Levosimendán ambulatorio repetitivo como puente al trasplante cardiaco / Repetitive ambulatory levosimendan as a bridge to heart transplantation

Introducción y objetivos:El levosimendán ambulatorio repetitivo es una opción como puente al trasplante cardiaco (TxC), aunque la evidencia sobre su eficacia y su seguridad es escasa. El objetivo del registro LEVO-T es describir a los pacientes en lista de TxC que reciben levosimendán, sus pautas y los eventos clínicos durante el seguimiento, en comparación con los que no lo reciben. Métodos: Se revisó en retrospectiva a los pacientes en lista de espera para TxC electivo de 14 centros españoles desde 2015 hasta 2020. Resultados: Se incluyó a 1.015 pacientes consecutivos; los 238 (23,4%) que recibieron levosimendán mostraron más ingresos por insuficiencia cardiaca (IC) el año anterior y peor perfil clínico. Las dosis fijas por necesidades clínicas fueron la pauta más frecuente. Dos pacientes (0,8%) presentaron arritmias ventriculares no mortales. No hubo diferencias en hospitalizaciones por IC entre los que comenzaron levosimendán en los primeros 30 días después de inclusión y los que no (el 33,6 frente al 34,5%; p=0,848). De estos últimos, 102 (32,9%) pasaron a levosimendán después de un ingreso por IC, y la tasa de ingresos por IC/mes varió de 0,57 antes del levosimendán a 0,21 después. El análisis mediante emparejamiento por puntuación de propensión no mostró diferencias entre los pacientes con y sin levosimendán en la supervivencia a 1 año tras la inclusión en lista (HR=1,03; IC95%, 0,36-2,97; p=0,958) ni en la supervivencia tras el TxC (HR=0,97; IC95%, 0,60-1,56; p=0,958). Conclusiones: El levosimendán ambulatorio repetitivo como puente al trasplante cardiaco es un tratamiento frecuente y seguro que podría reducir ingresos por IC. (AU)

Introduction and objectives: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. Methods: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. Results: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients’ clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). Conclusions: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations. (AU)

Practical Approaches to the Management of Cardiorenal Disease beyond Congestion.

BACKGROUND: The coexistence of heart and kidney diseases, also called cardiorenal syndrome, is very common, leads to increased morbidity and mortality, and poses diagnostic and therapeutic difficulties. There is a risk-treatment paradox, such that patients with the highest risk are treated with lesser disease-modifying medical therapies. SUMMARY: In this document, different scientific societies propose a practical approach to address and optimize cardiorenal therapies and related comorbidities systematically in chronic cardiorenal disease beyond congestion. Cardiorenal programs have emerged as novel models that may assist in delivering coordinated and holistic management for these patients. KEY MESSAGES: (1) Cardiorenal disease is a ubiquitous entity in clinical practice and is associated with numerous barriers that limit medical treatment. (2) The present article focuses on the practical approaches to managing chronic cardiorenal disease beyond congestion to overcome some of these barriers and improve the treatment of this high-risk population.

Prevalence and clinical profile of kidney disease in patients with chronic heart failure. Insights from the Spanish cardiorenal registry.

INTRODUCTION AND OBJECTIVES: Patients with combined heart failure (HF) and chronic kidney disease (CKD) have been underrepresented in clinical trials. The prevalence of CKD in these patients and their clinical profile require constant evaluation. This study aimed to analyze the prevalence of CKD, its clinical profile, and patterns of use of evidence-based medical therapies in HF across CKD stages in a contemporary cohort of ambulatory patients with HF. METHODS: From October 2021 to February 2022, the CARDIOREN registry included 1107 ambulatory HF patients from 13 HF clinics in Spain. RESULTS: The median age was 75 years, 63% were male, and 48% had heart failure with reduced left ventricular ejection fraction (HFrEF). A total of 654 (59.1%) had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, and 122 (11%) patients with eGFR ≥ 60 mL/min/1.73 m2 had a urine albumin-creatinin ratio ≥ 30 mg/g. The most important variables associated with lower eGFR were age (R2=61%) and furosemide dose (R2=21%). The proportion of patients receiving an angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin II receptor blockers (ARB), an angiotensin receptor-neprilysin inhibitor (ARNi), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), or a mineralocorticoid receptor antagonist (MRA) progressively decreased with lower eGFR categories. Notably, 32% of the patients with HFrEF and an eGFR <30 mL/min/1.73 m2 received the combination of ACEI/ARB/ARNi+beta-blockers+MRA+SGLT2i. CONCLUSIONS: In this contemporary HF registry, 70% of patients had kidney disease. Although this population is less likely to receive evidence-based therapies, structured and specialized follow-up approaches within HF clinics may facilitate the adoption of these life-saving drugs.

