Therapeutic augmentation of NO-sGC-cGMP signalling: lessons learned from pulmonary arterial hypertension and heart failure

Heart Failure Reviews - The nitric oxide (NO)–guanylate cyclase (GC)–cyclic guanosine monophosphate (cGMP) pathway plays an important role in cardiovascular, pulmonary and renal...     

Glucose lowering does not necessarily reduce cardiovascular risk in type 2 diabetes

Diabetes mellitus (DM) is a health condition characterized by glucose dysregulation and affects millions of people worldwide. The presentation of heart failure in diabetic cardiomyopathy extends over a wide phenotypic spectrum, commencing from asymptomatic, subclinical structural abnormalities to severely symptomatic biventricular dysfunction with increased mortality risk. Similarly, the spectrum of systolic dysfunction in diabetic-induced heart failure is diverse. DM leads also to cardiac electrical remodeling reacting on various targets. Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce glucagon and blood glucose levels by raising levels of the endogenous hormones glucagon-like-peptide 1 and glucose-dependent insulinotropic peptide and constitute a safe and effective glucose lowering treatment option in patients with type 2 DM. Despite DPP-4 inhibitors’ efficacy regarding glycemic control, their effect on cardiovascular outcomes (myocardial infarction, stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization, and cardiovascular death) in diabetic patients has been neutral. The potential correlation between atrial flutter and DPP-4 inhibitors administration needs further investigation.     

Efficacy and safety of high dose versus low dose furosemide with or without dopamine infusion: The Dopamine in Acute Decompensated Heart Failure II (DAD-HF II) Trial

Aims

The role of low-dose dopamine infusion in patients with acute decompensated heart failure (ADHF) remains controversial. We aim to evaluate the efficacy and safety of high- versus low-dose furosemide with or without low-dose dopamine infusion in this patient population.

Methods and results

161 ADHF patients (78 years; 46% female; ejection fraction 31%) were randomized to 8-hour continuous infusions of: a) high-dose furosemide (HDF, n = 50, 20 mg/h), b) low-dose furosemide and low-dose dopamine (LDFD, n = 56, 5 mg/h and 5 μg kg^− 1 min^− 1 respectively), or c) low-dose furosemide (LDF, n = 55, furosemide 5 mg/h). The main outcomes were 60-day and one-year all-cause mortality (ACM) and hospitalization for HF (HHF). Dyspnea relief (Borg index), worsening renal function (WRF, rise in serum creatinine (sCr) ≥ 0.3 mg/dL), and length of stay (LOS) were also assessed. The urinary output at 2, 4, 6, 8, and 24 h was not significantly different in the three groups. Neither the ACM at day 60 (4.0%, 7.1%, and 7.2%; P = 0.74) or at one year (38.1%, 33.9% and 32.7%, P = 0.84) nor the HHF at day 60 (22.0%, 21.4%, and 14.5%, P = 0.55) or one year (60.0%, 50.0%, and 47%, P = 0.40) differed between HDF, LDFD, and LDF groups, respectively. No differences in the Borg index or LOS were noted. WRF was higher in the HDF than in LDFD and LDF groups at day 1 (24% vs. 11% vs. 7%, P < 0.0001) but not at sCr peak (44% vs. 38% vs. 29%, P = 0.27). No significant differences in adverse events were noted.

Conclusions

In ADHF patients, there were no significant differences in the in-hospital and post-discharge outcomes between high- vs. low-dose furosemide infusion; the addition of low-dose dopamine infusion was not associated with any beneficial effects.     

Arterial phase left atrial opacification in acute massive pulmonary embolism

Classic angiographic features in acute massive pulmonary embolism include main or lobar arterial branch cut-off, and/or arterial filling defects with matching impaired venous drainage. Six haemodynamically compromised patients with acute massive pulmonary embolism (mean pulmonary artery pressure 55 +/- 12 mmHg), confirmed by pulmonary arteriography, are described. Early opacification of the left atrium during the arterial phase of the pulmonary angiogram was seen in all patients. Follow-up pulmonary arteriography after successful thrombolytic therapy was performed 4 days later in 2 cases. A marked haemodynamic improvement was accompanied by resolution of the previous abnormal angiographic signs, including early opacification of the left atrium. The latter might be a response to intensive reactive vasodilatation of the remaining perfused lung fields resulting in a more rapid pulmonary transit time and the opening of arteriovenous channels with further systemic desaturation. This angiographic sign is a marker of severe, but reversible, vasoconstriction in acute massive pulmonary embolism.     

Hemodynamic effects of dobutamine in patients with an exacerbation of chronic systolic heart failure treated with low doses of carvedilol

Although most patients in Europe with systolic heart failure (SHF) are treated with I(2)-blocking agents at doses significantly lower than the recommended dose, there is limited information available regarding the hemodynamic effects of dobutamine in this patient population. Therefore, a study was carried out in patients (n=31) admitted to the University Hospital, Larissa, Greece with an acute exacerbation of chronic SHF (25 men and 6 women, mean age 58 years, range 32 a 80 years, left ventricular (LV) ejection fraction 相似文献   

Submitral left ventricular aneurysm compressing the left main coronary artery

This report describes a 43-yr-old black woman who was referred for evaluation of severe mitral regurgitation. Conventional echocardiography revealed a large submitral left ventricular aneurysm. A selective coronary angiography demonstrated compression of the left main coronary artery by submitral aneurysm. Successful surgical repair was performed. Cathet. Cardiovasc. Diagn. 40:173–175, 1997. © 1997 Wiley-Liss, Inc.     

Diabetic cardiovascular autonomic neuropathy: clinical implications

Diabetic cardiovascular autonomic neuropathy (DCAN), the impairment of the autonomic balance of the cardiovascular system in the setting of diabetes mellitus (DM), is frequently observed in both Type 1 and 2 DM, has detrimental effects on the quality of life and portends increased mortality. Clinical manifestations include: resting heart rate disorders, exercise intolerance, intraoperative cardiovascular lability, orthostatic alterations in heart rate and blood pressure, QT-interval prolongation, abnormal diurnal and nocturnal blood pressure variation, silent myocardial ischemia and diabetic cardiomyopathy. Clinical tests for autonomic nervous system evaluation, heart rate variability analysis, autonomic innervation imaging techniques, microneurography and baroreflex analysis are the main diagnostic tools for DCAN detection. Aldose reductase inhibitors and antioxidants may be helpful in DCAN therapy, but a regular, more generalized and multifactorial approach should be adopted with inclusion of lifestyle modifications, strict glycemic control and treatment of concomitant traditional cardiovascular risk factors, in order to achieve the best therapeutic results. In the present review, the authors provide aspects of DCAN pathophysiology, clinical presentation, diagnosis and an algorithm regarding the evaluation and management of DCAN in DM patients.