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.

Transapical mitral valve implantation for treatment of symptomatic mitral valve disease: a real-world multicentre experience.

AIMS: Transcatheter mitral valve implantation (TMVI) is a new treatment option for patients with symptomatic mitral valve (MV) disease. Real-world data have not yet been reported. This study aimed to assess procedural and 30-day outcomes of TMVI in a real-world patient cohort. METHOD AND RESULTS: All consecutive patients undergoing implantation of a transapically delivered self-expanding valve at 26 European centres from January 2020 to April 2021 were included in this retrospective observational registry. Among 108 surgical high-risk patients included (43% female, mean age 75 ± 7 years, mean STS-PROM 7.2 ± 5.3%), 25% was treated for an off-label indication (e.g. previous MV intervention or surgery, mitral stenosis, mitral annular calcification). Patients were highly symptomatic (New York Heart Association [NYHA] functional class III/IV in 86%) and mitral regurgitation (MR) was graded 3+/4+ in 95% (38% primary, 37% secondary, and 25% mixed aetiology). Technical success rate was 96%, and MR reduction to ≤1+ was achieved in all patients with successful implantation. There were two procedural deaths and 30-day all-cause mortality was 12%. At early clinical follow-up, MR reduction was sustained and there were significant reductions of pulmonary pressure (systolic pulmonary artery pressure 52 vs. 42 mmHg, p < 0.001), and tricuspid regurgitation severity (p = 0.013). Heart failure symptoms improved significantly (73% in NYHA class I/II, p < 0.001). Procedural success rate according to MVARC criteria was 80% and was not different in patients treated for an off-label indication (74% vs. 81% for off- vs. on-label, p = 0.41). CONCLUSION: In a real-world patient population, TMVI has a high technical and procedural success rate with efficient and durable MR reduction and symptomatic improvement.

Single-center experience with partial support device in destination therapy for end-stage heart failure.

Ventricular assist devices (VADs) are considered the standard of care for end-stage heart failure (HF) patients. Despite increasing confidence in the technology, evidence data, endorsement by scientific societies and guidelines, the number of implants reached a steady state and is not increasing at the expected pace. This is most likely related to complications that are still burdening the technology and consequently excluding the most needy, ill, and fragile population. In this manuscript we are reporting a single-center experience in a very fragile, elderly and end-stage HF population, with a superficial, partial support device: the CircuLite Synergy. The patients were included in the pre-CE mark clinical study and consequently the device underwent technical adjustment during the support, based on the complications recorded. At our institution were implanted 6 patients overall: 3 patients survived to discharge and 2 survived up to 5 years. Most of the complications recorded were due to patients' frailty and overall clinical conditions. The initial experience with the CircuLite Synergy device is proving that a more "superficial" device might be more tolerable in an elderly, frail population. Partial support has proven hemodynamically efficacious and efficient in relieving heart failure symptoms, improving medical therapy tolerability, and improving quality of life. Unfortunately, the technology was not made available due to financial uncertainty and poor management, but we hope that once the concept has been proved someone will collect the legacy.

Single-Cell Sequencing of Mouse Heart Immune Infiltrate in Pressure Overload-Driven Heart Failure Reveals Extent of Immune Activation.

BACKGROUND: Inflammation is a key component of cardiac disease, with macrophages and T lymphocytes mediating essential roles in the progression to heart failure. Nonetheless, little insight exists on other immune subsets involved in the cardiotoxic response. METHODS: Here, we used single-cell RNA sequencing to map the cardiac immune composition in the standard murine nonischemic, pressure-overload heart failure model. By focusing our analysis on CD45+ cells, we obtained a higher resolution identification of the immune cell subsets in the heart, at early and late stages of disease and in controls. We then integrated our findings using multiparameter flow cytometry, immunohistochemistry, and tissue clarification immunofluorescence in mouse and human. RESULTS: We found that most major immune cell subpopulations, including macrophages, B cells, T cells and regulatory T cells, dendritic cells, Natural Killer cells, neutrophils, and mast cells are present in both healthy and diseased hearts. Most cell subsets are found within the myocardium, whereas mast cells are found also in the epicardium. Upon induction of pressure overload, immune activation occurs across the entire range of immune cell types. Activation led to upregulation of key subset-specific molecules, such as oncostatin M in proinflammatory macrophages and PD-1 in regulatory T cells, that may help explain clinical findings such as the refractivity of patients with heart failure to anti-tumor necrosis factor therapy and cardiac toxicity during anti-PD-1 cancer immunotherapy, respectively. CONCLUSIONS: Despite the absence of infectious agents or an autoimmune trigger, induction of disease leads to immune activation that involves far more cell types than previously thought, including neutrophils, B cells, Natural Killer cells, and mast cells. This opens up the field of cardioimmunology to further investigation by using toolkits that have already been developed to study the aforementioned immune subsets. The subset-specific molecules that mediate their activation may thus become useful targets for the diagnostics or therapy of heart failure.

