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Digoxin is used to treat atrial fibrillation and heart failure. Previous studies have reported an association between digoxin and higher mortality, but the results have been conflicting. This study assessed the association between digoxin use and all-cause mortality using comprehensive health data of patients treated for acute coronary syndrome (ACS). This was a retrospective analysis of 8,388 consecutive ACS patients treated in Tays Heart Hospital between 2007 and 2017, with a follow-up until the end of 2018. The adjusted Cox regression model was used to analyze the association between digoxin treatment and all-cause mortality with and without the inverse probability of treatment weighting (IPTW) method. IPTW was applied to estimate the residual confounding by the treatment selection. Clinical phenotype data were collected from various sources, including a prospectively updated online database maintained by physicians. The median follow-up time was 6.0 years (interquartile range 3.5 to 9.0 years). During the follow-up, 30.8% (n = 2,580) of the patients died. Altogether, 4.0% (n = 333) of the patients were treated with digoxin during hospitalization. In the Cox regression model, digoxin associated with increased mortality (age- and sex-adjusted hazard ratio [HR] 1.76 [1.51 to 2.05], p <0.001 and in the full risk factor–adjusted HR 1.23 [1.04 to 1.45], p = 0.016). The IPTW Cox analysis average treatment effect HR was 1.71 (1.12 to 2.62, p = 0.013), standardized average treatment effect HR was 1.35 (0.96 to 1.90, p = 0.082), and treatment effect among the treated HR was 1.32 (1.09 to 1.59, p = 0.004). In conclusion, digoxin treatment during ACS associates with increased mortality, despite adjusting for other risk factors and after accounting for factors explaining the residual confounding by selection bias.
Objectives: Stroke is a known complication after myocardial infarction (MI) and it is associated with increased mortality. We aimed to establish the true cumulative incidence of stroke and its subtypes and the associated mortality in a contemporary setting among patients treated for acute coronary syndrome (ACS). Materials and methods: A retrospective registry study based on the data of 8,049 consecutive patients treated for ACS in a sole provider of specialized cardiac and neurologic care for a catchment area of over 0.5 million residents between 2007 and 2018. Incident strokes and their subtypes were identified by in-depth review of written hospital records, hospital discharge registry data and causes of death registry data maintained by Statistics Finland up until December 31st 2020. Results: During a median follow-up of 5.8 years (IQR 3.2-9.0) 570 ACS patients suffered a stroke. The cumulative incidences of stroke for first week, first month, first year and at thirteen years were: 0.8 %, 1.1 %, 2.2 % and 10.3 %. In long-term, patients with different ACS subtypes had similar cumulative incidence of strokes, although the incidence of in-hospital strokes was highest among myocardial infarction patients. Stroke mortality rate was 32.5 % (n=185/570). The majority (88.8 %) of strokes were ischemic with the proportion being most substantial for in-hospital strokes (95.6 %). Conclusions: The risk of stroke among patients treated for ACS and the related mortality are still notable in a contemporary setting. A distinctive majority of strokes following ACS were ischemic especially early on after ACS.
BACKGROUND: Sudden cardiac arrests (SCA) and sudden cardiac deaths (SCD) are believed to account for a large proportion of deaths due to cardiovascular causes. The purpose of this study is to provide comprehensive information on the epidemiology of SCAs and SCDs after acute coronary syndrome. METHODS: The incidence of SCA (including SCDs) was studied retrospectively among 10,316 consecutive patients undergoing invasive evaluation for acute coronary syndrome (ACS) between 2007 and 2018 at Tays Heart Hospital (sole provider of specialized cardiac care for a catchment area of over 0.5 million residents). Baseline and follow-up information was collected by combining information from the hospital's electronic health records, death certificate data, and a full-disclosure review of written patient records and accounts of the circumstances leading to death. RESULTS: During twelve years of follow-up, the cumulative incidence of SCAs (including SCDs) was 9.8% (0.8% annually) and that of SCDs 5.4% (0.5% annually). Cumulative incidence of SCAs in patients with ST-elevation myocardial infarction, non-ST-elevation myocardial infarction and unstable angina pectoris were: 11.9%,10.2% and 5.7% at twelve years. SCAs accounted for 30.5% (n = 528/1,732) of all deaths due to cardiovascular causes. The vast majority of SCAs (95.6%) occurred in patients without implantable cardioverter defibrillator (ICD) devices or among patients with no recurrent hospitalizations for coronary artery disease (89.1%). CONCLUSIONS: SCAs accounted for less than a third of all deaths due to cardiovascular causes among patients with previous ACS. Incidence of SCA is highest among STEMI and NSTEMI patients. After the hospital discharge, most of SCAs happen to NSTEMI patients.
