Periodic Repolarization Dynamics Identifies ICD-responders in Non-ischemic Cardiomyopathy: A DANISH Substudy

Author(s):  
Rune Boas ◽  
Nikolay Sappler ◽  
Lukas von Stülpnagel ◽  
Mathias Klemm ◽  
Ulrik Dixen ◽  
...  

Background: Identification of patients with non-ischemic cardiomyopathy who benefit from prophylactic implantation of a cardioverter-defibrillator (ICD) remains an unmet clinical need. We hypothesized that periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity, could be used to identify patients that benefit from prophylactic ICD-implantation. Methods: Heart-failure (DANISH) study, in which patients with non-ischemic cardiomyopathy, left-ventricular ejection fraction (LVEF) ≤35% and elevated N-terminal pro-brain natriuretic peptides (NT-proBNP) were randomized to ICD-implantation or control group. Patients were included in the PRD-substudy if they had a 24-hour Holter monitor recording at baseline with technically acceptable ECG signals during the night hours (00:00-06.00 AM). PRD was assessed using wavelet analysis according to previously validated methods. Primary endpoint was all-cause mortality. Cox-regression models were adjusted for age, sex, NT-proBNP, estimated glomerular filtration rate, LVEF, atrial fibrillation, ventricular pacing, diabetes mellitus, cardiac resynchronization therapy and mean heart rate. We proposed PRD ≥10deg 2 as exploratory cut-off value for ICD-implantation. Results: Seven-hundred and forty-eight of the 1,116 DANISH patients qualified for the PRD-substudy. During a mean follow−up period of 5.1±2.0 years, 82 of 385 patients died in the ICD group and 85 of 363 patients died in the control group (p−value=0.40). In Cox-regression analysis, PRD was independently associated with mortality (HR 1.28 [1.09−1.50] per SD increase; p−value = 0.003). Moreover, PRD was significantly associated with mortality in the control group (HR 1.51 [1.25−1.81]; p<0.001) but not in the ICD-group 1.04 [0.83−1.54]; p−value=0.71). There was a significant interaction between PRD and the effect of ICD−implantation on mortality (p−value 0.008), with patients with higher PRD having the greater benefit in terms of mortality reduction. ICD-implantation was associated with an absolute mortality reduction of 17.5% in the 280 patients with PRD ≥10deg 2 (HR 0.54 [0.34-0.84]; p−value=0.006; number needed to treat 6), but not in the 468 patients with PRD<10deg 2 (HR 1.17 [0.77−1.78]; p−value=0.46; p−value for interaction 0.01). Conclusions: Increased PRD identified patients with non-ischemic cardiomyopathy, where prophylactic ICD-implantation led to significant mortality reduction.

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yoshimori An ◽  
Kenji Ando ◽  
Michio Nagashima ◽  
Masato Fukunaga ◽  
Kenichi Hiroshima ◽  
...  

Background: There are still limited data on the mortality for a long-term follow-up and the clinical factors influencing appropriate therapies in Japanese patients with implantable cardioverter-defibrillator (ICD) for primary prevention, who satisfied the criteria in Multicenter Automatic Defibrillator Implantation Trial 2 (MADIT2). Methods: Between January 2000 and December 2012, a total of 436 patients without prior ventricular arrhythmic event underwent ICD implantation for primary prevention at our institution. Among these patients, we enrolled consecutive 122 patients (69±10 years, male: 84%, biventricular-pacing: 54%, median follow-up: 1390 days) who met the MADIT2 criteria; left ventricular ejection fraction (LVEF) ≤30% with ischemic heart disease, more than 4 weeks after myocardial infarction. Results: At the 3 years of follow-up, the mortality rate (21%) was comparable with that of the original MADIT2 ICD group (20%). The Kaplan-Meier event rate for appropriate ICD therapy (shock and anti-tachycardia pacing therapy) (35%) was also similar to that of the original MADIT2 ICD group (32%). Multivariate analysis by Cox regression model revealed that left ventricular diastolic diameter (LVDd) ≥60mm (Hazard Ratio [HR]: 1.65, 95% Confidence Interval [CI]: 1.16-2.14, P=0.004) and non-sustained ventricular tachycardia (NSVT) (HR: 1.55, 95%CI: 1.13-2.15, P=0.007) were independent predictors for appropriate ICD therapy. On the other hand, LVEF, NYHA class, biventricular-pacing, amiodarone or inducibility of ventricular arrhythmia was not associated with appropriate ICD therapy. Conclusion: Appropriate ICD therapy was delivered in Japanese primary prevention patients as often as in the original MADIT2 ICD group and strongly predicted by dilated left ventricle and NSVT.


