Diagnostic Work-Up in Patients with Nonbacterial Thrombotic Endocarditis.

Nonbacterial thrombotic endocarditis (NBTE) is a form of endocarditis that occurs in patients with predisposing conditions, including malignancies, autoimmune diseases (particularly antiphospholipid antibody syndrome, which accounts for the majority of lupus-associated cases), and coagulation disturbances for which the correlation with classical determinants is unclear. The condition is commonly referred to as "marantic", "verrucous", or Libman-Sacks endocarditis, although these are not synonymous, representing clinical-pathological nuances. The clinical presentation of NBTE involves embolic events, while local valvular complications, generally regurgitation, are typically less frequent and milder compared to infective forms of endocarditis. In the past, the diagnosis of NBTE relied on post mortem examinations, while at present, the diagnosis is primarily based on echocardiography, with the priority of excluding infective endocarditis through comprehensive microbiological and serological tests. As in other forms of endocarditis, besides pathology, transesophageal echocardiography remains the diagnostic standard, while other imaging techniques hold promise as adjunctive tools for early diagnosis and differentiation from infective vegetations. These include cardiac MRI and 18FDG-PET/CT, which already represents a major diagnostic criterion of infective endocarditis in specific settings. We will herein provide a comprehensive review of the current knowledge on the clinics and therapeutics of NBTE, with a specific focus on the diagnostic tools.

Surgical Challenges in Infective Endocarditis: State of the Art.

Infective endocarditis (IE) is still a life-threatening disease with frequent lethal outcomes despite the profound changes in its clinical, microbiological, imaging, and therapeutic profiles. Nowadays, the scenario for IE has changed since rheumatic fever has declined, but on the other hand, multiple aspects, such as elderly populations, cardiovascular device implantation procedures, and better use of multiple imaging modalities and multidisciplinary care, have increased, leading to escalations in diagnosis. Since the ESC and AHA Guidelines have been released, specific aspects of diagnostic and therapeutic management have been clarified to provide better and faster diagnosis and prognosis. Surgical treatment is required in approximately half of patients with IE in order to avoid progressive heart failure, irreversible structural damage in the case of uncontrolled infection, and the prevention of embolism. The timing of surgery has been one of the main aspects discussed, identifying cases in which surgery needs to be performed on an emergency (within 24 h) or urgent (within 7 days) basis, irrespective of the duration of antibiotic treatment, or cases where surgery can be postponed to allow a brief period of antibiotic treatment under careful clinical and echocardiographic observation. Mainly, guidelines put emphasis on the importance of an endocarditis team in the handling of systemic complications and how they affect the timing of surgery and perioperative management. Neurological complications, acute renal failure, splenic or musculoskeletal manifestations, or infections determined by multiresistant microorganisms or fungi can affect long-term prognosis and survival. Not to be outdone, anatomical and surgical factors, such as the presence of native or prosthetic valve endocarditis, a repair strategy when feasible, anatomical extension and disruption in the case of an annular abscess (mitral valve annulus, aortic mitral curtain, aortic root, and annulus), and the choice of prosthesis and conduits, can be equally crucial. It can be hard for surgeons to maneuver between correct pre-operative planning and facing unexpected obstacles during intraoperative management. The aim of this review is to provide an overview and analysis of a broad spectrum of specific surgical scenarios and how their challenging management can be essential to ensure better outcomes and prognoses.

Characterization of the electrophysiological substrate in patients with Barlow's disease.

