Diagnosis, management, and outcome of cardiac sarcoidosis and giant cell myocarditis: a Swedish single center experience.

BACKGROUND: Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) are rare diseases that share some similarities, but also display different clinical and histopathological features. We aimed to compare the demographics, clinical presentation, and outcome of patients diagnosed with CS or GCM. METHOD: We compared the clinical data and outcome of all adult patients with CS (n = 71) or GCM (n = 21) diagnosed at our center between 1991 and 2020. RESULTS: The median (interquartile range) follow-up time for patients with CS and GCM was 33.5 [6.5-60.9] and 2.98 [0.6-40.9] months, respectively. In the entire cohort, heart failure (HF) was the most common presenting manifestation (31%), followed by ventricular arrhythmias (25%). At presentation, a left ventricular ejection fraction of < 50% was found in 54% of the CS compared to 86% of the GCM patients (P = 0.014), while corresponding proportions for right ventricular dysfunction were 24% and 52% (P = 0.026), respectively. Advanced HF (NYHA ≥ IIIB) was less common in CS (31%) than in GCM (76%). CS patients displayed significantly lower circulating levels of natriuretic peptides (P < 0.001) and troponins (P = 0.014). Eighteen percent of patients with CS included in the survival analysis reached the composite endpoint of death or heart transplantation (HTx) compared to 68% of patients with GCM (P < 0.001). CONCLUSION: GCM has a more fulminant clinical course than CS with severe biventricular failure, higher levels of circulating biomarkers and an increased need for HTx. The histopathologic diagnosis remained key determinant even after adjustment for markers of cardiac dysfunction.

Risk stratification in chronic thromboembolic pulmonary hypertension predicts survival.

OBJECTIVES: To investigate if the pulmonary arterial hypertension (PAH) risk assessment tool presented in the 2015 ESC/ERS guidelines is valid for patients with chronic thromboembolic pulmonary hypertension (CTEPH) when taking pulmonary endarterectomy (PEA) into account. Design. Incident CTEPH patients registered in the Swedish PAH Registry (SPAHR) between 2008 and 2016 were included. Risk stratification performed at baseline and follow-up classified the patients as low-, intermediate-, or high-risk using the proposed ESC/ERS risk algorithm. Results. There were 250 CTEPH patients with median age (interquartile range) 70 (14) years, and 53% were male. Thirty-two percent underwent PEA within 5 (6) months. In a multivariable model adjusting for age, sex, and pharmacological treatment, patients with intermediate-risk or high-risk profiles at baseline displayed an increased mortality risk (Hazard Ratio [95% confidence interval]: 1.64 [0.69-3.90] and 5.39 [2.13-13.59], respectively) compared to those with a low-risk profile, whereas PEA was associated with better survival (0.38 [0.18-0.82]). Similar impact of risk profile and PEA was seen at follow-up. Conclusion. The ESC/ERS risk assessment tool identifies CTEPH patients with reduced survival. Furthermore, PEA improves survival markedly independently of risk group and age. Take home message: The ESC/ERS risk stratification for PAH predicts survival also in CTEPH patients, even when taking PEA into account.

Parvovirus B19 in Endomyocardial Biopsy of Patients With Idiopathic Dilated Cardiomyopathy: Foe or Bystander?

BACKGROUND: Parvovirus B19 (PVB19) has emerged as one of the viruses possibly inducing chronic myocarditis and subsequent idiopathic dilated cardiomyopathy (IDCM). The aim of this work was to investigate the presence and long-term consequences of PVB19-DNA within myocardial biopsies from patients with IDCM and to compare the findings with those from donor hearts (control group). METHODS AND RESULTS: Forty hospitalized IDCM patients (age 47 ± 12 y) with mean left ventricular ejection fraction 27 ± 12% were included. The presence of PVB19-DNA in myocardial biopsies and of IgG and IgM antibodies in patient sera was analyzed. The control group consisted of 20 donor hearts. The follow-up time was 112 ± 57 months. PVB19-DNA was found in myocardial biopsies of both patients (73%) and control samples (55%; P = .25).Three deaths and 8 heart transplantations occurred in the IDCM group, and 6 deaths in the control group (ie, the recipients of the control hearts). No difference in transplantation-free survival between the PVB19-DNA positive/negative IDCM patients or transplant recipients was found. CONCLUSIONS: PVB19-DNA is a common finding in both patients with IDCM and in healthy donor hearts, not affecting prognosis. These findings support the view that PVB19 is an innocent bystander, frequently found in myocardium with low DNA copies, and not a plausible cause of IDCM.

