Determinants of Ventricular Arrhythmias in Mitral Valve Prolapse.

BACKGROUND: Mitral valve prolapse (MVP) may be associated with ventricular arrhythmias (VA) even in the absence of significant valvular regurgitation. Curling, mitral annulus disjunction (MAD) and myocardial fibrosis (late gadolinium enhancement [LGE]) may account for arrhythmogenesis. OBJECTIVES: This study investigated the determinants of VA in patients with MVP without significant regurgitation. METHODS: This study included 108 patients with MVP (66 female; median age: 48 years) without valve regurgitation. All patients underwent 12-lead electrocardiography, 12-lead 24-hour electrocardiographic Holter monitoring, exercise stress test, and cardiac magnetic resonance. Patients were divided into 2 groups (arrhythmic and no-arrhythmic MVP), according to the presence of VA with a right bundle branch block pattern. RESULTS: The 62 patients (57%) with arrhythmic MVP showed: 1) higher MAD (median length: 6.0 vs 3.2 mm; P = 0.017); 2) higher prevalence of curling (79% vs 52%; P = 0.012); and 3) higher prevalence of left ventricular LGE (79% vs 52%; P = 0.012). Mediation analysis showed that curling had both a direct (P = 0.03) and indirect effect mediated by LGE (P = 0.04) on VA, whereas the association between MAD and VA was completely mediated by LGE. Patients with severe VA showed more pronounced morphofunctional alterations, in terms of MAD (7.0 vs 4.6 mm; P = 0.004) and presence and severity of curling (respectively, 91% vs 64%; P = 0.010; and 4 vs 3 mm; P = 0.004), compared to those without severe VA. CONCLUSIONS: In patients with MVP the occurrence of VA with right bundle branch block morphology is the expression of more severe morphologic, mechanical, and tissue alterations. Curling has both a direct and an indirect effect on VA.

Thinning of compact layer and systolic dysfunction in isolated left ventricular non-compaction: A cardiac magnetic resonance study.

BACKGROUND: The Petersen' index reflects an excess of myocardial trabeculation which is not a specific morpho-functional feature of left ventricular non-compaction (LVNC) cardiomyopathy, but a "phenotypic trait" even observed in association with other myocardial diseases and over-loading conditions. The present study was designed to evaluate the relation between a critical thinning of compact layer and the development of systolic dysfunction and LVNC cardiomyopathy. METHODS: We compared CMR morpho-functional features and measurements of LV wall thickness using a 17 segment model of a cohort of patients fulfilling the Petersen criterion for LVNC with LV systolic dysfunction versus those of a cohort of age- and sex-matched controls with LVNC and preserved LV systolic function. All the study patients had an "isolated" LVNC defined as positive Petersen criterion in the absence of other diseases such as hypertrophic and dilated cardiomyopathy, valvular heart disease, or congenital heart disease and over-loading conditions. RESULTS: he study population included 33 patients with "isolated" LVNC: 11 consecutive index patients with a reduced LV ejection fraction (LVNCrEF) and 22 controls with a preserved LVEF (LVNCpEF). The compact myocardial layer was thinner in patients with LVNCrEF than in those with LVNCpEF patients, both in mid-ventricular and apical LV segments. On linear regression analysis, there was a linear correlation between median thickness of mid-ventricular free wall segments and left ventricular ejection fraction (r = 0.51, p = 0.005). On the ROC curves analysis, ≥2 segments with a compact myocardial layer <5 mm in the free wall mid-ventricular segments showed the best accuracy for reduced LVEF (100% sensitivity and 60% specificity; AUC 0.81, p < 0.01). The negative predictive value for LV systolic dysfunction of <2 free wall mid ventricular segments <5 mm was 100%. On quantitative analysis, the mass of papillary muscles was lower in patients with LVNCrEF [1.2 (0.8-1.4) versus 1.6 (1.1-1.8) g/mq; p = 0.08]. CONCLUSIONS: A thinned compact layer of mid-ventricular segments of the LV free wall was associated with a reduced systolic function and "isolated" LVNC cardiomyopathy.

Left ventricular fibrosis in arrhythmic mitral valve prolapse: quantification and comparison of semi-automated techniques assessed by cardiac magnetic resonance.