T cell costimulation blockade blunts pressure overload-induced heart failure.

Heart failure (HF) is a leading cause of mortality. Inflammation is implicated in HF, yet clinical trials targeting pro-inflammatory cytokines in HF were unsuccessful, possibly due to redundant functions of individual cytokines. Searching for better cardiac inflammation targets, here we link T cells with HF development in a mouse model of pathological cardiac hypertrophy and in human HF patients. T cell costimulation blockade, through FDA-approved rheumatoid arthritis drug abatacept, leads to highly significant delay in progression and decreased severity of cardiac dysfunction in the mouse HF model. The therapeutic effect occurs via inhibition of activation and cardiac infiltration of T cells and macrophages, leading to reduced cardiomyocyte death. Abatacept treatment also induces production of anti-inflammatory cytokine interleukin-10 (IL-10). IL-10-deficient mice are refractive to treatment, while protection could be rescued by transfer of IL-10-sufficient B cells. These results suggest that T cell costimulation blockade might be therapeutically exploited to treat HF.

Long-Term Preservation of Left Ventricular Systolic Function in Patients With Refractory Angina Pectoris and Inducible Myocardial Ischemia on Optimal Medical Therapy.

Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p <0.0001). The duration time and the number of angina attacks did not correlate with EF in the whole population and in patients without previous myocardial infarction. In patients with previous myocardial infarction, the number of anginal attacks did not correlate with EF, but EF appeared higher in patients with angina duration >5 years (<5 years EF 37% ± 1 [n = 26]; >5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function.

Blood cyst of the mitral valve.

Blood cysts of the mitral valve are mostly benign diverticuli lined by endothelium and filled with blood and can be safely monitored with echocardiographic follow-up. We report a case of asymptomatic blood cyst of the mitral valve in a 63-year-old woman referred for a systolic murmur. At 3-year echo follow-up, the patient is free from notable clinical events.

Polypoid atrial myxoma.

Myxomas are by far the most common tumours of the heart. A 75-year-old man with no notable medical history presented with a 2-month progressive weight loss and dyspnoea on exertion. Physical examination revealed an opening snap and a diastolic decrescendo murmur at the apex. Transthoracic echocardiography showed a large, 85 × 30  mm, mobile, polypoid mass arising from the atrial fossa ovalis and protruding into the left ventricle during diastole. Irregular shape, multilobated surface and soft-tissue echogenicity were consistent with emboligenic myxoma. Surgical inspection confirmed a reddish gelatinous myxoma with villous, friable, thrombus-like surface prone to embolize. The mass was successfully removed and the histologic report confirmed the diagnosis.At 3-year follow-up, the patient is asymptomatic and no further mass has been detected. The case confirms that echocardiography remains a primary tool for the assessment of cardiac masses, providing morphological clues to define the potential risk of complications such as valve obstruction and systemic embolization.

Dynamic assessment of 'valvular reserve capacity' in patients with rheumatic mitral stenosis.

