Impact of annual volume of cases and intensive cardiac care unit availability on mortality of patients with acute myocardial infarction-related cardiogenic shock treated at revascularization capable centres.

AIMS: Cardiogenic shock (CS) is associated with high mortality. The purpose of this study was to assess the impact of hospital structure-related variables on mortality in patients with CS treated at percutaneous and surgical revascularization capable centres (psRCC) from a large nationwide registry. METHODS AND RESULTS: Retrospective observational study including consecutive patients with main or secondary diagnosis of CS and ST elevation myocardial infarction (STEMI). Patients discharged from Spanish National Healthcare System psRCC were included (2016-20). The association between the volume of CS cases attended by each centre, availability of intensive cardiac care unit (ICCU) and heart transplantation (HT) programmes, and in-hospital mortality was assessed by multilevel logistic regression models. The study population consisted of 3074 CS-STEMI episodes, of whom 1759 (57.2%) occurred in 26 centres with ICCU. A total of 17/44 hospitals (38.6%) were high-volume centres, and 19/44 (43%) centres had HT programmes availability. Treatment at HT centres was not associated with a lower mortality (P = 0.121). Both high volume of cases and ICCU showed a trend to an association with lower mortality in the adjusted model [odds ratio (OR): 0.87 and 0.88, respectively]. The interaction between both variables was significantly protective (OR 0.72; P = 0.024). After propensity score matching, mortality was lower in high-volume hospitals with ICCU (OR 0.79; P = 0.007). CONCLUSION: Most CS-STEMI patients were attended at psRCC with high volume of cases and ICCU available. The combination of high volume and ICCU availability showed the lowest mortality. These data should be taken into account when designing regional networks for CS management.

Coronary angiography in patients without ST-segment elevation following out-of-hospital cardiac arrest. COUPE clinical trial.

INTRODUCTION AND OBJECTIVES: The role of emergency coronary angiography (CAG) and percutaneous coronary intervention (PCI) following out-of-hospital cardiac arrest (OHCA) in patients without ST-segment elevation myocardial infarction (STEMI) remains unclear. We aimed to assess whether emergency CAG and PCI would improve survival with good neurological outcome in this population. METHODS: In this multicenter, randomized, open-label, investigator-initiated clinical trial, we randomly assigned 69 survivors of OHCA without STEMI to undergo immediate CAG or deferred CAG. The primary efficacy endpoint was a composite of in-hospital survival free of severe dependence. The safety endpoint was a composite of major adverse cardiac events including death, reinfarction, bleeding, and ventricular arrhythmias. RESULTS: A total of 66 patients were included in the primary analysis (95.7%). In-hospital survival was 62.5% in the immediate CAG group and 58.8% in the delayed CAG group (HR, 0.96; 95%CI, 0.45-2.09; P=.93). In-hospital survival free of severe dependence was 59.4% in the immediate CAG group and 52.9% in the delayed CAG group (HR, 1.29; 95%CI, 0.60-2.73; P=.4986). No differences were found in the secondary endpoints except for the incidence of acute kidney failure, which was more frequent in the immediate CAG group (15.6% vs 0%, P=.002) and infections, which were higher in the delayed CAG group (46.9% vs 73.5%, P=.003). CONCLUSIONS: In this underpowered randomized trial involving patients resuscitated after OHCA without STEMI, immediate CAG provided no benefit in terms of survival without neurological impairment compared with delayed CAG. CLINICALTRIALS: gov Identifier: NCT02641626.

Design and Rationale for a Real-World Prospective, Multicenter Registry of Myocardial Revascularization Failure and Secondary Revascularization: The REVASEC Study.

AIM: To investigate key aspects of the problem of myocardial revascularization failure (MRF) and repeat or secondary myocardial revascularization (SR) in contemporary practice. METHODS: The registry of secondary revascularization (REVASEC) is an investigator-initiated, multicenter, prospective registry enhanced with data monitoring and independent event adjudication (ClinicalTrials.govNCT03349385). It includes patients with prior revascularization referred to coronary angiography for suspected MRF with broad inclusion criteria. The main objectives are to describe the characteristics of patients with prior revascularization referred for repeat angiography, to describe and the rate and mechanisms of MRF (stent or graft failure, coronary artery disease progression or residual coronary artery disease); to evaluate the management including medical treatment and SR of these patients; and to assess the prognosis according to the outlined causative mechanisms. The registry has one year follow up for the primary endpoint (Patient-oriented composite endpoint including all-cause death, any myocardial infarction or any new unplanned revascularization according to subsets of MRF), but extended follow-up will be carried out up to 5 years. CONCLUSION: The REVASEC Registry will provide updated data on the characteristics, patterns of treatment, and 1-year outcomes of patients with MRF and SR in contemporary clinical practice.