Background and objectives: Atrial fibrillation and flutter (AF/AFL) can be easily detected in patients who have a dual-chamber pacemaker (PM). This can result in a high detection rate of these arrhythmias especially if patients are monitored remotely and detection limits are sensitive. Materials and methods: A single-center retrospective registry analysis of 1,285 consecutive AF/AFL and anticoagulation naïve patients from a limited geographical area undergoing implantation of a new dual-chamber PM (between 2013 and 2019). Seven-year follow-up data for incident AF/AFL, initiation of new oral anticoagulation and for incident strokes and bleeds was obtained from an in-depth review of all relevant patient records including written medical records and death certificates detailing causes of death. Results: During the follow-up, mortality reached 22.2 % and cumulative incidence of AF/AFL, new anticoagulation, strokes, and bleeds were 52.6 %, 40.4 %, 4.7 % and 10.4 %. In 92.6 % of the cases, AF/AFL was discovered by PM. Remote monitoring was initiated in 67 % (n = 856). Risk factor adjusted mortality in this group was significantly lower when compared to patients in regular out-patient clinic controls (HR 0.45, 95 % CI 0.35–0.57). Despite of their better overall prognosis, the AF/AFL was discovered, and oral anticoagulation was initiated more often in remote monitoring group (HR 1.58, 95 % CI 1.23–1.79 for AF/AFL and HR 1.67, 95 % CI 1.33–2.09 for anticoagulation). There was no significant difference in the incidence of strokes or bleeds. Conclusions: The incidence of new AF/AFL is high in this population. Remote monitoring is associated with higher diagnostic yields of AF/AFL and initiated anticoagulation, but not with stroke and significant bleeds.
OBJECTIVE: Statin therapy, associated with improved short-term survival after treatment of abdominal aortic aneurysms, may also predispose to muscle side effects. Evidence on statin-related sarcopenia is limited mainly to muscle function, and it is subject to several sources of bias. In the long term, postoperative development of sarcopenia is linked to mortality after endovascular repair (EVAR). We investigated statin use and long-term postoperative mortality after EVAR in relation to objective measurable markers of sarcopenia (psoas muscle surface area and density). METHODS: Altogether 216 abdominal aortic aneurysm patients treated with EVAR between 2006 and 2014 at Tampere University Hospital (Finland) were retrospectively studied. Psoas muscle parameters at the L3 level were evaluated from baseline and mainly 1- to 3-year follow-up computed tomography studies. Cox regression was used to study the association between statin medication, psoas muscle changes, and all-cause mortality. RESULTS: The majority of patients were male (87%), and the mean age was 77.7 years (standard deviation, 7.4). The median duration of follow-up was 6.3 years (interquartile range, 3.5) with a total mortality of 54.2% (n = 117). Regardless of a higher burden of comorbidities, statin users (n = 119) had lower mortality when compared with nonusers (multivariable hazard ratio [HR]: 0.69, 95% confidence interval: 0.48-0.99, P = .048). Furthermore, statin use was not associated with inferior muscle parameter values, and the relative change in psoas muscle area was actually lower in statin users compared with nonusers (-15.7% and -21.1%, P < .046). CONCLUSIONS: Statin use is associated with lower long-term mortality among patients undergoing EVAR without predisposing to increased sarcopenia.
Aim: We explored the pre-intervention (first medical contact) electrocardiographic (ECG) patterns and their relation to survival among patients with acute myocardial infarction, who presented either with ST elevation (ST elevation myocardial infarction, STEMI) or LBBB, and who underwent emergent coronary angiography in a region with a 24/7/365 STEMI network. Methods: This is a retrospective analysis of 1363 consecutive patients hospitalized for first STEMI between the years 2014 and 2018. We assessed the prognostic significance of a variety of ECG categories, including location of ST elevation, severity of ischemia, intraventricular and atrioventricular conduction disorders, atrial fibrillation or flutter, junctional rhythms, heart rate, left ventricular hypertrophy and Q waves. The primary outcome was all-cause mortality between January 2014 and the end of 2020. Results: The mean age of the patients was 67.9 (SD 12.8) years. The majority were treated by percutaneous coronary intervention (93.8%, n = 1278). Median follow-up time was 3.7 years (IQR 2.5–5.1 years) during which 22.5% (n = 307) of the patients died. According to Cox regression analysis, adjusted for pre-existing conditions and age, the ECG variables with statistically significant association with survival were elevated heart rate (>100 bpm) (HR 2.34, 95% CI 1.75–3.12), atrial fibrillation or flutter (HR 1.94, 95% CI 1.41–2.67), left bundle branch block (LBBB) (HR 2.62, 95% CI 1.49–4.63) and non-specific intraventricular conduction delay (NIVCD) (HR 1.85, 95% CI 1.22–2.89). Conclusion: Higher heart rate, atrial fibrillation or flutter, LBBB and NIVCD are associated with worse outcome in all-comers with STEMI. Ischemia severity was not associated with impaired prognosis.