Author(s):  
Chaman Lal Kaushal ◽  
Danquale Vance Kynshikhar ◽  
Anupam Jhobta ◽  
Dimple Kaushal

Background: The cardiomyopathies are defined as “heterogenous group of diseases of the myocardium associated with mechanical or electrical dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation and are due to variety of causes that frequently are genetic. Methods: The cross sectional hospital based study was conducted in the Department of Radiodiagnosis in patients with heart failure with LVEF (Left Ventricular Ejection Fraction) of <45% without RWM (Regional Wall Motion) abnormality on echocardiography evaluated in department of cardiology at IGMC, Shimla over a period of one year. Demographics: Demographics Overall Group Male Female Mean Age (year ) ± SD 53.86  ± 16.34  54.45  ± 19.41 53.94  ± 16.36 Gender (n) 38 17 (44.73%) 21(55.26%) Results: Myocardial fibrosis was seen in 4 (100%) patients of ischemic cardiomyopathy and 3 (18.75%) patients of non ischemic cardiomyopathy with significant P value of 0.01 and odd ratio of 1.67.  The subendocardial myocardial fibrosis was seen in 3 (75%) patients of ischemic cardiomyopathy while it was not seen in non ischemic cardiomyopathy with significant P value of < 0.01 and odd ratio of 3.59. Conclusion: Cardiac MRI has important role in dilated cardiomyopathies for distinguishing ischemic and non ischemic types as well as in evaluation of various etiological types. Keywords: MRI, Myocardial, Cardiomyopathies


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T E Verstraelen ◽  
F H M Van Lint ◽  
L P Bosman ◽  
B G S Abeln ◽  
F W Asselbergs ◽  
...  

Abstract Background/Introduction The founder mutation p.Arg14del in the gene encoding phospholamban (PLN) is a known cause of arrhythmogenic cardiomyopathy (ACM) with distinct clinical features, such as microvoltages on the ECG and right or left ventricular dysfunction or both. At present, risk stratification for ICD implantation in carriers of this mutation is based on left ventricular ejection fraction and previous ventricular arrhythmia's, which are not specific risk factors for the PLN p.Arg14del cardiomyopathy. Purpose Our goal is to develop a mutation specific prediction model for incident malignant ventricular arrhythmia to guide ICD implantation. Methods Data were collected from p.Arg14del carriers with no history of malignant VA at baseline, identified between September 2009 and June 2018 in three Dutch university hospitals. Genetic analysis of PLN was performed in a clinical setting in index patients with clinical signs of DCM/ACM, or in family members of p.Arg14del carriers. We collected clinical data from the first cardiac evaluation and follow-ups. Malignant VAs were defined as sustained VA, appropriate ICD intervention or (aborted) sudden cardiac death. A prediction model was developed using Cox Proportional Hazard regression. Candidate baseline predictors were pre specified based on literature and clinical expertise. Age, sex, proband status, sudden cardiac death (SCD) in 1st degree relative, repolarization abnormalities, microvoltages, premature ventricular complexes (PVC) burden on 24hrs Holter monitoring, LVEF and non-sustained ventricular arrhythmias (NSVT) were considered. The multivariable model was fitted using stepwise backward selection based on Akaike's Information Criterion. Results We included 440 p.Arg14del carriers with a mean age of 41±18 years and 41% males. During a median follow-up of 4.7 years (IQR 1.7–7.3), 44 incident malignant VA occurred, 20 sustained VAs and 24 appropriate ICD therapies. The multivariable HR's of selected predictors were: 2.2 for minor and 4.5 for major repolarization abnormalities vs no abnormalities (p value respectively 0.06 and 0.01), 2.2 for LVEF <45% (p value 0,1) and 7.7 for >500PVC/24hrs (p value 0.003). Carriers with and without events could be accurately distinguished with this model, with an optimism corrected C-statistic of 0.81. The model calibrated well, with agreement of observed and predicted 5 year malignant VA risk. Risk groups were split into quintiles of predicted risk, figure 1 shows the Kaplan Meier curve of incident malignant VA per risk group. The 5 year risk of incident malignant VA in the lowest 3 quintiles was 0%, 9% in the 4th quintile and 25.2% in the highest quintile. Conclusion We created a PLN p.Arg14del mutation specific prediction model to estimate risk of incident malignant VA. With this model a clear distinction between high risk and low risk patients can be made and can be used to guide ICD implantation for primary prevention.