PURPOSE: Left ventricular (LV) fibrosis has a key role in arrhythmogenesis in patients with mitral valve prolapse (MVP). Cardiac magnetic resonance identifies LV fibrosis by using late gadolinium enhancement (LGE) technique. LGE assessment and quantification in patients with MVP lacks of standardization protocols. METHODS: 66 MVP patients with normal systolic function and without significant regurgitation were enrolled. Semi-automated gray-scale thresholding techniques using full width at half maximum (FWHM) and 2, 3 and 5 standard deviation (SD) above the remote myocardium were used and compared with the visual assessment, considered as the gold standard. RESULTS: LGE was identified in 41 MVP patients (62%) and quantified. The mean quantity of LGE visually assessed was 2.40 ± 1.07% or 1.40 ± 0.82 g. With FWHM, LGE resulted 3.56 ± 1.23% or 1.99 ± 1.13 g. Using thresholding, the mean LGE quantity was 9.2 ± 3.1% or 4.82 ± 2.28 g for 2-SD, 5.72 ± 1.75% or 3.06 ± 1.47 g for 3-SD and 2.36 ± 0.99% or 1.29 ± 0.79 g for 5-SD. The 5-SD measurement in percentage demonstrated a good correlation with LGE quantification visually assessed (2.40 ± 1.07 vs. 2.363 ± 0.9909, p = 0.543). When compared with the gold standard, the 5-SD threshold quantification, both in percentage and in grams, revealed the least intra-observer (respectively, ICC: 0.976 and 0.966) and inter-observer variability (respectively ICC: 0.948 and 0.935). CONCLUSION: The 5-SD gray-scale threshold technique in percentage revealed the best correlation with the visual assessment and an optimal reproducibility in MVP patient.

Electrocardiographic characteristics of right-bundle-branch-block premature ventricular complexes predicting absence of left ventricular scar in athletes with apparently structural normal heart.

AIMS: Left ventricular scar is an arrhythmic substrate that may be missed by echocardiography and diagnosed only by cardiac magnetic resonance (CMR), which is a time-consuming and expensive imaging modality. Premature ventricular complexes (PVCs) with a right-bundle-branch-block (RBBB) pattern are independent predictors of late gadolinium enhancement (LGE) but their positive predictive value is low. We studied which electrocardiographic features of PVCs with an RBBB pattern are associated with a higher probability of the absence of an underlying LGE. METHODS: The study included 121 athletes (36 ± 16 years; 48.8% men) with monomorphic PVCs with an RBBB configuration and normal standard clinical investigations who underwent CMR. LGE was identified in 35 patients (29%), predominantly in those with PVCs with a superior/intermediate axis (SA-IntA) compared to inferior axis (IA) (38% vs. 10%, P = 0.002). Among patients with SA-IntA morphology, the contemporary presence of qR pattern in lead aVR and V1 was exclusively found in patients without LGE at CMR (51.0% vs. 0%, P < 0.0001). Among patients with IA, the absence of LGE correlated to a narrow ectopic QRS (145 ± 16 vs. 184 ± 27 msec, P < 0.001). CONCLUSIONS: Among athletes with apparently idiopathic PVCs with a RBBB configuration, the presence of a concealed LGE at CMR was documented in 29% of cases, mostly in those with a SA-IntA. In our experience, the contemporary presence of qR pattern in lead aVR and V1 in PVCs with RBBB/SA-IntA morphology or, on the other hand, a relatively narrow QRS in PVCs with an IA, predicted absence of LGE.

Scarring/arrhythmogenic cardiomyopathy.

The designation of 'arrhythmogenic cardiomyopathy' reflects the evolving concept of a heart muscle disease affecting not only the right ventricle (ARVC) but also the left ventricle (LV), with phenotypic variants characterized by a biventricular (BIV) or predominant LV involvement (ALVC). Herein, we use the term 'scarring/arrhythmogenic cardiomyopathy (S/ACM)' to emphasize that the disease phenotype is distinctively characterized by loss of ventricular myocardium due to myocyte death with subsequent fibrous or fibro-fatty scar tissue replacement. The myocardial scarring predisposes to potentially lethal ventricular arrhythmias and underlies the impairment of systolic ventricular function. S/ACM is an 'umbrella term' which includes a variety of conditions, either genetic or acquired (mostly post-inflammatory), sharing the typical 'scarring' phenotypic features of the disease. Differential diagnoses include 'non-scarring' heart diseases leading to either RV dilatation from left-to-right shunt or LV dilatation/dysfunction from a dilated cardiomyopathy. The development of 2020 upgraded criteria ('Padua criteria') for diagnosis of S/ACM reflected the evolving clinical experience with the expanding spectrum of S/ACM phenotypes and the advances in cardiac magnetic resonance (CMR) imaging. The Padua criteria aimed to improve the diagnosis of S/ACM by incorporation of CMR myocardial tissue characterization findings. Risk stratification of S/ACM patients is mostly based on arrhythmic burden and ventricular dysfunction severity, although other ECG or imaging parameters may have a role. Medical therapy is crucial for treatment of ventricular arrhythmias and heart failure. Implantable cardioverter defibrillator (ICD) is the only proven life-saving treatment, despite its significant morbidity because of device-related complications and inappropriate shocks. Selection of patients who can benefit the most from ICD therapy is one of the most challenging issues in clinical practice.

