Severe multifocal coronary artery spasms after cessation of vasodilators in a patient with a spontaneous coronary artery dissection: a case report.

Background: Vasospastic angina (VSA) and spontaneous coronary artery dissection (SCAD) are challenging causes of non-atherosclerotic acute coronary syndromes (ACS). Here, we report a unique ACS case with coexisting VSA and SCAD, highlighting specific strategies in diagnosis and management of these poorly studied conditions. Case summary: A woman in her mid-60s with a history of suspected microvascular angina and no atherosclerosis in a previously performed coronary computed tomography angiography presented with worsening chest pain. Invasive coronary angiography revealed a focal SCAD with a resulting high-degree stenosis of the right coronary artery. Shortly after successful percutaneous coronary intervention with stent implantation and stopping her previous vasodilator therapy with nitroglycerine and molsidomine, the patient developed recurrent anterior non-ST-segment elevation myocardial infarction. Surprisingly, repeat coronary angiography revealed severe multifocal coronary artery spasms that were successfully treated with intracoronary nitroglycerine. Vasospastic angina was subsequently managed with diltiazem, molsidomine, and nitrates. Discussion: Our report underscores the challenges in diagnosing and managing SCAD and VSA in ACS. The possible interplay between SCAD and VSA highlights the need for careful vasodilator therapy management, as seen in our patient, where therapy discontinuation led to severe multifocal VSA. This emphasizes the need for a comprehensive approach for optimal outcomes in complex ACS cases.

Association of chocolate consumption with neurological and cardiovascular outcomes in atrial fibrillation: data from two Swiss atrial fibrillation cohort studies (Swiss-AF and BEAT-AF).

AIM: To assess the associations of chocolate consumption with neurocognitive function, brain lesions on magnetic resonance imaging (MRI), and cardiovascular outcome in patients with atrial fibrillation (AF). METHODS: We analysed data from patients of two prospective multicentre Swiss atrial fibrillation cohort studies (Swiss-AF) and (BEAT-AF). Assessments of MRI findings and neurocognitive function were performed only in the Swiss-AF population (in 1727 of 2415 patients [71.5%] with a complete data set), as patients enrolled in BEAT-AF were not systematically evaluated for these outcomes. Otherwise, the two cohorts had an equivalent set of clinical assessments. Clinical outcome analysis was performed in 3931 patients of both cohorts. Chocolate consumption was assessed by questionnaire. Patients were categorised as no/low chocolate consumption (No/Low-Ch) ≤1 servings/week, moderate chocolate consumption (Mod-Ch) >1-6 servings/week, and high chocolate consumption (High-Ch) >6 servings/week, respectively. Brain lesions were evaluated by MRI. Assessment of cognitive function was performed by neurocognitive functional testing and included global cognition measurement with a cognitive construct score. Cerebral MRI and cognition were evaluated at baseline. Cross-sectional associations between chocolate consumption and MRI findings were analysed by multivariate logistic regression models and associations with neurocognitive function by multivariate linear regression models. Clinical outcome events during follow-up were recorded and assessed by a clinical event committee. The associations between chocolate consumption and clinical outcomes were evaluated by Cox regression models. The median follow-up time was 6 years. RESULTS: Chocolate consumption was not associated with prevalence or volume of vascular brain lesions on MRI, nor major adverse cardiac events (ischaemic stroke, myocardial infarction, cardiovascular death). However, No/Low-Ch was independently associated with a lower cognitive construct score compared to Mod-Ch (No/Low-Ch vs. Mod-Ch: coeff. -0.05, 95% CI -0.10-0), whereas other neurocognitive function tests were not independently associated with chocolate consumption categories. In addition, there was a higher risk of heart failure hospitalisation (No/Low-Ch vs. Mod-Ch: HR 1.24, 95% CI 1.01-1.52) and of all-cause mortality (No/Low-Ch vs. Mod-Ch: HR 1.29, 95% CI 1.06-1.58) in No/Low-Ch compared to Mod-Ch. No significant associations with the evaluated outcomes were observed when High-Ch was compared to Mod-Ch. CONCLUSION: While chocolate consumption was not associated with MRI findings and major adverse cardiac events in an atrial fibrillation population, No/Low-Ch was associated with a lower cognitive construct score, higher risk of heart failure hospitalisation and increased all-cause mortality compared to Mod-Ch. CLINICALTRIALS: gov Identifier: NCT02105844.

