Scoring of medial arterial calcification predicts cardiovascular events and mortality after kidney transplantation.

BACKGROUND: Progression of vascular calcification causes cardiovascular disease, which is the most common cause of death in chronic kidney failure and after kidney transplantation (KT). The prognostic impact of the extent of medial vascular calcification at KT is unknown. METHODS: In this prospective cohort study, we investigated the impact of medial calcification compared to a mix of intimal and medial calcification represented by coronary artery calcification (CAC score) and aortic valve calcification in 342 patients starting on kidney failure replacement therapy. The primary outcomes were cardiovascular events (CVE) and death. The median follow-up time was 6.4 years (interquartile range 3.7-9.6 years). Exposure was CAC score and arteria epigastrica medial calcification scored as none, mild, moderate, or severe by a pathologist at time of KT (n = 200). We divided the patients according to kidney failure replacement therapy during follow-up, that is, living donor KT, deceased donor KT, or dialysis. RESULTS: Moderate to severe medial calcification in the arteria epigastrica was associated with higher mortality (p = 0.001), and the hazard ratio for CVE was 3.1 (95% confidence interval [CI] 1.12-9.02, p < 0.05) compared to no or mild medial calcification. The hazard ratio for 10-year mortality in the dialysis group was 33.6 (95% CI, 10.0-113.0, p < 0.001) compared to living donor recipients, independent of Framingham risk score and prevalent CAC. CONCLUSION: Scoring of medial calcification in the arteria epigastrica identified living donor recipients as having 3.1 times higher risk of CVE, independent of traditional risk factors. The medial calcification score could be a reliable method to identify patients with high and low risk of CVE and mortality following KT.

COVID-19 in solid organ transplant recipients: A national cohort study from Sweden.

Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1-2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6-7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.

Heart failure: the grim reaper of the cardio-renal-metabolic triad.

AIMS: Current understanding of the prognosis for patients with chronic kidney disease (CKD) and overlapping cardio-renal-metabolic components, specifically heart failure (HF) and diabetes mellitus (DM), remains limited. While previous studies have explored the interactions between CKD, HF, and DM, they have predominantly focused on cohorts of HF or DM patients. This study aims to fill this gap by investigating the long-term outcomes and treatment patterns in a cohort of CKD patients, particularly those with coexisting HF and DM. METHODS AND RESULTS: We analysed data from the Swedish national CKD patient cohort, the Swedish Renal Registry, with a follow-up period extending up to 10 years. The study examined the risks of all-cause mortality, major adverse cardiovascular events (MACE)-defined as a composite of non-fatal myocardial infarction, hospitalization for congestive HF, non-fatal stroke, or cardiovascular death-and the initiation of kidney replacement therapy (KRT). Analyses were conducted using Cox proportional hazards and competing risk models. Among the 27 647 patients, 48% had CKD alone, 12% had CKD with HF, 27% had CKD with DM, and 13% had CKD with both HF and DM. After 5 years, mortality rates were 23% for patients with CKD, 30% for those with CKD/DM, 54% for CKD/HF, and 55% for CKD/HF/DM. The 10 year absolute risk of MACE was 28% for CKD alone, 35% for CKD/DM, 67% for CKD/HF, and 73% for CKD/HF/DM. The adjusted hazard ratio (HR) for mortality was approximately three times higher in patients with any HF combination, with HRs of 2.57 [95% confidence interval (CI) 2.43-2.71] for CKD/HF and 3.22 (95% CI 3.05-3.39) for CKD/HF/DM, compared with CKD alone. The impact of HF on MACE prognosis was even more pronounced, with adjusted sub-hazard ratios (SHRs) of 3.33 (95% CI 3.14-3.53) for CKD/HF and 4.26 (95% CI 4.04-4.50) for CKD/HF/DM. Additionally, CKD patients diagnosed with HF were less likely to commence KRT, and the risk of death prior to KRT initiation was roughly twice as high for these groups, with SHRs of 2.05 (95% CI 1.93-2.18) for CKD + HF and 2.43 (95% CI 2.29-2.58) for CKD + HF + DM. CONCLUSIONS: In a cohort of CKD patients, having HF contributes substantially to increased mortality and the risk of MACE, and these patients are less likely to start KRT. These findings highlight the urgent need for targeted therapeutic strategies and management plans for CKD patients, particularly those with concurrent HF, to enhance patient prognosis.