Repetitive ambulatory levosimendan as a bridge to heart transplantation.

INTRODUCTION AND OBJECTIVES: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. METHODS: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. RESULTS: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients' clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). CONCLUSIONS: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations.

Incidence and Prognosis of Colorectal Cancer After Heart Transplantation: Data From the Spanish Post-Heart Transplant Tumor Registry.

In this observational and multicenter study, that included all patients who underwent a heart transplantation (HT) in Spain from 1984 to 2018, we analyzed the incidence, management, and prognosis of colorectal cancer (CRC) after HT. Of 6,244 patients with a HT and a median follow-up of 8.8 years since the procedure, 116 CRC cases (11.5% of noncutaneous solid cancers other than lymphoma registered) were diagnosed, mainly adenocarcinomas, after a mean of 9.3 years post-HT. The incidence of CRC increased with age at HT from 56.6 per 100,000 person-years among under 45 year olds to 436.4 per 100,000 person-years among over 64 year olds. The incidence rates for age-at-diagnosis groups were significantly greater than those estimated for the general Spanish population. Curative surgery, performed for 62 of 74 operable tumors, increased the probability of patient survival since a diagnosis of CRC, from 31.6% to 75.7% at 2 years, and from 15.8% to 48.6% at 5 years, compared to patients with inoperable tumors. Our results suggest that the incidence of CRC among HT patients is greater than in the general population, increasing with age at HT.

Mechanical circulatory support in severe primary graft dysfunction: Peripheral cannulation but not earlier implantation improves survival in heart transplantation.

BACKGROUND: Primary graft dysfunction (PGD) still affects 2% to 28% of heart transplants (HT). Severe PGD requires mechanical circulatory support (MCS) and is the main cause of death early after HT. Earlier initiation has been suggested to improve prognosis but the best cannulation strategy is unknown. METHODS: Analysis of all HT in Spain between 2010 and 2020. Early (<3 hours after HT) vs late initiation (≥3 hours after HT) of MCS was compared. Special focus was placed on peripheral vs central cannulation strategy. RESULTS: A total of 2376 HT were analyzed. 242 (10.2%) suffered severe PGD, 171 (70.7%) received early MCS and 71 (29.3%) late MCS. Baseline characteristics were similar. Patients with late MCS had higher inotropic scores and worse renal function at the moment of cannulation. Early MCS had longer cardiopulmonary bypass times and late MCS was associated with more peripheral vascular damage. No significant differences in survival were observed between early and late implant at 3 months (43.82% vs 48.26%; log-rank p = 0.59) or at 1 year (39.29% vs 45.24%, log-rank p = 0.49). Multivariate analysis did not show significant differences favoring early implant. Survival was higher in peripheral compared to central cannulation at 3 months (52.74% vs 32.42%, log-rank p = 0.001) and 1 year (48.56% vs 28.19%, log-rank p = 0.0007). In the multivariate analysis, peripheral cannulation remained a protective factor. CONCLUSIONS: Earlier MCS initiation for PGD was not superior, compared to a more conservative approach with deferred initiation. Peripheral compared to central cannulation showed superior 3-month and 1-year survival rates.

Utility of the IMPACT score for predicting heart transplant mortality. Analysis on a contemporary cohort of the Spanish Heart Transplant Registry.

