002 were analyzed. Ventricular tachycardia (VT) was defined as the presence of 3 or more consecutive ventricular beats, at a rate equal to or higher than 100 beats per minute. Percentage distribution of patients presenting VT by seasons and its correlation with ambient temperature were analyzed. RESULTS: Mean age was 59.2 ± 17.4 years, with a predominance of the female sex (61.9 percent). Patient distribution by season of the year was: 561 (18.5 percent) in summer, 756 (24.9 percent) in fall, 843 (27.8 percent) in winter and 874 (28.8 percent) in spring. Fifty-two patients (9.3 percent) presented VT episodes in summer, 39 (5.2 percent) in autumn, 56 (6.6 percent) in winter and 60 (6.9 percent) in spring (p = 0.035). There was a 40 percent relative increase in the proportion of patients presenting VT during summer in comparison to winter. There was a trend of increase in the proportion of patients presenting VT with rising temperatures (r = 0.57; p = 0.052). CONCLUSION: The occurrence of VT presents seasonal variations in southern Brazil, with a higher proportion of episodes occurring in summer. There is an association trend between VT and temperature increase.