Integrating Pharmacomechanical Treatments for Pulmonary Embolism Management within a Hub-and-Spoke System in the Swiss Ticino Region.

The Swiss Ticino regional pulmonary embolism response team (PERT) features direct access to various pharmacomechanical PE management options within a hub/spoke system, by integrating evidence, guidelines' recommendations and personal experiences. This system involves a collaborative management of patients among the hospitals distributed throughout the region, which refer selected intermediate-high or high PE patients to a second-level hub center, located in Lugano at Cardiocentro Ticino, belonging to the Ente Ospedaliero Cantonale (EOC). The hub provides 24/7 catheterization laboratory activation for catheter-based intervention (CBI), surgical embolectomy and/or a mechanical support system such as extracorporeal membrane oxygenation (ECMO). The hub hosts PE patients after percutaneous or surgical intervention in two intensive care units, one specialized in cardiovascular anesthesiology, to be preferred for patients without relevant comorbidities or with hemodynamic instability and one specialized in post-surgical care, to be preferred for PE patients after trauma or surgery or with relevant comorbidities, such as cancer. From April 2022 to December 2023, a total of 65 patients were referred to the hub for CBI, including ultrasound-assisted catheter-directed thrombolysis (USAT) or large-bore aspiration intervention. No patient received ECMO or underwent surgical embolectomy.

Microvascular obstruction identifies a subgroup of patients who benefit from stem cell therapy following ST-elevation myocardial infarction.

BACKGROUND: Microvascular obstruction (MVO) is associated with greater infarct size, adverse left-ventricular (LV) remodeling and reduced ejection fraction following ST-elevation myocardial infarction (STEMI). We hypothesized that patients with MVO may constitute a subgroup of patients that would benefit from intracoronary stem cell delivery with bone marrow mononuclear cells (BMCs) given previous findings that BMCs tended to improve LV function only in patients with significant LV dysfunction. METHODS AND RESULTS: We analyzed the cardiac MRIs of 356 patients (303 M, 53 F) with anterior STEMIs who received autologous BMCs or placebo / control as part of 4 randomized clinical trials that included the Cardiovascular Cell Therapy Research Network (CCTRN) TIME trial and its pilot, the multicenter French BONAMI trial and SWISS-AMI trials. A total of 327 patients had paired imaging data at 1 year. All patients received 100 to 150 million intracoronary autologous BMCs or placebo / control 3 to 7 days following primary PCI and stenting. LV function, volumes, infarct size and MVO were assessed prior to infusion of BMCs and 1 year later. Patients with MVO (n = 210) had reduced LVEF and much greater infarct size and LV volumes compared to patients without MVO (n = 146) (P < .01). At 12 months, patients with MVO who received BMCs had significantly greater recovery of LVEF compared to those patients with MVO who received placebo (absolute difference = 2.7%; P < .05). Similarly, left-ventricular end-diastolic (LVEDVI) and end-systolic volume indices (LVESVI) demonstrated significantly less adverse remodeling in patients with MVO who received BMCs compared to placebo. In contrast, no improvement in LVEF or LV volumes was observed in those patients without MVO who received BMCs compared to placebo. CONCLUSIONS: The presence of MVO on cardiac MRI following STEMI identifies a subgroup of patients who benefit from intracoronary stem cell therapy.

Impact of mitral regurgitation aetiology on MitraClip outcomes: the MitraSwiss registry.