BACKGROUND: Myxomatous mitral valve prolapse (MVP) and mitral-annular disjunction (Barlow disease) are at-risk for ventricular arrhythmias (VA). Fibrosis involving the papillary muscles and/or the infero-basal left ventricular (LV) wall was reported at autopsy in sudden cardiac death (SCD) patients with MVP. OBJECTIVES: We investigated the electrophysiological substrate subtending VA in MVP patients with Barlow disease phenotype. METHODS: Twenty-three patients with VA were enrolled, including five with syncope and four with a history of SCD. Unipolar (Uni < 8.3 mV) and bipolar (Bi < 1.5 mV) low-voltage areas were analyzed with electro-anatomical mapping (EAM), and VA inducibility was evaluated with programmed ventricular stimulation (PES). Electrophysiological parameters were correlated with VA patterns, electrocardiogram (ECG) inferior negative T wave (nTW), and late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance. RESULTS: Premature ventricular complex (PVC) burden was 12 061.9 ± 12 994.6/24 h with a papillary-muscle type (PM-PVC) in 18 patients (68%). Twelve-lead ECG showed nTW in 12 patients (43.5%). A large Uni less than 8.3 mV area (62.4 ± 45.5 cm2 ) was detected in the basal infero-lateral LV region in 12 (73%) patients, and in the papillary muscles (2.2 ± 2.9 cm2 ) in 5 (30%) of 15 patients undergoing EAM. A concomitant Bi less than 1.5 mV area (5.0 ± 1.0 cm2 ) was identified in two patients. A history of SCD, and the presence of nTW, and LGE were associated with a greater Uni less than 8.3 mV extension: (32.8 ± 3.1 cm2 vs. 9.2 ± 8.7 cm2 ), nTW (20.1 ± 11.0 vs. 4.1 ± 3.8 cm2 ), and LGE (19.2 ± 11.7 cm2 vs. 1.0 ± 2.0 cm2 , p = .013), respectively. All patients with PM-PVC had a Uni less than 8.3 mV area. Sustained VA (ventricular tachycardia 2 and VF 2) were induced by PES only in four patients (one with resuscitated SCD). CONCLUSIONS: Low unipolar low voltage areas can be identified with EAM in the basal inferolateral LV region and in the papillary muscles as a potential electrophysiological substrate for VA and SCD in patients with MVP and Barlow disease phenotype.

Targeting Alcohol Septal Ablation in Patients with Obstructive Hypertrophic Cardiomyopathy Candidates for Surgical Myectomy: Added Value of Three-Dimensional Intracoronary Myocardial Contrast Echocardiography.

BACKGROUND: Myocardial contrast two-dimensional echocardiography (MC-2DE) is widely used to address alcohol septal ablation (ASA) in obstructive hypertrophic cardiomyopathy (HCM). Owing to its limited cut-planes, MC-2DE may inaccurately identify the contrast misplacement associated with an unsuccessful or complicated ASA outcome. OBJECTIVE: The aim of this study was to assess the added value of myocardial contrast three-dimensional echocardiography (MC-3DE) compared with MC-2DE to identify the appropriate matching between the target septal zone (TSZ) and coronary artery branch for safe and long-term effective ASA in HCM patients. METHODS: A consecutive series of 52 symptomatic obstructive HCM patients referred for isolated surgical myectomy (SM) was analyzed with MC-2DE and MC-3DE following injection of echocontrast into one or more septal branches. MC-2DE and MC-3DE patterns were categorized according to complete (Type 1) or incomplete (Type 2) TSZ covering, high-risk (Type 3) exceeding TSZ, or life-threatening outside TSZ distribution (Type 4). RESULTS: MC-2DE per patient analysis showed a Type 1 pattern in 32 patients and Types 2-4 in the remaining 20 patients; subsequent MC-3DE analysis provided a re-phenotyping of MC-2DE findings in 22 of the 52 patients (42%), showing a high-risk Type 2 pattern in 17 of the 32 patients with Type 1, and a new life-threatening Type 4 in three patients with Type 2, respectively. All patients with MC-3DE Type 1 pattern underwent safe and effective ASA with a long-term uneventful follow-up, while the remaining patients underwent SM. CONCLUSIONS: Refining high risk or life-threatening contrast misplacement, MC-3DE is more accurate than conventional MC-2DE to target safe and long-term effective septal reduction with ASA in obstructive HCM patients referred for isolated SM.

New and old echographic parameters in heart failure.

Echography (ECHO) is a first-line technology for diagnostic evaluation and prognostic stratification of patients with heart failure (HF). Recognizing specific diseases or conditions amenable to specific treatment is a crucial step in the work-up of patients with HF. Left ventricular ejection fraction (EF) measurement, despite its pathophysiological and methodological limitations, is the primary parameter for the HF classification, incorporating forms with reduced, moderately reduced, and preserved ejection fraction. The cardiac filling parameters could characterize the haemodynamic profile of the various forms of HF and guide different clinical therapeutic strategies. Besides the conventional parameters, widely validated by the clinical practice (old parameters), ECHO provides new information on cardiac function (deformation index), which prospectively could refine our phenotypic classification, beyond EF, thus opening new prospects in the pre-clinical identification, and in the selection of the appropriate treatment for HF patients Stemming from the recent technologic improvements, it is possible to analyse conventional parameters with innovative and automatic approaches, which are quickly available, and able to open new perspectives in the treatment of patients with HF.

