Coronary Artery Dissection and Myocardial Infarction With Nonobstructed Coronary Arteries: Insights From a UK Nationwide Autopsy-Based Registry-Brief Report.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) and myocardial infarction with nonobstructed coronary arteries (MINOCA) are increasingly recognized causes of acute coronary syndrome and potentially of sudden cardiac death (SCD). SCAD has been correlated to coronary fibromuscular dysplasia (FMD), but the prevalence of SCAD and FMD among SCD victims is unclear. Therefore, we sought to assess characteristics of decedents with SCAD found at autopsy and to compare their clinical and pathological profile with MINOCA victims. METHODS: We reviewed a database of 5325 consecutive cases of SCDs referred to our cardiac pathology center between 1994 and 2017. RESULTS: We identified 18 (0.3%) cases with SCAD and 37 (0.7%) with MINOCA. No signs of coronary FMD were found among SCAD and MINOCA victims. Compared to MINOCA, SCAD decedents were mostly females (78% versus 38%, P=0.006) and SCD occurred during peripartum more frequently in SCAD rather than MINOCA female victims (28% versus 3%, P=0.012) Infarcted myocardium was identified in all cases of MINOCA but only in 5 (28%) of SCAD decedents (P<0.001). Premortem cardiac symptoms were present in 100% of SCAD and 49% of MINOCA victims (P<0.001); substances use or abuse was reported in none of SCAD versus 43% of MINOCA decedents (P=0.001). CONCLUSIONS: SCAD and MINOCA are rare causes of SCD. At autopsy, coronary FMD is not present among SCAD victims. Compared to MINOCA, SCAD victims are more frequently females, are linked to pregnancy, and always experienced premortem cardiac symptoms. Among MINOCA victims' substance use or abuse is common.

A Novel Approach to Cardiac Magnetic Resonance Scar Characterization in Patients Affected by Cardiac Amyloidosis: A Pilot Study.

Background and Objectives: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. Materials and Methods: This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. Results: A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary (p = 0.003) and the secondary outcome of pacemaker implantation (p = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance (p = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. Conclusions: CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study.

Myocardial bridge evaluation towards personalized medicine: study design and preliminary results of the RIALTO registry.

Myocardial bridge (MB) is the most frequent inborn coronary artery variant in which a portion of the myocardium overlies an epicardial coronary artery segment. Although MB has long been considered a benign entity, a growing body of evidence has suggested its association with angina and adverse cardiac events. However, to date, no data on long-term prognosis are available, nor on therapies improving cardiovascular outcomes. We are currently conducting an ambispective, observational, multicentre, study in which we enrol patients with a clinical indication to undergo coronary angiography (CA) and evidence of MB, aiming to describe the incidence of symptoms and cardiovascular events at baseline and at long-term follow-up (FUP). The role of invasive full-physiology assessment in modifying the discharge therapy and eventually the perceived quality of life and the incidence of major cardiovascular events will be analysed. Basal clinical-instrumental data of eligible and consenting patients have been acquired after CA; FUP was performed 6, 12, and 24 months after the angiographic diagnosis of MB. The primary endpoint of the study is the incidence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction, cardiac hospitalization, and target vessel revascularization; the secondary endpoints are the rate of patients with Seattle Angina Questionnaire (SAQ) summary score <70 and the incidence of MACE in patients undergoing invasive intracoronary assessment. Among patients undergone FUP visits, we recorded 31 MACE at 6 months (11.6%), 16 MACE at 12 months (6.5%), and 26 MACE at 24 months (13.5%). The rate of patients with SAQ <70 is 18.8% at 6 months, 20.6% at 12 months, and 21.8% at 24 months. To evaluate the prognostic role of invasive intracoronary assessment, we compared MB patients who underwent only angiographic evaluation (Angio group) to those who underwent acetylcholine (ACH) provocative test with indication to calcium-channel blockers (CCBs) at discharge (Angio + ACH + CCBs group) and those who underwent functional assessment with fractional flow reserve (FFR) with indication to beta-blockers (BBs) at discharge (Angio + FFR + BBs group). After 2 years of FUP, the rate of MACE was significantly reduced in both Angio + ACH + CCBs group (6 vs. 25%, P = 0.029) and Angio + FFR + BBs group (3 vs. 25%, P = 0.005) compared with Angio group. The preliminary results of our study showed that MB may be a cause of angina and adverse cardiac events in patients referred to CA for suspected coronary artery disease (CAD). Full-physiology assessment unmasking MB-related ischaemia mechanisms, allowed to guide the treatment, personalizing the clinical management, improving the quality of life, and cardiovascular outcomes in patients with MB.