AIMS: The Swiss national registry on percutaneous mitral valve interventions (MitraSwiss) was established in 2011 to monitor safety/efficacy of percutaneous mitral valve repair (PMVR) with the MitraClip device. The aim of this analysis was to report the outcome after PMVR in a real-world, all-comers population and its predictors after inclusion of more than 1,200 patients, stratifying the results according to mitral regurgitation (MR) aetiology. Here we report the in-hospital, short and midterm outcomes of all patients prospectively enrolled. METHODS AND RESULTS: Since 2011, MitraSwiss has enrolled 1,212 patients with moderate and severe MR of functional (FMR) or degenerative (DMR) aetiology treated with PMVR in 10 centres. Pre-specified endpoints included clinical, echocardiographic and functional parameters with follow-up planned up to five years. Outcomes are compared according to MR aetiology. Acute procedural success was achieved in 91.5% of cases, with no differences between FMR and DMR and sustained good midterm results. NYHA class and pulmonary pressure improved significantly in both cohorts. Cumulative probability of death at five years was 54% (95% CI: 45-63) in FMR and 45% (95% CI: 37-54) in DMR (HR 1.15, p=0.009). Age, anaemia, impaired renal function and reduced left ventricular ejection fraction resulted in being independent predictors of death at five years. CONCLUSIONS: In a large contemporary cohort of non-surgical patients with severe MR, the safety and effectiveness of PMVR have been confirmed. At midterm follow-up, mortality and MACE were lower in DMR patients, though MR aetiology was not directly and independently associated with outcome.

Intractable coronary fibromuscular dysplasia leading to end-stage heart failure and fatal heart transplantation.

Coronary fibromuscular dysplasia is uncommon, and even rarer its unstable and recurrent course. We present the unique case of a 52-year-old woman who underwent in total 12 coronary angiographies and three percutaneous coronary intervention within 24 months because of repetitive acute coronary syndromes due to refractory spasm, dissection, restenosis all leading to end-stage heart failure, and heart transplantation. The patient died 12 days after the heart transplantation complicated by intraoperative acute thrombotic occlusion of left anterior descending artery of the graft despite normal pretransplant coronary angiography. Autopsy of the recipient heart confirmed coronary fibromuscular dysplasia with massive intimal hyperplasia and restenosis.

Closure of Large Percutaneous Femoral Venous Access Using a Modified "Figure-of-Eight" Suture.

Recent advances in different percutaneous treatments made insertion of large-caliber sheaths in the femoral veins more common. Venous punctures are historically managed by initial manual compression with subsequent application of a compression bandage and bed rest. We describe a modified "figure-of-eight" suture technique for minimizing the risk of accidental puncture of the vein while grabbing the subcutaneous tissue. We examined the safety and feasibility of this technique combined with early mobilization in a real-world setting. We performed a retrospective analysis on 56 consecutive patients undergoing percutaneous mitral valve repair using large femoral venous access. The patient population was heterogeneous and bleeding risk characteristics were common. Bleeding Academic Research Consortium Consensus (BARC)-classifiable bleeding complications occurred in eight patients (14%), BARC of two events or more in five patients (8.9%), and BARC of three or more event in only one patient (1.8%), which is a comparable success rate to large venous access closure with suture-mediated closure devices. No BARC Type 3b or BARC Type 5 bleeding occurred. During routine clinical follow-up, no groin-related problems were reported in all patients. Closure of large femoral venous access using a modified temporary subcutaneous figure-of-eight suture in combination of a light compression bandage and bed rest for 2 to 4 hours provides a safe and low-cost alternative to closure devices for early mobilization.

Evaluation of a protocol for same-day discharge after radial lounge monitoring in a southern Swiss referral percutaneous coronary intervention centre.