INTRODUCTION AND OBJECTIVES: The Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score was derived and validated as a predictor of mortality after heart transplantation (HT). The primary objective of this work is to externally validate the IMPACT score in a contemporary Spanish cohort. METHODS: Spanish Heart Transplant Registry data were used to identify adult (>16 years) HT patients between January 2000 and December 2015. Retransplantation, multiorgan transplantation and patients in whom at least one of the variables required to calculate the IMPACT score was missing were excluded from the analysis (N = 2810). RESULTS: Median value of the IMPACT score was five points (IQR: 3, 8). Overall, 1-year survival rate was 79.1%. Kaplan-Meier 1-year survival rates by IMPACT score categories (0-2, 3-5, 6-9, 10-14, ≥15) were 84.4%, 81.5%, 79.3%, 77.3%, and 58.5%, respectively (Log-Rank test: p < .001). Performance analysis showed a good calibration (Hosmer-Lemeshow chi-square for 1 year was 7.56; p = .47) and poor discrimination ability (AUC-ROC .59) of the IMPACT score as a predictive model. CONCLUSIONS: In a contemporary Spanish cohort, the IMPACT score failed to accurately predict the risk of death after HT.

Spanish heart transplant registry. 33rd official report of the Heart failure Association of the Spanish Society of Cardiology.

INTRODUCTION AND OBJECTIVES: This report updates the annual data of the Spanish Heart Transplant Registry with the procedures performed in 2021. METHODS: We describe the clinical profile, therapeutic characteristics and outcomes in terms of survival of the procedures performed in 2021. Their temporal trends are updated for the 2012 to 2020 period. RESULTS: In 2021, 302 heart transplants were performed (8.6% increase versus 2020). The tendency in 2021 confirmed that of prior years, with fewer urgent transplants and a preference for the use of ventricular assist devices. The remaining characteristics and survival showed a clear trend toward stability in the last decade. Compared with 2019, the SARS-CoV-2 pandemic (2020 and 2021) did not affect short- or long-term survival. CONCLUSIONS: In 2021, transplant activity returned to prepandemic levels. The SARS-CoV-2 pandemic did not significantly affect transplant outcomes. The main transplant features and outcomes have clearly stabilized in the last decade.

Dose of furosemide before admission predicts diuretic efficiency and long-term prognosis in acute heart failure.

AIMS: The outpatient diuretic dose is a marker of diuretic resistance and prognosis in chronic heart failure (HF). Still, the impact of the preadmission dose on diuretic efficiency (DE) and prognosis in acute HF is not fully known. METHODS AND RESULTS: We conducted an observational and prospective study. All patients admitted for acute HF treated with intravenous diuretic and at least one criterion of congestion on admission were evaluated. Decongestion [physical examination, hemoconcentration, N-terminal pro-brain natriuretic peptide (NT-proBNP) change, and lung ultrasound], DE (weight loss and urine output per unit of 40 mg furosemide), and urinary sodium were monitored on the fifth day of admission. DE was dichotomized into high-low based on the median value. A multivariate Cox regression analysis was conducted to find predictors of HF readmission or mortality. A total of 105 patients were included between July 2017 and July 2019. Mean age was 74.5 ± 12.0 years, 64.8% were male, 33.3% had de novo HF, and mean left ventricular ejection fraction was 46 ± 17%. Median follow-up was 26 [15-35] months. Low DE based on weight loss was associated with a higher previous dose of furosemide (odds ratio [OR] 1.01 [1.00-1.02]), thiazide treatment before admission (OR 9.37 [2.19-40.14]), and lower diastolic blood pressure (OR 0.95 [0.91-0.98]) in the multivariate regression model. Only previous dose of furosemide (OR 1.01 [1.00-1.02]) and haemoglobin at admission (OR 0.76 [0.58-0.99]) were associated with low DE based on urine output in the multivariate analysis. The correlation between the previous dose of furosemide and DE based on weight loss was poor (r = -0.12; P = 0.209) and with DE based on urine output was weak to moderate (r = -0.33; P < 0.001). Low DE based on weight loss and urine output was associated with lesser decongestion measured by NT-proBNP (P = 0.011; P = 0.007), hemoconcentration (P = 0.006; P = 0.044), and lung ultrasound (P = 0.034; P = 0.029), but not by physical examination (P = 0.506; P = 0.560). Survival and event-free survival in acute decompensated HF (ADHF) were lower than in de novo HF; a preadmission dose of furosemide > 80 mg in ADHF identified patients with particularly poor prognosis (log-rank < 0.001). In ADHF, the preadmission dose of furosemide (hazard ratio [HR] 1.34 [1.08-1.67] per 40 mg) and NT-proBNP at admission (HR 1.03 [1.01-1.06] per 1000 pg/mL) were independently associated with mortality or HF readmission in the multivariate Cox regression analysis. CONCLUSIONS: The outpatient dose of furosemide before acute HF admission predicts DE and must be taken into account when deciding on the initial diuretic dose. In ADHF, the outpatient dose of furosemide can predict long-term prognosis better than DE during hospitalization.