Background: Partial and advanced interatrial block (IAB) and P terminal force (PTF) in lead V1 are markers of atrial remodeling and risk factors for atrial fibrillation (AF). There is a lack of information about constancy and possible factors influencing the development of these P-wave abnormalities. Methods: The study sample consisted of 6058 Finnish participants (mean age 52.16 ± 14.60 years, 45.0% male) from the general population with an ECG taken in a health examination, and from 3224 of these participants, who had a re-examination 11 years later. Risk factors for incident partial and advanced IAB and PTF were studied using binomial logistic regression analysis, and the prognostic significance of these ECG changes for new AF was studied using time-varying Cox regression analysis. Results: The rate of reversal to normal of the studied ECG parameters were 47.4% for partial IAB, 40.0% for advanced IAB and 79.3% for PTF. Age, male sex, hypertension, higher BMI, higher LDL cholesterol, ECG left ventricular hypertrophy, use of beta blocker, and use of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist were independently associated with a risk to develop incident P-wave abnormality. Partial IAB was independently associated with increased AF risk (HR 1.28 [95% CI 1.04–1.58]), as was also advanced IAB (HR 1.72 [95% CI 1.07–2.75]). Conclusion: Traditional cardiovascular risk factors increase the risk of a new P-wave abnormality. Partial and advanced IAB are associated with increased AF risk. Surprisingly, P-wave abnormalities are often reversible during long-term follow-up in the general population.
Background: Intraventricular conduction delays (IVCDs) are hallmarks of heart failure (HF) and structural heart disease (SHD) but their prognostic value for HF and SHD is unclear. Methods: Relation of eight IVCDs and the incidence of first-time HF or SHD was studied in a nationally representative random sample of 6080 Finnish subjects aged ≥ 30 years (mean age 52.1, SD 14.5 years) who participated in the health examination including 12-lead ECG. Results: During 16.5 years’ follow up, half of the subjects with left bundle branch block (LBBB) and one third of the subjects with non-specific IVCD developed HF. After controlling for known clinical risk factors the hazard ratio (HR) for new-onset HF for LBBB was 3.29 (95% confidence interval 1.93–5.63, P < 0.001) and 3.53 for non-specific IVCD (1.65–7.55, P = 0.001). In corresponding analysis, LBBB predicted SHD with HR 2.60 (1.21–5.62, P = 0.015). Excluding subjects with history of heart disease, including coronary heart disease, did not have impact on results. Right bundle branch block and other IVCDs displayed no relation to endpoints. Conclusion: LBBB and non-specific IVCD were associated with more than three-fold risk of new-onset HF. Furthermore, LBBB was associated with novel SHD. Their presence should alert clinician even in subjects free from any known heart disease.
Abstract Background: Electrocardiographic (ECG) left ventricular hypertrophy (LVH) is an established risk factor for cardiovascular events. However, limited data is available on the prognostic values of different ECG LVH criteria specifically to sudden cardiac death (SCD). Our goal was to assess relationships of different ECG LVH criteria to SCD. Methods: Three traditional and clinically useful (Sokolow–Lyon, Cornell, RaVL) and a recently proposed (Peguero–Lo Presti) ECG LVH voltage criteria were measured in 5730 subjects in the Health 2000 Survey, a national general population cohort study. Relationships between LVH criteria, as well as their selected composites, to SCD were analyzed with Cox regression models. In addition, population-attributable fractions for LVH criteria were calculated. Results: After a mean follow-up of 12.5 ± 2.2 years, 134 SCDs had occurred. When used as continuous variables, all LVH criteria except for RaVL were associated with SCD in multivariable analyses. When single LVH criteria were used as dichotomous variables, only Cornell was significant after adjustments. The dichotomous composite of Sokolow–Lyon and Cornell was also significant after adjustments (hazard ratio for SCD 1.82, 95% confidence interval 1.20–2.70, P = 0.006) and was the only LVH measure that showed statistically significant population-attributable fraction (11.0%, 95% confidence interval 1.9–19.2%, P = 0.019). Conclusions: Sokolow–Lyon, Cornell, and Peguero–Lo Presti ECG, but not RaVL voltage, are associated with SCD risk as continuous ECG voltage LVH variables. When SCD risk assessment/adjustment is performed using a dichotomous ECG LVH measure, composite of Sokolow–Lyon and Cornell voltages is the preferred option.
