Cardiac Function Before Sepsis and Clinical Outcomes.

This cohort study characterizes heterogeneity in cardiac function prior to sepsis and describes associations with hospitalization outcomes and mortality.

Trastornos inespecíficos de la repolarización ventricular: un lobo con piel de oveja / Nonspecific ventricular repolarization abnormalities: A wolf in sheep's clothing

El término trastornos inespecíficos de la repolarización ventricular se refiere a un conjunto de alteraciones menores del segmento ST y/o la onda T. Durante mucho tiempo han sido de escaso interés clínico al no traducir diagnósticos específicos. De forma extrema, se ha aseverado que constituyen hallazgos electrocardiográficos benignos. Su presencia se ha reportado en diversos estados patológicos cardiovasculares y no cardiovasculares. Sin embargo, con frecuencia se identifica en personas asintomáticas aparentemente sanas. Un creciente número de estudios demuestran su importancia como predictores de morbimortalidad cardiovascular, expandiendo su espectro hacia la prevención cardiovascular. A la luz de las evidencias científicas acumuladas se impone un cambio en la visión tradicional que se ha tenido con los trastornos inespecíficos de la repolarización ventricular. (AU)

The term nonspecific ventricular repolarization abnormalities refers to a set of minor alterations of the ST segment and/or the T wave. For a long time, they have been of little clinical interest as they do not translate into specific diagnoses. It has even been asserted that they constitute benign electrocardiographic findings. Their presence has been reported in various cardiovascular and non-cardiovascular diseases. However, it is frequently identified in apparently healthy asymptomatic people. A growing number of studies demonstrate their importance as predictors of cardiovascular morbidity and mortality, expanding their spectrum towards cardiovascular prevention. In light of the body of scientific evidence, it is imperative that the traditional view of nonspecific ventricular repolarization abnormalities changes. (AU)

Longitudinal diastolic strain slope as an early sign for systolic dysfunction among patients with active cancer.

BACKGROUND: Diastolic dysfunction is a common finding in patients receiving cancer therapy. This study evaluated the correlation of diastolic strain slope (Dss) with routine echocardiography diastolic parameters and its role in early detection of systolic dysfunction and cardiovascular (CV) mortality within this population. METHODS: Data were collected from the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling adult patient receiving cancer therapy. All patients performed at least three echocardiography exams (T1, T2, T3), including left ventricle Global Longitudinal Strain (LV GLS) and Dss. Systolic dysfunction was determined by either LV GLS relative reduction of ≥ 15% or LV ejection fraction reduction > 10% to < 53%. Dss was assessed as the early lengthening rate, measured by the diastolic slope (delta%/sec). RESULTS: Among 144 patients, 114 (79.2%) were female with a mean age of 57.31 ± 14.3 years. Dss was significantly correlated with e' average. Mid segment Dss change between T1 and T2 showed significant association to systolic dysfunction development (Odds Ratio (OR) = 1.04 [1.01,1.06]. p = 0.036). In multivariate prediction, Dss increase was a significant predictor for the development of systolic dysfunction (OR = 1.06 [1.03,1.1], P < 0.001).An 8% increase in Dss between T1 and T2 was associated with a trend in increased CV mortality (HR = 3.4 [0.77,15.4], p = 0.085). CONCLUSIONS: This study is the first to use the novel measurement of Dss in patients treated with cancer therapies and to show significant correlation between routine diastolic dysfunction parameters and Dss. Changes in the mid segment were found to have significant independent early predictive value for systolic dysfunction development in univariate and multivariate analyses.

Clinical Importance of Fontan Circuit Thrombus in the Adult Population: Significant Association With Increased Risk of Cardiovascular Events.