Clinical phenotypes of embolic strokes of undetermined source.

BACKGROUND AND PURPOSE: The embolic stroke of undetermined source (ESUS) represents a heterogeneous clinical entity. The aim of this study was to investigate whether distinct clinical phenotypes may be identified in the ESUS population. METHODS: We retrospectively identified consecutive patients hospitalized for acute ischemic stroke who met the ESUS diagnostic criteria. Baseline characteristics and diagnostic workup findings were collected. Hierarchical cluster analysis was carried out to classify clinical features and identify different groups of ESUS patients. RESULTS: One hundred twenty-seven patients with a mean age of 68.6 (12.5) years were included. Three main clusters were identified. The first cluster associated young age, male sex, presence of patent foramen ovale, and posterior circulation infarct. The second phenotype linked hypertension, severe stroke, left atrial cardiopathy, diabetes mellitus, and involvement of multiple vascular territories. The third cluster gathered smoking, dyslipidemia, ipsilateral vulnerable sub-stenotic carotid plaque, and infarct of anterior vascular territory. CONCLUSIONS: Distinct clinical phenotypes have been identified within the ESUS population, which may supply clues to the underlying pathogenic mechanisms.

Myocardial Inflammation, Sports Practice, and Sudden Cardiac Death: 2021 Update.

Myocardial inflammation is an important cause of cardiovascular morbidity and sudden cardiac death in athletes. The relationship between sports practice and myocardial inflammation is complex, and recent data from studies concerning cardiac magnetic resonance imaging and endomyocardial biopsy have substantially added to our understanding of the challenges encountered in the comprehensive care of athletes with myocarditis or inflammatory cardiomyopathy (ICM). In this review, we provide an overview of the current knowledge on the epidemiology, pathophysiology, diagnosis, and treatment of myocarditis, ICM, and myopericarditis/perimyocarditis in athletes, with a special emphasis on arrhythmias, patient-tailored therapies, and sports eligibility issues.

Sports Activity and Arrhythmic Risk in Cardiomyopathies and Channelopathies: A Critical Review of European Guidelines on Sports Cardiology in Patients with Cardiovascular Diseases.

The prediction and prevention of sudden cardiac death is the philosopher's stone of clinical cardiac electrophysiology. Sports can act as triggers of fatal arrhythmias and therefore it is essential to promptly frame the athlete at risk and to carefully evaluate the suitability for both competitive and recreational sports activity. A history of syncope or palpitations, the presence of premature ventricular complexes or more complex arrhythmias, a reduced left ventricular systolic function, or the presence of known or familiar heart disease should prompt a thorough evaluation with second level examinations. In this regard, cardiac magnetic resonance and electrophysiological study play important roles in the diagnostic work-up. The role of genetics is increasing both in cardiomyopathies and in channelopathies, and a careful evaluation must be focused on genotype positive/phenotype negative subjects. In addition to being a trigger for fatal arrhythmias in certain cardiomyopathies, sports also play a role in the progression of the disease itself, especially in the case arrhythmogenic right ventricular cardiomyopathy. In this paper, we review the latest European guidelines on sport cardiology in patients with cardiovascular diseases, focusing on arrhythmic risk stratification and the management of cardiomyopathies and channelopathies.