Potential Role of Natriuretic Response to Furosemide Stress Test During Acute Heart Failure.

BACKGROUND: Poor natriuresis has been associated with a poorer response to diuretic treatment and worse prognosis in acute heart failure. Recommendations on how and when to measure urinary sodium (UNa) are lacking. We aim to evaluate UNa quantification after a furosemide stress test (FST) capacity to predict appropriate decongestion during acute heart failure hospitalization. METHODS: Patients underwent an FST on day-1 of admission, and UNa was measured 2 hours after, dividing patients into low or high UNa based on the sample median value. A semiquantitative composite congestive score (CCS; 0-9) and NT pro-BNP (N-terminal pro-B-type natriuretic peptide) quantification were assessed before the FST and at day 5 after the FST. RESULTS: Median UNa after FST in the 65 patients included was 113 (97-122) mmol/L. At day 5, a lower proportion of patients with a low UNa reached a 30% decrease in NT-proBNP levels (21 [66%] for low UNa versus 31 [94%] for high UNa; P=0.005) and an appropriate grade of decongestion (CCS<3) (20 [62%] for low UNa versus 32 [97%] for high UNa; P<0.001). A UNa>83 mmol/L 2 hours after FST had a 96% sensitivity to predict an NT-proBNP reduction ≥30% and 95% to predict a CCS<3 at day 5. Low UNa patients presented a lower cumulative diuresis and weight loss and presented more often with prolonged hospitalization, worsening heart failure, and readmission because of acute heart failure or death at 6 months. CONCLUSIONS: Low natriuresis after an FST identified patients at a higher risk of an inadequate diuretic response and an inappropriate decongestion. FST-guided diuretic treatment might help to improve decongestion, shorten hospitalizations, and to reduce adverse outcomes.

The development of chronic diuretic resistance can be predicted during a heart-failure hospitalization. Results from the REDIHF registry.

INTRODUCTION: Diuretic resistance (DR) is a common condition during a heart failure (HF) hospitalization, and is related to worse prognosis. Although the risk factors for DR during a HF hospitalization are widely described, we do not know whether the risk of chronic DR could be predicted during admission. MATERIAL AND METHODS: We conducted a multicenter, prospective observational study between July 2017 and July 2019. All patients admitted for acute HF with intravenous diuretic treatment and at least one criterion of congestion on admission were invited to participate. Patients on renal replacement therapy, under intravenous diuretic treatment for >72 hours before screening and those who were unable to sign the informed consent were excluded. We monitored decongestion (physical exam, hemoconcentration, NTproBNP change and lung ultrasound) and DR (diuresis and weight loss per unit of 40mg furosemide and fractional excretion of sodium) on the fifth day of admission. Chronic DR was evaluate two months after hospitalization and was defined as persistent signs of congestion despite ≥80 mg furosemide per day. We compared variables from the hospitalization between patients with and without chronic DR. A multivariate logistic regression analysis was conducted to find predictors of chronic DR. RESULTS: A total of 105 patients were included in the study. Mean age was 74.5±12.0 years, 64.8% were male and mean LVEF was 46±17%. In the two months follow-up, five patients have died and one patient has had a heart transplant. Of the 99 remaining patients, 21 patients (21.2%) had chronic DR. The dose of furosemide before admission and the decrease in NT-proBNP ≤30% during admission were predictors of chronic DR in the multivariate analysis. CONCLUSIONS: We can predict during a HF hospitalization which patients will develop chronic DR. The dose of furosemide before admission and the change in NT-proBNP are independent predictors of chronic DR.