BACKGROUND: The impact of Fontan circuit thrombus is poorly understood. The objectives of this study were to determine (1) the incidence of Fontan circuit thrombus and proportion of silent thrombus; (2) any association between Fontan circuit thrombus and markers of Fontan circulatory dysfunction; and (3) the association of Fontan circuit thrombus with adverse cardiac outcomes. METHODS: We conducted a retrospective review of adult patients who underwent the Fontan procedure (aged > 18 years) followed at St. Paul's Hospital who underwent cardiac computed tomography or magnetic resonance imaging assessment (n = 67). Fontan circulatory dysfunction markers included clinical heart failure, N-terminal pro-brain natriuretic peptide, ventricular dysfunction, atrioventricular valvular regurgitation, refractory arrhythmias, declining exercise capacity, and hepatic/renal dysfunction. Adverse cardiac outcomes were death, heart transplantation, or surgery for Fontan revision or atrioventricular valve replacement. RESULTS: Fontan circuit thrombus was present in 15 of 67 patients (22%): 41% (7/17) classic/modified Fontan and 16% (8/50) total cavopulmonary connection. Incidence was 36% among those suspected to have Fontan circuit thrombus; 14% in those with no clinical/echocardiographic suspicion; and clinically silent in 40% diagnosed with Fontan thrombus. The time from Fontan surgery to Fontan circuit thrombus diagnosis was 22 ± 6 years in the classic/modified group vs 14 ± 8 years in the total cavopulmonary connection group (P = 0.03. Fontan circuit thrombus was associated with adverse cardiac outcomes (27% [4/15] vs 8% [4/52], P = 0.02), but there was no difference in Fontan circulatory dysfunction markers. CONCLUSION: Given the incidence of Fontan circuit thrombus and association with adverse cardiac outcomes, routine surveillance of the Fontan circuit should strongly be considered. The identification of thrombus should lead to anticoagulation implementation/optimization, along with screening/intervention for reversible Fontan circulatory issues in an attempt to prevent adverse cardiac outcomes.

Utility of High-Sensitivity and Conventional Troponin in Patients Undergoing Transcatheter Aortic Valve Replacement: Incremental Prognostic Value to B-type Natriuretic Peptide.

High-sensitivity Troponin (hs-Tn) has emerged as a useful marker for patients with myocardial injury or heart failure. However, few studies have compared intermediate and hs-Tn in patients undergoing transcatheter aortic valve replacement (TAVR). Moreover, there remains uncertainty of which thresholds are the most useful for discriminating ventricular dysfunction or outcome. In this study we prospectively enrolled 105 patients with severe aortic stenosis (AS) who underwent TAVR as well as blood sampling for high-sensitivity (hs-TnI) and conventional troponin I (EXL-LOCI and RXL) assessment. Patients underwent comprehensive pre-procedure echocardiography. Ventricular dysfunction was defined using left ventricular mass index (LVMI), LV global longitudinal strain (LVGLS) and LV end-diastolic pressure. The mean age was 84.0 ± 8.7 years old and 60% were male sex with mean transaortic pressure gradient of 50.1 ± 16.0 mmHg and AVA of 0.63 ± 0.19 cm2. When using a threshold of 6 ng/L, 77% had positive hs-TnI while 27% had positive hs-TnI using recommended thresholds (16 ng/L for female and 34 ng/L for male). Troponin levels were higher in the presence of abnormal LV phenotypes. The strongest correlate of troponin was LVMI. During median follow-up of 375 days, 21 patients (20%) died. Lower threshold of hs-TnI and EXL-TnI was more discriminatory for overall mortality (Log-rank P = 0.03 for both), while higher threshold of hs-TnI (p = 0.75) and RXL-TnI were not (p = 0.30). Combining hs-TnI and BNP improved to predict long-term outcome (p = 0.004). In conclusion, hs-TnI levels correlated with the degree of LV dysfunction phenotypes. Furthermore, applying a lower threshold for hs-TnI performed better for outcome prediction than a recommended threshold in patients undergoing TAVR. Combining hs-TnI with BNP helped better risk stratification.

Severe Cardiac Dysfunction and Death Caused by Arrhythmogenic Right Ventricular Cardiomyopathy Type 5 Are Improved by Inhibition of Glycogen Synthase Kinase-3ß.