Electrocardiogram for the Diagnosis of Acute Myocardial Infarction in Patients with Right Ventricular Paced Rhythm: Old but Gold.

Ventricular pacing may interfere with the interpretation of ECG among patients with suspected acute myocardial infarction (AMI), with possible delay of reperfusion therapy. Since left bundle branch block has a similar ECG morphology to right ventricular paced rhythm, Sgarbossa and modified Sgarbossa criteria could be useful in this setting. We present four clinical cases in which a recently proposed clinical-instrumental algorithm has been adopted to manage patients with right ventricular paced rhythm and suspected AMI.

Prediction of Outcome in Embolic Strokes of Undetermined Source.

BACKGROUND AND AIM: Predicting outcome after stroke is a major goal and research field. The Embolic Stroke of Undetermined Source (ESUS) is a recently introduced clinical construct, and the prediction of outcome in this population has to be further explored. The aim of the study was to evaluate the prognostic validity and accuracy of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) score in patients with ESUS. METHODS: Consecutive patients hospitalized for acute ischemic stroke who met the ESUS diagnostic criteria were identified and the ASTRAL scores estimated. The study endpoint was the 3-month unfavorable outcome (modified Rankin Scale>2). Predictive performance was investigated through logistic regression analysis and discrimination and calibration tests. RESULTS: Among 202 patients with ESUS, 67 (33.2%) had unfavourable 3-month outcome. The ASTRAL score was an independent predictor of poor outcome [adjOR = 1.44, 95% confidence interval (CI) 1.30-1.60, P < .001], showed good discriminatory power (area under the receiver operating characteristic curve .913, 95% CI .871-.956) and was well calibrated (Hosmer-Lemeshow test P = .496). CONCLUSIONS: The ASTRAL score was an independent predictor of 3-month functional outcome and showed high predictive accuracy in patients with ESUS.

[Ten questions about myocardial infarction with non-obstructed coronary arteries]. / Dieci quesiti in tema di infarto miocardico in assenza di coronaropatia ostruttiva.

The term "MINOCA" refers to myocardial infarction with non-obstructed coronary arteries and has been used to define acute myocardial infarction with no angiographic evidence of significant epicardial coronary artery stenosis. Patients with MINOCA represent a rather heterogeneous group of acute coronary syndrome, and this may account for the wide variation in the incidence of MINOCA in different studies. Several pathogenic mechanisms have been suggested to underlie MINOCA, but the condition continues to represent a diagnostic and therapeutic challenge for the cardiologist. Therefore, an adequate diagnostic assessment, carefully characterizing the pathogenic mechanisms, and a selection of more targeted treatments are needed to improve clinical outcomes. In this focused review, we will try to provide answers to the most common questions on the causes, diagnosis, treatment, and outcomes of MINOCA.

Left Ventricular Twist and the "Rigid Body Rotation" Pattern in Patients Treated with Anthracyclines or Anti-HER2.

Background: During the physiological cardiac cycle, the helix orientation of the muscle fibres induces the rotation of the apex relative to the base of the left ventricular (LV). In heart failure, LV torsion is impaired, and rotation at basal and apical levels occurs in the same direction, a phenomenon called rigid body rotation (RBR). We aimed to evaluate whether the RBR pattern and GLS together could improve the diagnosis of cardiotoxicity in patients treated with anthracyclines and/or anti-HER2. Methods: With an observational, retrospective study involving 175 patients (mean age 55 ± 12 years, 94% females), we evaluated the development of cancer therapeutic-related cardiac dysfunction (CTRCD) defined according to ESC guidelines. We characterised LV dysfunction by echocardiographic standard and speckle-tracking (GLS and RBR pattern) measurements. Patients with a previous diagnosis of structural heart disease or atrial fibrillation were excluded. Results: At the time of enrolment, the chemotherapy regimen included trastuzumab (96%), pertuzumab (21%), and anthracyclines (13%). Twenty-two patients (12.5%) developed cardiotoxicity, and thirteen patients developed an RBR within 6 months of follow-up. In all cases, the RBR pattern was associated with cardiotoxicity (p < 0.001), reporting an optimal specificity but poor sensitivity at three and six months. However, the addition of the RBR pattern to the global longitudinal strain (GLS) ≥ -16% increased the odds ratio (OR) from 25.6 to 32.6 at three months and from 32.5 to 49.6 at six months rather than GLS alone. Conclusions: The RBR pattern improves the diagnostic accuracy of GLS for the detection of cardiotoxicity secondary to anthracyclines and anti-HER2-based treatments.