Feasibility of alcohol interventions in cardiology: A qualitative study of clinician perspectives in Sweden.

AIM: To identify barriers and facilitators to implementing alcohol screening and brief interventions (SBI) in cardiology services. METHODS AND RESULTS: Qualitative study. Individual, semi-structured interviews were conducted with 24 clinical cardiology staff (doctors, nurses, assistant nurses) of varying experience levels, and from various clinical settings (high dependency unit, ward, outpatient clinic), in three regions of Sweden. Reflexive thematic analysis was used, with deductive coding applying the Capability, Opportunity, Motivation (COM-B) theoretical framework. A total of 41 barriers and facilitators were identified, including twelve related to capability, nine to opportunity, and 20 to motivation. Four themes were developed: 1. Uncharted territory, where clinicians expressed a need to address alcohol use but lacked knowledge and a roadmap for implementing SBI; 2. Cardiology as a cardiovascular specialty, where tasks were prioritized according to established roles; 3. Alcohol stigma, where alcohol was reported to be a sensitive topic that staff avoid discussing with patients; 4. Window of opportunity, where staff expressed potential for implementing SBI in routine cardiology care. CONCLUSION: Findings suggest that opportunities exist for early identification and follow-up of hazardous alcohol use within routine cardiology care. Several barriers, including low knowledge, stigma, a lack of ownership, and a greater focus on other risk factors must be addressed prior to the implementation of SBI in cardiology. To meet current clinical guidelines, there is a need to increase awareness and to improve pathways to addiction care. In addition, there may be a need for clinicians dedicated to alcohol interventions within cardiology services. REGISTRATION: OSF (osf.io/hx3ts).

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.

Chronic pancreatitis and the heart disease: Still terra incognita?

BACKGROUND: It has been suggested that chronic pancreatitis (CP) may be an independent risk factor for development of cardiovascular disease (CVD). At the same time, it seems that congestive heart failure (CHF) and CP share the responsibility for the development of important clinical conditions such as sarcopenia, cachexia and malnutrition due to development of cardiac cachexia and pancreatic exocrine insufficiency (PEI), respectively. AIM: To explore the evidence regarding the association of CP and heart disease, more specifically CVD and CHF. METHODS: A systematic search of MEDLINE, Web of Science and Google Scholar was performed by two independent investigators to identify eligible studies where the connection between CP and CVD was investigated. The search was limited to articles in the English language. The last search was run on the 1st of May 2019. The primary outcomes were: (1) Incidence of cardiovascular event [acute coronary syndrome (ACS), chronic coronary disease, peripheral arterial lesions] in patients with established CP; and (2) Incidence of PEI in patients with CHF. RESULTS: Out of 1166 studies, only 8 were eligible for this review. Studies regarding PEI and CHF showed an important incidence of PEI as well as associated malabsorption of nutritional markers (vitamin D, selenium, phosphorus, zinc, folic acid, and prealbumin) in patients with CHF. However, after substitution of pancreatic enzymes, it seems that, at least, loss of appetite was attenuated. On the other side, studies investigating cardiovascular events in patients with CP showed that, in CP cohort, there was a 2.5-fold higher incidence of ACS. In another study, patients with alcohol-induced CP with concomitant type 3c diabetes had statistically significant higher incidence of carotid atherosclerotic plaques in comparison to patients with diabetes mellitus of other etiologies. Earlier studies demonstrated a marked correlation between the clinical symptoms in CP and chronic coronary insufficiency. Also, statistically significant higher incidence of arterial lesions was found in patients with CP compared to the control group with the same risk factors for atherosclerosis (hypertension, smoking, dyslipidemia). Moreover, one recent study showed that PEI is significantly associated with the risk of cardiovascular events in patients with CP. CONCLUSION: Current evidence implicates a possible association between PEI and malnutrition in patients with CHF. Chronic pancreatic tissue hypoxic injury driven by prolonged splanchnic hypoperfusion is likely to contribute to malnutrition and cachexia in patients with CHF. On the other hand, CP and PEI seem to be an independent risk factor associated with an increased risk of cardiovascular events.

