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Hypokalaemia is common in patients with cardiovascular disease. In this review, we emphasize the importance of tight potassium regulation in patients with cardiovascular disease based on findings from observational studies. To enhance the understanding, we also describe the mechanisms of potassium homeostasis maintenance, the most common causes of hypokalaemia and present strategies for monitoring and management of low potassium levels. We propose elevation of potassium in asymptomatic patients with lower normal concentrations and concurrent cardiovascular disease. These proposals are intended to assist clinicians until more evidence is available.

AIMS: To investigate wheather incident Atrial fibrillation or flutter (AF) diagnosis increases the risk of psychiatric outcomes compared to the general population.METHODS AND RESULTS: First-time AF patients and population controls naïve to psychiatric disease or filled presciptions for psychotropic drugs were identified in Danish nationwide registries during 2005-2014. AF patients were matched 1:2 with exposure density matching. Patients and controls were compared for 1-year cumulative incidences of depression, anxiety and stress disorders, and for filled drug prescriptions for antidepressant, anxiolytic, selected antipsychotics and hypnotics. Lastly, we examined 1-year cumulative incidences of a composite endpoint of the above mentioned diagnoses or drug redemptions. We included 146,377 AF patients and 292,754 matched controls, 55% men and median age 74 (25%-75% 65-82) years. AF patients had significantly higher cumulative incidences of composite endpoints. Furthermore, filled prescriptions for anxiolytics and hypnotics were significantly higher for AF patients compared to healthy population controls. The cumulative incidence of the composite endpoint was significantly higher in AF patients relative to controls 11.1% vs. 8.3%. For the composite endpoint, a significantly higher risk was apparent both in unadjusted (HR: 2.76, 95% CI: 2.67-2.85) and adjusted (HR: 2.51, 95% CI: 2.43-2.60) models for AF patients versus controls in the first three months after study inclusion.CONCLUSION: First-time AF patients were significantly more likely to have psychiatric outpatient or hospital contacts and to fill presciptions for psychotropic drugs compared to healthy population controls. The risk was significantly elevated only during the first three months after AF diagnosis.

Background: In patients with cardiac resynchronization therapy defibrillators (CRT-Ds), intracardiac impedance measured by dedicated CRT-D software may be used to monitor hemodynamic changes. We investigated the relationship of hemodynamic parameters assessed by intracardiac impedance and by echocardiography in a controlled clinical setting. Methods: The study enrolled 68 patients (mean age, 66 ± 9 years; 74% males) at 12 investigational sites. The patients had an indication for CRT-D implantation, New York Heart Association class II/III symptoms, left ventricular ejection fraction 15%–35%, and a QRS duration ≥150 ms. Two months after a CRT-D implantation, hemodynamic changes were provoked by overdrive pacing. Intracardiac impedance was recorded at rest and at four pacing rates ranging from 10 to 40 beats/min above the resting rate. In parallel, echocardiography measurements were performed. We hypothesized that a mean intra-individual correlation coefficient (rmean) between stroke impedance (difference between end-systolic and end-diastolic intracardiac impedance) measured by CRT-D and the aortic velocity time integral (i.e., stroke volume) determined by echocardiography would be significantly larger than 0.65. Results: The hypothesis was evaluated in 40 patients with complete data sets. The rmean was 0.797, with a lower confidence interval bound of 0.709. The study hypothesis was met (p = 0.007). A stepwise reduction of stroke impedance and stroke volume was observed with increasing heart rate. Conclusions: Intracardiac impedance measured by implanted CRT-Ds correlated well with the aortic velocity time integral (stroke volume) determined by echocardiography. The impedance measurements bear potential and are readily available technically, not requiring implantation of additional material beyond standard CRT-D system.

