Search

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.

The Italian school building heritage built between the seventies and eighties is every year increasingly abandoned and it remains in a state of neglect. It is increasingly necessary a recovery and enhancement methodology that preserves the memory of the place and at the same time, it makes it capable of adapting to the new needs of the city. The proposed research project originates from the study of the interactions between man and the environment applied to an architectural context with the identification of emotions. This methodology applied to citizenship, aims to make the population participate in the improvement from the point of view of well-being. This process was possible thanks to the combined use of immersive reality (VR) and the use of the GEW model, the data of which are the foundation and verification of the choices of architectural design, analyzed through the impacts on humans.

Neutral platinum(II) complex 2-PTPC-BF3a was easily prepared from benzofulvene derivative 2-Pyr-BF3a in order to evaluate the effects in the aggregation/polymerization behavior of a bulky substituent capable of establishing intermolecular metal–metal interactions in the close proximity of the putative polymerization center. Complex 2-PTPC-BF3a was found to aggregate into an ordered crystalline solid-state without significant spontaneous polymerization, but the UV-light irradiation of its dispersions in chloroform produced corresponding oligomers, which were characterized by NMR spectroscopy and MALDI-TOF mass spectrometry. On the other hand, the UV-irradiation of the platinum complex in the solid-state produced different results probably depending on the aggregate architecture. Notably, the crystalline films deposited from THF solutions on quartz substrates showed weak emissions, which progressively increased upon irradiation with the formation of oligomers devoid of the aggregation-induced quenching sites that seemed to affect the emission of poly-2-PTPC-BF3a. Finally, DFT calculations were performed on platinum complex 2-PTPC-BF3a in the aim of rationalizing the observed photophysical features.

Introduction Left atrial appendage thrombosis (LAAT) is a dangerous condition that mainly affects patients with atrial fibrillation (AF) or those with mitral stenosis (MS), increasing their risk of stroke. Transesophageal echocardiography (TEE) is the gold standard for the diagnosis of LAAT but some technical issues and the suboptimal sensitivity in identifying small thrombi, especially within a side lobe, can limit its clinical usefulness. Reliable non-invasive diagnostic methods could be useful in clinical practice. D-dimer, a fibrin degradation product already commonly used in the diagnostic work-up of conditions such as venous thromboembolism, may have a role as a non-invasive marker of LAAT. Purpose To evaluate the diagnostic performance of D-dimer for the detection of LAAT in patients with AF and/or MS, using TEE as the reference standard. Methods We searched the literature for studies that evaluated the ability of D-dimer to predict LAAT. For each study a 2x2 table of D-dimer positivity and LAAT presence was constructed. Sensitivity, specificity, positive predictive value and negative predictive value were calculated. Considering the different diagnostic thresholds used in the included studies, the overall sensitivity and specificity were calculated using a hierarchal summary receiver operating characteristic (HSROC) model and a SROC curve was generated. Results 6 studies, evaluating 1380 patients of whom 154 had LAAT, were included in the analysis. The prevalence of LAAT in the studies ranged from 9% to 26%, with a median of 12%. The mean age was 60±13 years, 63% were male. The mean left atrial diameter was 43±3 mm. The D-dimer diagnostic threshold ranged from 200 mcg/l to 1150 mcg/l. The overall sensitivity calculated with the HSROC model was 85%±28% and the overall specificity was 82%±29%. The negative predictive value was 98%. Figure 1 shows the summary ROC curve: individual studies are depicted by a clear circle; the red circle marks the pooled sensitivity and specificity across the 6 studies. The red dot-dashed-curve marks the boundary of the 95% credible region for the pooled estimates of sensitivity and specificity. Conclusions Our analysis shows that D-dimer has a good diagnostic performance with a very high negative predictive value for LAAT and therefore it might be of clinical aid for ruling out the presence of LAAT in patients with AF and/or MS. Further studies are needed to determine the best diagnostic threshold. Figure 1 Funding Acknowledgement Type of funding source: None

Benzofulvene derivative 2-Pyr-BF3a was designed and synthesized to evaluate the effects of a pyridine ring in position 2 of the 3-phenylbenzofulvene moiety on the spontaneous solid-state polymerization. The monomer was found to organize into an ordered crystalline solid-state without significant spontaneous polymerization, but the irradiation of amorphous film samples with UV-light produced photopolymerization. Resulting poly-2-Pyr-BF3a was characterized by NMR spectroscopy, MALDI-TOF mass spectrometry, and photophysical studies in comparison with the corresponding monomer. Interestingly, monomer 2-Pyr-BF3a was weakly emissive in diluted solutions, but increased its PLQY in the crystalline solid. Conversely, after photopolymerization the monomeric unit in the polymer enhanced its emission intensity in solution while in the solid state results weakly emissive. Even more interestingly, this benzofulvene monomer and its synthetic precursors 2 and 3 showed long-lived emission suggesting a phosphorescence nature of the emission process. Finally, DFT and TDDFT calculations were performed in order to rationalize the experimental data.

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.

Infective endocarditis (IE) due to group A β-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.

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 TAPSE≤15 mm and left ventricular eccentricity index ≥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.

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

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 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.

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.

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·sec·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·sec·cm −5 , indication for surgical intervention needs to be carefully evaluated.