[Update Valvular Heart Disease: Heart Team Decision-Making Based on Patient Examples]. / Update valvuläre Herzkrankheiten: Entscheidungen im interdisziplinären Herzteam anhand von Beispielen.

INTRODUCTION: In Europe, mitral regurgitation and aortic stenosis are the most common valve lesions requiring interventions. In advanced stages, these valve pathologies affect patients' quality of life and prognosis. The prevalence of mitral regurgitation and aortic stenosis is increasing with age. In view of an aging population and the comorbidities associated with age, these valve defects represent an increasing challenge to health care providers. Nowadays, surgical as well as catheter-based treatment options are available to treat affected patients. Therapeutic strategies suitable to the individual patient should be discussed in interdisciplinary heart teams. The aim of the present article is to give an overview of possible guideline-conform heart team decisions based on patient examples.

Evaluation of metabolic equivalents of task (METs) in the preoperative assessment in aortic repair.

BACKGROUND: Reliable prediction of the preoperative risk is of crucial importance for patients undergoing aortic repair. In this retrospective cohort study, we evaluated the metabolic equivalent of task (MET) in the preoperative risk assessment with clinical outcome in a cohort of consecutive patients. METHODS: Retrospective analysis of prospectively collected data in a single center unit of 296 patients undergoing open or endovascular aortic repair from 2009 to 2016. The patients were divided into four anatomic main groups (infrarenal (endo: n = 94; open: n = 88), juxta- and para-renal (open n = 84), thoraco-abdominal (open n = 13) and thoracic (endo: n = 11; open: n = 6). Out of these, 276 patients had a preoperative statement of their functional capacity in metabolic units and were evaluated concerning their postoperative outcome including survival, in-hospital mortality, postoperative complications, myocardial infarction and stroke, and the need of later cardiovascular interventions. RESULTS: The median follow-up of the cohort was 10.8 months. Patients with < 4MET had a higher incidence of diabetes mellitus (p = 0.0002), peripheral arterial disease (p < 0.0001), history of smoking (p = 0.003), obesity (p = 0.03) and chronic obstructive pulmonary disease (p = 0.05). Overall in-hospital mortality was 4.4% (13 patients). There was no significant difference in the survival between patients with a functional capacity of more than 4 MET (220 patients, mean survival: 74.5 months) and patients with less than 4 MET (56 patients, mean survival: 65.4 months) (p = 0.64). The mean survival of the infrarenal cohort (n = 169) was 74.3 months with no significant differences between both MET groups (> 4 MET: 131 patients, mean survival 75.5 months; < 4 MET: 38 patients, mean survival 63.6 months. p = 0.35). The subgroup after open surgical technique with less than 4 MET had the lowest mean survival of 38.8 months. In 46 patients with > 4MET (20.9%) perioperative complications occurred compared to the group with < 4MET with 18 patients (32.1%) (p = 0.075). There were no significant differences in both groups in the late cardiovascular interventions (p = 0.91) and major events including stroke and myocardial infarction (p = 0.4) monitored during the follow up period. The risk to miss a potential need for cardiac optimization in patients > 4MET was 7%. CONCLUSION: The functional preoperative evaluation by MET in patients undergoing aortic surgery is a useful surrogate marker of perioperative performance but cannot be seen as a substitute for preoperative cardiopulmonary testing in selected individuals. Trial registration clinicaltrials.gov, registration number NCT03617601 (retrospectively registered).

First in Switzerland: concomitant off-pump transapical transcatheter aortic valve implantation and mitral valve reconstruction with the NeoChord system.

