Possible genetic implications in the response to cardiac resynchronisation therapy in a patient affected by heart failure

This report presents a case of a patient with idiopathic dilated cardiomyopathy and severe left ventricular systolic dysfunction who underwent cardiac resynchronisation therapy (CRT). During the follow-up a progressive increase in left ventricular ejection fraction was observed, as well as clinical improvement. No cardiovascular events occurred during the follow-up, except for appropriate Implantable Cardioverter Defibrillator (ICD) bursts for fast ventricular tachycardia. Genotyping for adrenoceptor gene polymorphisms detected that the patient was Glu27Glu homozygous carrier. There’s a large interindividual variability in response to CRT. Despite attempts to identify factors having an impact on this therapy, only QRS duration is accepted according to guidelines. Beta-adrenoceptors polymorphisms, modulating sympathetic drive in heart failure and left ventricular remodelling, may have a role in identifying patients with a better response to CRT, in order to target and individualise the patients’ treatment

Sudden death prevention in heart failure: The case of CIBIS III

CIBIS III completes a fundamental scientific phase of a sequence of large clinical trials (1-7) which has established the current therapeutic principles for the management of chronic heart failure (CHF) patients (8). These comprise the use of ACE inhibitors and beta- blockers. However, while ACE inhibitors, by antagonizing the synthesis of angiotensin II, found their natural pathway from hypertension into CHF, betablockers followed a controversial trail. They appeared effective in the BEHAT (9) trial after myocardial infarction (MI) even in patients with depressed left ventricular (LV) function. Nonetheless, the general view of CHF as an almost exclusively cardio-circulatory mechanical disease/remodelling led to the use of inotropic interventions, with non-infrequent negative consequences on mortality (10). Furthermore, this view prevented the conception of using antiadrenergic interventions in CHF which consequently remained a strong contraindication to the use of beta- blockers for many years. Beginning with CIBIS II, a number of trials have proven that beta-blocker therapy improves survival in CHF, with a specific action on arrhythmic sudden cardiac death (SCD) in patients with optimum background therapy, including the use of ACE inhibitors. This did not happen by chance, as a strong experimental ground had already existed.....

Non-compaction of the ventricular myocardium

Non-compaction of the left ventricle (LVNC) is a disorder of endomyocardial morphogenesis that results in multiple trabeculations in the left ventricular (LV) myocardium. This rare disorder is characterized by an excessively prominent trabecular meshwork and deep intratrabecular recesses. This idiopathic cardiomyopathy is characterized by an altered structure of the myocardial wall as a result of intrauterine arrest of compaction of the myocardial fibers in the absence of any coexisting congenital lesion. It can be associated with neuromuscular disorders and can co-exist with other cardiac malformations, and it is accompanied by depressed ventricular function, systemic embolism and ventricular arrhythmia. Echocardiography is the method of choice for diagnosing LVNC, but the correct diagnosis is often missed or delayed due to a lack of knowledge concerning this uncommon disease and its similarity to other diseases of the myocardium and endocardium. There is a two-layered structure of the myocardial wall consisting of a thin compacted epicardial layer and a thick non-compacted endocardial layer with prominent trabeculations and deep recesses

rationale for the use of high dose sustained release isosorbide 5 mononitrate in ischemic heart disease and chronic heart failure

Isosorbide-5-mononitrate is one of the two pharmacologically active metabolites of isosorbide dinitrate. At variance from its parent drug, it has a longer elimination half-life, no metabolic first-pass, and greater bioavailability, allowing once-daily administration as standard or as sustained-release formulations. Several trials have shown that isosorbide-5-mononitrate, in the form of sustained-released capsules administered once daily at doses ranging between 50 and 100 mg, is an effective symptomatic drug for the treatment of stable angina and chronic heart failure (CHF), and is now indicated for these conditions by American and European guide- lines. In particular, at 80 mg once-daily sustained-release isosorbide-5-mononitrate has been shown to have trough plasma levels below the minimum therapeutic concentration (100 ng/mL), ensuring a nitrate-free period as sufficient as to avoid nitrate tolerance. This 80 mg dosage is the only high dose sustained-release formulation of isosorbide-5-mononitrate currently marketed in Italy. Isosorbide-5-mononitrate also exerts positive hemodynamic effects (reduction in filling pressure and systemic vascular resistance, with increase in cardiac output) in heart failure in as- sociation with standard medical therapy and hydralazine, with a positive impact on patient prog- nosis. (Heart International 2007; 3: 98-111