Phenotyping Left Ventricular Obstruction With Postprandial Re-Test Echocardiography in Hypertrophic Cardiomyopathy.

Dynamic left ventricular (LV) obstruction has important clinical and therapeutic implications in patients with hypertrophic cardiomyopathy (HC). Although absent at rest, LV obstruction may be elicited using varying stressors. Meal-related hemodynamic changes may favor LV obstruction and support postprandial (PP) symptoms in HC patients. The aim of this study was to evaluate PP-LV obstruction inducibility in HC patients in comparison with fasting Valsalva maneuver and exercise test. Ninety-two HC patients without LV obstruction underwent at-rest Transthoracic Echocardiography (TTE) during Valsalva maneuver and exercise test under fasting condition followed by at-rest re-test PP-TTE 30 to 60 minutes after a standardized midday meal. LV obstruction was noted and classified as being related to systolic anterior motion (SAM) of the mitral valve (SAM-related) and/or non-SAM-related (mid-cavity or apical), and intraventricular gradient was measured. At-rest re-test PP-TTE showed significant intraventricular gradient (>30 mm Hg) in 68 patients (60 SAM-related, 8 non-SAM related, 30 combined) with a higher prevalence (74%) of HC phenotype re-classified as obstructive compared with the fasting Valsalva maneuver (23%) or exercise test (33%) (p < 0.001). At multivariate analysis, a clinical history of PP symptoms and mitral anterior leaflet length and/or LV outflow ratio >2 were independently correlated with PP-TTE obstruction. In conclusion, PP TTE re-test is a simple and effective approach to unmask latent LV dynamic obstruction in daily clinical practice over fasting Valsalva maneuver or exercise test. PP clinical phenotype refinement may be relevant in targeting and evaluating HC therapy.

Transcatheter or surgical repair for degenerative mitral regurgitation in elderly patients: A propensity-weighted analysis.

OBJECTIVE: To compare the outcomes of MitraClip and surgical mitral repair in low-intermediate risk elderly patients affected by degenerative mitral regurgitation (DMR). METHODS: We retrospectively selected patients aged ≥75 years, with Society of Thoracic Surgeons Predicted Risk Of Mortality (STS-PROM) <8%, submitted to MitraClip (n = 100) or isolated surgical repair (n = 206) for DMR at 2 centers between January 2005 and May 2017. To adjust for baseline imbalances, we used a propensity score model for average treatment effect on survival. RESULTS: After weighting, MitraClip showed fewer postoperative complications (P < .05) but increased residual mitral regurgitation (MR) ≥2 (27.0% vs 2.8%, P < .001) compared with surgery. One-year survival was greater after MitraClip compared with surgery (97.6% vs 95.3%, hazard ratio [HR], 0.09; confidence interval [CI], 0.02-0.37, P = .001), whereas 5-year survival was lower (34.5% vs 82.2% respectively, HR, 4.12; CI, 2.31-7.34, P < .001). Greater STS-PROM (HR, 1.18; CI, 1.12-1.24, P < .001) and MR ≥3+ recurrence (HR, 2.18; CI, 1.07-4.48, P = .033) were associated with reduced survival. 5-year MR ≥3+ was more frequent after MitraClip compared with surgery: 36.9% versus 3.9%, odds ratio, 11.4; CI, 4.40-29.68, P < .001. CONCLUSIONS: In elderly patients affected by DMR and STS-PROM <8%, the average effect of MitraClip resulted in lower acute postoperative complications and improved 1-year survival compared with surgery. However, MitraClip was associated with greater MR recurrence and reduced survival beyond 1 year. Long-term survival was impaired by patients' greater risk profile and MR recurrence. Early results are promising, but in the setting of operable patients with life expectancy beyond 1 year, the quality bar for transcatheter mitral repair needs to be raised.

MitraClip for radiotherapy-related mitral valve regurgitation.