Aim: Long-term risks of stroke, atrial fibrillation, or flutter (AF), acute coronary syndrome (ACS), and heart failure (HF) among survivors of out-of-hospital cardiac arrest (OHCA) are unknown. We aimed to examine 5-year risks of these outcomes among 30-day survivors of OHCA. Methods: Thirty-day survivors of OHCA without a prior (or within 30 days after cardiac arrest) history of stroke, AF, ACS, or HF and population controls without a prior history of these conditions were identified using Danish nationwide registries. Five-year risks of stroke, AF, ACS, and HF standardized to the distributions of age, sex, and comorbidities among OHCA survivors and controls were obtained using multivariable regression. Results: Of 4,362 30-day OHCA-survivors, 1,051 were stroke-, AF-, ACS-, and HF-naïve and matched with controls using age, sex, and time of OHCA event. Absolute five-year risks for OHCA survivors vs. controls were for stroke: 6.3% [95% confidence interval (CI) 4.1–8.5] vs. 2.0% [1.6–2.5], AF: 7.9% [5.7–10.2] vs. 2.6% [2.1–3.1], ACS: 5.0% [3.2–6.8] vs. 1.5% [1.1–1.9], and HF: 12.7% [10.1–15.4] vs. 1.2% [0.9–1.6], respectively. Corresponding relative risks were 3.18 [95% CI 1.76–4.61] for stroke, 3.03 [1.93–4.14] for AF, 3.23 [1.69–4.77] for ACS, and 10.40 [6.57–14.13] for HF. Conclusion: When compared with population controls, OHCA survivors had significantly increased five-year risks of incident stroke, AF, ACS, and HF.

Objective Incidence and severity of acute myocarditis vary significantly in previous reports and there is a lack of epidemiological studies on the short-term risks of mortality, heart failure and ventricular arrhythmias in patients with acute myocarditis. Therefore, study aims were to examine 90-day risks of mortality, heart failure (HF) and ventricular arrhythmias in patients with acute myocarditis in comparison to age-matched and sex-matched background population controls. Methods In this nationwide register-based follow-up study of patients hospitalised with myocarditis between 2002 and 2018 in Denmark, 90-day risks of all-cause mortality, HF, ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation (VF)), cardiac arrest and implantable cardioverter-defibrillator (ICD) implantation were compared with age-matched and sex-matched controls from the background population (1:5 matching). Absolute risks standardised to the age, sex and comorbidity distribution of the entire study population were derived from multivariable Cox regression. Results A total of 2523 patients hospitalised with myocarditis were included. Median age was 48 years (Q1-Q3: 30-69) and 67.7% were men. Comorbidity burden was more pronounced among patients with myocarditis relative to controls. Standardised 90-day all-cause mortality risk was 4.9% for patients with acute myocarditis versus 0.3% for controls (p<0.001). Ninety-day standardised risks for other endpoints were 7.5% versus 0.1% for HF, 1.9% versus <0.1% for VF/VF/arrest risk and 1.6% versus <0.1% for ICD implantation (all p<0.001). Conclusions In this large nationwide register-based follow-up study, patients hospitalised with myocarditis had significantly higher 90-day risks of all-cause mortality, HF, ventricular arrhythmias, cardiac arrest and ICD implantation compared with background population controls.