Old and polymorbid patients with multivalvular heart disease comprise a special patient group, with high perioperative morbidity and mortality. We report the case of an 80-year-old, female, polymorbid patient with severe mitral valve regurgitation and moderate to severe aortic valve stenosis. This is the first case in Switzerland of a concomitant transapical transcatheter aortic valve implantation and mitral valve reconstruction with the NeoChord system, on a beating heart and with a minimally invasive approach through a left anterolateral thoracotomy. This case emphasises the possibility of a low-risk minimally invasive procedure on this high-risk patient-group and shows the importance of interdisciplinary discussion and cooperation in heart teams for optimal patient treatment.

Gender differences in patient and system delay for primary percutaneous coronary intervention: current trends in a Swiss ST-segment elevation myocardial infarction population.

BACKGROUND: Women with ST-segment elevation myocardial infarction (STEMI) experience greater delays for percutaneous coronary intervention-facilitated reperfusion than men. Whether women and men benefit equally from current strategies to reduce ischaemic time and whether there are gender differences in factors determining delays is unclear. METHODS: Patient delay (symptom onset to first medical contact) and system delay (first medical contact to percutaneous coronary intervention-facilitated reperfusion) were compared between women ( n=967) and men ( n=3393) in a Swiss STEMI treatment network. Trends from 2000 to 2016 were analysed, with additional comparisons between three time periods (2000-2005, 2006-2011 and 2012-2016). Factors predicting delays and hospital mortality were determined by multivariate regression modelling. RESULTS: Female gender was independently associated with greater patient delay ( P=0.02 vs. men), accounting for a 12% greater total ischaemic time among women in 2012-2016 (median 215 vs. 192 minutes, P<0.001 vs. men). From 2000-2005 to 2012-2016, median system delay was reduced by 18 and 25 minutes in women and men, respectively ( P<0.0001 for trend, P=n.s. for gender difference). Total occlusion of the culprit artery, stent thrombosis, a Killip class of 3 or greater, and presentation during off-hours predicted delays in men, but not in women. A Killip class of 3 or greater and age, but not gender or delays, were independently associated with hospital mortality. CONCLUSIONS: STEMI-related ischaemic time in women remains greater than in men due to persistently greater patient delays. In contrast to men, clinical signs of ongoing chest discomfort do not predict delays in women, suggesting that female STEMI patients are less likely to attribute symptoms to a condition requiring urgent treatment.

Screening For Pulmonary Hypertension With Multidetector Computed Tomography Among Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.

Aim: To assess the accuracy of multi-detector computed tomography (MDCT) derived pulmonary vessel measurements in predicting pulmonary hypertension (PH) among patients with severe symptomatic aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Background: PH is common among patients with severe AS undergoing TAVI and is associated with adverse outcomes. MDCT is the imaging modality of choice to assess anatomical dimensions among patients selected for TAVI. Methods: One hundred and thirty-nine patients with severe AS undergoing TAVI with both CT scans and right heart catheterizations (RHC) were included. CT diameters of the main pulmonary artery (MPA), right (RPA) and left (LPA), and ascending aorta (AA) were measured. The relationship between CT measurements and PA pressures assessing using RHC was tested with linear regression. Results: The CT derived ratio of the diameter of the MPA to the diameter of the AA (PA/AAratio) correlated best with mean PA pressure (R2 = 0.48) and PA systolic pressure (R2 = 0.50). Receiver operating characteristic curve analysis showed that the PA/AAratio is a moderate predictor of PH (AUC 0.74, 95% CI 0.65-0.83, p < 0.0001) and that the optimal cut off point is 0.80 (sensitivity 56%, specificity 88%, positive predictive value 95.5%, negative predictive value 30.6% for PH). Conclusions: Elderly patients with severe AS and PA/AAratio values ≥ 0.80 on MDCT are more likely to have PH but PH cannot be reliably excluded among such patients with lower PA/AAratio values.

Heart failure with mid-range ejection fraction: a distinct clinical entity? Insights from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF).