AIMS: The aim of the study was to retrospectively evaluate safety and patient satisfaction of same-day discharge after elective radial coronary angiography/percutaneous coronary intervention (PCI) after the implementation of a radial lounge facility. METHODS: All patients admitted to our radial lounge with a planned same-day discharge after an uncomplicated coronary angiography/PCI, having a co-living caregiver, were day enrolled in the study. Rates of same-day discharge, unplanned overnight stay, and in-hospital and first complications [death, myocardial infarction (MI), unplanned coronary angiography, access site hematoma, bleedings requiring hospitalization] were analysed; satisfaction was also evaluated through a questionnaire. RESULTS: From February 2015 to January 2016, 312 patients with a mean age of 66.6 ±â€Š10.8 years were admitted to the radial lounge (coronary angiography, n = 232; PCIs, n = 80). Of them, 245 (78.5%) were discharged the same day. Mean radial lounge monitoring was 6:35 h (interquartile range 5:30-7:30 h). No episodes of death/MI/unplanned coronary angiography were observed both in same-day discharged and postponed patients. Reasons to postpone discharge were: PCI deemed to need prolonged monitoring in 31, patient's preference in 14, femoral shift in 13, surgery in four, chest pain in four, and bleeding in one. At day 1, 11 access site hematoma and one hospitalization for access site bleeding were reported. Patients reported complete satisfaction in 97% of cases. Unplanned overnight stay was common among PCIs patients (RR 6.2, 95% CI 3.9-9.9, P < 0.001). CONCLUSION: A low rate of minor complications was observed in elective radial coronary angiography and PCIs showing the feasibility and safety of the development of an institutional protocol for same-day discharge after the implementation of a radial lounge facility.

The relation between local repolarization and T-wave morphology in heart failure patients.

BACKGROUND: Both duration and morphology of the T-wave are regarded important parameters describing repolarization of the ventricles. Conventionally, T-wave concordance is explained by an inverse relation between the time of depolarization (TD) and repolarization (TR). Little is known about T-wave morphology and TD-TR relations in patients with heart failure. METHODS: Electro-anatomic maps were obtained in the left (LV) and right ventricle (RV) and in the coronary sinus (CS) in patients with heart failure with narrow (nQRS, n=8) and wide QRS complex with (LBBB, n=15) and without left bundle branch block (non-LBBB, n=7). TD and TR were determined from the thus acquired electrograms. RESULTS: In nQRS and non-LBBB patients, TD-TR relations had a slope between 0 and +1, indicating that repolarization followed the sequence of depolarization. In LBBB patients, repolarization occurred significantly earlier in the RV than in the LV, fitting with the idea that the discordant T-waves in LBBB are secondary to the abnormal depolarization sequence. However, the slopes of the TD-TR relations in the LV and CS were not significantly different from zero, indicating no major spatial gradient in LV repolarization, despite a considerable gradient in depolarization. Remarkable was also the large (~100ms) transseptal gradient in repolarization. Values of the slopes of the TD-TR relation overlapped between the three patient groups, despite a difference in T-wave morphology between LBBB (all discordant) and nQRS patients (all flat/biphasic). CONCLUSIONS: Discordant T-waves in LBBB patients are explained by interventricular dispersion in repolarization. T-wave morphology is determined by more factors than the TD-TR relation alone.

SYNTAX score II in patients with coronary artery disease undergoing percutaneous mitral repair with the MitraClip.

BACKGROUND: Percutaneous mitral valve repair (PMVR) using the MitraClip™ system has become a valuable alternative in patients with severe mitral regurgitation (MR) and high surgical risk. We sought to evaluate the prognostic value of the SYNTAX II score (SSII) in patients with concomitant coronary artery disease (CAD) undergoing a Mitraclip procedure. METHODS: In seventy-five consecutive patients who underwent PMVR at the University Heart Center Zürich and the Cardiocentro Ticino, the SSSII was calculated at baseline. Clinical endpoints comprised of all-cause mortality, mitral valve surgery due to failure of PMVR or reoperation, hospitalization for congestive heart failure, heart transplantation and the composite of all four endpoints. RESULTS: Patients were followed for a median of 271days. And were divided in tertiles of SSII: SSII low ≤46.5 (n=25), SSII mid 46.6-54.4 (n=25) and SSII high ≥54.5 (n=25). Patients in the highest SSII tertile had a lower left ventricular ejection fraction (33% vs. 40% vs. 53%) with a higher log-BNP (3.6 vs. 3.45 vs. 3.16) when compared to SSII mid and SSII low, respectively. However, the anatomical syntax score (SS) did not differ significantly within the tertiles (9.1±6.3 (SSII Low) vs 9.5±7.6 (SSII Mid) vs 10.2±6.7(SSII High), p=0.837). The primary endpoint occurred in 33% of patients (n=25). By multivariate analysis patients in the high SSII tertile (OR=6.12, 95% confidence interval, [CI] 1.45-25.86, p=0.014) and patients with a history of MI (OR=3.57, 95% confidence interval, [CI] 1.17-10.88, p=0.025) were at significantly higher risk of experiencing adverse events. Furthermore, in a combined outcome ROC curve analysis, the SSII showed good discrimination with an AUC of 0.73, p=0.001. A cutoff SSII >49 has been identified to have a sensitivity of 83% and specificity of 53% with approximately 45% of the patients experiencing an event during follow-up. CONCLUSION: Using SSII in CAD patients undergoing PMVR is feasible and of prognostic significance hence widening its clinical utility in valvular heart disease.