Layer-specific global longitudinal strain (GLS) has been demonstrated to predict outcome in various patient cohorts. However, little is known regarding the prognostic value of layer-specific GLS in the general population and whether different layers entail differential prognostic information. The aim of the present study was to investigate the prognostic value of whole wall (GLSWW), endomyocardial (GLSEndo), and epimyocardial (GLSEpi) GLS in the general population. Method A total of 4,013 citizens were included in the present study. All 4,013 had 2D-speckle tracking echocardiography performed and analyzed. Outcome was a composite endpoint of incident heart failure (HF) and/or cardiovascular death (CVD). Results Mean age was 56 years and 57up time of 3.5 years, 133 participants (3.3 reached the composite outcome. Sex modified the relationship between all GLS parameters and outcome. In sex stratified analysis, no GLS parameter remained significant predictors of outcome in females. In contrast, GLSWW (HR=1.16, 951.02;1.31], per 1 and GLSEpi (HR=1.19, 951.04;1.38], per 1 remained as significant predictors of outcome in males after multivariable adjustment (including demographic, clinical, biochemistry, and echocardiographic parameters). Lastly, only in males did GLS parameters provide incremental prognostic information to general population risk models. Conclusions In the general population, sex modifies the prognostic value of GLS resulting in GLSEpi being the only layer-specific prognosticator in males, while no GLS parameter provides independent prognostic information in females., Aims Layer-specific global longitudinal strain (GLS) has been demonstrated to predict outcome in various patient cohorts. However, little is known regarding the prognostic value of layer-specific GLS in the general population and whether different layers entail differential prognostic information. The aim of the present study was to investigate the prognostic value of whole wall (GLSWW), endomyocardial (GLSEndo), and epimyocardial (GLSEpi) GLS in the general population. Methods and results A total of 4013 citizens were included in the present study. All 4013 had two-dimensional speckle tracking echocardiography performed and analysed. Outcome was a composite endpoint of incident heart failure and/or cardiovascular death. Mean age was 56 years and 57% were female. During a median follow-up time of 3.5 years, 133 participants (3.3%) reached the composite outcome. Sex modified the relationship between all GLS parameters and outcome. In sex-stratified analysis, no GLS parameter remained significant predictors of outcome in females. In contrast, GLSWW [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.02–1.31, per 1% decrease] and GLSEpi (HR 1.19, 95% CI 1.04–1.38, per 1% decrease) remained as significant predictors of outcome in males after multivariable adjustment (including demographic, clinical, biochemistry, and echocardiographic parameters). Lastly, only in males did GLS parameters provide incremental prognostic information to general population risk models. Conclusions In the general population, sex modifies the prognostic value of GLS resulting in GLSEpi being the only layer-specific prognosticator in males, while no GLS parameter provides independent prognostic information in females.

Aims The degree of cardiovascular sequelae following COVID-19 remains unknown. The aim of this study was to investigate whether cardiac function recovers following COVID-19. Methods and results A consecutive sample of patients hospitalized with COVID-19 was prospectively included in this longitudinal study. All patients underwent an echocardiographic examination during hospitalization and 2 months later. All participants were successfully matched 1:1 with COVID-19-free controls by age and sex. A total of 91 patients were included (mean age 63 ± 12 years, 59% male). A median of 77 days (interquartile range: 72–92) passed between the two examinations. Right ventricular (RV) function improved following resolution of COVID-19: tricuspid annular plane systolic excursion (TAPSE) (2.28 ± 0.40 cm vs. 2.11 ± 0.38 cm, P < 0.001) and RV longitudinal strain (RVLS) (25.3 ± 5.5% vs. 19.9 ± 5.8%, P < 0.001). In contrast, left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) did not significantly improve (17.4 ± 2.9% vs. 17.6 ± 3.3%, P = 0.6). N-terminal pro-B-type natriuretic peptide decreased between the two examinations [177.6 (80.3–408.0) ng/L vs. 11.7 (5.7–24.0) ng/L, P < 0.001]. None of the participants had elevated troponins at follow-up compared to 18 (27.7%) during hospitalization. Recovered COVID-19 patients had significantly lower GLS (17.4 ± 2.9% vs. 18.8 ± 2.9%, P < 0.001 and adjusted P = 0.004), TAPSE (2.28 ± 0.40 cm vs. 2.67 ± 0.44 cm, P < 0.001 and adjusted P < 0.001), and RVLS (25.3 ± 5.5% vs. 26.6 ± 5.8%, P = 0.50 and adjusted P < 0.001) compared to matched controls. Conclusion Acute COVID-19 affected negatively RV function and cardiac biomarkers but recovered following resolution of COVID-19. In contrast, the observed reduced LV function during acute COVID-19 did not improve post-COVID-19. Compared to the matched controls, both LV and RV function remained impaired.