Percutaneous mitral valve repair with MitraClip device in hemodynamically unstable patients: A systematic review.

BACKGROUND: Very few data exist on percutaneous mitral valve repair (PMVr) in unstable patients with concomitant moderate-severe mitral regurgitation (MR). The purpose of this systematic review was to evaluate baseline characteristics, management and clinical outcomes of critically ill patients undergoing PMVr with MitraClip. METHODS: We conducted a systematic review of the published data on MitraClip from its first use in 2003 to December 2020. Studies referring to critically ill patients in cardiogenic shock or acute refractory pulmonary edema were included. A total of 40 publications including 254 patients with significant MR (Grade 4 in 91%) were included. RESULTS: Mean age was 70 ± 12 years with mean Euroscore II and STS of 21 ± 13 and 20.5 ± 16, respectively. Clinical presentation was with cardiogenic shock and acute myocardial infarction in 72.8 and 60.0% of patients, respectively. Device success was achieved in 238 (93.7%) patients with a significant reduction in MR (Grade ≤ 2 in 91.8%, p < .001). The median weaning time from the procedure, to discontinuation of mechanical circulatory or respiratory support, was 2 days (IQR 1-4), with an in-hospital mortality and non-fatal complication rate of 12.6 and 9.1%, respectively. Kaplan-Meier curves estimated an overall mortality rate of 39.1% at 12-month follow-up, with persistent reduction in MR severity for survivors (Grade ≤ 2 in 81.3%) and one case of mitral valve reintervention. CONCLUSIONS: Percutaneous mitral valve repair with MitraClip device is a technically feasible and potentially viable management option in high-risk patients with cardiogenic shock or refractory pulmonary edema and concomitant moderate-severe MR. Prospective trials are required to confirm these findings, and definitively determine the value of MitraClip in hemodynamically unstable patients.

Impact of delirium in acute cardiac care unit after transcatheter aortic valve replacement.

BACKGROUND: Delirium is a cognitive disorder that commonly occurs during hospitalization in acute cardiac care units (ACCU), but its effect after transcatheter aortic valve replacement (TAVR) has not been well evaluated. The objective of this study is to determine the incidence, predictive factors and prognostic impact of delirium following TAVR. METHODS: A total of 501 consecutive patients admitted to an ACCU after TAVR were included. The Confusion Assessment Method was used to evaluate delirium during ACCU stay. Risk factors, preventive pharmacological treatment, peri-procedural characteristics and complications were assessed. Clinical events were recorded with a median follow-up of 24 months. RESULTS: The incidence of delirium after TAVR was 22.0% (n = 110). Previous cognitive impairment (OR 4.17; 95% CI 1.11-15.71; p = 0.035), peripheral arterial disease (OR 4.54; 95% CI 1.79-11.54; p = 0.001), the use of general anaesthesia (OR 2.55; 95% CI 1.32-4.90; p = 0.005), and prolonged mechanical ventilation (OR 18.86; 95% CI 1.85-192.58; p = 0.013) were significantly associated with the development of delirium. Patients with delirium had a greater hospital length of stay (7.5 [5.5-13.5] vs 5.6 [4.6-8.2] days, mean difference - 3.49; 95% CI -5.45 to -1.52; p < 0.001), and higher in-hospital (OR 2.68; 95% CI 1.02-6.99; p = 0.045), 1-year (HR 2.09; 95% CI 1.13-3.87; p = 0.018) and 2-year mortality (HR 1.94; 95% CI 1.12-3.34; p = 0.017). CONCLUSIONS: Delirium is a frequent complication in patients admitted to ACCU after TAVR, and is associated with prolonged hospital stay and higher in-hospital and mid-term mortality.

Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families.

The two major subtypes of bipolar disorder (BD), BD-I and BD-II, are distinguished based on the presence of manic or hypomanic episodes. Historically, BD-II was perceived as a less severe form of BD-I. Recent research has challenged this concept of a severity continuum. Studies in large samples of unrelated patients have described clinical and genetic differences between the subtypes. Besides an increased schizophrenia polygenic risk load in BD-I, these studies also observed an increased depression risk load in BD-II patients. The present study assessed whether such clinical and genetic differences are also found in BD patients from multiplex families, which exhibit reduced genetic and environmental heterogeneity. Comparing 252 BD-I and 75 BD-II patients from the Andalusian Bipolar Family (ABiF) study, the clinical course, symptoms during depressive and manic episodes, and psychiatric comorbidities were analyzed. Furthermore, polygenic risk scores (PRS) for BD, schizophrenia, and depression were assessed. BD-I patients not only suffered from more severe symptoms during manic episodes but also more frequently showed incapacity during depressive episodes. A higher BD PRS was significantly associated with suicidal ideation. Moreover, BD-I cases exhibited lower depression PRS. In line with a severity continuum from BD-II to BD-I, our results link BD-I to a more pronounced clinical presentation in both mania and depression and indicate that the polygenic risk load of BD predisposes to more severe disorder characteristics. Nevertheless, our results suggest that the genetic risk burden for depression also shapes disorder presentation and increases the likelihood of BD-II subtype development.

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.

Cardiogenic Shock Clinical Presentation, Management, and In-Hospital Outcomes in Patients Admitted to the Acute Cardiac Care Unit of a Tertiary Hospital: Does Gender Play a Role?

Cardiogenic shock (CS), as the most severe form of heart failure, is associated with very high mortality rates despite therapeutic advances in the last decades. Gender differences in outcomes have been widely reported regarding several cardiovascular diseases. The aim of our study was to evaluate potential gender disparities in clinical presentation, management, and in-hospital outcomes of all (n = 138) patients admitted to the Acute Cardiac Care Unit of a tertiary hospital from 2013 to 2019. Information on demographic characteristics, past medical history, haemodynamic and clinical status at admission, therapeutic management, and in-hospital outcomes was retrospectively collected. Women represented 31.88% of the cohort, were significantly older than the men and had a lower proportion of smokers, chronic obstructive pulmonary disease, and previous acute myocardial infarction (AMI). Most CSs in both groups were AMI-related. Left ventricular ejection fraction at admission was higher in women, who were less likely to receive vasopressors. No differences were observed regarding mechanical circulatory support use and in-patient outcomes, with age being the only factor associated with in-hospital mortality on multivariate analysis.

Late Migration of a Paravalvular Leak Closure Device.

Paravalvular leak (PVL) is a serious complication of surgical valve replacement, often affecting elderly, multimorbid, high-risk patients. The risk of surgical intervention is often prohibitive in these cases, and so percutaneous PVL closure emerged as a feasible and effective management strategy, with a low complication rate. Specific devices for closure of PVL's are currently not widely available, and so PVLs are closed using generic vascular closure devices, which may result in residual paravalvular regurgitation or even closure device displacement. Although rare, late displacement of the closure device with prosthetic impingement can be life threatening, requiring urgent intervention.We present a case of a seventy-year-old gentleman with rheumatic heart disease and multiple previous mechanical aortic and mitral valve replacements. After repeated admissions for decompensated heart failure, secondary to paravalvular mitral regurgitation, a percutaneous paravalvular leak closure was performed with successful reduction of the leak. He represented 30 days later with cardiogenic shock and multiorgan failure secondary to torrential central mitral regurgitation caused by late displacement of the closure device with mitral prosthesis impingement. Due to an excessively high surgical risk, his case was successfully managed percutaneously with retrieval of the displaced device and closure of the PVL using two Amplatzer Vascular Plug III devices. At the six-month review, he remains asymptomatic.Percutaneous PVL closure is an effective strategy for patients with prohibitive surgical risk. Late closure device displacement can be a life-threatening complication. Our case demonstrates that percutaneous management of this complication is feasible even in patients presenting in extremis.