A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension.

Aims: Guidelines recommend a goal-oriented treatment approach in pulmonary arterial hypertension (PAH). The aim is to reach a low-risk profile, as determined by a risk assessment instrument. This strategy is incompletely validated. We aimed to investigate the bearing of such risk assessment and the benefit of reaching a low-risk profile. Methods and results: Five hundred and thirty PAH patients were included. Follow-up assessments performed after a median of 4 (interquartile range 3-5) months were available for 383 subjects. Patients were classified as 'Low', 'Intermediate', or 'High risk' and the benefit of reaching the 'Low risk' group was estimated. Survival differed (P < 0.001) between the risk groups at baseline and at follow-up. Survival was similar for patients who remained in or improved to the 'Low risk' group. Survival was similar for patients who remained in or worsened to the 'Intermediate risk' or 'High risk' groups. Irrespective of follow-up risk group, survival was better (P < 0.001) for patients with a higher proportion of variables at low risk. Results were unchanged after excluding patients with idiopathic PAH >65 years at diagnosis, and when patients with idiopathic or connective tissue disease-associated PAH were analysed separately. Patients in the 'Low risk' group at follow-up exhibited a reduced mortality risk (hazard ratio 0.2, 95% confidence interval 0.1-0.4 in multivariable analysis adjusted for age, sex and PAH subset), as compared to patients in the 'Intermediate risk' or 'High risk' groups. Conclusion: These findings suggest that comprehensive risk assessments and the aim of reaching a low-risk profile are valid in PAH.

Impact of age and comorbidity on risk stratification in idiopathic pulmonary arterial hypertension.

Recent reports from worldwide pulmonary hypertension registries show a new demographic picture for patients with idiopathic pulmonary arterial hypertension (IPAH), with an increasing prevalence among the elderly.We aimed to investigate the effects of age and comorbidity on risk stratification and outcome of patients with incident IPAH.The study population (n=264) was categorised into four age groups: 18-45, 46-64, 65-74 and ≥75 years. Individual risk profiles were determined according to a risk assessment instrument, based on the European Society of Cardiology and the European Respiratory Society guidelines. The change in risk group from baseline to follow-up (median 5 months) and survival were compared across age groups. In the two youngest age groups, a significant number of patients improved (18-45 years, Z= -4.613, p<0.001; 46-64 years, Z= -2.125, p=0.034), but no significant improvement was found in the older patient groups. 5-year survival was highest in patients aged 18-45 years (88%), while the survival rates were 63%, 56% and 36% for patients in the groups 46-64, 65-74 and ≥75 years, respectively (p<0.001). Ischaemic heart disease and kidney dysfunction independently predicted survival.These findings highlight the importance of age and specific comorbidities as prognostic markers of outcome in addition to established risk assessment algorithms.

Severe heart failure in a unique case of cobalamin-C-deficiency resolved with LVAD implantation and subsequent heart transplantation.