Effect of Bone Marrow-Derived Mononuclear Cell Treatment, Early or Late After Acute Myocardial Infarction: Twelve Months CMR and Long-Term Clinical Results.

RATIONALE: Intracoronary delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction (AMI). OBJECTIVE: To demonstrate long-term efficacy of BM-MNC treatment after AMI. METHODS AND RESULTS: In a multicenter study, we randomized 200 patients with large AMI in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were either administered 5 to 7 days (early) or 3 to 4 weeks (late) after AMI. Cardiac magnetic resonance imaging was performed at baseline and after 12 months. The current analysis investigates the change from baseline to 12 months in global LV ejection fraction, LV volumes, scar size, and N-terminal pro-brain natriuretic peptide values comparing the 2 treatment groups with control in a linear regression model. Besides the complete case analysis, multiple imputation analysis was performed to address for missing data. Furthermore, the long-term clinical event rate was computed. The absolute change in LV ejection fraction from baseline to 12 months was -1.9±9.8% for control (mean±SD), -0.9±10.5% for the early treatment group, and -0.7±10.1% for the late treatment group. The difference between the groups was not significant, both for complete case analysis and multiple imputation analysis. A combined clinical end point occurred equally in all the groups. Overall, 1-year mortality was low (2.25%). CONCLUSIONS: Among patients with AMI and LV dysfunction, treatment with BM-MNC either 5 to 7 days or 3 to 4 weeks after AMI did not improve LV function at 12 months, compared with control. The results are limited by an important drop out rate. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.

Thrombus formation in the left ventricle after large myocardial infarction ­ assessment with cardiac magnetic resonance imaging.

INTRODUCTION: Left ventricular thrombus (LVT) formation may worsen the post-infarct outcome as a result of thromboembolic events. It also complicates the use of modern antiplatelet regimens, which are not compatible with long-term oral anticoagulation. The knowledge of the incidence of LVT may therefore be of importance to guide antiplatelet and antithrombotic therapy after acute myocardial infarction (AMI). METHODS: In 177 patients with large, mainly anterior AMI, standard cardiac magnetic resonance imaging (CMR) including cine and late gadolinium enhancement (LGE) imaging was performed shortly after AMI as per protocol. CMR images were analysed at an independent core laboratory blinded to the clinical data. Transthoracic echocardiography (TTE) was not mandatory for the trial, but was performed in 64% of the cases following standard of care. In a logistic model, 3 out of 61 parameters were used in a multivariable model to predict LVT. RESULTS: LVT was detected by use of CMR in 6.2% (95% confidence interval [CI] 3.1%-10.8%). LGE sequences were best to detect LVT, which may be missed in cine sequences. We identified body mass index (odds ratio 1.18; p = 0.01), baseline platelet count (odds ratio 1.01, p = 0.01) and infarct size as assessed by use of CMR (odds ratio 1.03, p = 0.02) as best predictors for LVT. The agreement between TTE and CMR for the detection of LVT is substantial (kappa = 0.70). DISCUSSION: In the current analysis, the incidence of LVT shortly after AMI is relatively low, even in a patient population at high risk. An optimal modality for LVT detection is LGE-CMR but TTE has an acceptable accuracy when LGE-CMR is not available.