Clinical picture, management and risk stratification in patients with cardiogenic shock: does gender matter?

BACKGROUND: Early recognition and risk stratification are crucial in cardiogenic shock (CS). A lower adherence to recommendations has been described in women with cardiovascular diseases. Little information exists about disparities in clinical picture, management and performance of risk stratification tools according to gender in patients with CS. METHODS: Data from the multicenter Red-Shock registry were used. All consecutive patients with CS were included. Both CardShock and IABP-SHOCK II risk scores were calculated. The primary end-point was in-hospital mortality. The discriminative ability of both scores according to gender was assessed by binary logistic regression, calculating Receiver operating characteristic (ROC) curves and the corresponding area under the curve (AUC). RESULTS: A total of 793 patients were included, of whom 222 (28%) were female. Women were significantly older and had a lower proportion of chronic obstructive pulmonary disease and prior myocardial infarction. CS was less often related to acute coronary syndromes (ACS) in women. The use of vasoactive drugs, renal replacement therapy, invasive ventilation, therapeutic hypothermia and mechanical circulatory support was similar between both groups. In-hospital mortality was 346/793 (43.6%). Mortality was not significantly different according to gender (p = 0.194). Cardshock risk score showed a good ability for predicting in-hospital mortality both in man (AUC 0.69) and women (AUC 0.735). Likewise, the IABP-II successfully predicted in-hospital mortality in both groups (man: AUC 0.693; women: AUC 0.722). CONCLUSIONS: No significant differences were observed regarding management and in-hospital mortality according to gender. Both the CardShock and IABP-II risk scores depicted a good ability for predicting mortality also in women with CS.

Whole-exome sequencing of 81 individuals from 27 multiply affected bipolar disorder families.

Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of depression and mania. Research suggests that the cumulative impact of common alleles explains 25-38% of phenotypic variance, and that rare variants may contribute to BD susceptibility. To identify rare, high-penetrance susceptibility variants for BD, whole-exome sequencing (WES) was performed in three affected individuals from each of 27 multiply affected families from Spain and Germany. WES identified 378 rare, non-synonymous, and potentially functional variants. These spanned 368 genes, and were carried by all three affected members in at least one family. Eight of the 368 genes harbored rare variants that were implicated in at least two independent families. In an extended segregation analysis involving additional family members, five of these eight genes harbored variants showing full or nearly full cosegregation with BD. These included the brain-expressed genes RGS12 and NCKAP5, which were considered the most promising BD candidates on the basis of independent evidence. Gene enrichment analysis for all 368 genes revealed significant enrichment for four pathways, including genes reported in de novo studies of autism (padj < 0.006) and schizophrenia (padj = 0.015). These results suggest a possible genetic overlap with BD for autism and schizophrenia at the rare-sequence-variant level. The present study implicates novel candidate genes for BD development, and may contribute to an improved understanding of the biological basis of this common and often devastating disease.

External validation and comparison of the CardShock and IABP-SHOCK II risk scores in real-world cardiogenic shock patients.

BACKGROUND: Mortality from cardiogenic shock remains high and early recognition and risk stratification are mandatory for optimal patient allocation and to guide treatment strategy. The CardShock and the Intra-Aortic Balloon Counterpulsation in Acute Myocardial Infarction Complicated by Cardiogenic Shock (IABP-SHOCK II) risk scores have shown good results in predicting short-term mortality in cardiogenic shock. However, to date, they have not been compared in a large cohort of ischaemic and non-ischaemic real-world cardiogenic shock patients. METHODS: The Red-Shock is a multicentre cohort of non-selected cardiogenic shock patients. We calculated the CardShock and IABP-SHOCK II risk scores in each patient and assessed discrimination and calibration. RESULTS: We included 696 patients. The main cause of cardiogenic shock was acute coronary syndrome, occurring in 62% of the patients. Compared with acute coronary syndrome patients, non-acute coronary syndrome patients were younger and had a lower proportion of risk factors but higher rates of renal insufficiency; intra-aortic balloon pump was also less frequently used (31% vs 56%). In contrast, non-acute coronary syndrome patients were more often treated with mechanical circulatory support devices (11% vs 3%, p<0.001 for both). Both risk scores were good predictors of in-hospital mortality in acute coronary syndrome patients and had similar areas under the receiver-operating characteristic curve (area under the curve: 0.742 for the CardShock vs 0.752 for IABP-SHOCK II, p=0.65). Their discrimination performance was only modest when applied to non-acute coronary syndrome patients (0.648 vs 0.619, respectively, p=0.31). Calibration was acceptable for both scores (Hosmer-Lemeshow p=0.22 for the CardShock and 0.68 for IABP-SHOCK II). CONCLUSIONS: In our cohort, both the CardShock and the IABP-SHOCK II risk scores were good predictors of in-hospital mortality in acute coronary syndrome-related cardiogenic shock.

