Response to acute vasodilator challenge and haemodynamic modifications after MitraClip in patients with functional mitral regurgitation and pulmonary hypertension.

The effectiveness of transcatheter edge-to-edge repair (TEER) in patients with functional mitral regurgitation (FMR) and pulmonary hypertension (PH) is still debated and pre-procedural predictors of haemodynamic improvement after TEER in this setting are currently unknown. We investigated whether normalization of pulmonary artery wedge pressure (PAWP) in response to sodium nitroprusside (SNP) during baseline right heart catheterization might be predictive of a favourable haemodynamic response to MitraClip in patients with FMR and PH. Among 22 patients enrolled, 13 had a positive response to SNP (responders), nine were non-responders. At 6-months follow-up, responders showed a 33% reduction in PAWP and a 25% reduction in mean pulmonary artery pressure (PAP) (P = 0.002 and 0.004, respectively); no significant change occurred in non-responders. In patients with FMR and PH, pre-procedural vasodilator challenge with SNP may help define patients who may have haemodynamic improvement after TEER.

Mitral Valve Infective Endocarditis due to Streptococcus pyogenes: A Case Report.

Infective endocarditis (IE) due to group A ß-hemolytic streptococcus (Streptococcus pyogenes) has rarely been reported in the literature. We herein report a Streptococcus pyogenes native mitral valve endocarditis in a young patient and a review of the literature. The patient had a native mitral valve endocarditis with vegetation; his hemodynamic stability and a short course of antibiotic treatment prevented urgent surgery on the mitral valve. He was previously treated with cefixime and azithromycin for four days and then, upon hospital admission, with vancomycin plus amoxicillin-clavulanate. After the diagnosis of IE due to Streptococcus pyogenes, treatment with gentamicin (3 mg/kg daily) and ampicillin (12 g/day) was implemented. The patient underwent weekly echocardiographic evaluations during antibiotic treatment to document the resolution of the vegetations. He was discharged to home in good clinical conditions after a four-week course of antibiotic treatment.

MitraClip procedure as 'bridge to list', the ultimate therapeutic option for end-stage heart failure patients not eligible for heart transplantation due to severe pulmonary hypertension.

Patients with end-stage heart failure (HF), pulmonary hypertension and elevated pulmonary vascular resistance (PVR) despite medical therapy are not eligible for heart transplantation (HTx). In this 'proof of concept' case series, we demonstrate the feasibility and efficacy of the MitraClip procedure as 'bridge to list' in end-stage HF patients not eligible for HTx. In fact, in the three patients reported, who were initially excluded from the HTx list because of elevated PVR, the MitraClip procedure was followed by a sustained improvement of PVR, allowing the patients' risk to be reclassified, and they were then considered eligible for HTx.

Prognostic relevance of the echocardiographic assessment of right ventricular function in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: In patients with idiopathic pulmonary hypertension (IPAH) progression of the disease and survival are related to the capability of the right ventricle to adapt to the chronically elevated pulmonary artery pressure. Although several echocardiographic variables have been associated with outcome in previous studies, a comparative evaluation of all right ventricular (RV) function indices obtainable at echocardiography has never been performed. METHODS: 59 patients consecutively admitted in a tertiary referral centre because of IPAH (22 males, mean age 46.3+/-16.1 years, 68% in WHO class III/IV at referral) underwent right heart catheterization and echocardiography. During a median follow-up period of 52 months, 21 patients died and 2 underwent lung transplantation in emergency conditions. RESULTS: The following parameters were associated with survival: tricuspid annular plane systolic excursion (TAPSE), RV fractional area change, degree of tricuspid regurgitation, inferior vena cava collapsibility, superior vena cava flow velocity pattern, left ventricular diastolic eccentricity index. Patients with TAPSEor=1.7 had the highest event rate (51.7 per 100 person year); patients with TAPSE>15 mm and mild or no tricuspid regurgitation had the lowest event rate (2.6 per 100 person year). CONCLUSIONS: A comprehensive echocardiographic assessment of RV systolic and diastolic function based on TAPSE, left ventricular diastolic eccentricity index and degree of tricuspid regurgitation allows an accurate prognostic stratification of patients with IPAH.

Relevance of echocardiographic evaluation of right ventricular function in patients undergoing cardiac resynchronization therapy.