Comparison of clinical and angiographic prognostic risk scores in elderly patients presenting with acute coronary syndrome and referred for percutaneous coronary intervention.

BACKGROUND: Multiple risk prediction models have been validated in all-age patients presenting with acute coronary syndrome (ACS) and treated with percutaneous coronary intervention (PCI); however, they have not been validated specifically in the elderly. METHODS: We calculated the GRACE (Global Registry of Acute Coronary Events) score, the logistic EuroSCORE, the AMIS (Acute Myocardial Infarction Swiss registry) score, and the SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) score in a consecutive series of 114 patients ≥75 years presenting with ACS and treated with PCI within 24 hours of hospital admission. Patients were stratified according to score tertiles and analysed retrospectively by comparing the lower/mid tertiles as an aggregate group with the higher tertile group. The primary endpoint was 30-day mortality. Secondary endpoints were the composite of death and major adverse cardiovascular events (MACE) at 30 days, and 1-year MACE-free survival. Model discrimination ability was assessed using the area under receiver operating characteristic curve (AUC). RESULTS: Thirty-day mortality was higher in the upper tertile compared with the aggregate lower/mid tertiles according to the logistic EuroSCORE (42% vs 5%; odds ratio [OR] = 14, 95% confidence interval [CI] = 4-48; p <0.001; AUC = 0.79), the GRACE score (40% vs 4%; OR = 17, 95% CI = 4-64; p <0.001; AUC = 0.80), the AMIS score (40% vs 4%; OR = 16, 95% CI = 4-63; p <0.001; AUC = 0.80), and the SYNTAX score (37% vs 5%; OR = 11, 95% CI = 3-37; p <0.001; AUC = 0.77). CONCLUSIONS: In elderly patients presenting with ACS and referred to PCI within 24 hours of admission, the GRACE score, the EuroSCORE, the AMIS score, and the SYNTAX score predicted 30 day mortality. The predictive value of clinical scores was improved by using them in combination.

Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data.

RATIONALE: The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy. OBJECTIVE: We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). METHODS AND RESULTS: The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization). The secondary end point was freedom from hard clinical end points (death, AMI recurrence, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy end points included changes in end-diastolic volume, end-systolic volume, and ejection fraction, analyzed with random-effects meta-analyses and ANCOVA. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on major adverse cardiac and cerebrovascular events (14.0% versus 16.3%; hazard ratio, 0.86; 95% confidence interval, 0.63-1.18) or death (1.4% versus 2.1%) or death/AMI recurrence/stroke (2.9% versus 4.7%) was identified in comparison with controls. No changes in ejection fraction (mean difference: 0.96%; 95% confidence interval, -0.2 to 2.1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters. CONCLUSIONS: This meta-analysis of individual patient data from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098591.

Two-year outcomes after percutaneous mitral valve repair with the MitraClip system: durability of the procedure and predictors of outcome.

OBJECTIVE: Analyse 2-year outcomes after MitraClip therapy and identify predictors of outcome. METHODS: Consecutive patients (n=74) undergoing MitraClip therapy were included in the MitraSWISS registry and followed prospectively. RESULTS: A reduction of mitral regurgitation (MR) to ≤ mild was achieved in 32 (43%) patients and to moderate in 31 (42%) patients; 16/63 (25%) patients with initially successful treatment developed recurrent moderate to severe or severe MR during the first year and only 1 patient did so during the second year. At 2 years, moderate or less MR was more frequently present in patients with a transmitral mean gradient <3 mm Hg at baseline (73% vs 23%, p < 0.01) and in patients with a left atrial volume index (LAVI) <50 mL/m(2) at baseline (86% vs 52%, p=0.03). More than mild MR post MitraClip, N-terminal probrain natriuretic peptide ≥5000 ng/L at baseline, chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) were associated with reduced survival. CONCLUSIONS: A mean transmitral gradient <3 mm Hg at baseline, an LAVI <50 mL/m(2), the absence of COPD and CKD, and reduction of MR to less than moderate were associated with favourable outcome. Given a suitable anatomy, such patients may be excellent candidates for MitraClip therapy. Between 1 and 2 years follow-up, clinical and echocardiographic outcomes were stable, suggesting favourable, long-term durability of the device.