Introduction Cobalamin c deficiency (cblC), an inborn error of vitamin B12 metabolism, is caused by mutations of the MMACHC gene. It usually leads to a multisystemic disease; 50% of all patients with cblC have various structural heart defects. Severe congestive heart failure (HF) may also occur and its prognosis is poorly documented. Case report We present the case of a young man who had been diagnosed with cblC due to C331T mutation in the MMACHC gene at the age of 3 days and had been treated with substitution therapy (OH-Cbl, mecobalamine, carnitine, betaine, and calcium folinate) since then. He had mildly impaired cognitive function; an ectopic hypophysis/pituitary insufficiency, with adequate hormone replacement therapy; obstructive sleep apnea syndrome, treated with CPAP, bronchial asthma, and obesity (BMI of 30). The liver and kidney functions were normal. He developed severe dilated cardiomyopathy and HF at the age of 12y. With medical treatment, his condition improved and he was stable (NYHA class II) for several years. Six years later, his status deteriorated rapidly, as he developed advanced HF, INTERMACS 3. The cardiac ultrasound revealed dilated ventricles with severely depressed ejection fraction (EF), increased filling pressures, and pulmonary hypertension (sPAP 60 mmHg). Cardiac MRI showed extremely dilated chambers (LVedv 609 mL, RVedv 398 mL) with pronounced non-compaction, and a left ventricle EF of 13%. A primary prophylactic ICD and a left ventricular assist device (LVAD/HM3) were implanted, and the patient was subsequently listed for heart transplantation (HTx). After 25 months on the waiting list, he underwent an uncomplicated HTx. However postoperatively, he got two episodes of cardiac tamponade, as well as mediastinitis, treated with antibiotics and vaccum assisted closure. He developed severe kidney failure, which fully recovered after two months, and was treated successfully for an early moderate allograft rejection (ISHT 2). At the latest outward visit, twelve months after HTx, the patient was doing excellent. Summary To the best of our knowledge, this is the first ever reported case of a patient with CblC undergoing an LVAD implantation and subsequently a HTx. Although both interventions were complicated with bleeding events, this seems to be a treatment option for advanced HF in patients with CblC.

Heart dysfunction in patients with acute ischemic stroke or TIA does not predict all-cause mortality at long-term follow-up.

BACKGROUND: Despite heart failure being a substantial risk factor for stroke, few studies have evaluated the predictive value of heart dysfunction for all-cause mortality in patients with acute ischemic stroke, in particular in the elderly. The aim of this study was to investigate whether impaired heart function in elderly patients can predict all-cause mortality after acute ischemic stroke or transient ischemic attack (TIA). METHODS: A prospective long-term follow-up analysis was performed on a hospital cohort consisting of n = 132 patients with mean age 73 ± 9 years, presenting with acute ischemic stroke or transient ischemic attack, without atrial fibrillation. All patients were examined by echocardiography during the hospital stay. Data about all-cause mortality were collected at the end of the follow-up period. The mean follow-up period was 56 ± 22 months. RESULTS: In this cohort, 58% of patients with acute ischemic stroke or TIA had heart dysfunction. Survival analysis showed that heart dysfunction did not predict all-cause mortality in this cohort. Furthermore, in multivariate regression analysis age (HR 5.401, Cl 1.97-14.78, p < 0.01), smoking (HR 3.181, Cl 1.36-7.47, p < 0.01), myocardial infarction (HR 2.826, Cl 1.17-6.83, p < 0.05) were independent predictors of all-cause mortality. CONCLUSION: In this population with acute ischemic stroke or TIA and without non-valvular atrial fibrillation, impaired heart function does not seem to be a significant predictor of all-cause mortality at long-term follow-up.

Electrocardiographic abnormalities and elevated cTNT at admission for intracerebral hemorrhage: predictors for survival?

BACKGROUND: Cerebrovascular lesions are often associated with electrocardiographic (ECG) abnormalities. The main purpose of this work was to investigate the prognostic value of ECG abnormalities and/or elevated cardiac troponin (cTNT) on admission in patients with nontraumatic intracerebral hemorrhage (ICH). METHODS: Ninety-seven consecutive patients with ICH were included. The predictive value of ECG abnormalities and increased TNT on survival were evaluated using Cox proportional hazard model. RESULTS: The most frequently observed ECG abnormalities were the presence of a Q wave (39.6%), followed by prolonged QTc (>0.44 s; 35.4%), which was an independent predictor for long-term mortality (P = 0.019). No difference in QTc was observed between patients with right versus left ICH. Increased cTNT levels at admission had no prognostic value. CONCLUSION: Various ECG changes were common in patients presenting with an ICH, but only prolonged QTc was found to be an independent predictor of poor survival during follow-up after ICH.

Sex Differences in Treatment and Prognosis of Acute Intracerebral Hemorrhage.

