Incretin-based drugs and hospitalization for heart failure in the clinical practice: A nested case-control study.

BACKGROUND AND AIMS: There are concerns that incretin-based antidiabetic drugs - including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists - increase the risk of hospitalization for heart failure (HF). To further analyse this issue, we conducted a nested case-control study within a cohort of antidiabetic users in a real world setting. METHODS AND RESULTS: Within a cohort of 133,639 subjects with a first prescription of an antidiabetic drug (new-users) between 2010 and 2016 in Lombardy, Italy, and were followed-up to 2016, we identified 4057 subjects with a first hospitalization for HF and 80,450 controls matched on sex, age, and date of cohort-entry. The multivariate odds ratios (ORs) of HF in relation to current use of incretin-based drugs as compared to current use of two or more oral antidiabetics was 1.06 (95% confidence interval, CI, 0.83-1.35), with no evidence of a trend in risk with increasing duration of use. The corresponding ORs were 1.10 (95% CI 0.85-1.41) for DPP-4 inhibitors and 0.84 (95% CI 0.48-1.47) for GLP-1 receptor agonists. Estimates were consistent in various sensitivity analyses. CONCLUSIONS: This study indicates that incretin-based drugs are not associated with an increased risk of hospitalization for HF, thus providing further reassurance on the cardiovascular safety of these antidiabetic drugs in the clinical practice.

Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-atrial fibrillation trial.

OBJECTIVE: we evaluated the prognostic role of circulating cardiovascular biomarkers in patients with a history of recent atrial fibrillation (AF). BACKGROUND: predicting long-term maintenance of sinus rhythm in patients with AF is difficult. METHODS: plasma concentrations of three specific cardiac markers [high-sensitivity troponin T (hsTnT), N-terminal probrain natriuretic peptide (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP)] and three stable fragments of vasoactive peptides [mid-regional proadrenomedullin (MR-proADM), copeptin (CT-proAVP) and CT-proendothelin-1 (CT-proET-1)] were measured at baseline and after 6 and 12 months in 382 patients enrolled in the GISSI-AF study, a prospective randomized trial to determine the effect of valsartan to reduce the recurrence of AF. The association between these markers, clinical characteristics and recurrence of AF was tested by univariate and multivariate Cox models. RESULTS: mean patient age was 68 ± 9 years (37.2% females). A total of 84.8% of patients had a history of hypertension. In total, 59.7% qualified for history of AF because of successful cardioversion, 11.8% because of two or more episodes of AF in the 6 months preceding randomization and 28.5% because of both. Patients in AF at 6 or 12 months (203 (53.1%) with first recurrence) had significantly higher concentrations of most biomarkers. Despite low baseline levels, higher concentrations of hsTnT {adjusted hazard ratio (HR) [95% confidence intervals (CIs) for 1 SD increment] (1.15 [1.04-1.28], P = 0.007), MR-proANP (1.15 [1.01-1.30], P = 0.04), NT-proBNP (1.24 [1.11-1.39], P = 0.0001) and CT-proET-1 (1.16 [1.01-1.33], P = 0.03) independently predicted higher risk of a first recurrence of AF. Changes over time of MR-proANP tended to predict subsequent recurrence (adjusted HR [95%CI]) (1.53 [0.98-2.37], P = 0.06). CONCLUSION: circulating markers of cardiomyocyte injury/strain and endothelin are related to recurrence of AF in patients in sinus rhythm with a history of recent AF.

Cardiac mesoangioblasts are committed, self-renewable progenitors, associated with small vessels of juvenile mouse ventricle.

Different cardiac stem/progenitor cells have been recently identified in the post-natal heart. We describe here the identification, clonal expansion and characterization of self-renewing progenitors that differ from those previously described for high spontaneous cardiac differentiation. Unique coexpression of endothelial and pericyte markers identify these cells as cardiac mesoangioblasts and allow prospective isolation and clonal expansion from the juvenile mouse ventricle. Cardiac mesoangioblasts express many cardiac transcription factors and spontaneously differentiate into beating cardiomyocytes that assemble mature sarcomeres and express typical cardiac ion channels. Cells similarly isolated from the atrium do not spontaneously differentiate. When injected into the ventricle after coronary artery ligation, cardiac mesoangioblasts efficiently generate new myocardium in the peripheral area of the necrotic zone, as they do when grafted in the embryonic chick heart. These data identify cardiac mesoangioblasts as committed progenitors, downstream of earlier stem/progenitor cells and suitable for the cell therapy of a subset of juvenile cardiac diseases.