OBJECTIVE: Owing to mediastinal and cardiac damage burden, the surgical treatment of radiotherapy-related mitral regurgitation (MR) may be associated with high operative risk or might even contraindicated. We evaluated the feasibility and outcome of MitraClip therapy in patients with radiotherapy-related MR as an alternative to surgery. METHODS: Based on Doppler Echocardiography, 15 of 33 screened patients underwent MitraClip implantation. RESULTS: Following MitraClip MR improved (residual MR ≤2+) without significant mitral valve stenosis (planimetric area 2.83 ± 0.8 cm2, mean gradient 4.6 ± 1.8 mm Hg). All patients completed a 6-month follow-up, while 14 of 15 patients achieved a longer follow-up, ranging from 12 to 72 months (median 24 months, IQR 42 months). At 6-month follow-up we observed NYHA improvement in 13 patients with an increase of 6-min walking covered distance (from 260 ± 34 to 367 ± 70, p < 0.001), sustained moderate or less MR, mild mitral stenosis in 3 patients, and significant systolic Pulmonary Artery Pressure (PAPs) reduction (from 52.5 ± 14 to 42 ± 9, p < 0.01). Sustained clinical improvement and ≤2+ MR was observed in 13 of 14 patients who completed the 12-month follow-up. Two patients died of acute pneumonia (11 months and 60 months, respectively). One patient developed moderate MV stenosis (MVA 1.4 cm2) at last follow-up (48 months) without related clinical instability. Tricuspid regurgitation improved in 12 patients with further improvement at late follow-up in 2 of 3 patient with 3+. CONCLUSION: MitraClip may be an effective treatment for RT-induced MR, although unexpected late stenosis may occur in the context of sustained reactive mitral apparatus damage following mediastinal radiation.

Mid-term outcomes (up to 5 years) of percutaneous edge-to-edge mitral repair in the real-world according to regurgitation mechanism: A single-center experience.

OBJECTIVES: To report mid-term results after MitraClip repair, according to mitral regurgitation (MR) mechanism, in a real-world single-center experience. BACKGROUND: Mid-term outcomes of percutaneous edge-to-edge mitral repair in the real world are still limited. METHODS: We assessed the follow-up results of patients treated with MitraClip at a single high-volume mitral center from 2008 to 2016. All patients underwent Heart-Team discussion, prospective data collection and enrolment in a dedicated outpatient clinic. Functional (FMR, n = 242, 68.6%) and degenerative (DMR, n = 97, 27.5%) MR patients were separately analyzed. RESULTS: 5-Year survival was 53.5 ± 4.5% in FMR vs 57.1 ± 7.5% in DMR (P = 0.087). Reduced survival was strongly associated with worse left ventricle remodeling (ESV HR 1.01, CI 1.01-1.02, P < 0.001) in FMR, and with worse symptoms (New York Heart Association IV HR 6.72, CI 1.78-25.45, P = 0.005) in DMR. 5-Year cumulative incidence function for MR ≥ 3 was 23.7 ± 3.4% in FMR vs 27.9 ± 5.9% in DMR (P = 0.39), being associated with residual MR = 2 both in FMR (HR 4.67, CI 2.49-8.74, P < 0.001) and DMR (HR 7.15, CI 2.72-18.75, P < 0.001). At 5-year, patients in NYHA class I-II increased from 17.9% to 45.3% in FMR (P < 0.001) and from 33.3% to 51.3% in DMR (P < 0.001). CONCLUSIONS: In this single-center real-world experience, 5-year after MitraClip, half of the patients were alive and 3/4 were free from MR, both in FMR and DMR. Symptoms benefit was sustained in both groups. Advanced ventricular remodeling, advanced symptoms, and suboptimal MR reduction were associated with worse results. Refined patient selection, improved efficacy and more data will be all required to improve long-term outcomes.

Unilateral Pulmonary Edema in a Patient with Worsening Tricuspid Valve Regurgitation: A Secret Inside Pulmonary Veins.

We present the case of a 69-year-old patient who was referred to the Department of Echocardiography for surgical treatment of severe tricuspid valve regurgitation (TVR) with advanced congestive heart failure. In 2013 the patient underwent unsuccessful percutaneous ablation for permanent atrial fibrillation. In 2015, following numerous episodes of atrial fibrillation and congestive heart failure with left pleural effusion, the patient was admitted to another center. A transthoracic echocardiogram showed severe TVR and moderate precapillary pulmonary hypertension, confirmed at right cardiac catheterization. He showed bilateral ankle swelling, mild systolic cardiac murmur and localized leftmost decreased breath sounds. Chest X-ray revealed left-sided pulmonary edema and ipsilateral large pleural effusion. Following percutaneous drainage of the left pulmonary effusion, the patient underwent transthoracic and transesophageal echocardiography (TEE), confirming severe TVR due to annular dilation, severe pulmonary hypertension (60 mmHg) and right ventricular overload. At TEE, we found a narrowed single left pulmonary vein. Coronary artery angiography showed no critical stenosis. The patient underwent cardiac magnetic resonance and Angiography that confirmed ostial stenosis of a single left pulmonary vein. We performed successful bare-metal stent implantation. After the procedure, we observed progressive improvement in the patient's clinical condition, concomitant with reverse pulmonary hypertension, significant TVR reduction and chest X-ray normalization. This is a rare case of unilateral pulmonary edema following percutaneous ablation of atrial fibrillation.