Bone marrow-derived cells for cardiovascular cell therapy: an optimized GMP method based on low-density gradient improves cell purity and function.

BACKGROUND: Cardiovascular cell therapy represents a promising field, with several approaches currently being tested. The advanced therapy medicinal product (ATMP) for the ongoing METHOD clinical study ("Bone marrow derived cell therapy in the stable phase of chronic ischemic heart disease") consists of fresh mononuclear cells (MNC) isolated from autologous bone marrow (BM) through density gradient centrifugation on standard Ficoll-Paque. Cells are tested for safety (sterility, endotoxin), identity/potency (cell count, CD45/CD34/CD133, viability) and purity (contaminant granulocytes and platelets). METHODS: BM-MNC were isolated by density gradient centrifugation on Ficoll-Paque. The following process parameters were optimized throughout the study: gradient medium density; gradient centrifugation speed and duration; washing conditions. RESULTS: A new manufacturing method was set up, based on gradient centrifugation on low density Ficoll-Paque, followed by 2 washing steps, of which the second one at low speed. It led to significantly higher removal of contaminant granulocytes and platelets, improving product purity; the frequencies of CD34+ cells, CD133+ cells and functional hematopoietic and mesenchymal precursors were significantly increased. CONCLUSIONS: The methodological optimization described here resulted in a significant improvement of ATMP quality, a crucial issue to clinical applications in cardiovascular cell therapy.

Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction: a collaborative meta-analysis.

AIMS: The objective of the present analysis was to systematically examine the effect of intracoronary bone marrow cell (BMC) therapy on left ventricular (LV) function after ST-segment elevation myocardial infarction in various subgroups of patients by performing a collaborative meta-analysis of randomized controlled trials. METHODS AND RESULTS: We identified all randomized controlled trials comparing intracoronary BMC infusion as treatment for ST-segment elevation myocardial infarction. We contacted the principal investigator for each participating trial to provide summary data with regard to different pre-specified subgroups [age, diabetes mellitus, time from symptoms to percutaneous coronary intervention, infarct-related artery, LV end-diastolic volume index (EDVI), LV ejection fraction (EF), infarct size, presence of microvascular obstruction, timing of cell infusion, and injected cell number] and three different endpoints [change in LVEF, LVEDVI, and LV end-systolic volume index (ESVI)]. Data from 16 studies were combined including 1641 patients (984 cell therapy, 657 controls). The absolute improvement in LVEF was greater among BMC-treated patients compared with controls: [2.55% increase, 95% confidence interval (CI) 1.83-3.26, P < 0.001]. Cell therapy significantly reduced LVEDVI and LVESVI (-3.17 mL/m², 95% CI: -4.86 to -1.47, P < 0.001; -2.60 mL/m², 95% CI -3.84 to -1.35, P < 0.001, respectively). Treatment benefit in terms of LVEF improvement was more pronounced in younger patients (age <55, 3.38%, 95% CI: 2.36-4.39) compared with older patients (age ≥ 55 years, 1.77%, 95% CI: 0.80-2.74, P = 0.03). This heterogeneity in treatment effect was also observed with respect to the reduction in LVEDVI and LVESVI. Moreover, patients with baseline LVEF <40% derived more benefit from intracoronary BMC therapy. LVEF improvement was 5.30%, 95% CI: 4.27-6.33 in patients with LVEF <40% compared with 1.45%, 95% CI: 0.60 to 2.31 in LVEF ≥ 40%, P < 0.001. No clear interaction was observed between other subgroups and outcomes. CONCLUSION: Intracoronary BMC infusion is associated with improvement of LV function and remodelling in patients after ST-segment elevation myocardial infarction. Younger patients and patients with a more severely depressed LVEF at baseline derived most benefit from this adjunctive therapy.