BACKGROUND: Arrhythmogenic cardiomyopathy/arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease characterized by fibrofatty replacement of the myocardium, resulting in heart failure and sudden cardiac death. The most aggressive arrhythmogenic cardiomyopathy/ARVC subtype is ARVC type 5 (ARVC5), caused by a p.S358L mutation in TMEM43 (transmembrane protein 43). The function and localization of TMEM43 are unknown, as is the mechanism by which the p.S358L mutation causes the disease. Here, we report the characterization of the first transgenic mouse model of ARVC5. METHODS: We generated transgenic mice overexpressing TMEM43 in either its wild-type or p.S358L mutant (TMEM43-S358L) form in postnatal cardiomyocytes under the control of the α-myosin heavy chain promoter. RESULTS: We found that mice expressing TMEM43-S358L recapitulate the human disease and die at a young age. Mutant TMEM43 causes cardiomyocyte death and severe fibrofatty replacement. We also demonstrate that TMEM43 localizes at the nuclear membrane and interacts with emerin and ß-actin. TMEM43-S358L shows partial delocalization to the cytoplasm, reduced interaction with emerin and ß-actin, and activation of glycogen synthase kinase-3ß (GSK3ß). Furthermore, we show that targeting cardiac fibrosis has no beneficial effect, whereas overexpression of the calcineurin splice variant calcineurin Aß1 results in GSK3ß inhibition and improved cardiac function and survival. Similarly, treatment of TMEM43 mutant mice with a GSK3ß inhibitor improves cardiac function. Finally, human induced pluripotent stem cells bearing the p.S358L mutation also showed contractile dysfunction that was partially restored after GSK3ß inhibition. CONCLUSIONS: Our data provide evidence that TMEM43-S358L leads to sustained cardiomyocyte death and fibrofatty replacement. Overexpression of calcineurin Aß1 in TMEM43 mutant mice or chemical GSK3ß inhibition improves cardiac function and increases mice life span. Our results pave the way toward new therapeutic approaches for ARVC5.

Results of primary biventricular support: an analysis of data from the EUROMACS registry.

OBJECTIVES: The purpose of this study was to describe pre- and postoperative data from the EUROMACS registry with regard to indications, for and survival and complication rates of patients with primary continuous flow and pulsatile biventricular long-term assist devices (BiVADs) versus total artificial hearts (TAHs) or left ventricular assist devices (LVADs) + short-term right ventricular assist device (RVAD) implants. METHODS: We investigated patients who received implants between 1 January 2011 and 21 October 2017. Clinical baseline information about comorbidities, laboratory results, medical and device therapies and echocardiographic, haemodynamic and right ventricle (RV) parameters were evaluated along with the rates of deaths and complications. RESULTS: A total of 413 of 3282 patients (12.5%) needed a biventricular pump. We investigated 37 long-term BiVADs, 342 LVAD + short-term RVAD implants and 34 TAHs. Minor differences were found in the baseline characteristics of our population, which had an overall high morbidity profile. The 1-year survival rate was 55% for patients with a continuous flow BiVAD; 52% for patients with an LVAD + short-term RVAD; 37% for patients with pulsatile BiVADs; and 36% for patients with a TAH. No statistical difference was observed among the groups. Over 50% of patients with BiVAD support were classified as INTERMACS profiles 1 and 2. The percent of patients with ambulatory heart failure (INTERMACS 4‒7) undergoing BiVAD implants was modest at <15%. No patients with a pulsatile BiVAD (n = 15) or a TAH (n = 34) were implanted as destination therapy, but 27% of the patients with continuous flow BiVADs (n = 6) and 23% of the patients with LVAD + short-term RVAD (n = 342) were implanted as 'destination'. The adverse events profile remained high, with no significant difference among pump types. The right ventricular stroke work index and right heart failure scores indicated poor RV function in all groups. After 3 months of LVAD + short-term RVAD support, 46.7% still required ongoing support, and only 18.5% were weaned from RVAD support; 33.1% died. CONCLUSIONS: The mortality rate after BiVAD support was high. Survival rates and adverse events were statistically not different among the investigated groups. In the future, composite study end points examining quality of life and adverse events beyond survival may help in shared decision-making prior to general mechanical circulatory support, particularly in patients with BiVAD implants.

Early conversion of classic Fontan conversion may decrease term morbidity: single centre outcomes.

BACKGROUND: The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts. METHODS: A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion. RESULTS: A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure. CONCLUSIONS: Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.

Updates on His bundle pacing: The road more traveled lately.

His bundle pacing (HBP) has continued to evolve over the past decade and has started to become a global phenomenon. Evidence is mounting of its clinical benefits as compared to both right ventricular and left ventricular pacing. In this paper, we review recent data in support of His bundle pacing and some of the challenges facing us as we advocate its increasing role in clinical practice.

Comorbidities and Ventricular Dysfunction Drive Excess Mid-Term Morbidity in an Indigenous Australian Coronary Revascularisation Cohort.