Does implantation of a single clip provide reliable durability after transcatheter mitral repair?

OBJECTIVES: A single MitraClip implant is often considered enough to achieve adequate mitral regurgitation (MR) reduction. The aim of this study was to compare MR recurrence in patients with an initial optimal result treated with a single clip versus those treated with two clips. METHODS: From October 2008 to May 2016, 322 patients were treated with the MitraClip procedure at our institution. We retrospectively selected all patients treated for functional MR (FMR) and degenerative MR (DMR) aetiologies with residual MR ≤1+, excluding patients who required >2 clips. FMR and DMR were analysed separately. RESULTS: In FMR, a single clip was used in 45 patients and 2 clips in 99 patients. The single clip group had smaller coaptation depth (1.1 ± 0.3 vs 1.3 ± 0.3 mm, P = 0.022) and jet extension (10.5 ± 2.1 vs 13.0 ± 3.6 mm, P = 0.026) as well as left ventricular end-diastolic diameter (64.4 ± 7.3 vs 69.0 ± 7.9 mm, P = 0.001). Freedom from MR ≥ 3+ after 4 years was 71.9 ± 8.9% in patients receiving a single clip vs 88.0 ± 5.2% in those receiving 2 clips, single clip use being an independent predictor of MR recurrence (HR 3.48, CI 1.24-9.81, P = 0.018). In DMR, a single clip was deployed in 24 patients and 2 clips in 30 patients. The single clip group had a smaller flail gap (3.6 ± 0.7 vs 6.8 ± 2.5, P = 0.002). Freedom from MR ≥ 3+ after 2 years was 82.5 ± 8% in patients with a single clip vs 100% in those with 2 clips, P = 0.014. The residual mitral area was reduced in patients with 2 clips compared with those with single clip, both in FMR ( P = 0.015) and DMR ( P = 0.039), but it was not associated with increased death rate during the follow-up period (all P > 0.05). CONCLUSIONS: Despite favourable anatomical characteristics and an optimal initial result, implantation of a single clip was associated with an increased recurrence of MR compared with that of 2 clips, both in FMR and in DMR. Caution should be exercised with the implantation of a single clip.

An increased endothelial-independent vasodilation is the hallmark of the neurally mediated syncope.

BACKGROUND: The neurally mediated syncope (NMS) is sustained by complex cardiac and vascular reflexes, acting on and amplified by central autonomic loops, resulting in bradycardia and hypotension. HYPOTHESIS: Our aim was to assess whether the pathophysiology of NMS is also related to an abnormal peripheral vasoreactivity. METHODS: We evaluated by ultrasound the flow-mediated vasodilation (FMD) and the nitrate-mediated dilation (NMD) in 17 patients with NMS, induced by drug-free tilt test in 6 subjects and by nitrate-potentiated tilt test in the other 11 cases; the syncope was classified as vasodepressive (VD) in 8 cases, cardioinhibitory (CI) in 7, and mixed in 2. RESULTS: The FMD was not different from controls (10.2 ± 4.5 vs 11.4 ± 3.9, P = ns), with normal recovery times; the NMD was greater in fainting subjects than in controls (26.7 ± 7.3 vs 19.0 ± 3.6, P < 0.05), with higher values in VD than in CI syncope (31.1 ± 7.0 vs 23.1 ± 5.0, P = ns); compared to controls, subjects with NMS showed normal recovery times after FMD but longer recovery times after nitrate administration (13.0 ± 5.6 vs 6.3 ± 0.7 minutes, P < 0.05). CONCLUSIONS: The evaluation of endothelial function supports evidence that NMS is characterized by a marked and sustained endothelial-independent vasodilation, in the presence of a normal FMD; vascular hyperreactivity in response to nitrate administration is particularly overt in vasodepressive syncope and can explain the high rate of responses to nitrate administration during tilt test.