Reproducibility of ventricular arrhythmias at exercise testing for prediction of non-ischaemic left ventricular scar in athletes.

AIMS: The non-ischaemic left ventricular scar (NILVS) is an emerging substrate of ventricular arrhythmias (VA) in the athlete. We tested the diagnostic value of VA reproducibility at repeated exercise testing (ET). METHODS AND RESULTS: We included consecutive athletes who underwent cardiac magnetic resonance (CMR) for evaluation of VA and two consecutive ET off-therapy within 12 months. Those with a positive family history of premature sudden death/cardiomyopathy, syncope/pre-syncope, ECG or echocardiography abnormalities, or low-risk VA (exercise-suppressed infundibular or fascicular VA) were excluded. The NILVS was defined as subepicardial/midmyocardial stria of late gadolinium enhancement involving >5% of the LV mass. Reproducibility was defined as the occurrence of VA with the same pattern and behaviour during repeated ET. Of 325 athletes who underwent CMR for evaluation of VA, 75 were included, and 30 showed NILVS involving three [2-4] LV segments. At first ET, athletes with NILVS showed a higher prevalence of exercise-induced VA (93% vs. 53%, P < 0.001), while other VA characteristics did not differ between groups. At repeated ET, reproducibility was observed in 97% of athletes with vs. 13% without NILVS (P < 0.001). The remaining 87% of athletes with normal CMR either did not show any VA at repeated ET (59%) or showed arrhythmias with different patterns, mostly infundibular. Reproducibility yielded a positive predictive value for NILVS of 83% and a negative predictive value of 98%. CONCLUSION: VA reproducibility at repeated ET predicted an underlying NILVS in athletes with VA and otherwise normal clinical work-up. This finding may improve risk stratification and appropriate CMR referral of athletes with apparently idiopathic VA.

May Strenuous Endurance Sports Activity Damage the Cardiovascular System of Healthy Athletes? A Narrative Review.

The positive effects of physical activity are countless, not only on the cardiovascular system but on health in general. However, some studies suggest a U-shape relationship between exercise volume and effects on the cardiovascular system. On the basis of this perspective, moderate-dose exercise would be beneficial compared to a sedentary lifestyle, while very high-dose physical activity would paradoxically be detrimental. We reviewed the available evidence on the potential adverse effects of very intense, prolonged exercise on the cardiovascular system, both acute and chronic, in healthy athletes without pre-existing cardiovascular conditions. We found that endurance sports activities may cause reversible electrocardiographic changes, ventricular dysfunction, and troponin elevation with complete recovery within a few days. The theory that repeated bouts of acute stress on the heart may lead to chronic myocardial damage remains to be demonstrated. However, male veteran athletes with a long sports career show an increased prevalence of cardiovascular abnormalities such as electrical conduction delay, atrial fibrillation, myocardial fibrosis, and coronary calcifications compared to non-athletes. It must be underlined that the cause-effect relationship between such abnormalities and the exercise and, most importantly, the prognostic relevance of such findings remains to be established.

Certainties and Uncertainties of Cardiac Magnetic Resonance Imaging in Athletes.