Background: Early systolic lengthening (ESL), a paradoxical stretch of myocardial fibers, has been linked to loss of myocardial viability and contractile dysfunction. We assessed the long-term prognostic potential of ESL in coronary artery bypass graft (CABG) patients. Methods: We retrospectively included patients (n = 709; mean age 68 years; 85% men) who underwent speckle tracking echocardiography (median 15 days) prior to CABG. Endpoints were cardiovascular death (CVD) and all-cause mortality. We assessed amplitude of ESL (%), defined as peak positive strain, and duration of ESL (ms), determined as time from Q-wave on the ECG to peak positive strain. We applied Cox models adjusted for clinical risk assessed as EuroSCORE II. Results: During median follow-up of 3.8 years [IQR 2.7–4.9 years], 45 (6%) experienced CVD and 80 (11%) died. In survival analyses adjusted for EuroSCORE II, each 1% increase in amplitude of ESL was associated with CVD (HR 1.35 [95%CI 1.09–1.68], P = 0.006) and all-cause mortality (HR 1.29 [95%CI 1.08–1.54], P = 0.004). Similar findings applied to duration of ESL (per 10ms increase) and CVD (HR 1.12 [95%CI 1.02–1.23], P = 0.016) and all-cause mortality (HR 1.09 [95%CI 1.01––1.17], P = 0.031). The prognostic value of ESL amplitude was modified by sex (P interaction < 0.05), such that the prognostic value was greater in women for both endpoints. When adding ESL duration to EuroSCORE II, the net reclassification index improved significantly for both CVD and all-cause mortality. Conclusions: Assessment of ESL provides independent and incremental prognostic information in addition to the EuroSCORE II for CVD and all-cause mortality in CABG patients.

Objective: To determine the prognostic value of global longitudinal strain (GLS) after coronary artery bypass grafting (CABG). Methods: We performed a retrospective cohort study on patients undergoing CABG between 2006 and 2011 who had an echocardiogram available for strain analysis. The patients were followed up through nationwide registries for development of all-cause mortality, cardiovascular death (CVD) and major adverse cardiovascular events (MACEs) defined as heart failure hospitalisation and/or CVD. Multivariable Cox regression was applied to adjust for the European System for Cardiac Operative Risk Evaluation II (EuroSCORE-II). Additive value was assessed by Net Reclassification Index (NRI) improvement. Results: Of the 709 patients included, 80 died during a median follow-up of 3.8 years. Of these, 45 had CVD, and 72 patients experienced MACE. Mean age was 68 years and 85% were men. Left ventricular ejection fraction (LVEF) was 50% and GLS was -13%. GLS was an independent predictor when adjusted for the EuroSCORE-II (all-cause mortality: HR=1.07 (1.01-1.13), p=0.018; CVD: HR=1.11 (1.03-1.20), p=0.007; MACE: HR=1.12 (1.06-1.19), p<0.001, per 1% absolute decrease). GLS significantly improved the NRI score by 0.30 when added to the EuroSCORE-II for predicting MACE, but not significantly for the other endpoints. LVEF modified the association between GLS and outcomes (p for interaction<0.05 for CVD and MACE). GLS remained an independent predictor of outcomes in patients with preserved LVEF (LVEF≥50%) and improved the NRI score when added to the EuroSCORE-II for predicting CVD and MACE, but not all-cause mortality in these patients. Conclusion: GLS is an independent predictor of long-term outcomes after CABG. The predictive value appears strongest among patients with preserved LVEF.

AIMS: To examine socioeconomic differences in care and outcomes in a one-year period beginning 30 days after hospital discharge for first-time AF hospitalization.METHODS AND RESULTS: This nationwide register-based follow-up cohort study investigated AF 30-day discharge survivors in Denmark during 2005-2014 and examined associations between patient's socioeconomic status (SES) and selected outcomes during a 1-year follow-up period beginning 30 days post-discharge after first-time hospitalization for AF. Patient SES was defined in four groups (lowest, second lowest, second highest and highest) according to each patient's equivalized income. SES of the included 150,544 patients was: 27.7% lowest (n = 41,648), 28.1% second lowest (n = 42,321), 23.7% second highest (n = 35,656) and 20.5% highest (n = 30,919). Patients of lowest SES were older and more often women. Within 1-year follow-up, patients of lowest SES were less often re-hospitalized or seen in outpatient clinics due to AF, or treated with cardioversion or ablation, and were slightly more often diagnosed with stroke and heart failure and significantly more likely to die (16.1% vs. 14.9%, 11.3% and 8.1%). Hazard ratios for all-cause mortality were 0.64 (95% CI 0.61-0.68) for highest vs. lowest SES, adjusted for CHA2DS2-VASc-score, COPD, rate- and rhythm-controlling drugs and cohabitation status.CONCLUSION: In 30-day survivors of first-time hospitalization due to AF, lowest SES is associated with increased 1-year all-cause and cardiovascular mortality and fewer cardioversions, ablations, readmissions and outpatient contacts due to AF. Our findings indicate a need for socially differentiated rehabilitation following hospital discharge for first-time AF.