BACKGROUND: There is a paucity of data in regards to longer term morbidity outcomes in Indigenous Australian patients undergoing coronary artery bypass grafting (CABG). No comparative data on re-infarction, stroke or reintervention rates exist. Outcome data following percutaneous coronary intervention (PCI) is also extremely limited. Addressing this gap in knowledge forms the major aim of our study. METHODS: This was a single centre cohort study conducted at the Townsville Hospital, Australia which provides tertiary adult cardiac surgical services to the northern parts of the state of Queensland. It incorporated consecutive patients (n=350) undergoing isolated CABG procedures, 2008-2010, 20.9% (73/350) of whom were Indigenous Australians. The main outcome measures were major adverse cardiac or cerebrovascular events (MACCE) at mid-term follow-up (mean 38.9 months). RESULTS: The incidence of MACCE among Indigenous Australian patients was approximately twice that of non-Indigenous patients at mid-term follow-up (36.7% vs. 18.6%; p=0.005; OR 2.525 (1.291-4.880)). Following adjustment for preoperative and operative variables, Indigenous Australian status itself was not significantly associated with MACCE (AOR 1.578 (0.637-3.910)). Significant associations with MACCE included renal impairment (AOR 2.198 (1.010-4.783)) and moderate-severe left ventricular impairment (AOR 3.697 (1.820-7.508)). An association between diabetes and MACCE failed to reach statistical significance (AOR 1.812 (0.941-3.490)). CONCLUSIONS: Indigenous Australians undergoing CABG suffer an excess of MACCE when followed-up in the longer term. High rates of comorbidities in the Indigenous Australian population likely play an aetiological role.

Right-to-left ventricular end diastolic diameter ratio in severe sepsis and septic shock.

PURPOSE: The ratio of right ventricular end-diastolic diameter (EDD) to left ventricular EDD (RV/LV) is a measure predictive of right ventricular failure. We hypothesized that an increase in RV/LV would be associated with poor prognosis in severe sepsis and septic shock. MATERIALS AND METHODS: This is a retrospective chart review of patients with severe sepsis and septic shock admitted to a medical intensive care unit (ICU) at a single tertiary care hospital. Patients were identified by ICD-9 codes: 995.92 for severe sepsis and 785.52 for septic shock; and had to have an echocardiogram within 48 h of ICU admission. Increased RV/LV was defined as RV/LV ≥ 0.9. Left and right-sided chamber dimensions were measured according to American Society of Echocardiography guidelines. RESULTS: We included 146 consecutive ICU patients admitted with septic shock (72) or severe sepsis (74). There was no significant difference in ICU mortality in patients with RV/LV ≥ 0.9 versus RV/LV < 0.9 (p = .49). CONCLUSIONS: An increased RV/LV does not predict mortality in severe sepsis or septic shock.

Incidence and Outcomes of Patients with Functionally Univentricular Heart Born in Latvia, 2007 to 2015.

Background and Objectives: A functionally univentricular heart is the term used to describe congenital heart defects where it is impossible to restore two pumping chambers. These lesions are associated with high mortality, morbidity, and medical resource utilization. The aim of this study was to review incidence and outcomes of patients with a functionally univentricular heart at the only pediatric cardiac surgery center in Latvia. Methods: We performed a retrospective review of medical records of (i) all children with a functionally univentricular heart treated at the Clinic of Pediatric Cardiology and Cardiac Surgery, and (ii) all prenatally diagnosed cases of univentricular heart at Children's Clinical University Hospital in Latvia. We reviewed data regarding children born from January 1, 2007, to December 31, 2015. The children's cardiac anatomy and interventions were categorized in accordance with the International Pediatric and Congenital Cardiac Code (v3.3). Results: During the study period, 49 patients with a functionally univentricular heart were admitted to Children's Clinical University Hospital with a corrected incidence of 0.69 per 1000 live births per year. There were 26 patients that had a hypoplastic left ventricle, and 22 patients that had a hypoplastic right ventricle, while one patient had an indeterminate ventricle. Thirty (61.2%) patients had died by the end of data collection. Twenty-one of the 30 deaths occurred before or immediately after stage I surgical palliation. Cumulative neonatal and 5-year survival of patients with a hypoplastic right ventricle was 81.8% and 63.6%, respectively; for patients with hypoplastic left ventricle-46.2% and 17.3%, respectively. Discussion: This is the first mid-term outcome study of patients with a univentricular heart in Latvia. The high mortality reflects the challenges of a small-volume, developing congenital cardiac surgery center. Data from this study will be used as a baseline for quality improvement.