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.The substudy randomized 112 patients in 29 European centres, of whom 104 were evaluable for the study; 43 had an ejection fraction (EF)or=35% and 61 had an EF35%. 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 EF/=35%, nebivolol reduced ESV (adjusted difference between treatments 25.8 mL, 95%CI: -46.6; -5.0, P=0.016) and improved EF (adjusted difference between treatments 4.6%, 95%CI: 1.3;7.9, P=0.008); no changes were observed in the E/A ratio or E-wave deceleration time. In EF35% group, no significant changes in either systolic or diastolic parameters were observed.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.

Objectives To test the diagnostic impact of the non-invasive rescreening of relatives of index patients consecutively diagnosed as having dilated cardiomyopathy. Background The aim of rescreening asymptomatic healthy relatives of DCM patients is to diagnose newly affected subjects and evaluate the predictive significance of the instrumental abnormalities found at the first screening. Methods and results Two hundred and three healthy relatives of 73 consecutive index patients with DCM (18 with familial disease at first screening) underwent rescreening involving a clinical examination, electro- and echocardiography, and biochemical tests a median of 29.3 months after the first screening. Seven relatives had developed the diagnostic criteria for DCM during the screening–rescreening interval. Of the 24 healthy relatives with left ventricular end-diastolic diameter enlargement and normal function at the first screening, nine had normalised, seven showed persistent enlargement, three had worsened, and five had developed the disease criteria at rescreening. Of the three relatives with atrioventricular block at the first screening, one had developed DCM. Finally, one of the relatives with normal echocardiographic and electrocardiographic results at the first screening, had developed the disease. Three of the newly diagnosed subjects came from families with evidence-based familial DCM, and four from families with what was defined as sporadic DCM at the first screening. Conclusions Medium-term rescreening of the relatives of DCM patients can identify a significant number of newly affected patients (3.5%).

Aim To evaluate the role of right ventricular function in different clinical models of heart failure. Methods 22 patients with pulmonary hypertension (PH) in WHO class III and IV (group A) were evaluated by echocardiography, brain natriuretic peptide (BNP) measurements and right heart catheterization at baseline and after a mean follow-up of 15±4 months. 63 patients with chronic heart failure of different etiology, NYHA class IIIb–IV, followed-up for 18±3 months (group B), underwent echocardiography, BNP measurements, right heart catheterization at study entry and follow-up. Results In group A patients, among hemodynamic parameters consistent with severe PH, right atrial pressure significantly increased (from 6.7±4.8 to 10±6.5 mmHg, p

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.

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).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) reductionor =15% at 6 months.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) P0.001), 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%, P0.001). All the indexes of RV function significantly correlated with the percentage of LVESV reduction after CRT. Severe RV dysfunction was defined as TAPSEor =14 mm and the population was stratified into two groups based on baseline TAPSEor = or14 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%, P0.001).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.

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.The CARE-HF trial enrolled patients with New York Heart Association (NYHA) class III or IV HF, with a QRS durationor =120 ms, left ventricular (LV) ejection fraction (EF)or =35% and LV end diastolic diameteror =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 IVMD40 ms was present in 455 patients (62%). Clinical, electrocardiographic and standard echocardiographic variables were only loosely associated with IVMD.Interventricular dyssynchrony appears to be an independent characteristic of patients with advanced HF, and is poorly related to clinical, electrocardiographic or standard echocardiographic variable.

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.

Mitochondrial (mt)DNA defects, both deletions and tRNA point mutations, have been associated with cardiomyopathies. The aim of the study was to determine the prevalence of pathological mtDNA mutations and to assess associated defects of mitochondrial enzyme activity in dilated cardiomyopathy (DCM) patients with ultrastructural abnormalities of cardiac mitochondria. In a large cohort of 601 DCM patients we performed conventional light and electron microscopy on endomyocardial biopsy samples. Cases with giant organelles, angulated, tubular, and concentric cristae, and crystalloid or osmiophilic inclusion bodies were selected for mtDNA analysis. Mutation screening techniques, automated DNA sequencing, restriction enzyme digestion, and densitometric assays were performed to identify mtDNA mutations, assess heteroplasmy, and quantify the amount of mutant in myocardial and blood DNA. Of 601 patients (16 to 63 years; mean, 43.5 +/- 12.7 years), 85 had ultrastructural evidence of giant organelles, with abnormal cristae and inclusion bodies; 19 of 85 (22.35%) had heteroplasmic mtDNA mutations (9 tRNA, 5 rRNA, and 4 missense, one in two patients) that were not found in 111 normal controls and in 32 DCM patients without the above ultrastructural mitochondrial abnormalities. In all cases, the amount of mutant was higher in heart than in blood. In hearts of patients that later underwent transplantation, cytochrome c oxidase (Cox) activity was significantly lower in cases with mutations than in those without or controls (P = 0.0008). NADH dehydrogenase activity was only slightly reduced in cases with mutations (P = 0.0388), whereas succinic dehydrogenase activity did not significantly differ between DCM patients with mtDNA mutations and those without or controls. The present study represents the first attempt to detect a morphological, easily identifiable marker to guide mtDNA mutation screening. Pathological mtDNA mutations are associated with ultrastructurally abnormal mitochondria, and reduced Cox activity in a small subgroup of non-otherwise-defined, idiopathic DCMs, in which mtDNA defects may constitute the basis for, or contribute to, the development of congestive heart failure.