Background: Intracerebral hemorrhage (ICH) accounts for 10%-15% of all stroke cases and is associated with a high risk of death and disability. Prior studies in ischemic stroke have demonstrated a less favorable outcome in women compared with men, but there is a paucity of data regarding differences in outcome by sex in ICH. The aim of the present study was to investigate possible sex differences in acute care and the 3-months follow-up of patients with ICH. Methods: Data were collected from the Swedish National Stroke Registry (Riksstroke). Demographic and baseline characteristics were collected, based on in-hospital data and data from 3-months follow-up. Results: Variables of interest were collected from 1,403 patients. Women (45.1%) were significantly older than men, with a mean age ± standard deviation of 77 ± 13years, versus 71 ± 14 years, p < 0.01. On admission, the ICH severity was similar in men and women. There was no significant association between sex and reception of neuroimaging or neurosurgery. Women were less likely to be treated in a stroke unit (80.8% vs. 85.3%, p = 0.03), or discharged to home (51.5% vs. 63.4%, p < 0.01). At 3-months follow-up, there were no sex-related differences regarding dependence, post-ICH self-reported depression, or case fatality. Conclusions: Women were less likely to be treated in a stroke unit, and were less often discharged to home. However, no significant differences in 3-month functional outcome or survival between men and women with ICH were found in this study.

No obesity paradox in out-of-hospital cardiac arrest: Data from the Swedish registry of cardiopulmonary resuscitation.

Background: Although an "obesity paradox", which states an increased chance of survival for patients with obesity after myocardial infarction has been proposed, it is less clear whether this phenomenon even exists in patients suffering out-of-hospital cardiac arrest (OHCA) and if diabetes, which is often associated with obesity, implies an additional risk. Objective: To investigate if and how obesity, with or without diabetes, affects the survival of patients with OHCA. Methods: This study included 55,483 patients with OHCA reported to the Swedish Registry of Cardiopulmonary Resuscitation between 2010 and 2020. Patients were classified in five groups: obesity only (Ob), type 1 diabetes only (T1D), type 2 diabetes only (T2D), obesity and any diabetes (ObD), or belonging to the group other (OTH). Patient characteristics and outcomes were studied using descriptive statistics, logistic, and Cox proportional regression. Results: Obesity only was found in 2.7% of the study cohort, while 3.2% had obesity and any type of diabetes. Ob patients were significantly younger than all other patients (p ≤ 0.001); the 30 day-survival was 9.6% in Ob, and 10.6%, 7.3%, 6.9%, and 12.7% in T1D, T2D, ObD, and OTH, respectively, with OR (95% CI) of 0.69 (0.57-0.82), 0.78 (0.56-1.05), 0.65 (0.59-0.71), and 0.55 (0.45-0.66) for Ob, T1D, T2D, and ObD, respectively (reference group OTH). No time-related trends in 30-days survival were found. Conclusion: Obesity was present in 6% of the population and was associated with younger age and a 30% reduction in survival; a combination of obesity and diabetes further reduced the survival rate.

Clinical Outcomes and Predictors of Long-Term Survival in Patients With and Without Previously Known Extracardiac Sarcoidosis Using Machine Learning: A Swedish Multicenter Study.

Background Cardiac involvement can be an initial manifestation in sarcoidosis. However, little is known about the association between various clinical phenotypes of cardiac sarcoidosis (CS) and outcomes. We aimed to analyze the relation of different clinical manifestations with outcomes of CS and to investigate the relative importance of clinical features influencing overall survival. Methods and Results A retrospective cohort of 141 patients with CS enrolled at 2 Swedish university hospitals was studied. Presentation, imaging studies, and outcomes of de novo CS and previously known extracardiac sarcoidosis were compared. Survival free of primary composite outcome (ventricular arrhythmias, heart transplantation, or death) was assessed. Machine learning algorithm was used to study the relative importance of clinical features in predicting outcome. Sixty-two patients with de novo CS and 79 with previously known extracardiac sarcoidosis were included. De novo CS showed more advanced New York Heart Association class (P=0.02), higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) (P<0.001), and troponins (P<0.001), as well as a higher prevalence of right ventricular dysfunction (P<0.001). During a median (interquartile range) follow-up of 61 (44-77) months, event-free survival was shorter in patients with de novo CS (P<0.001). The top 5 features predicting worse event-free survival in order of importance were as follows: impaired tricuspid annular plane systolic excursion, de novo CS, reduced right ventricular ejection fraction, absence of ß-blockers, and lower left ventricular ejection fraction. Conclusions Patients with de novo CS displayed more severe disease and worse outcomes compared with patients with previously known extracardiac sarcoidosis. Using machine learning, right ventricular dysfunction and de novo CS stand out as strong overall predictors of impaired survival.