External validation and comparison of the CardShock and IABP-SHOCK II risk scores in real-world cardiogenic shock patients.

BACKGROUND: Mortality from cardiogenic shock remains high and early recognition and risk stratification are mandatory for optimal patient allocation and to guide treatment strategy. The CardShock and the Intra-Aortic Balloon Counterpulsation in Acute Myocardial Infarction Complicated by Cardiogenic Shock (IABP-SHOCK II) risk scores have shown good results in predicting short-term mortality in cardiogenic shock. However, to date, they have not been compared in a large cohort of ischaemic and non-ischaemic real-world cardiogenic shock patients. METHODS: The Red-Shock is a multicentre cohort of non-selected cardiogenic shock patients. We calculated the CardShock and IABP-SHOCK II risk scores in each patient and assessed discrimination and calibration. RESULTS: We included 696 patients. The main cause of cardiogenic shock was acute coronary syndrome, occurring in 62% of the patients. Compared with acute coronary syndrome patients, non-acute coronary syndrome patients were younger and had a lower proportion of risk factors but higher rates of renal insufficiency; intra-aortic balloon pump was also less frequently used (31% vs 56%). In contrast, non-acute coronary syndrome patients were more often treated with mechanical circulatory support devices (11% vs 3%, p<0.001 for both). Both risk scores were good predictors of in-hospital mortality in acute coronary syndrome patients and had similar areas under the receiver-operating characteristic curve (area under the curve: 0.742 for the CardShock vs 0.752 for IABP-SHOCK II, p=0.65). Their discrimination performance was only modest when applied to non-acute coronary syndrome patients (0.648 vs 0.619, respectively, p=0.31). Calibration was acceptable for both scores (Hosmer-Lemeshow p=0.22 for the CardShock and 0.68 for IABP-SHOCK II). CONCLUSIONS: In our cohort, both the CardShock and the IABP-SHOCK II risk scores were good predictors of in-hospital mortality in acute coronary syndrome-related cardiogenic shock.

Role of coronary angiography in patients with a non-diagnostic electrocardiogram following out of hospital cardiac arrest: Rationale and design of the multicentre randomized controlled COUPE trial.

BACKGROUND: Coronary artery disease (CAD) is a major cause of out-of-hospital cardiac arrest (OHCA). The role of emergency coronary angiography (CAG) and percutaneous coronary intervention (PCI) following cardiac arrest in patients without ST-segment elevation myocardial infarction (STEMI) remains unclear. AIMS: We aim to assess whether emergency CAG and PCI, when indicated, will improve survival with good neurological outcome in post-OHCA patients without STEMI who remain comatose. METHODS: COUPE is a prospective, multicentre and randomized controlled clinical trial. A total of 166 survivors of OHCA without STEMI will be included. Potentially non-cardiac aetiology of the cardiac arrest will be ruled out prior to randomization. Randomization will be 1:1 for emergency (within 2 h) or deferred (performed before discharge) CAG. Both groups will receive routine care in the intensive cardiac care unit, including therapeutic hypothermia. The primary efficacy endpoint is a composite of in-hospital survival free of severe dependence, which will be evaluated using the Cerebral Performance Category Scale. The safety endpoint will be a composite of major adverse cardiac events including death, reinfarction, bleeding and ventricular arrhythmias. CONCLUSIONS: This study will assess the efficacy of an emergency CAG versus a deferred one in OHCA patients without STEMI in terms of survival and neurological impairment.

Electrocardiographic Distinction of Left Circumflexand Right Coronary Artery Occlusion in PatientsWith Inferior Acute Myocardial Infarction.