Haemodynamic effects of levosimendan in advanced but stable chronic heart failure.

AIMS: Levosimendan improves haemodynamics in acute decompensated heart failure (HF). However, it is increasingly used for repetitive or intermittent infusions in advanced but stable chronic HF, without clear indication, selection criteria, or effect. We tested the hypotheses that (1) levosimendan improves haemodynamics in stable chronic HF and (2) that the response is dependent on baseline clinical and haemodynamic factors. METHODS AND RESULTS: Twenty-three patients [median age 56 (49-64) years, four (17%) women] with stable New York Heart Association (NYHA) III and IV HF received a single 24 h levosimendan infusion. Non-invasive haemodynamics (inert gas re-breathing technique), estimated glomerular filtration rate, and N-terminal pro-brain natriuretic peptide were assessed before and after infusion. Levosimendan had the following effects (median change): a significant increase in cardiac output (+9.8 ± 21.6%; P = 0.026) and decrease in N-terminal pro-brain natriuretic peptide (-28.1 ± 16.3%, P < 0.001), estimated total peripheral resistance (-16.9 ± 18.3%, P = 0.005), and mean arterial pressure (-5.9 ± 8.2%, P = 0.007), but no change in estimated glomerular filtration rate (+0.89 ± 14.0%, P = 0.955). There were no significant associations between baseline clinical and/or haemodynamic factors and the levosimendan effect on cardiac output. CONCLUSIONS: Levosimendan was associated with improved haemodynamics in patients with stable chronic HF, but we could not identify any predictors of the magnitude of haemodynamic response.

Association between cardiovascular vs. non-cardiovascular co-morbidities and outcomes in heart failure with preserved ejection fraction.

AIMS: The prevalence of cardiovascular and non-cardiovascular co-morbidities and their relative importance for outcomes in heart failure with preserved ejection fraction (HFPEF) remain poorly characterized. This study aimed to investigate this. METHODS AND RESULTS: The Karolinska-Rennes (KaRen) Study was a multinational prospective observational study designed to characterize HFPEF. Inclusion required acute HF, defined by the Framingham criteria, LVEF ≥ 45%, and NT-pro-BNP ≥ 300 ng/L or BNP ≥ 100 ng/L. Detailed clinical data were collected at baseline and patients were followed prospectively for 18 months. Predictors of the primary (HF hospitalization or all-cause mortality) and secondary (all-cause mortality) outcomes were assessed with multivariable Cox regression. A total of 539 patients [56% women; median (interquartile range) age 79 (72-84) years; NT-pro-BNP/BNP 2448 (1290-4790)/429 (229-805) ng/L] were included. Known history of HF was present in 40%. Co-morbidities included hypertension (78%), atrial fibrillation/flutter (65%), anaemia (51%), renal dysfunction (46%), CAD (33%), diabetes (30%), lung disease (25%), and cancer (16%). The primary outcome occurred in 268 patients [50%; 106 deaths (20%) and 162 HF hospitalizations (30%)]. Important independent predictors of the primary and/or secondary outcomes were age, history of non-cardiovascular syncope, valve disease, anaemia, lower sodium, and higher potassium, but no cardiovascular co-morbidities. Renin-angiotensin system antagonist and mineralocorticoid receptor antagonist use predicted improved prognosis. CONCLUSION: HFPEF was associated with higher age, female gender, hypertension, atrial fibrillation/flutter, and numerous non-cardiovascular co-morbidities. Prognosis was determined by non-cardiovascular co-morbidities, but use of conventional heart failure medications may still be associated with improved outcomes.