Gender differences in the development of cardiac complications: a multicentre study in a large cohort of thalassaemia major patients to optimize the timing of cardiac follow-up.

We assessed whether male gender was associated with a higher risk of cardiac iron accumulation and fibrosis, heart dysfunction and complications in a large, multicentre cohort of thalassaemia major (TM) patients, in order to optimize the timing in cardiac follow-up. We considered 1711 TM patients (899 females, 31·09 ± 9·08 years), enrolled in the Myocardial Iron Overload in Thalassaemia Network. Clinical/instrumental data are recorded from birth to the first Cardiovascular Magnetic Resonance Imaging scan. Although having a similar risk of accumulating iron, males showed a significantly higher risk of developing cardiac dysfunction, heart failure, arrhythmias and cardiac complications overall, when compared to females (P < 0·0001). Up to 20-30 years of follow-up, the Kaplan-Meier curves for the outcomes for which the male sex was a significant prognosticator almost overlapped, whereas they clearly diverged after this period. In patients with follow-up longer than 20 years, males exhibited a significantly higher risk of ventricular dysfunction, heart failure, arrhythmias, and cardiac complications. Female patients may have an intrinsically better tolerance for iron toxicity. International guidelines suggest annual cardiac evaluation for thalassaemia patients. It is possible that female patients can be evaluated at longer intervals, thus reducing health costs.

Survival to Stage II with Ventricular Dysfunction: Secondary Analysis of the Single Ventricle Reconstruction Trial.

Ventricular dysfunction affects survival in patients with single right ventricle (RV), and remains one of the primary indications for heart transplantation. Since it is challenging to predict the capacity of patients with ventricular dysfunction to proceed to the stage II procedure, we sought to identify factors that would be associated with death or heart transplantation without achieving stage II for single RV patients with ventricular dysfunction after Norwood procedure. The Single Ventricle Reconstruction (SVR) trial public-use database was used. Patients with a RV ejection fraction less than 44% or a RV fractional area of change less than 35% on the post-Norwood echocardiogram were included. Parametric risk hazard analysis was used to identify risk factors for death or transplantation without achieving stage II. Of 365 patients with ventricular function measurements on the post-Norwood echocardiogram, 123 (34%) patients had RV dysfunction. The transplantation-free survival was significantly lower for those with ventricular dysfunction compared to those with normal function (log rank Chi-square = 4.23, p = 0.04). Furthermore, having a Blalock-Taussig (BT) shunt, a large RV, a post-Norwood infectious complication, and a surgeon who performs five or less Norwood per year were independent risk factors for death or transplantation without achieving stage II. The predicted 6-month transplantation-free survival for patients with all four identified risk factors was 1% (70% CI 0-13%). Early heart transplantation referral might be considered for post-Norwood patients with BT shunt and RV dysfunction, especially if other high-risk features are present.

Cost-Effectiveness Analysis of Natriuretic Peptide Testing and Specialist Management in Patients with Suspected Acute Heart Failure.

OBJECTIVES: To determine the cost-effectiveness of natriuretic peptide (NP) testing and specialist outreach in patients with acute heart failure (AHF) residing off the cardiology ward. METHODS: We used a Markov model to estimate costs and quality-adjusted life-years (QALYs) for patients presenting to hospital with suspected AHF. We examined diagnostic workup with and without the NP test in suspected new cases, and we examined the impact of specialist heart failure outreach in all suspected cases. Inputs for the model were derived from systematic reviews, the UK national heart failure audit, randomized controlled trials, expert consensus from a National Institute for Health and Care Excellence guideline development group, and a national online survey. The main benefit from specialist care (cardiology ward and specialist outreach) was the increased likelihood of discharge on disease-modifying drugs for people with left ventricular systolic dysfunction, which improve mortality and reduce re-admissions due to worsened heart failure (associated with lower utility). Costs included diagnostic investigations, admissions, pharmacological therapy, and follow-up heart failure care. RESULTS: NP testing and specialist outreach are both higher cost, higher QALY, cost-effective strategies (incremental cost-effectiveness ratios of £11,656 and £2,883 per QALY gained, respectively). Combining NP and specialist outreach is the most cost-effective strategy. This result was robust to both univariate deterministic and probabilistic sensitivity analyses. CONCLUSIONS: NP testing for the diagnostic workup of new suspected AHF is cost-effective. The use of specialist heart failure outreach for inpatients with AHF residing off the cardiology ward is cost-effective. Both interventions will help improve outcomes for this high-risk group.