AIMS: Mitral stenosis (MS) may exhibit a dynamic valvular reserve. When resting gradients and systolic pulmonary pressure (sPAP) do not reflect the real severity of the disease, a dynamic evaluation becomes necessary. The aim of the study was to assess the clinical utility of exercise echocardiography in symptomatic patients with apparently subcritical MS. METHODS AND RESULTS: One hundred and thirty consecutive patients were referred for symptomatic MS. Patients with unimpressive resting MVA (>1-1.5 cm(2)) and mean PG (≥5-9 mmHg) underwent exercise echocardiography. Cardiac performance and mitral indices (MVA, peak/mean PG, sPAP) were measured. Exhaustion of valvular reserve capacity under exercise was defined as appearance of symptoms and sPAP > 60 mmHg. Forty-six patients (35%) (age: 53 ± 10 years; 74%, female) with resting MVA (1.2 ± 0.36 cm(2)), mean PG (6.8 ± 2.7 mmHg), and sPAP (38 ± 7 mmHg) inconsistent with symptoms underwent stress echocardiography. Exercise was stopped for dyspnoea (76%) or fatigue (24%). At peak workloads (57.2 ± 21.8 Watts), increased mean PG (17.2 ± 4.8 mmHg, P< 0.001) and sPAP (67.4 ± 11.4 mmHg; P< 0.0001) were observed, without change in MVA (1.25 ± 0.4 cm(2); P= n.s.). At univariate analysis, predictors of adaptation to exercise were age (-0.345; P = 0.024), mean PG (0.339; P= 0.023), and sPAP (0.354; P= 0.024); at multivariate analysis, best predictor was resting mean PG, although correlation was poor (-0.339; P= 0.015). CONCLUSION: In MS with limiting symptoms despite unimpressive findings at rest, valvular capacity exhaustion should be tested on a dynamic background, as no single resting index can predict potential haemodynamic adaptation to exercise. In such context, the contribution of exercise echocardiography remains extremely valuable.

[Spinal cord stimulation for refractory chronic angina pectoris: 100 patients treated in our 12-year experience]. / La stimolazione spinale nell'angina pectoris cronica refrattaria: 100 soggetti trattati in 12 anni di esperienza.

BACKGROUND: The aim of this study was to evaluate the quality of life (QoL) benefit of patients with chronic refractory angina treated with spinal cord stimulation (SCS) in our experience. METHODS: Between February 1998 and August 2010, 100 patients with chronic refractory angina who could not benefit from myocardial revascularization underwent SCS at the San Raffaele Scientific Institute of Milan (Italy). All patients were prospectively followed up at our outpatient clinic. The Spitzer index was used to evaluate QoL of patients before the procedure and at follow-up. RESULTS: Mean age was 66 ± 8 years (range 46-79). Ninety-four patients (94%) were in CCS class III-IV (mean CCS class 3.5 ± 0.1) and 62 patients (62%) were in NYHA class III-IV (mean NYHA class 2.6 ± 0.1). The preoperative Spitzer index was 4.4 ± 1.4. Mean angina episodes per week were 12.6 ± 9.3 and mean consumption of sublingual nitrates was 11.0 ± 9.4. At follow-up, overall mortality was 11% (n = 11), and cardiovascular death was 3%. A reduction in angina episodes per week >50% was observed in 88% of patients (from 12.6 ± 9.3 to 2.7 ± 1.13; p<0.0001). Mean consumption of sublingual nitrates decreased from 11.0 ± 9.4 to 2.3 ± 0.1 (p<0.0001). The Spitzer index significantly improved (from 4.4 ± 0.1 to 2.3 ± 0.1; p<0.0001). NYHA class and CCS class decreased from 2.6 ± 0.1 to 2.0 ± 0.1 and from 3.5 ± 0.1 to 1.7 ± 0.1, respectively (both p<0.0001). CONCLUSIONS: SCS is an effective and safe therapeutic option for patients with chronic refractory angina and it is associated with improved functional status and QoL at follow-up.

Preservation of endothelium nitric oxide release during beating heart surgery with respect to continuous flow cardiopulmonary bypass.