Characteristics, survival and neurological outcome in out-of-hospital cardiac arrest in young adults in Sweden: A nationwide study.

Aim: The aim of this study was to present a comprehensive overview of out-of-hospital cardiac arrests (OHCA) in young adults. Methods: The data set analyzed included all cases of OHCA from 1990 to 2020 in the age-range 16-49 years in the Swedish Registry of Cardiopulmonary Resuscitation (SRCR). OHCA between 2010 and 2020 were analyzed in more detail. Clinical characteristics, survival, neurological outcomes, and long-time trends in survival were studied. Logistic regression was used to study 30-days survival, neurological outcomes and Utstein determinants of survival. Results: Trends were assessed in 11,180 cases. The annual increase in 30-days survival during 1990-2020 was 5.9% with no decline in neurological function among survivors. Odds ratio (OR) for heart disease as the cause was 0.55 (95% CI 0.44 to 0.67) in 2017-2020 compared to 1990-1993. Corresponding ORs for overdoses and suicide attempts were 1.61 (95% CI 1.23-2.13) and 2.06 (95% CI 1.48-2.94), respectively. Exercise related OHCA was noted in roughly 5%. OR for bystander CPR in 2017-2020 vs 1990-1993 was 3.11 (95% CI 2.57 to 3.78); in 2020 88 % received bystander CPR. EMS response time increased from 6 to 10 minutes. Conclusion: Survival has increased 6% annually, resulting in a three-fold increase over 30 years, with stable neurological outcome. EMS response time increased with 66% but the majority now receive bystander CPR. Cardiac arrest due to overdoses and suicide attempts are increasing.

Comparative evaluation of treatment with low-dose aspirin plus dipyridamole versus aspirin only in patients with acute ischaemic stroke.

BACKGROUND: Previous studies have suggested that pre-stroke treatment with low-dose aspirin (A) could reduce the severity of acute ischaemic stroke, but less is known on the effect of pre-stroke treatment with a combination of aspirin and dipyridamole (A + D) and post-stroke effects of these drugs. The aim of the present study was to evaluate the effect of this drug combination on acute and long-term prognosis of ischaemic stroke. METHODS: Patients without atrial fibrillation admitted to the stroke unit with acute ischaemic stroke (n = 554) or TIA (n = 108) were studied during acute hospital care and up to 12 months after discharge from hospital. RESULTS: Prior to acute stroke 62 patients were treated with A + D while 247 patients were treated with A only. No beneficial effects of the combination A + D compared to A only were noted on stroke severity and/or acute in-hospital mortality. However, survival analysis by Cox-proportional hazard model demonstrated lower 12-months all-cause mortality in patients discharged with A + D (n = 275) compared with patients on A only (HR, 0.52; CI, 0.32-0.86; p = 0.011; n = 262) after adjusting for age, baseline NIHSS, previous stroke, previous myocardial infarction and type 2 diabetes. We also noted a tendency towards lower all-cause mortality at 3 months with use of A + D, but this was not statistically significant (p = 0.12). CONCLUSIONS: Pre-stroke treatment with a combination of low-dose A + D does not reduce the severity of acute stroke, nor does it reduce the acute in-hospital mortality. However, treatment with A + D at discharge from hospital is seemingly associated with lower long-term mortality compared with A only, contrary to the results from previous randomised studies. However, our results must be interpreted with extreme caution considering the non-randomised study design.

Five year risk assessment and treatment patterns in patients with chronic thromboembolic pulmonary hypertension.