Improved graft patency rates and mid-term outcome of diabetic patients undergoing total arterial myocardial revascularization

Objectives: Diabetes negatively affects the outcome of patients undergoing percutaneous transluminal coronary angioplasty (PTCA) or coronary surgery. However, data are lacking with respect to the impact of arterial revascularization in the diabetic population. Methods: Between 1999 and 2003, 100 of 491 diabetics underwent coronary artery bypass graft surgery (CABG) with total arterial grafting (Group 1, G1); these patients were compared with 100 diabetics undergoing conventional CABG with saphenous veins (Group 2, G2), who were matched for Euroscore and other risk factors such as age, obesity, hypertension, left ventricular ejection fraction (LVEF), previous myocardial infarction and chronic obstructive pulmonary disease (COPD). Results: Both groups had a similar number of diseased coronary vessels (G1=2.6 vs G2= 2.7) and received a similar degree of myocardial revascularization (grafted vessels: G1=2.2 vs G2=2.4). Early outcome was comparable between the groups in terms of ventilatory support (G1=10.8±6 vs G2=10.4±5 hours), intensive care unit (ICU) stay (G1=24±12 vs G2=25±14 hours) and major post-operative complications such as atrial fibrillation (G1=26% vs G2=28%), peri-operative myocardial infarction (G1=1% vs G2=2%)and prolonged ventilatory support (G1=6% vs G2=5%). Hospital mortality was 2% in G1 and 3% in G2. Angiography was performed at a mean follow-up of 34 months in 65.9% and 71.1% of hospital survivors of G1 and G2 respectively: patients of G1 showed a significantly higher patency rate (G1=96% vs G2=83.6%, p=0.02). Additionally, patients of G1 showed a significantly lower incidence of recurrent myocardial ischemia (G1=7 pts. vs G2=18 pts., p=0.03), late myocardial infarction (G1=2 pts. vs G2=10 pts., p=0.03) and need for coronary reintervention (G1=1 pt. vs G2=12 pts, p=0.004). Conclusions: Total arterial grafting in diabetic patients significantly improved the benefits of coronary surgery providing at mid term a higher graft patency rate with a lower incidence of cardiac related events. (Heart International 2006; 3-4: 136-40

A Prospective, Randomized, Double-Blind Comparison of the Long-Term Effects of Metoprolol Versus Carvedilol

Background—Both metoprolol and carvedilol produce hemodynamic and clinical benefits in patients with chronic heart failure; carvedilol exerts greater antiadrenergic effects than metoprolol, but it is unknown whether this pharmacological difference results in hemodynamic and clinical differences between the 2 drugs. Methods and Results—We randomized 150 patients with heart failure (left ventricular ejection fraction ≤0.35) to double-blind treatment with either metoprolol or carvedilol. When compared with metoprolol (124±55 mg/d), patients treated with carvedilol (49±18 mg/d) showed larger increases in left ventricular ejection fraction at rest (+10.9±11.0 versus +7.2±7.7 U, P=0.038) and in left ventricular stroke volume and stroke work during exercise (both P<0.05) after 13 to 15 months of treatment. In addition, carvedilol produced greater decreases in mean pulmonary artery pressure and pulmonary wedge pressure, both at rest and during exercise, than metoprolol (all P<0.05). In contrast, the metoprolol gr..

The study of left ventricular diastolic function by Doppler echocardiography: the essential for the clinician

An abnormal diastolic function of left ventricle represents the main pathophysiological mechanism responsible for different clinical states such as restrictive cardiomyopathy, infiltrative myocardial disease and, specially, diastolic heart failure (also called heart failure with preserved systolic function), which is present in a large number of patients with a clinical picture of pulmonary congestion

Nitrates in Congestive Heart Failure

Organic nitrates remain among the oldest and most commonly employed drugs in cardiology. Although, in most cases, their use in acute and chronic heart failure is based on clinical practice, only a few clinical trials have been conducted to evaluate their use in acute and chronic heart failure, most of which compare them with other drugs to evaluate differing endpoints. The purpose of this review is to examine the various trials that have evaluated the use of nitrates in acute and chronic heart failure