High-power short-duration catheter ablation of atrial fibrillation: is it really a new era? Comparison between new and old radiofrequency contact force-sensing catheters.

BACKGROUND: The clinical performance of high-power, short-duration (HPSD) pulmonary vein isolation (PVI) with the novel flexible tip TactiFlex™ (TFSE) catheter, as compared to standard-power, long-duration (SPLD) PVI using the TactiCath™ (TCSE) catheter among patients undergoing catheter ablation (CA) of atrial fibrillation (AF) is currently unknown. METHODS: We conducted a prospective, observational, single-centre study including 40 consecutive patients undergoing PVI for paroxysmal/persistent AF, using HPSD ablation with the novel TFSE catheter (HPSD/TFSE group). Based on propensity score-matching, forty patients undergoing SPLD PVI with the TCSE catheter were identified (SPLD/TCSE group). In the HPSD/TFSE group, RF lesions were performed by delivering 40-50 W for 10-20 s, while in the SPLD/TCSE group, RF power was 30-35 W, targeting a lesion size index (LSI) of 4.0-5.5. The co-primary study outcomes were time required to complete PVI and first pass isolation (FPI). RESULTS: PVI was achieved in 100% of patients in both groups, and no major adverse events were observed. Remarkably, PVI time was shorter in the HPSD/TFSE, compared to the SPLD/TCSE group(9 [7-9] min vs. 50 [37-54] min; p < 0.001), while FPI rate was non-significantly higher in the former group(91% [146/160] vs 83% [134/160]; p = 0.063). Shorter procedural (108 [91-120] min vs. 173 [139-187] min, p < 0.001), total RF (9 [7-11] min vs. 43 [32-53] min, p < 0.001), fluoroscopy times(15 [10-19] min vs. 18 [13-26] min, p = 0.014), and lower DAP (1461 [860-2181] vs. 7200 [3400-20,800], p < 0.001) were recorded in the HPSD/TFSE group. A higher average impedance drop was obtained with HPSD/TFSE CA(17[17-18]Ω vs. 16 [15-17] Ω, p < 0.001). CONCLUSIONS: In our initial clinical experience, HPSD PVI with the TFSE catheter proved faster than SPLD PVI with the TCSE catheter, at least equally effective in terms of FPI, and it was associated with greater impedance drop.

Comprehensive diagnostic workup in patients with suspected heart failure and preserved ejection fraction.

Diagnosis of heart failure with preserved ejection fraction (HFpEF) can be challenging and it could require different tests, some of which are affected by limited availability. Nowadays, considering that new therapies are available for HFpEF and related conditions, a prompt and correct diagnosis is relevant. However, the diagnostic role of biomarker level, imaging tools, score-based algorithms and invasive evaluation, should be based on the strengths and weaknesses of each test. The aim of this review is to help the clinician in diagnosing HFpEF, overcoming the diagnostic uncertainty and disentangling among the different underlying causes, in order to properly treat this kind of patient.

Posterior wall ablation for persistent atrial fibrillation: Very-high-power short-duration versus standard-power radiofrequency ablation.