2021 ◽  
Vol 22 (13) ◽  
pp. 7115
Author(s):  
Laura Keil ◽  
Céleste Chevalier ◽  
Paulus Kirchhof ◽  
Stefan Blankenberg ◽  
Gunnar Lund ◽  
...  

Non-ischemic cardiomyopathy (NICM) is one of the most important entities for arrhythmias and sudden cardiac death (SCD). Previous studies suggest a lower benefit of implantable cardioverter–defibrillator (ICD) therapy in patients with NICM as compared to ischemic cardiomyopathy (ICM). Nevertheless, current guidelines do not differentiate between the two subgroups in recommending ICD implantation. Hence, risk stratification is required to determine the subgroup of patients with NICM who will likely benefit from ICD therapy. Various predictors have been proposed, among others genetic mutations, left-ventricular ejection fraction (LVEF), left-ventricular end-diastolic volume (LVEDD), and T-wave alternans (TWA). In addition to these parameters, cardiovascular magnetic resonance imaging (CMR) has the potential to further improve risk stratification. CMR allows the comprehensive analysis of cardiac function and myocardial tissue composition. A range of CMR parameters have been associated with SCD. Applicable examples include late gadolinium enhancement (LGE), T1 relaxation times, and myocardial strain. This review evaluates the epidemiological aspects of SCD in NICM, the role of CMR for risk stratification, and resulting indications for ICD implantation.


2020 ◽  
Vol 28 (3) ◽  
pp. 290-299
Author(s):  
Kira A. Ageeva ◽  
Evgenii V. Filippov

Aim. To study the prognostic value of the results of dynamic capnography in the complex assessment of parameters of the respiratory system in 6-minute walk test in patients with chronic heart failure (CHF). Materials and Methods. 73 Patients were examined: the group of study included 48 patients with IIA or IIB stage CHF (mean age 57.94.6 years, 23 men), the control group included 25 practically healthy volunteers (mean age 47.63.5 years, 9 men). The patients were conducted complex determination of parameters of the respiratory system: clinical scaling before and after 6-minute walk test (6MWT), instrumental examinations including spirometry, capnography and pulse oximetry before, during and after physical activity. The analysis of survival was conducted on the basis of the dynamic follow-up of patients within 5 years (60 months). Results. In the analysis of parameters of dyspnea at rest, all the parameters were higher in the group of patients with CHF (р0.05). The distance walked by the patients with CHF in 6 minutes was 488.2390.84 m, which was significantly less than in the control group (815.6053.89 m, р=0.009). Dyspnea as the cause of stoppage/slowing down of walking in 6MWT, was also more often recorded in patients with CHF (93.83.0% and 48.05.1%, р=0.049). Besides, in 6MWT the patients noted: weakness in legs (50.15.0% in the group of CHF and 40.05.0% in the control group, р=0.014), palpitation (29.04.6% and 20.04.1%, respectively, р=0.004). Worsening of dyspnea parameters in 6MWT was more evident in patients with CHF than in the control group (р0.01). In the CHF group, hypocapnic type of ventilation was revealed in 6MWT, analysis of РЕТСО2 trend graphs revealed a wave-like increase in the parameters, the so called periodic breathing (PB). CO2 trend was recorded in CHF group in 58.31.0% of cases (the difference with the control group with р=0.046), the trend of heart rate in 18.80.3% of cases (р=0.027). Cox proportional hazards regression analysis of mortality in patients with CHF showed a prognostic significance of a complex model comprising the following parameters of a patient: body mass index (р=0.005), left ventricular end-diastolic dimension (р=0.034), left ventricular end-systolic dimension (р=0.002), left ventricular ejection fraction (р=0.041), 6MWT distance (р=0.004), desaturation (р=0.009), and the presence of signs of PB during 6MWT (р=0.005). Model coefficients were statistically significant at р0.0001. Conclusions. Dynamic capnography and pulse oximetry allow to identify signs of PB in patients with CHF during 6MWT which may deepen a complex assessment of parameters of the cardio-respiratory system in patients with CHF in order to determine tolerance to physical exercise as well as the effectiveness of the conducted treatment. Complex assessment of survival of patients with CHF showed prognostic significance of the following parameters of a patient: body mass index, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, 6MWT distance, desaturation, PB during 6MWT.