AIM: We investigated the association between potassium levels and 90-day all-cause mortality in atrial fibrillation or flutter (AF) patients co-treated with diuretics and rate- or rhythm-controlling drugs.METHODS AND RESULTS: During 2000-2012, first-time AF patients treated with beta-blockers, amiodarone, sotalol, verapamil, and/or digoxin combined with any diuretic within 90 days post-AF discharge were included. Following co-treatment, a potassium measurement within 90 days after initiating diuretic treatment was required. Mortality risk associated with potassium <3.5, 3.5-3.7, 3.8-4.0, 4.5-4.7, 4.8-5.0, and >5.0 mmol/L (reference: 4.1-4.4 mmol/L) was assessed using Multivariable Cox regression. In total, 14,425 AF patients were included (median age: 78 years; women: 52%). Patients most often received beta-blocker monotherapy (29%), beta-blocker and digoxin combined (25%), digoxin monotherapy (24%), amiodarone monotherapy (3%), and verapamil monotherapy (3%). Increased 90-day mortality risk was associated with <3.5 mmol/L (HR 2.05, 95% CI: 1.68-2.50), 3.5-3.7 mmol/L (HR: 1.28, 95% CI 1.05-1.57), 4.5-4.7 mmol/L (HR: 1.20, 95% CI: 1.02-1.41), 4.8-5.0 mmol/L, (HR: 1.37, 95% CI: 1.14-1.66) and >5.0 mmol/L: (HR: 1.84, 95% CI: 1.53-2.21). Compared with beta-blocker monotherapy, rate- or rhythm-controlling drugs did not modify the association between potassium groups and mortality risk.CONCLUSION: In addition to hypo- and hyperkalemia, low and high normal range potassium levels were associated with increased 90-day mortality risk in AF patients co-treated with diuretics and rate- or rhythm-controlling drugs. These associations were independent of rate- or rhythm-controlling drugs.

Background Hyperkalemia can be harmful, but the effect of correcting hyperkalemia is sparsely studied. We used nationwide data to examine hyperkalemia follow-up in patients with hypertension. Methods and Results We identified 7620 patients with hypertension, who had the first plasma potassium measurement ≥4.7 mmol/L (hyperkalemia) within 100 days of combination antihypertensive therapy initiation. A second potassium was measured 6 to 100 days after the episode of hyperkalemia. All-cause mortality within 90 days of the second potassium measurement was assessed using Cox regression. Mortality was examined for 8 predefined potassium intervals derived from the second measurement: 2.2 to 2.9 mmol/L (n=37), 3.0 to 3.4 mmol/L (n=184), 3.5 to 3.7 mmol/L (n=325), 3.8 to 4.0 mmol/L (n=791), 4.1 to 4.6 mmol/L (n=3533, reference), 4.7 to 5.0 mmol/L (n=1786), 5.1 to 5.5 mmol/L (n=720), and 5.6 to 7.8 mmol/L (n=244). Ninety-day mortality in the 8 strata was 37.8%, 21.2%, 14.5%, 9.6%, 6.3%, 6.2%, 10.0%, and 16.4%, respectively. The multivariable analysis showed that patients with concentrations >5.5 mmol/L after an episode of hyperkalemia had increased mortality risk compared with the reference (hazard ratio [HR], 2.27; 95% CI, 1.60-3.20; P<0.001). Potassium intervals 3.5 to 3.7 mmol/L and 3.8 to 4.0 mmol/L were also associated with increased risk of death (HR, 1.71; 95% CI, 1.23-2.37; P<0.001; HR, 1.36; 95% CI, 1.04-1.76; P<0.001, respectively) compared with the reference group. We observed a trend toward increased risk of death within the interval 5.1 to 5.5 mmol/L (HR, 1.29; 95% CI, 0.98-1.69). Potassium concentrations <4.1 mmol/L and >5.0 mmol/L were associated with increased risk of cardiovascular death. Conclusions Overcorrection of hyperkalemia to levels <4.1 mmol/L was frequent and associated with increased all-cause and cardiovascular mortality. Potassium concentrations >5.5 mmol/L were also associated with an increased all-cause and cardiovascu