Previously reported electrocardiographic (ECG) criteria to distinguish left circumflex (LCCA) and right coronary artery (RCA) occlusion in patients with acute inferior ST-segment elevation myocardial infarction (STEMI) afford a modest diagnostic accuracy. We aimed to develop a new algorithm overcoming limitations of previous studies. Clinical, ECG, and coronary angiographic data were analyzed in 230 nonselected patients with acute inferior STEMI who underwent primary percutaneous coronary intervention. A decision-tree analysis was used to develop a new ECG algorithm. The diagnostic accuracy of reported ECG criteria was reviewed. LCCA occlusion occurred in 111 cases and RCA in 119. We developed a 3-step algorithm that identified LCCA and RCA occlusion with a sensitivity of 77%, specificity of 86%, accuracy of 82%, and Youden index of 0.63. The area under the ROC curve was 0.85 and resulted 0.82 after a 10-fold cross validation. The key leads for LCCA occlusion were V3 (ST depression in V3/ST elevation in III >1.2) and V6 (ST elevation ≥0.1 mV or greater than III). The key leads for RCA occlusion were I and aVL (ST depression ≥ 0.1 mV). Fifteen of 21 reviewed studies had less than 20 cases of LCCA occlusion, only 48% performed primary percutaneous coronary intervention, and previous infarction or multivessel disease were often excluded. The diagnostic accuracy of reported ECG criteria decreased when applied to our study population. In conclusion, we report a simple and highly discriminative 3-step ECG algorithm to differentiate LCCA and RCA occlusion in an "all comers" population of patients with acute inferior STEMI. The diagnostic key ECG leads were V3 and V6 for LCCA and I and aVL for RCA occlusion.

Angiographic characteristics and long-term prognostic impact of coronary artery disease in survivors after sudden cardiac arrest with a non-diagnostic electrocardiogram.

OBJECTIVES: Our purpose was to describe the prevalence, distribution, extension, and prognostic value of coronary artery disease (CAD) in patients resuscitated from sudden cardiac arrest (SCA) with non-diagnostic electrocardiogram (ECG). BACKGROUND: The impact of CAD and the indication for cardiac catheterization (CC) in patients resuscitated from SCA with non-diagnostic ECG are uncertain. METHODS: We included prospectively and consecutively 545 patients resuscitated from SCA with at least one CC during hospitalization. From them, 203 patients with a non-diagnostic ECG formed our study population. Patients were followed-up 5 years after discharge. RESULTS: Overall, 125 (61.6%) patients had significant CAD, and at least one acute culprit lesion was found in 25 (12.4%). Regarding the burden and complexity of CAD, 78 (38.4%) patients had a CAD Prognostic Index of 0 and a SYNTAX score of 0. There was higher 5-year mortality only in patients with very high burden of CAD: three vessels with severe stenosis (P = 0.015) and CAD Prognostic Index Score ≥ 56 (P < 0.001). Tertiles of SYNTAX score did not predict higher 5-year mortality. CONCLUSIONS: In survivors from SCA with a non-diagnostic ECG, significant CAD is highly prevalent. SYNTAX score was not associated with a different long-term prognosis in this patient population. Patients with severe disease in the three main coronary vessels and patients with higher (≥56) CAD Prognostic Index Score had a worse long-term prognosis.

The Andalusian Bipolar Family (ABiF) Study: Protocol and sample description. / El estudio Andalusian Bipolar Family (ABiF): protocolo y descripción de la muestra.

INTRODUCTION: Here, we present the first description of the Andalusian Bipolar Family (ABiF) Study. This longitudinal investigation of families from Andalusia, Spain commenced in 1997 with the aim of elucidating the molecular genetic causes of bipolar affective disorder. The cohort has since contributed to a number of key genetic findings, as reported in international journals. However, insight into the genetic underpinnings of the disorder in these families remains limited. METHOD: In the initial 1997-2003 study phase, 100 multiplex bipolar disorder and other mood disorder families were recruited. The ongoing second phase of the project commenced in 2013, and involves follow-up of a subgroup of the originally recruited families. The aim of the follow-up investigation is to generate: i) longitudinal clinical data; ii) results from detailed neuropsychological assessments; and iii) a more extensive collection of biomaterials for future molecular biological studies. RESULTS: The ABiF Study will thus generate a valuable resource for future investigations into the aetiology of bipolar affective disorder; in particular the causes of high disease loading within multiply affected families. DISCUSSION: We discuss the value of this approach in terms of new technologies for the identification of high-penetrance genetic factors. These new technologies include exome and whole genome sequencing, and the use of induced pluripotent stem cells or model organisms to determine functional consequences.