AIMS: While the conditions of heart failure (HF) with reduced (HFrEF, LVEF < 40%) and preserved (HFpEF, LVEF ≥ 50%) left ventricular ejection fraction (LVEF) are well characterized, it is unknown whether patients with HF and mid-range LVEF (HFmrEF, LVEF 40-49%) have to be regarded as a separate clinical entity. The aim of this study was to characterize these three populations and to compare outcome and response to therapy. METHODS AND RESULTS: The analysis was based on the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) comprising a population with established HF including the whole spectrum of LVEF. Of the 622 patients, 108 (17%) were classified as having HFmrEF. This group was in general found to be 'intermediate' regarding clinical characteristics with a comparable and high burden of comorbidities and equally impaired quality of life but was more likely to have coronary artery disease as compared with the HFpEF group. During a median follow-up of 794 days, mortality was 39.7% without significant differences between groups. N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided as compared with standard therapy resulted in improved survival free of HF hospitalizations in HFrEF and HFmrEF, but not in HFpEF. CONCLUSION: Although the 'intermediate' clinical profile of HFmrEF between HFrEF and HFpEF would support the conclusion that HFmrEF is a distinct clinical entity, we hypothesize that HFmrEF has to be categorized as HFrEF because of the high prevalence of coronary artery disease and the similar benefit of NT-proBNP-guided therapy in HFrEF and HFmrEF, in contrast to HFpEF.

Efficacy and safety of transcatheter closure in adults with large or small atrial septal defects.

BACKGROUND: In most patients with secundum atrial septal defects (ASD), transcatheter closure is the preferred treatment strategy, but whether device size affects clinical outcomes is unknown. We sought to study the efficacy and safety of large closure devices compared to the use of smaller devices. METHODS: Using a single-center, prospective registry of adult patients undergoing transcatheter ASD closure, patients receiving a large closure device (waist diameter ≥25 mm, n = 41) were compared to patients receiving smaller devices (waist diameter ≤24 mm, n = 66). We analyzed pre-interventional clinical, hemodynamic and echocardiographic data, interventional success and complication rates, and 6-month clinical and echocardiographic outcomes. The primary efficacy outcome was successful ASD closure achieved by a single procedure and confirmed by lack of a significant residual shunt at 6 months. The primary safety outcome was a composite of device embolization, major bleeding, and new-onset atrial arrhythmia occurring within 6 months. RESULTS: Transcatheter ASD closure using large devices was successful in 90 % compared to 97 % of patients receiving smaller devices as defined by the primary efficacy outcome (p = 0.20). The primary safety outcome occurred in 4 patients of the large and 6 patients of the small device group, resulting in an event-free rate of 90 and 91 %, respectively (p = 0.89). Similar significant symptomatic improvement was observed in both treatment groups after 6 months, indicated by a 50 % increase in the fraction of patients in NYHA class I (p < 0.0001 vs. baseline). CONCLUSIONS: Transcatheter closure in this cohort of patients with large or small ASD was effective with similar complication rates during short-term follow-up irrespective of the size of the implanted device.

Paradoxical embolism via a sinus venosus atrial septal defect causing an inferior ST-segment elevation myocardial infarction in a 23-year-old woman.

Cerebrovascular accidents constitute the most frequent clinical manifestation of paradoxical embolism. However, it is becoming increasingly recognised that acute myocardial infarction is also an important and potentially life-threatening clinical manifestation of paradoxical embolism. Various intracardiac or pulmonary shunts can provide a convenient conduit for an embolus to traverse from the venous vasculature into the systemic circulation with potentially devastating consequences. We present the case of a 23-year-old woman presenting with chest pain and ST-segment elevation myocardial infarction who ultimately was found to have a sinus venosus atrial septal defect associated with both partial anomalous pulmonary venous drainage and a persistent left superior vena cava.

Comparison of prasugrel and clopidogrel-treated patients with acute coronary syndrome undergoing percutaneous coronary intervention: A propensity score-matched analysis of the Acute Myocardial Infarction in Switzerland (AMIS)-Plus Registry.