Risk factors of postcardiotomy ventricular dysfunction in moderate-to-high risk patients undergoing open-heart surgery.

INTRODUCTION: Ventricular dysfunction requiring inotropic support frequently occurs after cardiac surgery, and the associated low cardiac output syndrome largely contributes to postoperative death. We aimed to study the incidence and potential risk factors of postcardiotomy ventricular dysfunction (PCVD) in moderate-to-high risk patients scheduled for open-heart surgery. METHODS: Over a 5-year period, we prospectively enrolled 295 consecutive patients undergoing valve replacement for severe aortic stenosis or coronary artery bypass surgery who presented with Bernstein-Parsonnet scores >7. The primary outcome was the occurrence of PCVD as defined by the need for sustained inotropic drug support and by transesophageal echography. The secondary outcomes included in-hospital mortality and the incidence of any major adverse events as well as Intensive Care Unit (ICU) and hospital length of stay. RESULTS: The incidence of PCVD was 28.4%. Patients with PCVD experienced higher in-hospital mortality (12.6% vs. 0.6% in patients without PCVD) with a higher incidence of cardiopulmonary and renal complications as well as a prolonged stay in ICU (median + 2 days). Myocardial infarct occurred more frequently in patients with PCVD than in those without PCVD (19 [30.2%] vs. 12 [7.6%]). By logistic regression analysis, we identified four independent predictors of PCVD: left ventricular ejection fraction <40% (odds ratio [OR] = 6.36; 95% confidence interval [CI], 2.59-15.60), age older than 75 years (OR = 3.35; 95% CI, 1.64-6.81), prolonged aortic clamping time (OR = 3.72; 95% CI, 1.66-8.36), and perioperative bleeding (OR = 2.33; 95% CI, 1.01-5.41). The infusion of glucose-insulin-potassium was associated with lower risk of PCVD (OR = 0.14; 95% CI, 0.06-0.33). CONCLUSIONS: This cohort study indicates that age, preoperative ventricular function, myocardial ischemic time, and perioperative bleeding are predictors of PCVD which is associated with poor clinical outcome.

Sudden cardiac death in adult congenital heart disease: can the unpredictable be foreseen?

AIMS: Sudden cardiac death (SCD) is a major cause of mortality in adults with congenital heart disease (CHD). Several risk factors for SCD including conduction disturbances and ventricular dysfunction have been described previously. However, electrocardiogram (ECG) and echocardiographic parameters may change over time, and the predictive value of such temporal changes, rather than their point estimates, for SCD remains unknown. METHODS AND RESULTS: This was a retrospective case-control study in adults with CHD and proven or presumed SCD and matched controls. Data were obtained from three databases including 25 000 adults with CHD. Sequential measurements were performed on electrocardiograms and echocardiograms. Ventricular function was assessed by echocardiography and graded on a four-point ordinal scale: 1, normal [ejection fraction (EF) ≥50%]; 2, mildly impaired (EF 40-49%); 3, moderately impaired (EF 30-39%); and 4, severely impaired (EF < 30%). Overall, 131 SCDs (mean age 36 ± 14 years, 67% male) and 260 controls (mean age 37 ± 13 years, 63% male) were included. At baseline, median QRS duration was 108 ms (range 58-168 ms) in SCDs and 97 ms (range 50-168 ms) in controls and increased over time at a rate of 1.6 ± 0.5 vs. 0.5 ± 0.2 ms/year in SCDs and controls, respectively (P = 0.011). QT dispersion at baseline was 61 ms (range 31-168 ms) in SCDs and 50 ms (range 21-129 ms) in controls. QT dispersion increased at a rate of 1.1 ± 0.4 ms/year in SCD victims and decreased at a rate of 0.2 ± 0.2 ms/year in controls (P = 0.004). Increase of QRS duration ≥5 ms/year was associated with an increased risk of SCD [OR 1.9, 95% confidence interval (CI) 1.1-3.3, P = 0.013]. Change from any baseline systemic ventricular function (normal, mild, or moderately impaired) to severe ventricular dysfunction over time was associated with the highest risk of SCD (OR 16.9, 95% CI 1.8-120.1, P = 0.008). CONCLUSION: In adults with CHD, QRS duration and ventricular dysfunction progress over time. Progression of QRS duration and the rate of impairment of ventricular function served to identify those at increased risk of SCD.