Combined delivery of bone marrow-derived mononuclear cells in chronic ischemic heart disease: rationale and study design.

BACKGROUND: Treatment with bone marrow-derived mononuclear cells (BM-MNC) may improve left ventricular (LV) function in patients with chronic ischemic heart disease (IHD). Delivery method of the cell product may be crucial for efficacy. HYPOTHESIS: We aimed to demonstrate that the combination of intramyocardial and intracoronary injection of BM-MNC is safe and improves LV function in patients with chronic IHD. METHODS: After a safety/feasibility phase of 10 patients, 54 patients will be randomly assigned in a 1:1:1 pattern to 1 control and 2 BM-MNC treatment groups. The control group will be treated with state-of-the-art medical management. The treatment groups will receive either exclusively intramyocardial injection or a combination of intramyocardial and intracoronary injection of autologous BM-MNC. Left ventricular function as well as scar size, transmural extension, and regional wall-motion score will be assessed by cardiac magnetic resonance imaging studies at baseline and after 6 months. The primary endpoint is the change in global LV ejection fraction by cardiac magnetic resonance from 6 months to baseline. RESULTS: The results, it is hoped, will have important clinical impact and provide essential information to improve the design of future regenerative-medicine protocols in cardiology. CONCLUSIONS: As cell delivery may play an important role in chronic IHD, we aim to demonstrate feasibility and efficacy of a combined cell-delivery approach in patients with decreased LV function.

Intracoronary injection of bone marrow-derived mononuclear cells early or late after acute myocardial infarction: effects on global left ventricular function.

BACKGROUND: Intracoronary administration of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. METHODS AND RESULTS: In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (i.e., 5 to 7 days) or late (i.e., 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was -0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, -1.83 to 4.32; P=0.42) for the early therapy group and 0.55 (95% confidence interval, -2.61 to 3.71; P=0.73) for the late therapy group. CONCLUSIONS: Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.

[Pecutaneous mitral valve repair]. / Perkutane Behandlung der Mitralinsuffizienz.

Over four million Europeans and a similar number Americans suffer from significant mitral regurgitation (MR). Approximately 250,000 new patients are diagnosed with the disease annually. The disorder generally evolves insidiously over many years because the heart compensates for the regurgitant volume by left atrial enlargement, left ventricular (LV) volume overload, and progressive (LV) dilatation. The most common causes of MR include ischemic heart disease, non-ischemic heart disease, and valve degeneration. Mitral valve surgery has long been the only treatment available with proven efficacy for MR. It alleviates clinical symptoms and prevents ventricular dilatation and heart failure, or attenuates further progression of this process. Surgical valve repair significantly improves clinical outcomes compared with valve replacement, reducing mortality by approximately 70%. However, patients with heart failure have both higher acute risk and significant rates of late MR recurrence after surgical repair of ischemic MR. Recently, a number of percutaneous modalities of mitral valve repair have been developed. Most of these techniques are still at early stages of clinical evaluation. The MitraClip System consists of a percutaneous edge-to-edge attachemnt system that mimics the surgical procedure. This technique creates a bridge between the anterior and posterior leaflet by means of a clip deployed through trans-septal catheterization. The growing experience show that percutaneous edge-to-edge repair using the MitraClip system is feasible, safe and, in overall, effective, with very promising clinical results when performed in carefully selected patients, The new technique does not represent a general alternative to conventional surgical valve repair, which remains the gold standard particularly in the patients with degenerative MR. However, it offers a valid option in patients unsuitable for surgery and those with functional MR secondary to advanced heart failure, where the surgical approach still remains empiric.

Real-time left ventricular pressure-volume loops during percutaneous mitral valve repair with the MitraClip system.