OBJECTIVE: The purpose of this study was to investigate outcomes of patients treated with prasugrel or clopidogrel after percutaneous coronary intervention (PCI) in a nationwide acute coronary syndrome (ACS) registry. BACKGROUND: Prasugrel was found to be superior to clopidogrel in a randomized trial of ACS patients undergoing PCI. However, little is known about its efficacy in everyday practice. METHODS: All ACS patients enrolled in the Acute Myocardial Infarction in Switzerland (AMIS)-Plus registry undergoing PCI and being treated with a thienopyridine P2Y12 inhibitor between January 2010-December 2013 were included in this analysis. Patients were stratified according to treatment with prasugrel or clopidogrel and outcomes were compared using propensity score matching. The primary endpoint was a composite of death, recurrent infarction and stroke at hospital discharge. RESULTS: Out of 7621 patients, 2891 received prasugrel (38%) and 4730 received clopidogrel (62%). Independent predictors of in-hospital mortality were age, Killip class >2, STEMI, Charlson comorbidity index >1, and resuscitation prior to admission. After propensity score matching (2301 patients per group), the primary endpoint was significantly lower in prasugrel-treated patients (3.0% vs 4.3%; p=0.022) while bleeding events were more frequent (4.1% vs 3.0%; p=0.048). In-hospital mortality was significantly reduced (1.8% vs 3.1%; p=0.004), but no significant differences were observed in rates of recurrent infarction (0.8% vs 0.7%; p=1.00) or stroke (0.5% vs 0.6%; p=0.85). In a predefined subset of matched patients with one-year follow-up (n=1226), mortality between discharge and one year was not significantly reduced in prasugrel-treated patients (1.3% vs 1.9%, p=0.38). CONCLUSIONS: In everyday practice in Switzerland, prasugrel is predominantly used in younger patients with STEMI undergoing primary PCI. A propensity score-matched analysis suggests a mortality benefit from prasugrel compared with clopidogrel in these patients.

Improved outcomes of elderly patients treated with drug-eluting versus bare metal stents in large coronary arteries: results from the BAsel Stent Kosten-Effektivitäts Trial PROspective Validation Examination randomized trial.

BACKGROUND: Drug-eluting stents (DES) improve outcomes in elderly patients with small coronary artery disease compared with bare-metal stents (BMS), but randomized data in elderly patients in need of large coronary stents are not available. METHODS: Planned secondary analysis of patients ≥75 years recruited to the "BASKET-PROVE" trial, in which 2,314 patients undergoing percutaneous coronary intervention for large (≥3.0 mm) native vessel disease were randomized 2:1 to DES (everolimus- vs sirolimus-eluting stents 1:1) versus BMS. All patients received 12 months of dual antiplatelet therapy. The primary end point was a composite of cardiac death or nonfatal myocardial infarction at 2 years. RESULTS: Comparison of DES versus BMS among 405 patients ≥75 years showed significantly lower rates of the primary end point for DES (5.0% vs 11.6%; hazard ration (HR) 0.64 [0.44-0.91]; P = .014). Rates of nonfatal myocardial infarction (1.2% vs 5.5%, hazard ration (HR) 0.44 [0.21-0.83]; P = .009), all-cause death (7.4% vs 14.4%; HR 0.7 [0.51-0.95]; P = .02), and target vessel revascularization (TVR) (2.3% vs 6.2%; HR 0.59 [0.34-0.99]; P = .046) were also lower, whereas stent thrombosis and bleeding rates were similar. In contrast, among patients <75 years (n = 1,909), the only significant benefit of DES was a reduced rate of TVR (4.0% vs 8.7%, HR 0.66 [0.55-0.80]; P < .0001). CONCLUSIONS: In patients ≥75 years requiring large (≥3.0 mm) coronary stents, use of DES was beneficial compared with BMS and reduced the rate of ischemic events, mortality, and TVR. These data suggest that DES should be preferred over BMS in elderly patients.

[Cardiovascular assessment and management before non-cardiac surgery]. / Kardiologische Abklärung und Behandlung vor chirurgischen Eingriffen.

