Luca Bontempi

Serum levels of carbohydrate antigen 125 in patients with chronic heart failure: relation to clinical severity, hemodynamic and Doppler echocardiographic abnormalities, and short-term prognosis.

OBJECTIVES The aim of this study was to evaluate the serum levels of carbohydrate antigen 125 (CA125) in patients with congestive heart failure (CHF). BACKGROUND CA125 is a glycoprotein produced by serosal epithelium, found to be increased in ovarian cancer. METHODS Serum levels of CA125 were obtained in 286 patients (122 males and 164 females; age 69 +/- 13 years) with CHF (left ventricular ejection fraction 30 +/- 11%). A non-invasive evaluation was obtained by Doppler echocardiography; right heart catheterization was performed in 88 patients. An attempt to adjust medical therapy to maximally tolerated doses was done, and CA125 was repeated after 18 days (range 7 to 40) in 80 patients. The mean follow-up duration was 6 +/- 3 months in 240 patients. RESULTS The mean value of CA125 was 68 +/- 83 U/ml (range 3 to 537): 71 +/- 85 in men and 56 +/- 64 U/ml in women (p = NS). CA125 above the normal value (<35 U/ml) was found in 152 (53%) of 286 patients; it was higher in patients with advanced New York Heart Association (NYHA) functional class (n = 140 in class I/II: 15 +/- 9 U/ml; n = 63 in class III: 57 +/- 18 U/ml; n = 83 in class IV: 167 +/- 94 U/ml; p < 0.005). CA125 was related to the deceleration time of early filling on transmitral Doppler (r = -0.63, p < 0.05) and to pulmonary artery wedge pressure (r = 0.66, p < 0.05) and right atrial pressure (r = 0.69, p < 0.05). During 6 +/- 3 months of follow-up, a combined end point of mortality and CHF hospitalization was observed in 16 of 127 patients with CA125 <35 U/ml, compared with 70 of 113 patients with CA125 >35 U/ml (p < 0.01). After medical treatment optimization, NYHA class decreased by more than one grade in 56 of 80 patients and was unchanged or increased in 24 patients: CA125 decreased from 125 +/- 98 to 53 +/- 61 U/ml (p < 0.001) in the former and changed from 130 +/- 81 to 153 +/- 61 U/ml (p = NS) in the latter. CONCLUSIONS Our data suggest that CA125 is related to CHF severity and short-term prognosis. Furthermore, fluctuations of CA125 serum levels over time may reflect changes induced by therapy. Therefore, measurements of CA 125 serum levels might be proposed for the serial assessment of CHF patients.

A rationale for the use of β-blockers as standard treatment for heart failure☆

Abstract Background Cardiac sympathetic activation is one of the major and earlier changes observed in patients with heart failure. Its relation to the severity of the disease and its independent prognostic value show that it may directly contribute to the progression of heart failure. β-Blockers are the most effective tool to counteract the untoward effects of sympathetic activation on the cardiovascular system. Methods and Results We reviewed the results of the placebo-controlled, double-blind studies about the effects of β-blockers in patients with heart failure. These studies have involved almost 10,000 patients to date and have consistently shown that the long-term administration of β-blockers is associated with a highly significant improvement in both left ventricular function and prognosis of the patients with heart failure. The evidence supporting the use of ν-blockers now equals or even surpasses that of angiotensin-converting enzyme inhibitors; therefore β-blockers should be considered part of standard therapy. Issues that remain unclarified include the mechanisms through which β-blockers may improve cardiac function and their tolerability and efficacy in specific groups of patients (such as those with asymptomatic left ventricular dysfunction, severe heart failure, the elderly, or those with left ventricular diastolic dysfunction). It is not currently clear whether the pharmacologic differences between indvidual β-blockers are clinically relevant. If they are, the potential for even greater benefit with certain agents exists. It is hoped that these issues will be clarified by the results of ongoing multicenter trials.