AIMS: Repeated risk assessments and treatment patterns over long time are sparsely studied in chronic thromboembolic pulmonary hypertension (CTEPH); thus, we aimed to investigate changes in risk status and treatment patterns in incident patients with CTEPH over a 5 year period. METHODS AND RESULTS: Descriptive and explorative study including 311 patients diagnosed with CTEPH 2008-2019 from the Swedish pulmonary hypertension registry, stratified by pulmonary endarterectomy surgery (PEA). Risk and PH-specific treatment were assessed in surgically treated (PEA) and medically treated (non-PEA) patients at diagnosis and up to 5 years follow-up. Data are presented as median (Q1-Q3), count or per cent. Prior to surgery, 63% in the PEA-group [n = 98, age 64 (51-71) years, 37% female] used PH-specific treatment and 20, 69, and 10% were assessed as low, intermediate or high risk, respectively. After 1 year post-surgery, 34% had no PH-specific treatment or follow-up visit registered despite being alive at 5 years. Of patients with a 5 year visit (n = 23), 46% were at low and 54% at intermediate risk, while 91% used PH-specific treatment. In the non-PEA group [n = 213, age 72 (65-77) years, 56% female], 28% were assessed as low, 61% as intermediate and 11% as high risk. All patients at high risk versus 50% at low risk used PH-specific treatment. The 1 year mortality was 6%, while the risk was unchanged in 57% of the patients; 14% improved from intermediate to low risk, and 1% from high to low risk. At 5 years, 27% had a registered visit and 28% had died. Of patients with a 5 year visit (n = 58), 38% were at low, 59% at intermediate and 1% at high risk, and 86% used PH-specific treatment. CONCLUSIONS: Risk status assessed pre-surgery did not foresee long-term post-PEA risk and pre-surgery PH-specific treatment did not foresee long-term post-PEA treatment. Medically treated CTEPH patients tend to remain at the same risk over time, suggesting a need for improved treatment strategies in this group.

Association between central haemodynamics and renal function in advanced heart failure: a nationwide study from Sweden.

AIMS: Renal dysfunction in patients with heart failure (HF) has traditionally been attributed to declining cardiac output and renal hypoperfusion. However, other central haemodynamic aberrations may contribute to impaired kidney function. This study assessed the relationship between invasive central haemodynamic measurements from right-heart catheterizations and measured glomerular filtration rate (mGFR) in advanced HF. METHODS AND RESULTS: All patients referred for heart transplantation work-up in Sweden between 1988 and 2019 were identified through the Scandiatransplant organ-exchange organization database. Invasive haemodynamic variables and mGFR were retrieved retrospectively. A total of 1001 subjects (49 ± 13 years; 24% female) were eligible for the study. Analysis of covariance adjusted for age, sex, and centre revealed that higher right atrial pressure (RAP) displayed the strongest relationship with impaired GFR [ß coefficient -0.59; 95% confidence interval (CI) -0.69 to -0.48; P < 0.001], followed by lower mean arterial pressure (MAP) (ß coefficient 0.29; 95% CI 0.14-0.37; P < 0.001), and finally reduced cardiac index (ß coefficient 3.51; 95% CI 2.14-4.84; P < 0.003). A combination of high RAP and low MAP was associated with markedly worse mGFR than any other RAP/MAP profile, and high renal perfusion pressure (RPP, MAP minus RAP) was associated with superior renal function irrespective of the degree of cardiac output. CONCLUSIONS: In patients with advanced HF, high RAP contributed more to impaired GFR than low MAP. A higher RPP was more closely related to GFR than was high cardiac index.

Risk of stroke in patients with heart failure and sinus rhythm: data from the Swedish Heart Failure Registry.