A correlation between perfusion modality and vascular dilation induced by endothelial nitric oxide (NO) release has been pointed out in the literature; nevertheless, only a few studies deal with the analysis of patients treated by cardiac surgery. The aim of this work is to analyze endothelial NO release in patients undergoing cardiac surgery under continuous flow cardiopulmonary bypass (CPB) or pulsatile perfusion. Pulsatile devices approved for clinical CPB do not accurately reproduce the physiological flow waveform provided by the left ventricle while, on the other hand, it is important to analyze pulsatile perfusion under both physiological flow waveform and pulsatile flow CPB. Physiological pulsatile perfusion (supplied by the left ventricle) was examined in this study. A total of 16 patients undergoing cardiac surgery were enrolled in the study and divided into two groups: 8 patients were put on continuous flow CPB while the others underwent beating heart surgery. Venous blood samples were withdrawn to quantify endothelial NO release through its bioactive forms in blood. Plasma was used for the chemiluminescent detection of nitrite (NO(2)(-)) and nitrate (NO(3)(-)), and the cellular component for electron spin resonance detection of nitrosylhemoglobin. Significant reduction in the intraoperative concentration with respect to the preoperative was observed only in the continuous group for both NO(2)(-) and NO(x) (NO(2)(-) + NO(3)(-)) concentration (p=0.003 and p=0.016, respectively). A significant difference in the intraoperative nitrite concentration was also observed between the groups (p=0.006). Nitrosylhemoglobin concentration, although not instrumentally detectable, resulted as negligible with respect to the other NO metabolites. Despite the small number of patients belonging to each group, this significant reduction of NO(2)(-) concentration under continuous flow CPB revealed a strong dependence on endothelial NO release and plasma nitrite concentration on perfusion modality.

Concurrent prophylactic left atrial appendage exclusion: results from a randomized controlled trial pilot study.

OBJECTIVE: The left atrial appendage is a significant source of cardioembolic thrombi. Open mitral valve surgery presents an opportune time to exclude this appendage from cardiovascular circulation. However, sparse randomized trial support exists for this concomitant procedure. We therefore designed a randomized controlled trial to assess the short- and long-term outcomes of concomitant left atrial appendage exclusion. This report details early outcomes of the pilot trial. METHODS: Forty-three patients were randomized to either undergo concomitant suture exclusion of their left atrial appendage under direct vision or not during their open mitral valve surgery. Clinical and biochemical postoperative outcomes, including hemodynamic and hemostatic parameters, were analyzed. RESULTS: There were no deaths in either group. The incidence of cerebrovascular events, myocardial infarction, respiratory failure, and acute renal injury were similar between groups; a composite outcome of 10 major postoperative complications occurred in 32% of the left atrial appendage exclusion group versus 38% of the control group (p=0.75). Intensive care (median stay 2 days vs 1 day in the control group, p=0.55) and hospital lengths of stay (median stay 9 days in both groups, p=0.98) were also similar between groups. Specifically, no additional hemodynamic alterations (need for intra-aortic balloon pump in 1 vs 2 patients in the control group, p=0.61) or hemostatic complications (no re-operations for bleeding in either group, need for blood product transfusion in 2 vs 1 patient in the control group, p=1.0) were noted in the left atrial appendage exclusion group. CONCLUSIONS: This pilot trial demonstrates the safety of and feasibility of a larger trial powered to detect clinically relevant short- and long-term outcomes of concomitant left atrial appendage exclusion with open mitral valve surgery.

Complete right atrial ablation with bipolar radiofrequency.

PURPOSE: Although it is deemed important, right atrial ablation is not considered feasible with bipolar radiofrequency alone. Normally, unipolar devices are used to complete the tricuspid connecting lines. We describe a simple technique to achieve a complete maze-like set of right ablations using a standard bipolar radiofrequency device. DESCRIPTION: Thirty-four patients underwent concomitant ablation with a right set of lines performed using bipolar radiofrequency only. The epicardium adjacent to the right atriotomy was entered and after separating the sulcus fat from the atrial wall, the deepest portion of the atrioventricular groove was developed bluntly with the scissors down to the tricuspid annulus. The tricuspid connecting lines were then performed with bipolar radiofrequency in an endo-epicardial fashion. EVALUATION: No ablation-related complications occurred. No patient died. Three patients required pacemaker implantation. At a mean follow-up of 8 +/- 5, 85% of the patients were free from arrhythmias. At 6 months 20 of 24 patients (83%) were in stable sinus rhythm. CONCLUSIONS: All the maze III right atrial ablations can be performed using a bipolar radiofrequency device alone. The procedure is safe and easily reproducible on a regular basis.

Complete left atrial ablation with bipolar radiofrequency.