BACKGROUND: There are limited data on electrocardiogram (ECG) characteristics and their association with psychotropic drugs in schizophrenia.METHODS: Using a cross-sectional design, we included Danish primary care patients with first-time digital ECGs from 2001 to 2015. Patients diagnosed with schizophrenia before ECG recording were matched 1:5 on age, sex, and ECG recording year to controls without psychiatric disease. Multivariable logistic regression was used to compute odds ratios (ORs) with 95% confidence intervals (CIs).RESULTS: We included 4486 patients with schizophrenia matched with 22 430 controls (median age, 47 years; male, 55%). Between groups, the prevalence of abnormal ECGs was similar (54%, P = .536), but patients with schizophrenia demonstrated higher median heart rate (79 vs 69 beats per minute, P < .001) and Fridericia-corrected QT (QTc) interval (416 vs 412 ms, P < .001) than controls. QTc prolongation was also more prevalent among patients with schizophrenia (3.4% vs 1.1%, P < .001), and so were pathological Q waves (5.3% vs 3.9%, P < .001). Patients with schizophrenia less frequently demonstrated left ventricular hypertrophy (6.1% vs 9.6%, P < .001) and atrial fibrillation or flutter (0.7% vs 1.4%, P < .001). Among patients with schizophrenia only, particularly antipsychotics were associated with abnormal ECGs (OR, 1.20; 95% CI, 1.04-1.39).CONCLUSIONS: Patients with schizophrenia demonstrate a different cardiovascular risk profile than matched controls without psychiatric disease, with higher prevalence of elevated heart rate, QTc prolongation, and pathological Q waves, and lower prevalence of left ventricular hypertrophy and atrial fibrillation or flutter. Particularly antipsychotics were associated with abnormal ECGs. This underscores an integrated care approach when ECG abnormalities are detected in this group.

Aims The present study had two aims: (i) compare echocardiographic parameters in COVID-19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ventricular (RV) function in relation to COVID-19 related death.Methods and results In this prospective multicentre cohort study, 214 consecutive hospitalized COVID-19 patients underwent an echocardiographic examination (by pre-determined research protocol). All participants were successfully matched 1:1 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69 years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID-19 cases as assessed by global longitudinal strain (GLS) (16.4% +/- 4.3 vs. 18.5% +/- 3.0,P <0.001), tricuspid annular plane systolic excursion (TAPSE) (2.0 +/- 0.4 vs. 2.6 +/- 0.5,P <0.001), and RV strain (19.8 +/- 5.9 vs. 24.2 +/- 6.5,P = 0.004). All parameters remained significantly reduced after adjusting for important cardiac risk factors. During follow-up (median: 40 days), 25 COVID-19 cases died. In multivariable Cox regression reduced TAPSE [hazard ratio (HR) = 1.18, 95% confidence interval (CI) [1.07-1.31],P = 0.002, per 1 mm decrease], RV strain (HR = 1.64, 95%CI[1.02;2.66],P = 0.043, per 1% decrease) and GLS (HR = 1.20, 95%CI[1.07-1.35],P = 0.002, per 1% decrease) were significantly associated with COVID-19-related death. TAPSE and GLS remained significantly associated with the outcome after restricting the analysis to patients without prevalent heart disease.Conclusions RV and LV function are significantly impaired in hospitalized COVID-19 patients compared with matched controls. Furthermore, reduced TAPSE and GLS are independently associated with COVID-19-related death.