Coronary angiography findings in cardiac arrest patients with non-diagnostic post-resuscitation electrocardiogram: A comparison of shockable and non-shockable initial rhythms.

AIM: To investigate the impact of coronary artery disease in a cohort of patients resuscitated from cardiac arrest with non-diagnostic electrocardiogram. METHODS: From March 2004 to February 2016, 203 consecutive patients resuscitated from in or out-of-hospital sudden cardiac arrest and non-diagnostic post-resuscitation electrocardiogram (defined as ST segment elevation or pre-sumably new left bundle branch block) who underwent invasive coronary angiogram during hospitalization were included. For purpose of analysis and comparison, patients were classified in two groups: Initial shockable rhythm (ventricular tachycardia or ventricular fibrillation; n = 148, 72.9%) and initial non-shockable rhythm (n = 55, 27.1%). Baseline characteristics, coronary angiogram findings including Syntax Score and long-term survival rates were compared. RESULTS: Sudden cardiac arrest was witnessed in 95.2% of cases, 66.7% were out-of-hospital patients and 72.4% were male. There were no significant differences in baseline characteristics between groups except for higher mean age (68.1 years vs 61 years, P = 0.001) in the non-shockable rhythm group. Overall 5-year mortality of the resuscitated patients was 37.4%. Patients with non-shockable rhythms had higher mortality (60% vs 29.1%, P < 0.001) and a worst neurological status at hospital discharge based on cerebral performance category score (CPC 1-2: 32.7% vs 53.4%, P = 0.02). Although there were no significant differences in global burden of coronary artery disease defined by Syntax Score (mean Syntax Score: 10.2 vs 10.3, P = 0.96) there was a trend towards a higher incidence of acute coronary lesions in patients with shockable rhythm (29.7% vs 16.4%, P = 0.054). There was also a higher need for ad-hoc percutaneous coronary intervention in this group (21.9% vs 9.1%, P = 0.03). CONCLUSION: Initial shockable group of patients had a trend towards higher incidence of acute coronary lesions and higher need of ad-hoc percutaneous intervention vs non-shockable group.

Cardiac activation-repolarization patterns and ion channel expression mapping in intact isolated normal human hearts.

BACKGROUND: The repolarization pattern of the human heart is unknown. OBJECTIVE: The purpose of this study was to perform a multisite analysis of the activation-repolarization patterns and mRNA expression patterns of ion channel subunits in isolated human hearts. METHODS: Hearts from 3 donors without reported cardiac disease were Langendorff perfused with the patient's own blood. A standard ECG was obtained before explantation. Up to 92 unipolar electrograms from 24 transmural needles were obtained during right atrial pacing. Local activation and repolarization times and activation-recovery intervals (ARI) were measured. The mRNA levels of subunits of the channels carrying the transient outward current and slow and rapid components of the delayed rectifier current were determined by quantitative reverse transcriptase polymerase chain reaction at up to 63 sites. RESULTS: The repolarization gradients in the 3 hearts were different and occurred along all axes without midmural late repolarization. A negative activation-repolarization relationship occurred along the epicardium, but this relationship was positive in the whole hearts. Coefficients of variation of mRNA levels (40%-80%) and of the Kv7.1 protein (alpha-subunit slow delayed rectifier channel) were larger than those of ARIs (7%-17%). The regional mRNA expression patterns were similar in the 3 hearts, unlike the ARI profiles. The expression level of individual mRNAs and of Kv7.1 did not correlate with local ARIs at the same sites. CONCLUSION: In the normal human heart, repolarization gradients encompass all axes, without late midmural repolarization. Last activated areas do not repolarize first as previously assumed. Gradients of mRNAs of single ion channel subunits and of ARIs do not correlate.