Hybrid approach for the treatment of long-standing persistent atrial fibrillation: electrophysiological findings and clinical results †

OBJECTIVES The sequential, staged hybrid approach has recently emerged as a novel strategy for the treatment of long-standing persistent atrial fibrillation (AF); nevertheless, the potential modifications in terms of electrophysiological findings and their correlation with mid-term results have not been fully elucidated so far. METHODS Forty-five patients with long-standing persistent AF underwent a hybrid procedure combining surgical closed-chest posterior left atrium (LA) and pulmonary veins (PV) isolation (box lesion) first, followed by transcatheter evaluation at least 1 month afterwards. Electrophysiological findings and their correlation with rhythm outcomes were assessed at different time points, i.e. following the surgical ablation (T1), during (T2) and at the end (T3) of the transcatheter evaluation and at 28-month follow-up (T4). RESULTS At T1, exit and entrance blocks were achieved in 100 and 91.1% (41 of 45) of patients, respectively. At T2, the percentage of conduction block was unchanged, while at T3 also entrance block was achieved in all instances. In terms of electrophysiological findings (at T2), PV reconnection occurred in 6.7% (3 of 45) of patients, fractionated electrograms were targeted in 44.4% (20 of 45) while right atrium isthmus lesion was performed in 24.4% (11 of 45) of patients. Sinus rhythm was restored in 75.6% (34 of 45) at T1, at T2 (with AF induction) in 68.9% (31 of 45), at T3 in 93.3% (42 of 45) and at T4 in 88.9% (40 of 45) of patients, respectively. In those patients with a bidirectional block at T1, sinus rhythm restoration steadily improved from 78 (32 of 41) at T1 to 82.9 (34 of 41) at T2 and finally 92.6% (38 of 41) at T4. CONCLUSION Complete posterior LA and PV isolation with the box lesion in a staged hybrid approach is associated with incremental benefits in terms of sinus rhythm maintenance in patients with long-standing persistent AF.

Absence of inferior vena cava as a rare cause of deep venous thrombosis complicated by liver and lung embolism

Congenital anomalies of the inferior vena cava such as absence or atresia are uncommon vascular defects and result from aberrant development during embryogenesis. We report a case of a young female patient affected by proximal deep venous thrombosis (DVT) complicated by liver and pulmonary embolism; subsequent extensive evaluation revealed the congenital absence of infrarenal inferior vena cava, with emboli probably occurring through collateral veins. Accordingly, in young patients with idiopathic DVT of the lower extremities and pelvic veins, the presence of inferior vena cava abnormalities should always be considered and investigated, together with classic coagulation factors, as a factor predisposing to thromboembolic complications.

Maximal and submaximal exercise testing in heart failure.

Although reduced exercise capacity is the main complaint of patients with congestive heart failure (CHF), the best method to measure it remains controversial. Peak VO2, obtained using maximal exercise testing, is the most accurate measure of maximal functional capacity. It is related to peak exercise cardiac output and is one of the most important independent variables for the prognostic assessment of patients with CHF. It has, however, a low sensitivity for measurement of changes induced by therapy and is poorly related to everyday physical activity, patient symptoms, and quality of life. The anerobic threshold may also be regarded as a parameter of maximal functional capacity. Its value is mainly indirect, because it shows that the patient is performing a maximal effort limited by the cardiovascular system. The VO2 kinetics at the start and at the end of exercise are probably more related to patient symptoms, but it is unresolved which protocols and parameters might best be used to study this aspect of exercise performance. Duration of a submaximal exercise at a constant work rate and the distance walked during a 6-min walking test are gaining wide popularity as parameters of submaximal performance. However, when these exams are carried out up to exhaustion in patients with severe functional limitation, they may involve attainment of the anerobic threshold and therefore their clinical meaning may be similar to the one of a maximal exercise test. Moreover, tests based on the assessment of submaximal exercise capacity have been useful for assessment of therapy in single-center trials but have been often inadequate in multicenter trials.

Longevity of implantable cardioverter-defibrillators for cardiac resynchronization therapy in current clinical practice: an analysis according to influencing factors, device generation, and manufacturer