AIMS: Right ventricular (RV) dysfunction is a marker of poor prognosis in heart failure (HF) patients. It is still unclear whether RV function might influence response to cardiac resynchronization therapy (CRT). METHODS: Forty-four consecutive patients with HF, large QRS, and either intraventricular or interventricular dyssynchrony underwent echocardiographic evaluation before, 1 month after, and 6 months after CRT. Response to CRT was considered in case of significant LV reverse remodeling, defined as the occurrence of LV end-systolic volume (LVESV) reduction > or =15% at 6 months. RESULTS: All echocardiographic indexes of baseline RV function and dimensions were significantly more impaired in nonresponders versus responders to CRT: tricuspid annular plane systolic excursion (TAPSE 15 +/- 4 mm vs 20 +/- 5 mm, P = 0.001), RV systolic pulmonary artery pressure (RVSP 39 +/- 14 mmHg vs 27 +/- 8 mmHg, P = 0.02), RV end-diastolic area (RVEDA 23 +/- 6 cm(2) vs 16 +/- 3 cm(2) P < 0.001), RV end-systolic area (RVESA 16 +/- 6 cm(2) vs 8 +/- 2 cm(2), P = 0.001), and RV fractional area change (30 +/- 12% vs 48 +/- 8%, P < 0.001). All the indexes of RV function significantly correlated with the percentage of LVESV reduction after CRT. Severe RV dysfunction was defined as TAPSE < or =14 mm and the population was stratified into two groups based on baseline TAPSE < or = or > 14 mm. As compared to those with high TAPSE (n = 30), patients with low TAPSE (n = 14) were less likely to show LV reverse remodeling after CRT (76% vs 14%, P < 0.001). CONCLUSIONS: Our study suggests that RV function significantly affects response to CRT. Poor LV reverse remodeling occurs after CRT in patients with HF having severe RV dysfunction at baseline.

Baseline and 6-month B-type natriuretic peptide changes are independent predictors of events in patients with advanced heart failure awaiting cardiac transplantation.

OBJECTIVE: To assess the prognostic role of B-type natriuretic peptide (BNP) measured at baseline and after 6 months in advanced heart failure patients, candidates for heart transplantation. METHODS: Ninety-nine patients with BNP evaluation (mean age 50.8 years, 85% men) were admitted in the heart transplantation waiting list; 39% were in New York Heart Association functional class IV; with hemodynamic patterns of severe heart failure, the cause was ischemic in 45% and idiopathic in 44%. In order to identify more severe patients, BNP values and changes at 6 months were dichotomized according to their upper tertile (>1100 and >or=70 pg/ml, respectively). RESULTS: Median baseline BNP was 719 pg/ml. After a median of 45 months, 40 events were observed (three cardiac assist device implants, 16 urgent heart transplantations, 13 sudden deaths and eight deaths from heart failure). The event rate was 10.0 and 32.3 per 100 person-years in patients with low and high BNP, respectively. In a bivariable Cox regression, BNP at entry in the list and change in BNP at 6 months were independent predictors of events, with hazard ratios of 4.10 (95% confidence interval 2.14-7.88, P<0.001) and 4.55 (95% confidence interval 2.36-8.80, P<0.001), respectively. Furthermore, the risk increased from neither BNP/BNP change, to one of them and to both of them present. CONCLUSION: Both high baseline and further increase in BNP levels during midterm follow-up are strong predictors of events in patients with advanced heart failure awaiting heart transplantation.

Long-term left ventricular reverse remodelling with cardiac resynchronization therapy: results from the CARE-HF trial.

AIMS: The aim of the present study was to assess the long-term effects of cardiac resynchronization therapy (CRT) on the reverse remodelling of the left ventricle (LV). METHODS AND RESULTS: The effects of CRT compared with controls on LV dimensions and function were assessed at 3, 9, and 18 months and at the end of study (average 29 months) in 735 (90%) patients with adequate echocardiographic examinations, randomized in the CARE-HF trial. Echocardiographic recordings were submitted to a core laboratory to ensure consistent quantitative analysis. LV volume decreased and ejection fraction increased substantially in the CRT group by 3 months and improved further at each assessment when compared with the control group. Effects were less marked in patients with ischaemic heart disease and those with right ventricular dysfunction, but not in patients with a restrictive LV filling pattern. The extent of reverse remodelling at 18 months showed a modest relationship with baseline interventricular mechanical delay (IVMD). CONCLUSION: CRT induces sustained LV reverse remodelling with the most marked effects occurring within the first 3-9 months. The extent of remodelling in response to CRT is related to the aetiology of heart failure and, to a lesser extent, to the IVMD.

Left ventricular pacing lead positioning in the target vein of the coronary sinus: description of a challenging case.