Murine models of myocardial and limb ischemia: diagnostic end-points and relevance to clinical problems.

Ischemic disease represents the new epidemic worldwide. Animal models of ischemic disease are useful because they can help us to understand the underlying pathogenetic mechanisms and develop new therapies. The present review article summarizes the results of a consensus conference on the status and future development of experimentation in the field of cardiovascular medicine using murine models of peripheral and myocardial ischemia. The starting point was to recognize the limits of the approach, which mainly derive from species- and disease-related differences in cardiovascular physiology. For instance, the mouse heart beats at a rate 10 times faster than the human heart. Furthermore, healing processes are more rapid in animals, as they rely on mechanisms that may have lost relevance in man. The main objective of the authors was to propose general guidelines, diagnostic end points and relevance to clinical problems.

[Andrea's story]. / La storia di Andrea.

First-hand accounts of illness experiences provide important insights for other patients and their carers and can be a powerful tool for patient information and professional education. Andrea was ran over by a motor-bike while he was carried by bike and reported a complicated femur fracture. Three different representations of the story are reported and confronted: the bold chronicle of events, that sets the scenery and time sequence; Andrea's mother point of view on what happened after the accident, and during the course of the illness; and Andrea's story, told with his words and drawings. The methodological comments offered as discussion, stress how the collection of relevant patients stories can be a valuable research resource because it can offer a broad perspective which cannot be obtained by other means.

Aspirin does not interact with ACE inhibitors when both are given early after acute myocardial infarction: results of the GISSI-3 Trial.

Aspirin (ASA) and angiotensin-converting enzyme inhibitor (ACEi) therapy reduce mortality when administered early after the onset of myocardial infarction. ASA can antagonize some effects of ACEi therapy by inhibiting the synthesis of vasodilating prostaglandins; however, the evidence for this effect from large controlled trials is contradictory. The authors analyzed a database of 18,895 patients of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio-3 (GISSI-3) Trial in which patients were allocated either to receive lisinopril or not to receive lisinopril within 24 hours of the onset of symptoms of myocardial infarction. The aim of the study was to verify the possible negative interaction between ASA and the ACEi lisinopril in the postacute phase of acute myocardial infarction. Of 18,895 analyzable patients, 15,841 received ASA at entry. Overall lisinopril reduced 42-day mortality from 7.1% to 6.3%. In patients receiving ASA, mortality was reduced by lisinopril from 6.0% to 5.4%, and from 13.0% to 10.8% in patients not receiving ASA. The difference in proportional reductions of mortality corresponds to the fact that a more marked lisinopril effect is seen in patients at higher baseline risk across all study subgroups, one of which coincides with the no-ASA group. The analysis of the inhospital incidence of major clinical events did not reveal a potentially negative interaction between ASA and lisinopril. The same findings were obtained from the analysis of reinfarction at 42 days. The interaction between ASA and lisinopril was also tested by multivariate analysis adjusted for confounding variables at entry, and the interaction tests were not statistically significant. Serum creatinine levels at 42 days were significantly higher in lisinopril group than in the control group. Systolic and diastolic blood pressures in lisinopril group were significantly lower than controls at 42 days. The effect of lisinopril on creatinine and blood pressure did not differ between the ASA and no-ASA groups. ASA does not decrease the mortality benefit of early lisinopril after myocardial infarction, nor does it increase the risk of major adverse events. Lisinopril is safe and effective when given early after the onset of myocardial infarction, regardless of a concomitant administration of ASA started early and continued over a 6-week period.

Intermittent 6-month low-dose dobutamine infusion in severe heart failure: DICE multicenter trial.

BACKGROUND: Patients with end-stage heart failure are often refractory to maximal oral therapy, and they have high mortality rates, poor quality of life, and frequent hospitalizations with elevated health care costs. Intermittent dobutamine therapy has been suggested as an additional option in this clinical setting. METHODS AND RESULTS: Thirty-eight patients clinically stable for at least 48 hours with standard treatment, New York Heart Association (NYHA) functional class III or IV, cardiac index

[The evolution of hospital mortality due to acute myocardial infarct in the first 2 GISSI studies. Participants in the GISSI 1 and GISSI 2 studies. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico]. / Evoluzione della mortalità ospedaliera per infarto miocardico acuto nei primi due studi GISSI. Partecipanti agli studi GISSI 1 e GISSI 2.