Aims Device replacement at the time of battery depletion of implantable cardioverter-defibrillators (ICDs) may carry a considerable risk of complications and engenders costs for healthcare systems. Therefore, ICD device longevity is extremely important both from a clinical and economic standpoint. Cardiac resynchronization therapy defibrillators (CRT-D) battery longevity is shorter than ICDs. We determined the rate of replacements for battery depletion and we identified possible determinants of early depletion in a series of patients who had undergone implantation of CRT-D devices. Methods and results We retrieved data on 1726 consecutive CRT-D systems implanted from January 2008 to March 2010 in nine centres. Five years after a successful CRT-D implantation procedure, 46% of devices were replaced due to battery depletion. The time to device replacement for battery depletion differed considerably among currently available CRT-D systems from different manufacturers, with rates of batteries still in service at 5 years ranging from 52 to 88% (log-rank test, P < 0.001). Left ventricular lead output and unipolar pacing configuration were independent determinants of early depletion [hazard ratio (HR): 1.96; 95% 95% confidence interval (CI): 1.57–2.46; P < 0.001 and HR: 1.58, 95% CI: 1.25–2.01; P < 0.001, respectively]. The implantation of a recent-generation device (HR: 0.57; 95% CI: 0.45–0.72; P < 0.001), the battery chemistry and the CRT-D manufacturer (HR: 0.64; 95% CI: 0.47–0.89; P = 0.008) were additional factors associated with replacement for battery depletion. Conclusion The device longevity at 5 years was 54%. High left ventricular lead output and unipolar pacing configuration were associated with early battery depletion, while recent-generation CRT-Ds displayed better longevity. Significant differences emerged among currently available CRT-D systems from different manufacturers.

How should we measure left atrium size and function

Echocardiographic assessment of left atrial size from M‐mode or 2D echocardiography measurements has been used in clinical and research studies for years, but its accuracy is now questioned. New techniques, such as 3D and tissue Doppler imaging, assessing velocities, strain and strain rate, provide improved prognostic value in a wide range of diseases. 2D strain imaging using speckle tracking on B‐mode images may yield even better, angle‐independent, results than tissue Doppler imaging‐derived strain echocardiography. Finally, velocity vector imaging is a novel image analysis technique that may be used to quantify left atrial volume.

A Focus on Antiarrhythmic Properties of Ranolazine

Ranolazine is an antianginal drug that inhibits a number of ion currents that are important for the genesis of transmembrane cardiac action potential. It was initially developed as an antianginal agent but was found to additionally exert antiarrhythmic actions, due to its multichannel-blocking properties. In recent years, several studies about the antiarrhythmic properties of ranolazine were conducted, demonstrating the beneficial effects of this drug in both atrial and ventricular arrhythmias, such as atrial fibrillation, ventricular premature beats, ventricular tachycardia, torsades de pointes, and ventricular fibrillation. Our aim is to briefly review the main points of these studies, most more experimental than clinical.

Implantation of a single chamber pacemaker in patients with triple mechanical valve prosthesis: Utilization of coronary sinus distal branches to stimulate the left ventricle

CURNIS, A., et al.: Implantation of a Single Chamber Pacemaker in Patients with Triple Mechanical Valve Prosthesis: Utilization of Coronary Sinus Distal Branches to Stimulate the Left Ventricle. The implantation of a permanent pacemaker and its relative leads is still a challenge in patients with mechanical tricuspid valve prosthesis. The implant is usually performed epicardially or during valve replacement to avoid any damage to the valve and/or early damages to the lead. We describe the case of a patient with a tricuspid valve prosthesis implanted with a permanent single‐chamber pacemaker using an endocardial lead positioned in a distal branch of the coronary sinus to stimulate the left ventricle.

Non-responders to cardiac resynchronization therapy: Insights from multimodality imaging and electrocardiography. A brief review

BACKGROUND Cardiac resynchronization therapy (CRT) is a successful strategy for heart failure (HF) patients. The pre-requisite for the response is the evidence of electrical dyssynchrony on the surface electrocardiogram usually as left bundle branch block (LBBB). Non-response to CRT is a significant problem in clinical practice. Patient selection, inadequate delivery and sub-optimal left ventricle lead position may be important causes. OBJECTIVES In an effort to improve CRT response multimodality imaging (especially echocardiography, computed tomography and cardiac magnetic resonance) could play a decisive role and extensive literature has been published on the matter. However, we are so far from routinary use in clinical practice. Electrocardiography (with respect to left ventricle capture and QRS narrowing) may represent a simple and low cost approach for early prediction of potential non-responder, with immediate practical implications. CONCLUSION This brief review covers the current recommendations for CRT in HF patients with particular attention to the potential benefits of multimodality imaging and electrocardiography in improving response rate.