Background: There is lack of studies exploring the incidence and association with diseases of the S1S2S3 electrocardiogram (ECG) pattern in the general population. Subjects and methods: This population study included 6299 individuals aged 30+, and explored the prevalence and association between S1S2S3 and cardiovascular and pulmonary diseases. Criteria for the S1S2S3-I and S1S2S3-II ECG pattern were fulfilled when there was an S wave in the leads I, II and III, and the S-wave amplitude was greater than the R-wave amplitude in one or two of the leads, respectively. Results: The S1S2S3-I ECG pattern was found in 2332 subjects (36.9%). After age adjustment, hypertension was associated with S1S2S3-I (Odds ratio [OR] 1.25, 95% CI 1.12–1.41, p < 0.001). This age-adjusted association was statistically significant among men but not among women (OR 1.37, 1.16–1.62, p < 0.001 and OR 1.13, 0.97–1.33, p = 0.126, respectively). The S1S2S3-II ECG pattern was present in 193 subjects (3.1%). After age adjustment, heart failure proved to be associated with S1S2S3-II (OR 1.85, 1.18–2.90, p = 0.007). Dividing the population by sex, resulted in a statistically significant age-adjusted association for men but not for women (OR 2.30, 1.22–4.33, p = 0.010 and OR 1.59, 0.83–3.03, p = 0.159, respectively). Interactions with sex were statistically non-significant. Conclusion: In the general adult population, the prevalence of the S1S2S3 ECG pattern is markedly affected by the diagnostic ECG criteria. The S1S2S3-I pattern was associated with hypertension, while S1S2S3-II was associated with heart failure, and both associations were enhanced in men. The associations with other studied cardiovascular and pulmonary diseases were minor and not clinically useful for risk stratification.
Abstract Background: Increased left ventricular mass (LVM) predicts cardiovascular events and mortality. The objective of this study was to determine whether early-life exposures to body mass index (BMI) and systolic blood pressure (SPB) affects the left ventricular structure in adulthood. Methods: We used longitudinal data from a 31-year follow-up to examine the associations between early-life (between ages 6–18) BMI and SPB on LVM in an adult population (N = 1864, aged 34–49). The burden of early-life BMI and SBP was defined as area under the curve. Results: After accounting for contemporary adult determinants of LVM, early-life BMI burden associated significantly with LVM (3.61 g/SD increase in early-life BMI; [1.94 − 5.28], p < 0.001). Overweight in early-life (age- and sex-specific BMI values corresponding to adult BMI > 25 kg/m2) associated with 4.7% (2.5–6.9%, p < 0.0001) higher LVM regardless of BMI status in adulthood. Overweight in early-life combined with obesity in adulthood (BMI > 30kg/m2) resulted in a 21% (17.3–32.9%, p < 0.0001) increase in LVM. Higher early-life BMI was associated with a risk of developing eccentric hypertrophy. The burden of early-life SPB was not associated with adult LVM or left ventricular remodeling. Conclusions: High BMI in early-life confers a sustained effect on LVM and the risk for eccentric hypertrophy independently of adulthood risk factors.
BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is associated with high morbidity and mortality worldwide. Simple electrocardiogram (ECG) tools, including ST-segment resolution (STR) have been developed to identify high-risk STEMI patients after primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: We evaluated the prognostic impact of STR in the ECG lead with maximal baseline ST-segment elevation (STE) 30-60 minutes after primary PCI in 7,654 STEMI patients included in the TOTAL trial. Incomplete or no STR was defined as < 70% STR and complete STR as ≥ 70% STR. The primary outcome was the composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock, or new or worsening New York Heart Association (NYHA) class IV heart failure at 1-year follow-up. RESULTS: Of 7,654 patients, 42.9% had incomplete or no STR and 57.1% had complete STR. The primary outcome occurred in 341 patients (10.4%) in the incomplete or no STR group and in 234 patients (5.4%) in the complete STR group. In Cox regression analysis, adjusted hazard ratio for STR < 70% to predict the primary outcome was 1.56 (95% confidence interval 1.32-1.89; P < .001) (model adjusted for all baseline comorbidities, clinical status during hospitalization, angiographic findings, and procedural techniques). CONCLUSION: In a large international study of STEMI patients, STR < 70% 30-60 minutes post primary PCI in the ECG lead with the greatest STE at admission was associated with an increased rate of the composite of cardiovascular death, recurrent MI, cardiogenic shock, or new or worsening NYHA class IV heart failure at 1-year follow-up. Clinicians should pay attention to this simple ECG finding.
Abstract Background: QRS duration and corrected QT (QTc) interval have been associated with sudden cardiac death (SCD), but no data are available on the significance of repolarization component (JTc interval) of the QTc interval as an independent risk marker in the general population. Objective: In this study, we sought to quantify the risk of SCD associated with QRS, QTc, and JTc intervals. Methods: This study was conducted using data from 3 population cohorts from different eras, comprising a total of 20,058 individuals. The follow-up period was limited to 10 years and age at baseline to 30–61 years. QRS duration and QT interval (Bazett’s) were measured from standard 12-lead electrocardiograms at baseline. JTc interval was defined as QTc interval — QRS duration. Cox proportional hazards models that controlled for confounding clinical factors identified at baseline were used to estimate the relative risk of SCD. Results: During a mean period of 9.7 years, 207 SCDs occurred (1.1 per 1000 person-years). QRS duration was associated with a significantly increased risk of SCD in each cohort (pooled hazard ratio [HR] 1.030 per 1-ms increase; 95% confidence interval [CI] 1.017–1.043). The QTc interval had borderline to significant associations with SCD and varied among cohorts (pooled HR 1.007; 95% CI 1.001–1.012). JTc interval as a continuous variable was not associated with SCD (pooled HR 1.001; 95% CI 0.996–1.007). Conclusions: Prolonged QRS durations and QTc intervals are associated with an increased risk of SCD. However, when the QTc interval is deconstructed into QRS and JTc intervals, the repolarization component (JTc) appears to have no independent prognostic value.
Photoplethysmography is a key sensing technology which is used in wearable devices such as smartwatches and fitness trackers. Currently, photoplethysmography sensors are used to monitor physiological parameters including heart rate and heart rhythm, and to track activities like sleep and exercise. Yet, wearable photoplethysmography has potential to provide much more information on health and wellbeing, which could inform clinical decision making. This Roadmap outlines directions for research and development to realise the full potential of wearable photoplethysmography. Experts discuss key topics within the areas of sensor design, signal processing, clinical applications, and research directions. Their perspectives provide valuable guidance to researchers developing wearable photoplethysmography technology.
Background: QRS duration and corrected QT (QTc) interval have been associated with sudden cardiac death (SCD), but no data are available on the significance of repolarization component (JTc interval) of the QTc interval as an independent risk marker in the general population. Objective: In this study, we sought to quantify the risk of SCD associated with QRS, QTc, and JTc intervals. Methods: This study was conducted using data from 3 population cohorts from different eras, comprising a total of 20,058 individuals. The follow-up period was limited to 10 years and age at baseline to 30–61 years. QRS duration and QT interval (Bazett's) were measured from standard 12-lead electrocardiograms at baseline. JTc interval was defined as QTc interval – QRS duration. Cox proportional hazards models that controlled for confounding clinical factors identified at baseline were used to estimate the relative risk of SCD. Results: During a mean period of 9.7 years, 207 SCDs occurred (1.1 per 1000 person-years). QRS duration was associated with a significantly increased risk of SCD in each cohort (pooled hazard ratio [HR] 1.030 per 1-ms increase; 95% confidence interval [CI] 1.017–1.043). The QTc interval had borderline to significant associations with SCD and varied among cohorts (pooled HR 1.007; 95% CI 1.001–1.012). JTc interval as a continuous variable was not associated with SCD (pooled HR 1.001; 95% CI 0.996–1.007). Conclusion: Prolonged QRS durations and QTc intervals are associated with an increased risk of SCD. However, when the QTc interval is deconstructed into QRS and JTc intervals, the repolarization component (JTc) appears to have no independent prognostic value.
Abstract Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74<rg<-0.55) and blood pressure (-0.35<rg<-0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.