Surface respiratory electromyography and dyspnea in acute heart failure patients.

INTRODUCTION AND OBJECTIVES: Dyspnea is the most common symptom among hospitalized patients with heart failure (HF) but besides dyspnea questionnaires (which reflect the subjective patient sensation and are not fully validated in HF) there are no measurable physiological variables providing objective assessment of dyspnea in a setting of acute HF patients. Studies performed in respiratory patients suggest that the measurement of electromyographic (EMG) activity of the respiratory muscles with surface electrodes correlates well with dyspnea. Our aim was to test the hypothesis that respiratory muscles EMG activity is a potential marker of dyspnea severity in acute HF patients. METHODS: Prospective and descriptive pilot study carried out in 25 adult patients admitted for acute HF. Measurements were carried out with a cardio-respiratory portable polygraph including EMG surface electrodes for measuring the activity of main (diaphragm) and accessory (scalene and pectoralis minor) respiratory muscles. Dyspnea sensation was assessed by means of the Likert 5 questionnaire. Data were recorded during 3 min of spontaneous breathing and after breathing at maximum effort for several cycles for normalizing data. An index to quantify the activity of each respiratory muscle was computed. This assessment was carried out within the first 24 h of admission, and at day 2 and 5. RESULTS: Dyspnea score decreased along the three measured days. Diaphragm and scalene EMG index showed a positive and significant direct relationship with dyspnea score (p<0.001 and p = 0.003 respectively) whereas pectoralis minor muscle did not. CONCLUSION: In our pilot study, diaphragm and scalene EMG activity was associated with increasing severity of dyspnea. Surface respiratory EMG could be a useful objective tool to improve assessment of dyspnea in acute HF patients.

Respuesta al ECG de enero de 2017 / Response to ECG, January 2017

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Clinical outcomes in myocardial infarction and multivessel disease after a cardiac rehabilitation programme: Partial versus complete revascularization.

BACKGROUND: Current guideline recommendations encourage culprit vessel only percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. However, recent studies have shown a better clinical outcome in patients who receive multivessel PCI. AIM: To measure and compare clinical outcomes between partial revascularization (PR) versus complete revascularization (CR) in patients with STEMI and multivessel disease who underwent a cardiac rehabilitation programme. METHODS: We retrospectively reviewed the medical records of 282 patients with STEMI and multivessel disease who received PR or CR and were subsequently enrolled in a cardiac rehabilitation programme between July 2006 and November 2013 at La Paz University Hospital. The incidences of cardiovascular events, new PCI, hospital admissions for cardiovascular reasons and mortality were compared between the PR and CR groups. RESULTS: Overall, 143 patients received PR and 139 received CR. Baseline characteristics were similar in both groups, except for mean age (59.3 vs. 56.7 years; P=0.02), diabetes mellitus prevalence (34.3% vs. 20.1%; P=0.01) and number of arteries with stenosis (2.6 vs. 2.3; P=0.001). During the mean follow-up of 48.0±25.9 months, a cardiovascular event occurred in 23 (16.1%) PR patients and 20 (14.4%) CR patients, with no statistically significant differences in the early (hazard ratio: 0.61, 95% confidence interval: 0.19-1.89) or late (hazard ratio: 1.40, 95% confidence interval: 0.62-3.14) follow-up periods. Cox regression, adjusted for age, sex, presence of diabetes mellitus and number of affected coronary vessels, showed no difference in new cardiovascular event risk. CONCLUSIONS: There were no statistical differences in clinical outcomes between PR and CR among patients who received cardiac rehabilitation.

ECG de enero de 2017 / ECG, January 2017

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