AIMS: We investigated the 2 year rate of ischaemic stroke/transient ischaemic attack (IS) in patients with heart failure (HF) who were in sinus rhythm (HF-SR) and aimed to develop a score for stratifying risk of IS in this population. METHODS AND RESULTS: A total of 15 425 patients (mean age 71.5 years, 39% women) with HF-SR enrolled in the Swedish Heart Failure Register were included; 28 815 age-matched and sex-matched controls, without a registered diagnosis of HF, were selected from the Swedish Population Register. The 2 year rate of IS was 3.0% in patients and 1.4% in controls. In the patient group, a risk score including age (1p for 65-74 years; 2p for 75-84 years; 3p for ≥85 years), previous IS (2p), ischaemic heart disease, diabetes, hypertension, kidney dysfunction, and New York Heart Association III/IV class (1p each) was generated. Over a mean follow-up of 20.1 (SD 7.5) months, the cumulative incidences (per 1000 person-years) of IS in patients with score 0 to ≥7 were 2.2, 5.3, 8.9, 13.2, 15.7, 20.4, 26.4, and 33.0, with hazard ratios for score 1 to ≥7 (with 0 as reference): 2.4, 4.1, 6.1, 7.2, 9.4, 12.2, and 15.3. The risk score performed modestly (area under the curve 63.7%; P = 0.4711 for lack of fit with a logistic model; P = 0.7062 with Poisson, scaled by deviance). CONCLUSIONS: In terms of absolute risk, only 27.6% of patients had an annual IS incidence of ≤1%. To which extent this would be amenable to anticoagulant treatment remains conjectural. A score compiling age and specific co-morbidities identified HF-SR patients with increased risk of IS with modest discriminative ability.

Predicting mortality during long-term follow-up in pulmonary arterial hypertension.

The European Society of Cardiology (ESC) and European Respiratory Society (ERS) guideline recommendation of comprehensive risk assessments, which classify patients with pulmonary arterial hypertension (PAH) as having low, intermediate or high mortality risk, has not been evaluated during long-term follow-up in a "real-life" clinical setting. We therefore aimed to investigate the utility of risk assessment in a clinical setting for up to 5 years post diagnosis. 386 patients with PAH from the Swedish PAH Registry were included. Risk group (low/intermediate/high) and proportion of low-risk variables were investigated at 3-, 4- and 5-year follow-ups after time of diagnosis. In an exploratory analysis, survival rates of patients with low-intermediate or high-intermediate risk scores were compared. A low-risk profile was in multivariate Cox proportional hazards regressions found to be a strong, independent predictor of longer transplant-free survival (p<0.001) at the 3-, 4- and 5-year follow-ups. Also, for the 3-, 4- and 5-year follow-ups, survival rates significantly differed (p<0.001) between the three risk groups. Patients with a greater proportion of low-risk variables had better (p<0.001) survival rates. Patients with a high-intermediate risk score had worse survival rates (p<0.001) than those with a low-intermediate risk score. Results were similar when excluding patients with ≥3 risk factors for heart failure with preserved ejection fraction, atrial fibrillation and/or age >75 years at diagnosis. Our findings suggest that the ESC/ERS guideline strategy for comprehensive risk assessments in PAH is valid also during long-term follow-up in a "real-life" clinical setting.

Grading right ventricular dysfunction in left ventricular disease using echocardiography: a proof of concept using a novel multiparameter strategy.

AIMS: Grading right ventricular dysfunction (RVD) in patients with left ventricular (LV) disease has earned little attention. In the present study, we established an echocardiographic RVD score and investigated how increments of the score correspond to RVD at right heart catheterization. METHODS AND RESULTS: We included 95 patients with LV disease consecutively referred for heart transplant or heart failure work-up with catheterization and echocardiography within 48 h. The RVD score (5 points) included well-known characteristics of the development from compensated to decompensated right ventricular (RV) function: pulmonary hypertension, reduced RV strain, RV area dilatation, moderate/severe tricuspid regurgitation, and increased right atrial pressure (RAP) by echocardiography. Comparing three groups with increments of RVD score [1 (mild), 2-3 (moderate), and 4-5 (severe)] showed more advanced RVD with increasing RV end-diastolic pressure (P < 0.001) and signs of uncoupling to load (reduced ratio between RV and pulmonary artery elastance, P < 0.001) and more spherical RV shape (RV area/length, P < 0.001). Receiver operating characteristic curve analysis for detection of severe RV (RAP ≥ 10 mmHg) showed for the RVD score an area under the curve of 0.88 compared with 0.69, 0.68, and 0.64 for RV strain, tricuspid annular plane systolic excursion, and fractional area change, respectively. A patient with RVD score ≥ 4 had a 6.7-fold increase in likelihood of severe RVD, and no patient with RVD score ≤ 1 had severe RVD. CONCLUSIONS: In this proof of concept study, a novel RVD score outperformed the widely used longitudinal parameters regarding grading of RVD severity, with a potential role for refined diagnosis, follow-up, and prognosis assessment in heart failure patients.