The optimal left ventricular pacing location for cardiac resynchronization therapy should be individualized according to the site of maximal mechanical delay. However, the presence of vein stenosis or kinking in coronary sinus (CS) anatomy could hamper lead implantation in the target vessel. We describe the case of a patient with dilated cardiomyopathy and a dual-chamber pacemaker referred for upgrading to a biventricular device owing to New York Heart Association III heart failure symptoms. Tissue Doppler analysis before implantation showed that the area of maximum activation delay was located in the posterolateral region of the left ventricle. Insertion of the lead into a posterolateral vein of the CS by means of the standard over-the-wire approach was unsuccessful due to the presence of a stenosis at the ostium of the vein. Lead placement in an anterior vein of the CS was unsatisfactory owing to a poor local delay from QRS onset. After balloon vein angioplasty, the pacing lead passed through the stenotic tract at the ostium of the target vein and was successfully positioned in the posterolateral region. Three months after pacemaker implantation, echocardiography showed an important reduction in the indexes of both inter- and intraventricular asynchrony and a significant left ventricular reverse remodeling.

Reverse right ventricular remodeling after pulmonary endarterectomy.

OBJECTIVES: We sought to evaluate the capability of the right ventricle to regain normal morphology and function after pulmonary endarterectomy, to correlate right ventricular reverse remodeling with functional status, and to identify independent predictors of clinical failure after surgical intervention. METHODS: From December 2000 through August 2003, 45 patients underwent isolated pulmonary endarterectomy. Morphology and function of the right ventricle were studied by using a combination of right heart catheterization, cardiac magnetic resonance, and transthoracic echocardiography. Functional status was evaluated by using New York Heart Association class. Full preoperative data were available for 37 candidates. All patients were evaluated before discharge, at 3 months, and at 1, 2, and 3 years postoperatively using the same modalities. RESULTS: Immediately after surgical intervention, right ventricular cavitary dimensions decreased significantly, and tricuspid regurgitation radically improved. Right ventricular ejection fraction and functional status improved and right ventricular hypertrophy reversed over a longer time period. Higher ventricular dimensions and lower ejection fraction of the right ventricle were associated with poorer functional status at any time postoperatively. At discharge, pulmonary vascular resistance of greater than 509 dyne x sec x cm(-5) and right ventricular ejection fraction of 24% or less predicted clinical failure at 12 months' follow-up. CONCLUSIONS: After pulmonary endarterectomy, the right ventricle recovers and maintains normal architecture and function over time, regardless of the severity of preoperative disease. Accurate preoperative evaluation of the hemodynamics and anatomy of the thromboembolic lesions are mandatory. If pulmonary endarterectomy is not expected to decrease pulmonary vascular resistance to less than 509 dyne x sec x cm(-5), indication for surgical intervention needs to be carefully evaluated.

Effects of nebivolol in elderly heart failure patients with or without systolic left ventricular dysfunction: results of the SENIORS echocardiographic substudy.

AIMS: The SENIORS trial recently demonstrated that nebivolol reduces the composite risk of all-cause mortality and cardiovascular hospital admission in elderly patients with chronic heart failure and, importantly, that ejection fraction does not influence the clinical effects of nebivolol. An echocardiographic substudy was designed to evaluate the effects of nebivolol on systolic and diastolic left ventricular (LV) function in patients stratified according to the presence or absence of systolic LV dysfunction. METHODS AND RESULTS: The substudy randomized 112 patients in 29 European centres, of whom 104 were evaluable for the study; 43 had an ejection fraction (EF) 35%. LV end-systolic volume (ESV), EF, mitral valve E/A ratio, and E-wave deceleration time were assessed at baseline and after 12 months. Echocardiograms were submitted to a core laboratory to perform quantitative analysis in blinded condition. In the group with EF35% group, no significant changes in either systolic or diastolic parameters were observed. CONCLUSION: In patients with heart failure and advanced systolic LV dysfunction, nebivolol reduces ventricular size and improves EF. The absence of detectable changes with standard echocardiography in patients with predominant diastolic heart failure questions the mechanism of benefit on morbidity/mortality in such patients.

Baseline echocardiographic characteristics of heart failure patients enrolled in a large European multicentre trial (CArdiac REsynchronisation Heart Failure study).