Background: Posterior wall ablation (PWA) is commonly added to pulmonary vein isolation (PVI) during catheter ablation (CA) of persistent atrial fibrillation (AF). Objective: The purpose of this study was to compare PVI plus PWA using very-high-power short-duration (vHPSD) vs standard-power (SP) ablation index-guided CA among consecutive patients with persistent AF and to determine the voltage correlation between microbipolar and bipolar mapping in AF. Methods: We compared 40 patients undergoing PVI plus PWA using vHPSD to 40 controls receiving PVI plus PWA using SP. The primary efficacy endpoint was recurrence of atrial tachyarrhythmias after a 3-month blanking period. The primary safety outcome was a composite of major complications within 30 days after CA. In the vHPSD group, high-density mapping of the posterior wall was performed using both a multipolar catheter and microelectrodes on the tip of the ablation catheter. Results: PVI was more commonly obtained with vHPSD compared to SP ablation (98%vs 75%; P = .007), despite shorter procedural and fluoroscopy times (P <.001). Survival free from recurrent atrial tachyarrhythmias at 18 months was 68% and 47% in the vHPSD and SP groups, respectively (log-rank P = .071), without major adverse events. The vHPSD approach was significantly associated with reduced risk of recurrent AF at multivariable analysis (hazard ratio 0.39; P = .030). Microbipolar voltage cutoffs of 0.71 and 1.69 mV predicted minimum bipolar values of 0.16 and 0.31 mV in AF, respectively, with accuracies of 0.67 and 0.88. Conclusion: vHPSD PWA plus PVI may be faster and as safe as SP CA among patients with persistent AF, with a trend for superior efficacy. Adapted voltage cutoffs should be used for identifying atrial low-voltage areas with microbipolar mapping.

Impact of coronary microvascular dysfunction in heart failure with preserved ejection fraction: a meta-analysis.

AIMS: Several mechanisms have been identified in the aetiopathogenesis of heart failure with preserved ejection fraction (HFpEF). Among these, coronary microvascular dysfunction (CMD) may play a key pathophysiological role. We performed a systematic review and meta-analysis to investigate the prevalence, echocardiographic correlates, and prognostic implications of CMD in patients with HFpEF. METHODS AND RESULTS: A systematic search for articles up to 1 May 2023 was performed. The primary aim was to assess the prevalence of CMD. Secondary aims were to compare key echocardiographic parameters (E/e' ratio, left atrial volume index [LAVi], and left ventricular mass index [LVMi]), clinical outcomes [death and hospitalization for heart failure (HF)], and prevalence of atrial fibrillation (AF) between patients with and without CMD. Meta-regressions according to baseline patient characteristics and study features were performed to explore potential heterogeneity sources. We identified 14 observational studies, enrolling 1138 patients with HFpEF. The overall prevalence of CMD was 58%. Compared with patients without CMD, patients with HFpEF and CMD had larger LAVi [mean difference (MD) 3.85 confidence interval (CI) 1.19-6.5, P < 0.01)], higher E/e' ratio (MD 2.76 CI 1.54-3.97; P < 0.01), higher prevalence of AF (odds ratio 1.61 CI 1.04-2.48, P = 0.03) and higher risk of death or hospitalization for HF [hazard ratio 3.19, CI 1.04-9.57, P = 0.04]. CONCLUSIONS: CMD is present in little more than half of the patients with HFpEF and is associated with echocardiographic evidence of more severe diastolic dysfunction and a higher prevalence of AF, doubling the risk of death or HF hospitalization.

Sex differences in patients presenting with acute coronary syndrome: a state-of-the-art review.