The preoperative cardiovascular risk management accounts for patient-related risk factors, the circumstances leading to the surgical procedure, and the risk of the operation. While urgent operations should not be delayed for cardiac testing, an elective surgical intervention should be postponed in unstable cardiac conditions. In stable cardiac situations, prophylactic coronary interventions to reduce the risk of perioperative complications are rarely indicated. Therefore, in most cases, the planned operation can be performed without previous cardiac stress testing or coronary angiography. Preoperative imaging stress testing is recommended for patients with poor functional capacities that are at high cardiovascular risk prior to a high-risk operation. According to the literature, preoperative prophylactic administration of betablockers and aspirin is controversial. Preoperative discontinuation of dual anti-platelet therapy within six months following drug-eluting stent implantation is not recommended.

Improvement in left ventricular ejection fraction and reverse remodeling in elderly heart failure patients on intense NT-proBNP-guided therapy.

BACKGROUND: In chronic heart failure, left ventricular ejection fraction (LVEF) is considered to be stable. Intensified therapy may improve survival, but little is known whether this is associated with reverse remodeling and dependent on age and NT-proBNP guidance. We aimed to define the evolution of LVEF under intensified therapy in relation to age and NT-proBNP guidance. METHODS AND RESULTS: Echocardiography was performed at baseline, 12 and 18months in TIME-CHF, a trial comparing NT-proBNP versus symptom-guided therapy in patients aged 60 to 74 and ≥75 years. LVEF, LV end diastolic volume index (LVEDVI) and end systolic volume index (LVESVI) were assessed. LVEF increased from 31.3 ± 10.7% to 39.1±11.8% at 18 months (p<0.001) in symptom-guided, and from 30.3 ± 11.7% to 44.0 ± 13.2% (p<0.001) in NT-proBNP-guided patients. The increase in LVEF was significantly larger in the NT-proBNP-guided treatment group (p for interaction=0.006), which was true for both age groups (p for interaction in both=0.091). LVEDVI and LVESVI decreased without influence by study group allocation. CONCLUSIONS: In elderly heart failure patients, intensified medical therapy leads to an improvement in LVEF and to reverse remodeling. NT-proBNP guided therapy was associated with a larger improvement in LVEF than symptom guided therapy both in patients aged 60 to 74 and ≥75 years. TRIAL REGISTRATION: http://isrctn.org Identifier: ISRCTN43596477.

Genome-wide microarray expression and genomic alterations by array-CGH analysis in neuroblastoma stem-like cells.

Neuroblastoma has a very diverse clinical behaviour: from spontaneous regression to a very aggressive malignant progression and resistance to chemotherapy. This heterogeneous clinical behaviour might be due to the existence of Cancer Stem Cells (CSC), a subpopulation within the tumor with stem-like cell properties: a significant proliferation capacity, a unique self-renewal capacity, and therefore, a higher ability to form new tumors. We enriched the CSC-like cell population content of two commercial neuroblastoma cell lines by the use of conditioned cell culture media for neurospheres, and compared genomic gains and losses and genome expression by array-CGH and microarray analysis, respectively (in CSC-like versus standard tumor cells culture). Despite the array-CGH did not show significant differences between standard and CSC-like in both analyzed cell lines, the microarray expression analysis highlighted some of the most relevant biological processes and molecular functions that might be responsible for the CSC-like phenotype. Some signalling pathways detected seem to be involved in self-renewal of normal tissues (Wnt, Notch, Hh and TGF-ß) and contribute to CSC phenotype. We focused on the aberrant activation of TGF-ß and Hh signalling pathways, confirming the inhibition of repressors of TGF-ß pathway, as SMAD6 and SMAD7 by RT-qPCR. The analysis of the Sonic Hedgehog pathway showed overexpression of PTCH1, GLI1 and SMO. We found overexpression of CD133 and CD15 in SIMA neurospheres, confirming that this cell line was particularly enriched in stem-like cells. This work shows a cross-talk among different pathways in neuroblastoma and its importance in CSC-like cells.