AIMS: Information on the prevalence and clinical, electrocardiographic and echocardiographic inter-relationships of mechanical dyssynchrony among patients with heart failure (HF) and left ventricular systolic dysfunction derives mainly from relatively small studies. The CARE-HF trial provides the opportunity to address these issues in a large population of patients with advanced HF. METHODS AND RESULTS: The CARE-HF trial enrolled patients with New York Heart Association (NYHA) class III or IV HF, with a QRS duration > or =120 ms, left ventricular (LV) ejection fraction (EF) < or =35% and LV end diastolic diameter > or =30 mm/m (height in m). Patients underwent a thorough echocardiographic evaluation, which included assessment of LV structure, systolic function, mitral inflow pattern, right ventricular (RV) dimensions and function, and interventricular mechanical delay (IVMD) as an index of interventricular dyssynchrony. Echocardiographic measurements were made in a Core Laboratory to ensure consistent quantitative analysis. Of the 813 patients enrolled, 735 had a baseline echocardiographic examination suitable for measurement. Overall patients had advanced LV dysfunction (mean EF 25.5%) but few had a restrictive mitral filling pattern (18%) and both the mean RV diameter and RV function were within normal limits. Interventricular dyssynchrony defined as IVMD >40 ms was present in 455 patients (62%). Clinical, electrocardiographic and standard echocardiographic variables were only loosely associated with IVMD. CONCLUSIONS: Interventricular dyssynchrony appears to be an independent characteristic of patients with advanced HF, and is poorly related to clinical, electrocardiographic or standard echocardiographic variable.

[Rationale, characteristics and study design of PREAMI (Perindopril and Remodelling in the Elderly with Acute Myocardial Infraction)]. / Razionale, peculiarità e disegno dello studio PREAMI (Perindopril and Remodelling in the Elderly with Acute Myocardial Infarction).

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality and morbidity in patients with heart failure and/or left ventricular systolic dysfunction and in patients with acute myocardial infarction (AMI), especially those with heart failure and/or evidence of left ventricular systolic dysfunction. ACE-inhibitors prevent cardiac events in patients at high cardiovascular risk and/or with documented coronary artery disease. There is a lack of data on the role of ACE-inhibitors in the elderly population with AMI and preserved left ventricular function. Nevertheless, the issue is of primary importance, considering the median age of patients with AMI and heart failure, the high risk of death, heart failure and left ventricular remodeling in the elderly, and the progressive aging of the general population. The multicenter and international (109 centers from five European countries), double-blind, randomized, parallel PREAMI (Perindopril and Remodelling in the Elderly with Acute Myocardial Infarction) trial evaluated the effects of the ACE-inhibitor perindopril in the elderly (aged > or =65 years) with AMI and preserved or mildly depressed left ventricular systolic function (ejection fraction > 40%). The combined primary endpoint was death, hospitalization for heart failure, and left ventricular remodeling (considered as an increase in left ventricular end-diastolic volume > or = 8%). Secondary endpoints included: each single primary endpoint, cardiovascular death, hospitalization for reinfarction or angina, and revascularization. The study involved 1252 patients, with an average age of 73 years, and AMI, treated with recommended usual therapy (antithrombotic drugs, beta-blockers, ACE-inhibitors). After 11 +/- 4 days from AMI, patients were randomized to receive either perindopril (4 mg/day for the first month and 8 mg/day for the remaining 11 months) or placebo, in addition to the recommended conventional therapy. Clinical assessment was performed at fixed times and included two-dimensional echocardiography (to evaluate left ventricular remodeling), Holter electrocardiographic monitoring (to assess heart rate variability and arrhythmias), and blood sampling (for safety evaluation). This review provides details on the background, rationale and study design of PREAMI.

The current therapeutic approach to chronic heart failure.

In the past 20 years, enormous progress has been made in the understanding of the pathophysiology and treatment of the complex clinical syndrome of heart failure. It has been a bidirectional process, with improvements in the understanding of the pathophysiology suggesting new therapeutic approaches and the success and failures of clinical trials refining our hypotheses or even suggesting the involvement of new pathophysiological mechanisms. In the past, heart failure was interpreted on the basis of a pathophysiological model according to which the hemodynamic abnormalities played a key role in determining the clinical presentation and the evolution of the disease. Therefore, the objective of pharmacological treatment was to improve these hemodynamic abnormalities. At the beginning of the '90s it became clear that the activation of the reninangiotensin-aldosterone system and of the sympathetic system caused by the abnormality in cardiac function had deleterious clinical effects in the long term. Heart failure was therefore considered as a "neurohormonal" disorder and the objective of pharmacological treatment was to improve survival by antagonizing this reflex activation. More recently, even the so-called "neurohormonal" hypothesis has itself evolved in several ways. In the present review the efficacy of each class of drug will be discussed in the light of the results of the most important clinical trials. In fact, from a practical point of view, since we learned so much from the published trials, it is very important that we know how these have been structured to evaluate the applicability of pharmacological treatments to individual patients.