Cardiovascular conditions in the spectrum of acute coronary syndromes are characterized by sex differences with regard to pathophysiology, risk factors, clinical presentation, invasive and pharmacologic treatment, and outcomes. This review delves into these differences, including specific subsets like myocardial infarction with non-obstructed coronary arteries or Spontaneous Coronary Artery Dissection, and alternative diagnoses like Takotsubo cardiomyopathy or myocarditis. Moreover, practical considerations are enclosed, on how a sex-specific approach should be integrated in clinical practice: in fact, personal history should focus on female-specific risk factors, and hormonal status and hormonal therapy should be assessed. Moreover, physical and psychological stressors should be investigated, particularly in the event of Spontaneous Coronary Artery Dissection or Takotsubo cardiomyopathy.

Characteristics and Clinical Value of Electroanatomic Voltage Mapping in Cardiac Amyloidosis.

BACKGROUND: Cardiac amyloidoses (CAs) are an increasingly recognised group of infiltrative cardiomyopathies associated with high risk of adverse cardiac events. We sought to characterise the characteristics and clinical value of right ventricular (RV) electroanatomic voltage mapping (EVM) in CA. METHODS: Fifteen consecutive patients undergoing endomyocardial biopsy (EMB) for suspected CA (median age 75 years, 1st-3rd quartiles 64-78 years], 67% male) were enrolled in an observational prospective study. Each patient underwent RV high-density EVM using a multipolar catheter and EMB. The primary outcome was death or heart failure hospitalisation at 1-year follow-up. We recorded electrographic features at EMB sampling sites and electroanatomic data in the overall RV, and explored their correlations with histopathologic findings and primary outcomes events. RESULTS: A final EMB-proven diagnosis of immunoglobulin light chain or transthyretin CA was formulated in 6 and 9 patients, respectively. Electrogram amplitudes in the bipolar and unipolar configurations averaged 1.55 ± 0.44 mV and 5.14 ± 1.50 mV, respectively, in the overall RV, with lower values in AL CA patients. We found a significant inverse correlation between both bipolar and unipolar electrogram amplitude and amyloid burden according to EMB (P = 0.001 and P = 0.025, respectively). At 1-year follow-up, 7 patients (47%) experienced a primary outcome event; the extent of bipolar dense scar area at RV EVM was an independent predictor of primary outcome events at multivariable analysis (odds ratio 2.40; P = 0.037). CONCLUSIONS: In CA, electrogram amplitudes are around the lower limit of normal yet disproportionately low compared with the increased wall thickness. Out data suggest that RV electrogram amplitude may be a quantitative marker of amyloid burden, and that RV EVM may have prognostic value.

[Definition, classification and diagnosis of myocardial infarction with non-obstructive coronary artery disease: where do we stand?] / Definizione, classificazione e diagnosi di infarto miocardico in assenza di coronaropatia ostruttiva: a che punto siamo?

The systematic use of coronary angiography and the availability of increasingly sensitive biomarkers of myocardial cytolysis have determined an increase in the diagnosis of myocardial infarction with non-obstructed coronary arteries (MINOCA), which is currently reported in 5-20% of patients with acute myocardial infarction. The first diagnostic criteria of MINOCA were reported by a position paper of the European Society of Cardiology in 2017; since then, these criteria have been revised several times until the current version. The diagnosis of MINOCA requires not only the presence of myocardial damage, indicated by the detection of a rise or fall in cardiac troponin with at least one value above the 99th percentile upper reference limit, but also the clinical evidence of acute myocardial infarction as shown by symptoms, ECG, or imaging. This definition resulted in the exclusion from the umbrella group of MINOCA of certain conditions, such as takotsubo syndrome and myocarditis, that do not have a clear ischemic etiology. The term MINOCA encompasses heterogeneous conditions from a pathophysiological, clinical and therapeutic perspective. For this reason, MINOCA should be used to identify a "working diagnosis", which is the first step of a diagnostic work-up aimed at clarifying the mechanisms and identifying the most appropriate therapy for the individual patient. The aim of this review is to describe the state of the art regarding the definition, classification, and diagnosis of MINOCA, providing an excursus on the principal documents proposed by scientific societies or experts in the field in recent years.