Prolonged and intensive exercise induces remodeling of all four cardiac chambers, a physiological process which is coined as the "athlete's heart". This cardiac adaptation, however, shows overlapping features with non-ischemic cardiomyopathies, such as dilated, arrhythmogenic and hypertrophic cardiomyopathy, also associated with athlete's sudden cardiac death. Cardiac magnetic resonance (CMR) is a well-suited, highly reproducible imaging modality that can help differentiate athlete's heart from cardiomyopathy. CMR allows accurate characterization of the morphology and function of cardiac chambers, providing full coverage of the ventricles. Moreover, it permits an in-depth understanding of the myocardial changes through specific techniques such as mapping or late gadolinium enhancement. In this narrative review, we will focus on the certainties and uncertainties of the role of CMR in sports cardiology. The main aspects of physiological adaptation due to regular and intensive sports activity and the application of CMR in highly trained athletes will be summarized.

Role of Cardiac Magnetic Resonance Imaging in the Evaluation of Athletes with Premature Ventricular Beats.

Premature ventricular beats (PVBs) in athletes are not rare. The risk of PVBs depends on the presence of an underlying pathological myocardial substrate predisposing the subject to sudden cardiac death. The standard diagnostic work-up of athletes with PVBs includes an examination of family and personal history, resting electrocardiogram (ECG), 24 h ambulatory ECG (possibly with a 12-lead configuration and including a training session), maximal exercise testing and echocardiography. Despite its fundamental role in the diagnostic assessment of athletes with PVBs, echocardiography has very limited sensitivity in detecting the presence of non-ischemic left ventricular scars, which can be revealed only through more in-depth studies, particularly with the use of contrast-enhanced cardiac magnetic resonance (CMR) imaging. The morphology, complexity and exercise inducibility of PVBs can help estimate the probability of an underlying heart disease. Based on these features, CMR imaging may be indicated even when echocardiography is normal. This review focuses on interpreting PVBs, and on the indication and role of CMR imaging in the diagnostic evaluation of athletes, with a special focus on non-ischemic left ventricular scars that are an emerging substrate of cardiac arrest during sport.

Strength of clinical indication and therapeutic impact of the implantable cardioverter defibrillator in patients with hypertrophic cardiomyopathy.

BACKGROUND: The implantable cardioverter defibrillator(ICD) has revolutionized the management of patients with hypertrophic cardiomyopathy (HCM) at risk of sudden cardiac death (SCD). However, the identification of ideal candidates remains challenging. We aimed to describe the long-term impact of the ICD for primary prevention in patients with HCM based on stringent (high SCD risk) vs lenient indications (need for pacing/personal choice). METHODS: Data from two Italian HCM Cardiomyopathy Units were retrospectively analyzed. Only patients >1 follow-up visits were divided into two groups according to ICD candidacy:stringent (high SCD risk) and lenient (need for pacing, patients' choice, physician advice despite lack of high SCD risk). Major cardiac events (composite of appropriate shock/intervention and SCD) was the primary endpoint. A safety endpoint was defined as a composite of inappropriate shocks and device-related complications. RESULTS: Of 2009 patients, 252(12.5%) received an ICD, including 27(1.3%) in secondary prevention and 225(11.2%) in primary prevention (age at implantation 49 ± 16 years; men 65.3%). Among those in primary prevention, 167(74.2%) had stringent, while 58(25.8%) had lenient indications. At 5 ± 4 years, only stringent ICD patients experienced major cardiac events (2.84%/year, 5-year cumulative incidence: 8.1%, 95%CI [3.5-14.1%]). ICD-related complications were similar across stringent and lenient subgroups. However, patients implanted >60 years had a significantly higher risk of adverse events. CONCLUSION: One third of ICD recipients with HCM in primary prevention received a lenient implantation and had no appropriate intervention. ICD implantation due to systematic upgrade in patients requiring pacing and increased risk perception may offer little advantage and increase complication rates.

The 2020 "Padua Criteria" for Diagnosis and Phenotype Characterization of Arrhythmogenic Cardiomyopathy in Clinical Practice.