2011 ◽  
pp. 36-42
Author(s):  
Hung Viet Bui ◽  
Thi Cu Nguyen

Objective: In Vietnam, obesity is increasing particularly in many large cities. Adult cardiovascular diseases are often derived from cardiovascular disorders during the children period. The implementation of early measures to prevent atherosclerosis, such as weight control, better lipid control will reduce the cardiovascular complications, such as hypertension (HTA), coronary heart diseases and some other diseases. Materials and Methods: Overweight - obese children from 5 to 15 years old who visited the Children's Hospital in Can Tho from May 2009 to May 2010. Total number of patients were chosen as 50 children. Method: Descriptive cross-sectional. Children in the study underwent Doppler ultrasound exam to evaluate cardiac morphology and cardiac function. Results: There were increases in left ventricular systolic diameter, left ventricular diastolic diameter, LV mass in overweight-obese children in the study compared with controls at all ages (p <0.05 ). Left ventricular ejection fraction in overweight-obese children in the study was lower than the control group at all ages (p> 0.05). The average rate of left ventricular shortening of overweight-obese children in the study was 34.8 ± 4.5(%). There was no difference in the rate of shortening of the left ventricle in overweight-obese children in the study compared with controls (p>0.05). There was no relationship between variation in morphology and left ventricular function with the degree of overweight-obesity in this study. Conclusion: The study showed that disturbances in morphology and left ventricular function in overweight-obese children but did not find a strong association with the disorder degree of overweight-obesity.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Yoshida ◽  
A Shibata ◽  
A Tanihata ◽  
H Hayashi ◽  
Y Ichikawa ◽  
...  

Abstract Background Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia is drawing attention. Furthermore, the importance of not only muscle mass but also intramuscular fat (IMF) has been pointed out. However, there is a lack of consensus on the implications of ectopic fat for the prognosis in patients with non-ischemic cardiomyopathy. Purpose We investigated whether ectopic fat in the thigh affects the prognosis with non-ischemic cardiomyopathy. Methods We recruited 105 patients who were diagnosed with non-ischemic cardiomyopathy by cardiac catheterization and echocardiographic date between September 2017 and November 2019. Finally 73 patients with reduced EF (EF 40% or less) enrolled in this prospective study. Functional status was evaluated by using cardiopulmonary exercise test at baseline. All patients were measured quantity of epicardial fat and thigh IMF percentage (%IMF) using computed tomography scan. Demographic, laboratory and echocardiographic date were collected from the patients' medical records. Clinical endpoints were unexpected readmission. Results During the follow-up period 18 patients had adverse events. The %IMF was significantly higher in the group with adverse events than without (5.57±5.70 and 3.02±2.44%, respectively; p&lt;0.01). Spearman correlation coefficient analysis showed a modest correlation between %IMF and lower limb extension strength (Spearman r=−0.280; p=0.0315), but there was no significant correlation between %IMF and exercise tolerance such as anaerobic threshold and peak oxygen uptake. Patients were divided into 2 groups according to the median values of %IMF. Kaplan-Meier analysis demonstrated that events were significantly higher in the high %IMF group (log-rank p=0.033). Multivariate Cox regression analysis adjusted for left ventricular end-diastolic diameter and peak ventricular oxygen consumption found %IMF as an independent factor of adverse events (hazard ratio 1.545; 95% confidential interval 1.151–2.087; p=0.004). Conclusions In non-ischemic cardiomyopathy patients with reduced EF, %IMF may have important adverse consequences such as increased cardiac-related events. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None