Prognostic Value of a New Marker of Ventricular Repolarization in Cirrhotic Patients / Valor Prognóstico de um Novo Marcador da Repolarização Ventricular em Pacientes Cirróticos

Abstract Background: There is still debate about the relationship between changes in ventricular repolarization on the surface electrocardiogram and cirrhosis severity. Objective: To study the relationship between variables related to ventricular repolarization and the clinical severity of the cirrhotic disease. Methods: We selected 79 individuals with hepatic cirrhosis, classified according to the Child-Pugh-Turcotte criteria (Child A, B, and C). We measured the QT and corrected QT (QTc) intervals, and the interval between the peak and the end of the T wave (TpTe), and we identified their minimum, maximum, and mean values in the 12-lead electrocardiogram. We also calculated the dispersion of the QT (DQT) and QTc (DQTc) intervals. Results: In 12 months of clinical follow-up, nine subjects underwent hepatic transplantation (Child A: 0 [0%]; Child B: 6 [23.1%]; Child C: 3 [18.8%]; p = 0.04) and 12 died (Child A: 3 [12.0%]; Child B: 4 [15.4%]; Child C: 5 [31.3%]; p = 0.002). No significant differences were observed between the cirrhotic groups related to the minimum, maximum, and mean values for the QT, QTc, TpTe, DQT, and DQTc intervals. A minimum TpTe interval ≤ 50 ms was a predictor for the composite endpoints of death or liver transplantation with a sensitivity of 90% and a specificity of 57% (p = 0.005). In the Cox multivariate analysis, the Child groups and a minimum TpTe of ≤ 50 ms were independent predictors of the composite endpoints. Conclusion: The intervals QT, QTc, DQT, DQTc, and TpTe have similar distributions between different severity stages in cirrhotic disease. The TpTe interval proved to be a prognostic marker in subjects with cirrhosis, regardless of disease severity (NCT01433848).

Resumo Fundamento: Ainda há debate sobre a relação de alterações da repolarização ventricular ao eletrocardiograma de superfície e a gravidade da cirrose. Objetivo: Estudar a relação entre variáveis relacionadas à repolarização ventricular e a gravidade clínica da doença cirrótica. Métodos: Foram selecionados 79 sujeitos com cirrose hepática, classificados segundo os critérios Child-Pugh-Turcotte (Child A, B e C). Foram medidos intervalos QT e QT corrigido (QTc), o intervalo entre o ápice e o final da onda T (TpTe) e identificados os respectivos valores mínimos, máximos e médios nas 12 derivações do eletrocardiograma. Foram calculados também as dispersões dos intervalos QT (DQT) e QTc (DQTc). Resultados: Em 12 meses de acompanhamento clínico, nove sujeitos foram submetidos a transplante hepático (Child A: 0 (0%); Child B: 6 (23,1%); Child C: 3 (18,8%); p=0,04) e 12 faleceram (Child A: 3 (12,0%); Child B: 4 (15,4%); Child C: 5 (31,3%); p=0,002). Não foram observadas diferenças significativas entre os grupos cirróticos relacionadas aos valores mínimos, máximos e médios dos intervalos QT, QTc, TpTe, DQT e DQTc. O intervalo TpTe mínimo ≤50ms foi preditor de desfecho composto de óbito ou transplante hepático com sensibilidade de 90% e especificidade de 57% (p=0,005). Na análise multivariada de Cox, grupos Child e TpTe mínimo ≤50ms foram preditores independentes de desfechos compostos. Conclusão: Os intervalos QT, QTc, DQT, DQTc e TpTe apresentam distribuições semelhantes entre diferentes estágios de gravidade da doença cirrótica. O intervalo TpTe mostra-se marcador prognóstico em sujeitos cirróticos, independente da gravidade da doença. (NCT01433848).