Arrhythmogenic Cardiomyopathy (ACM) is a heredo-familial cardiac disease characterized by fibro-fatty myocardial replacement and increased risk of sudden cardiac death. The diagnosis of ACM can be challenging due to the lack of a single gold-standard test: for this reason, it is required to satisfy a combination of multiple criteria from different categories including ventricular morpho-functional abnormalities, repolarization and depolarization ECG changes, ventricular arrhythmias, tissue characterization findings and positive family history/molecular genetics. The first diagnostic criteria were published by an International Task Force (ITF) of experts in 1994 and revised in 2010 with the aim to increase sensitivity for early diagnosis. Limitations of the 2010 ITF criteria include the absence of specific criteria for left ventricle (LV) involvement and the limited role of cardiac magnetic resonance (CMR) as the use of the late gadolinium enhancement technique for tissue characterization was not considered. In 2020, new diagnostic criteria ("the Padua criteria") were proposed. The traditional organization in six categories of major/minor criteria was maintained. The criteria for identifying the right ventricular involvement were modified and a specific set of criteria for identifying LV involvement was created. Depending on the combination of criteria for right and LV involvement, a diagnosis of classic (right dominant) ACM, biventricular ACM or left-dominant ACM is then made. The article reviews the rationale of the Padua criteria, summarizes the main modifications compared to the previous 2010 ITF criteria and provides three examples of the application of the Padua criteria in clinical practice.

Electrocardiographic Predictors of Primary Ventricular Fibrillation and 30-Day Mortality in Patients Presenting with ST-Segment Elevation Myocardial Infarction.

Primary ventricular fibrillation (PVF) may occur in the early phase of ST-elevation myocardial infarction (STEMI) prior to primary percutaneous coronary intervention (PCI). Multiple electrocardiographic STEMI patterns are associated with PVF and short-term mortality including the tombstone, Lambda, and triangular QRS-ST-T waveform (TW). We aimed to compare the predictive value of different electrocardiographic STEMI patterns for PVF and 30-day mortality. We included a consecutive cohort of 407 STEMI patients (75% males, median age 66 years) presenting within 12 h of symptoms onset. At first medical contact, 14 (3%) showed the TW or Lambda ECG patterns, which were combined in a single group (TW-Lambda pattern) characterized by giant R-wave and downsloping ST-segment. PVF prior to primary PCI occurred in 39 (10%) patients, significantly more often in patients with the TW-Lambda pattern than those without (50% vs. 8%, p < 0.001). For the multivariable analysis, Killip class ≥3 (OR 6.19, 95% CI 2.37-16.1, p < 0.001) and TW-Lambda pattern (OR 9.64, 95% CI 2.99-31.0, p < 0.001) remained as independent predictors of PVF. Thirty-day mortality was also higher in patients with the TW-Lambda pattern than in those without (43% vs. 6%, p < 0.001). However, only LVEF (OR 0.86, 95% CI 0.82-0.90, p < 0.001) and PVF (OR 4.61, 95% CI 1.49-14.3, p = 0.042) remained independent predictors of mortality. A mediation analysis showed that the effect of TW-Lambda pattern on mortality was mediated mainly via the reduced LVEF. In conclusion, among patients presenting with STEMI, the electrocardiographic TW-Lambda pattern was associated with both PVF before PCI and 30-day mortality. Therefore, this ECG pattern may be useful for early risk stratification of STEMI.

Coronary artery calcium on standard chest computed tomography predicts cardiovascular events after liver transplantation.

AIMS: Cardiac complications are a leading cause of mortality after orthotopic liver transplantation (LT) and pre-operative risk stratification is challenging. We evaluated whether coronary artery calcium (CAC) score calculated on a standard (non-thin layer, non-ECG gated) chest computed tomography (CT) predicted cardiac outcome after LT. METHODS: We included a consecutive series of LT recipients who underwent pre-operative cardiac evaluation including stress-testing or cardiac catheterization in high-risk patients. Patients with a history of coronary artery disease or coronary revascularization were excluded. The CAC score was calculated from the chest CT routinely performed before LT. CAC values were not available at the time of pre-transplant cardiac evaluation and did not affect LT eligibility. The primary end-point included peri-operative arrhythmic cardiac arrest and sustained ventricular arrhythmias; heart failure, myocardial infarction and cardiac death within 1-year after LT. RESULTS: The study population consisted of 301 patients (median age 56 years, 76% males). At chest CT, 49% had CAC = 0; 27% had CAC = 1-99, 15% had CAC = 100-399 and 9% CAC > 400. The primary end-point incidence increased from 7% in patients with CAC = 0 to 27% in patients with CAC > 400 (p = 0.007). At multivariable analysis including traditional risk factors, CAC remained an independent predictor of cardiac events (p = 0.01). CONCLUSIONS: CAC score calculated on a standard chest CT stratified the risk of cardiac events in patients who underwent LT after negative pre-transplant cardiac evaluation. These findings suggest that evaluation of CAC from a standard chest CT performed for other reasons can be used as an early cardiac risk stratification tool before LT.