OBJECTIVE: Despite its efficacy and swiftness, bipolar radiofrequency is generally not used on the left isthmus for concern of injuring a coronary branch. Incomplete lesion sets or use of an additional unipolar device are often considered. We report a technique to perform a full left lesion set involving the mitral line using a standard bipolar radiofrequency device. METHODS: An innovative complete left atrial lesion set was performed using only bipolar radiofrequency in 70 consecutive patients (study group). In 67/70 patients (96%) mitral valve disease was the main indication to surgery. Atrial fibrillation was permanent in 42 patients (60%), persistent in 25 (36%) and paroxysmal in three patients (4%). After beating-heart pulmonary vein isolation on-pump, the coronary-free area of the AV groove was marked epicardially by sticking a needle into the left atrial wall, behind the coronary sinus. The projection of the needle marker on the mitral annulus was then identified through the atriotomy and an endo-epicardial ablation was performed with the bipolar device involving the atrial wall, the coronary sinus, up to the annulus. The lesion set was then completed by connecting the encirclings and the left appendage, which was then sutured. Follow-up was 100% complete. Results were compared with those of a control group of 33 patients receiving bipolar radiofrequency left atrial ablations and a mitral connecting line with a second unipolar device. RESULTS: All patients survived. No major complication occurred. Haematoma of the AV groove was observed during retrograde cardioplegia in one case. No myocardial ischaemia or re-exploration for bleeding (median 325 cc, interquartile range 250-442) occurred. Two out of 70 patients required a permanent pacemaker for AV block. Freedom from atrial fibrillation was 84% (95% CI: 75%, 93%) at 6 months and 81% (95% CI: 70%, 93%) at 1 year. One patient had left flutter. Comparison with the control group did not show any difference in clinical outcomes, but revealed bipolar ablation to the mitral annulus to abate the per patient cost of the ablation devices (1245+/-50 euro vs 2403+/-17 euro; p<0.0001). CONCLUSIONS: Performing the mitral line with bipolar radiofrequency is safe and cost-effective. A complete left atrial ablation with a single bipolar radiofrequency device yields excellent clinical mid-term results.

Spinal cord stimulation for refractory chronic angina pectoris: influence on quality of life.

Percutaneous coronary revascularization, coronary artery bypass graft surgery and medical management are nowadays very effective in treating coronary artery disease. Nevertheless, the number of patients affected by refractory chronic angina pectoris is increasing. Epidemiological estimates for refractory angina pectoris predict the diagnosis of more than 100,000 patients each year in the USA and approximately 50,000 in Europe. Spinal cord stimulation is a valuable therapeutic option for patients who have failed multiple percutaneous and surgical revascularizations and who are not eligible for further revascularization procedures. The aim of this study is to assess the benefits, in terms of quality of life, of spinal cord stimulation in no-option patients affected by refractory angina pectoris.

Upper and lower spinal cord blood supply: the continuity of the anterior spinal artery and the relevance of the lumbar arteries.

OBJECTIVE: Thoracic and thoracoabdominal aortic repair are still complicated by spinal cord ischemia and paraplegia. The aim of the present article is to present the results of an anatomical study conducted by means of both postmortem injection of the vertebral artery and perfusion of the abdominal aorta. METHODS: The spinal cord blood supply was investigated in 51 Caucasian cadavers: in 40 cases a methylene blue solution was hand-injected into the vertebral artery, whereas in the remaining 11 cases the abdominal aorta was perfused with a methylene blue solution by means of a roller pump. The level and side of the arteria radicularis magna and the continuity of the anterior spinal artery were recorded. RESULTS: The anterior spinal artery was a continuous vessel without interruptions along the spinal cord in all 51 cases. The arteria radicularis magna level was variable, ranging from T9 to L5. The arteria radicularis magna arose from a lumbar artery in 36 cases (70.5%) and it was left-sided in 32 cases (62.7%). CONCLUSIONS: The anterior spinal artery constitutes an uninterrupted pathway between the vertebral arteries, the arteria radicularis magna, and the posterior intercostal and lumbar arteries. Moreover, the arteria radicularis magna arises from a lumbar artery in most of cases. Therefore, the sacrifice of the intercostal arteries during a thoracic aorta repair could be justified, at least from an anatomical standpoint. However, if an extended thoracoabdominal aortic repair is planned, it may be prudent to preserve the blood flow from the lumbar arteries.