Open Heart ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e001716
Author(s):  
Luke Byrne ◽  
Roisin Gardiner ◽  
Patrick Devitt ◽  
Caleb Powell ◽  
Richard Armstrong ◽  
...  

IntroductionThe COVID-19 pandemic has seen the introduction of important public health measures to minimise the spread of the virus. We aim to identify the impact government restrictions and hospital-based infection control procedures on ST elevation myocardial infarction (STEMI) care during the COVID-19 pandemic.MethodsPatients meeting ST elevation criteria and undergoing primary percutaneous coronary intervention from 27 March 2020, the day initial national lockdown measures were announced in Ireland, were included in the study. Patients presenting after the lockdown period, from 18 May to 31 June 2020, were also examined. Time from symptom onset to first medical contact (FMC), transfer time and time of wire cross was noted. Additionally, patient characteristics, left ventricular ejection fraction, mortality and biochemical parameters were documented. Outcomes and characteristics were compared against a control group of patients meeting ST elevation criteria during the month of January.ResultsA total of 42 patients presented with STEMI during the lockdown period. A significant increase in total ischaemic time (TIT) was noted versus controls (8.81 hours (±16.4) vs 2.99 hours (±1.39), p=0.03), with increases driven largely by delays in seeking FMC (7.13 hours (±16.4) vs 1.98 hours (±1.46), p=0.049). TIT remained significantly elevated during the postlockdown period (6.1 hours (±5.3), p=0.05), however, an improvement in patient delays was seen versus the control group (3.99 hours (±4.5), p=0.06). There was no difference seen in transfer times and door to wire cross time during lockdown, however, a significant increase in transfer times was seen postlockdown versus controls (1.81 hours (±1.0) vs 1.1 hours (±0.87), p=0.004).ConclusionA significant increase in TIT was seen during the lockdown period driven mainly by patient factors highlighting the significance of public health messages on public perception. Additionally, a significant delay in transfer times to our centre was seen postlockdown.


Author(s):  
Sahrai Saeed ◽  
Anastasia Vamvakidou ◽  
Spyridon Zidros ◽  
George Papasozomenos ◽  
Vegard Lysne ◽  
...  

Abstract Aims It is not known whether transaortic flow rate (FR) in aortic stenosis (AS) differs between men and women, and whether the commonly used cut-off of 200 mL/s is prognostic in females. We aimed to explore sex differences in the determinants of FR, and determine the best sex-specific cut-offs for prediction of all-cause mortality. Methods and results Between 2010 and 2017, a total of 1564 symptomatic patients (mean age 76 ± 13 years, 51% men) with severe AS were prospectively included. Mean follow-up was 35 ± 22 months. The prevalence of cardiovascular disease was significantly higher in men than women (63% vs. 42%, P &lt; 0.001). Men had higher left ventricular mass and lower left ventricular ejection fraction compared to women (both P &lt; 0.001). Men were more likely to undergo an aortic valve intervention (AVI) (54% vs. 45%, P = 0.001), while the death rates were similar (42.0% in men and 40.6% in women, P = 0.580). A total of 779 (49.8%) patients underwent an AVI in which 145 (18.6%) died. In a multivariate Cox regression analysis, each 10 mL/s decrease in FR was associated with a 7% increase in hazard ratio (HR) for all-cause mortality (HR 1.07; 95% CI 1.03–1.11, P &lt; 0.001). The best cut-off value of FR for prediction of all-cause mortality was 179 mL/s in women and 209 mL/s in men. Conclusion Transaortic FR was lower in women than men. In the group undergoing AVI, lower FR was associated with increased risk of all-cause mortality, and the optimal cut-off for prediction of all-cause mortality was lower in women than men.


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