During the short while of 5 years, between 1984 and 1985, two large clinical trials have been performed in Italy concerning fibrinolytic therapy in Acute Myocardial Infarction: GISSI 1 and GISSI 2. They made possible to evaluate the evolution of demographic and clinical features, the in-hospital mortality rate, and the causes of death of a huge number of patients admitted to CCU throughout the whole country. Out of 31,826 patients with acute myocardial infarction admitted to 176 CCU participating to the GISSI 1 16.9% were 75 years old and 24.7% were females; 21.8% and 26.4% were the percentages in the 38,086 patients admitted to the 223 CCU participating in the GISSI 2. Despite the higher prevalence of the two demographic characteristic with the worse prognosis, the in-hospital mortality rates were respectively 12.2% in the GISSI 1 and 10.0% in the GISSI 2 studies, with a statistically significant decrease (RR 0.84; C.L. 0.80-0.88). The significant decrease in the in-hospital mortality concerns also the patients populations selected according to the same criteria of inclusion in the two trials (within 6 hours from the onset of symptoms and with only ST elevation at the ECG of admission) and to the treatment with fibrinolytic drug (SK or rtPA). As a matter of fact 468 patients died of the 4,696 (10.0%) treated with SK in the GISSI 1 against 1,092 patients of 12,381 (8.8%) enrolled in the GISSI 2 and treated with SK or rtPA (RR 0.87; L.C. 0.78-0.98). The reduction of in-hospital mortality may be explained by some differences in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence and prognostic significance of ventricular arrhythmias after acute myocardial infarction in the fibrinolytic era. GISSI-2 results.

BACKGROUND: Several studies performed before the advent of thrombolysis have shown that the presence of ventricular arrhythmias is an independent risk factor for subsequent mortality in patients recovering from acute myocardial infarction. Since fibrinolysis affects the natural history of infarction and may alter the clinical relevance of different risk factors, the aim of the present study was to establish the prevalence and prognostic value of ventricular arrhythmias in post-myocardial infarction patients treated with fibrinolytic agents during the acute phase. METHODS AND RESULTS: Twenty-four-hour Holter recordings obtained before discharge from the hospital in 8,676 post-myocardial infarction patients of the GISSI-2 study were analyzed for the presence of ventricular arrhythmias. Patients were followed for 6 months from the acute event; total and sudden cardiovascular mortality rates were computed, and relative risks in univariate and multivariate analyses were calculated. Ventricular arrhythmias were present in 64.1% of the patients, more than 10 premature ventricular beats per hour were recorded in 19.7% of the patients, and nonsustained ventricular tachycardia was present in 6.8% of the patients. Ventricular arrhythmias were more frequent when signs or symptoms of left ventricular damage were present. During follow-up, there was a total of 256 deaths 2.0% in patients without ventricular arrhythmias, 2.7% in patients with one to 10 premature ventricular beats per hour, 5.5% in those with more than 10 premature ventricular beats per hour, and 4.8% in those with complex premature ventricular beats. Even after adjusting for several risk factors, the presence of frequent (more than 10 premature ventricular beats per hour) ventricular arrhythmias remained a significant predictor of total (RRCox, 1.62; 95% confidence interval, 1.16-2.26) and sudden mortality (RRCox, 2.24; 95% confidence interval, 1.22-4.08). On the other hand, the presence of nonsustained ventricular tachycardia was not associated with a worsening of the prognosis in the adjusted analysis (RRCox, 1.20; 95% confidence interval, 0.80-1.79). CONCLUSIONS: This study shows that approximately 36% of patients recovering from acute myocardial infarction presented with less than one premature ventricular beat per hour in Holter recordings obtained before discharge from the hospital, whereas almost 20% of patients showed frequent (more than 10 premature ventricular beats per hour) ventricular arrhythmias. Due to the large size of the population of this study, these figures may be used as a reliable estimate of the prevalence of arrhythmias in postinfarction patients treated with fibrinolytic agents during the acute phase. Frequent premature ventricular beats are confirmed as independent risk factors of total and sudden death in the first 6 months following the acute event; the significance of nonsustained ventricular tachycardia in this population appears more controversial.