Longitudinal changes in risk status in pulmonary arterial hypertension.

AIMS: Low-risk status in pulmonary arterial hypertension (PAH) predicts better survival. The present study aimed to describe changes in risk status and treatment approaches over multiple clinical assessments in PAH, taking age and comorbidity burden into consideration. METHODS AND RESULTS: The study included incident patients from the Swedish PAH registry, diagnosed with PAH in 2008-2019. Group A (n = 340) were ≤75 years old with <3 comorbidities. Group B (n = 163) were >75 years old with ≥3 comorbidities. Assessments occurred at baseline, first-year (Y1) and third-year (Y3) follow-ups. The study used an explorative and descriptive approach. Group A: median age was 65 years, 70% were female, and 46% had no comorbidities at baseline. Baseline risk assessment yielded low (23%), intermediate (66%), and high risk (11%). Among patients at low, intermediate, or high risk at baseline, 51%, 18%, and 13%, respectively, were at low risk at Y3. At baseline, monotherapy was the most common therapy among low (68%) and intermediate groups (60%), while dual therapy was the most common among high risk (69%). In patients assessed as low, intermediate, or high risk at Y1, 66%, 12%, and 0% were at low risk at Y3, respectively. Of patients at intermediate or high risk at Y1, 35% received monotherapy and 13% received triple therapy. In low-risk patients at Y1, monotherapy (40%) and dual therapy (43%) were evenly distributed. Group B: median age was 77 years, 50% were female, and 44% had ≥3 comorbidities at baseline. At baseline, 8% were at low, 80% at intermediate, and 12% at high risk. Monotherapy was the most common therapy (62%) in Group B at baseline. Few patients maintained or reached low risk at follow-ups. CONCLUSIONS: Most patients with PAH did not meet low-risk criteria during the 3 year follow-up. The first year from diagnosis seems important in defining the longitudinal risk status.

Early risk prediction in idiopathic versus connective tissue disease-associated pulmonary arterial hypertension: call for a refined assessment.

Despite systematic screening and improved treatment strategies, the prognosis remains worse in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) compared to patients with idiopathic/hereditary pulmonary arterial hypertension (IPAH). We aimed to investigate differences in clinical characteristics, outcome and performance of the European Society of Cardiology (ESC)/ European Respiratory Society (ERS) risk stratification tool in these patient groups. This retrospective analysis included incident patients with CTD-PAH (n=197, of which 64 had interstitial lung disease, ILD) or IPAH (n=305) enrolled in the Swedish PAH Register (SPAHR) 2008-2019. Patients were classified as low, intermediate or high risk at baseline, according to the "SPAHR-equation". One-year survival, stratified by type of PAH, was investigated by Cox proportional regression. At baseline, CTD-PAH patients had lower diffusing capacity for carbon monoxide and lower haemoglobin but, at the same time, lower N-terminal prohormone-brain natriuretic peptide, longer 6 min walk distance, better haemodynamics and more often a low-risk profile. No difference in age, World Health Organisation functional class (WHO-FC) or renal function between groups was found. One-year survival rates were 75, 82 and 83% in patients with CTD-PAH with ILD, CTD-PAH without ILD and IPAH, respectively. The 1-year mortality rates for low-, intermediate- and high-risk groups in the whole cohort were 0, 18 and 34% (p<0.001), respectively. Corresponding percentages for CTD-PAH with ILD, CTD-PAH without ILD and IPAH patients were: 0, 26, 67% (p=0.008); 0, 19, 39% (p=0.004); and 0, 16, 29% (p=0.001), respectively. The ESC/ERS risk assessment tool accurately identified low-risk patients but underestimated the 1-year mortality rate of CTD-PAH and IPAH patients assessed as having intermediate risk at diagnosis.