BACKGROUND: Percutaneous mitral valve repair with the MitraClip device has emerged as an alternative to surgery for treating severe mitral regurgitation. However, its effects on left ventricular loading conditions and contractility have not been investigated yet. METHODS AND RESULTS: Pressure-volume loops were recorded throughout the MitraClip procedure using conductance catheter in 33 patients (mean age, 78±10 years) with functional (45%), degenerative (48%), or mixed (6%) mitral regurgitation. Percutaneous mitral valve repair increased end-systolic wall stress (WSES; from [median] 184 mm Hg [interquartile range (IQR), 140-200 mm Hg] to 209 mm Hg [IQR, 176-232 mm Hg]; P=0.001) and decreased end-diastolic WS (WSED; from 48 mm Hg [IQR, 28-58 mm Hg] to 34 mm Hg [IQR, 21-46 mm Hg]; P=0.005), whereas the end-systolic pressure-volume relationship was not significantly affected. Conversely, cardiac index increased (from 2.6 L·min(-1)·m(-2) [IQR, 2.2-3.0 L·min(-1)·m(-2)] to 3.2 L·min(-1)·m(-2) [IQR, 2.6-3.8 L·min(-1)·m(-2)]; P<0.001) and mean pulmonary capillary wedge pressure decreased (from 15 mm Hg [IQR, 12-20 mm Hg] to 12 mm Hg [IQR, 10-13 mm Hg]; P<0.001). Although changes in WSES were not correlated with changes in cardiac index, changes in WSED correlated significantly with changes in mean pulmonary capillary wedge pressure (r=0.63, P<0.001). Total mechanical energy assessed by the pressure-volume area remained unchanged, resulting in a more favorable index of forward output (cardiac index) to mechanical energy (pressure-volume area) after mitral valve repair. On follow-up (153±94 days), New York Heart Association functional class was reduced from 2.9±0.6 to 1.9±0.5 (P<0.001) at 3 months, and echocardiographic follow-up documented a stepwise reduction in end-diastolic volume (from 147 mL [IQR, 95-191 mL] to 127 mL [IQR, 82-202 mL]; P=0.036). CONCLUSIONS: Percutaneous mitral valve repair improves hemodynamic profiles and induces reverse left ventricular remodeling by reducing left ventricular preload while preserving contractility. In nonsurgical candidates with compromised left ventricular function, MitraClip therapy could be considered an alternative to surgical mitral valve repair.

Predictors for efficacy of percutaneous mitral valve repair using the MitraClip system: the results of the MitraSwiss registry.

BACKGROUND: Percutaneous mitral valve repair (MVR) using the MitraClip system has become a valid alternative for patients with severe mitral regurgitation (MR) and high operative risk. OBJECTIVE: To identify clinical and periprocedural factors that may have an impact on clinical outcome. DESIGN: Multi-centre longitudinal cohort study. SETTING: Tertiary referral centres. PATIENTS: Here we report on the first 100 consecutive patients treated with percutaneous MVR in Switzerland between March 2009 and April 2011. All of them had moderate-severe (3+) or severe (4+) MR, and 62% had functional MR. 82% of the patients were in New York Heart Association (NYHA) class III/IV, mean left ventricular ejection fraction was 48% and the median European System for Cardiac Operative Risk Evaluation was 16.9%. INTERVENTIONS: MitraClip implantation performed under echocardiographic and fluoroscopic guidance in general anaesthesia. MAIN OUTCOME MEASURES: Clinical, echocardiographic and procedural data were prospectively collected. RESULTS: Acute procedural success (APS, defined as successful clip implantation with residual MR grade ≤2+) was achieved in 85% of patients. Overall survival at 6 and 12 months was 89.9% (95% CI 81.8 to 94.6) and 84.6% (95% CI 74.7 to 91.0), respectively. Univariate Cox regression analysis identified APS (p=0.0069) and discharge MR grade (p=0.03) as significant predictors of survival. CONCLUSIONS: In our consecutive cohort of patients, APS was achieved in 85%. APS and residual discharge MR grade are important predictors of mid-term survival after percutaneous MVR.