Dark papillary muscles sign: a novel prognostic marker for cardiac magnetic resonance.

OBJECTIVES: The prognostic role of left ventricular (LV) papillary muscle abnormalities in patients with preserved LV systolic ejection fraction (LVEF) is unknown. We sought to evaluate the prognosis role of LV papillary muscle abnormalities by CMR in patients with ventricular arrhythmias, preserved LVEF with no cardiac disease. METHODS: A total of 391 patients with > 500/24 h premature ventricular complexes and/or with non-sustained ventricular tachycardia (NSVT), preserved LVEF, and no cardiac disease were enrolled. Different features of LV papillary muscles were considered: supernumerary muscles, papillary thickness, the attachment, late gadolinium enhancement (LGE). Dark-Paps was defined as end-systolic signal hypointensity of both papillary muscles in early post-contrast cine CMR images. Mitral valve prolapse, mitral annular disjunction (MAD), and myocardial LGE were considered. RESULTS: Dark-Paps was found in 79 (20%) patients and was more frequent in females. It was associated with higher prevalence of mitral valve prolapse and MAD. During a median follow-up of 2534 days, 22 hard cardiac events occurred. At Kaplan-Meier curve analysis, patients with Dark-Paps were at higher risk of events than those without (p < 0.0001). Dark-Paps was significantly associated with hard cardiac events in all the multivariate models. Dark-Paps improved prognostic estimation when added to NSVT (p = 0.0006), to LGE (p = 0.005) and to a model including NSVT+LGE (p = 0.014). Dark-Paps allowed a significant net reclassification when added to NSVT (NRI 0.30, p = 0.03), to LGE (NRI 0.25, p = 0.04), and to NSVT + LGE (NRI 0.32, p  = 0.02). CONCLUSIONS: In LV papillary muscles, Dark-Paps is a novel prognostic marker in patients with ventricular arrhythmias and preserved ejection fraction. KEY POINTS: • Papillary muscle abnormalities are seen in patients with ventricular arrhythmias and preserved left ventricular ejection fraction. • Early post-contrast hypointensity of papillary muscles in end-systolic cine images (Dark-Paps) is a novel prognostic marker in patients with ventricular arrhythmias and preserved ejection fraction. • Dark-Paps had an additive prognostic role over late gadolinium enhancement and non-sustained ventricular tachycardia.

The Arrhythmic Phenotype in Cardiomyopathy.

In the wide phenotypic spectrum of cardiomyopathies, sudden cardiac death (SCD) has always been the most visible and devastating disease complication. The introduction of implantable cardioverter-defibrillators for SCD prevention by the late 1980s has moved the question from how to whom we should protect from SCD, leaving clinicians with a measure of uncertainty regarding the most reliable option to guide identification of the highest-risk patients. In this review, we will go through all the available evidence in the field of arrhythmic expression and arrhythmic risk stratification in the different phenotypes of cardiomyopathies to provide practical suggestions in daily clinical management.

Prognostic Role of the Progression of Late Gadolinium Enhancement in Hypertrophic Cardiomyopathy.

In hypertrophic cardiomyopathy (HCM), late gadolinium enhancement (LGE) extent ≥15% of left ventricular mass is considered a prognostic risk factor. LGE extent increases over time and the clinical role of the progression of LGE over time (LGE rate) was not prospectively evaluated. We sought to evaluate the prognostic role of the LGE rate in HCM. We enrolled 105 patients with HCM who underwent cardiac magnetic resonance (CMR) at baseline (CMR-I) and after ≥2 years of follow-up (CMR-II). LGE rate was defined as the ratio between the increase of LGE extent (grams) and the time interval (months) between examinations. A combined end point of sudden cardiac death, resuscitated cardiac arrest, appropriate Implanted Cardioverter Defibrillator (ICD) intervention, and sustained ventricular tachycardia was used (hard events). The percentage of patients with LGE extent ≥15% increased from 9% to 20% from CMR-I to CMR-II (p = 0.03). During a median follow-up of 52 months, 25 hard events were recorded. The presence of LGE ≥15% at CMR-II allowed a significant reclassification of the risk of patients than at LGE ≥15% at CMR-I (net reclassification improvement 0.21, p = 0.046). On the MaxStat analysis, the optimal prognostic cut point for LGE rate was >0.07 g/month. On the Kaplan-Meier curve, patients with LGE rate >0.07 had worse prognosis than those without (p <0.0001). LGE rate >0.07 allowed a significant reclassification of the risk compared with LGE ≥15% at CMR-I and at CMR-II (net reclassification improvement 0.49, p = 0.003). In the multivariable models, LGE rate >0.07 was the best independent predictor of hard events. In conclusion, CMR should be repeated after 2 years to reclassify the risk for sudden death of those patients. A high LGE rate may be considered a novel prognostic factor in HCM.

Cardiac Magnetic Resonance Feature-Tracking Identifies Preclinical Abnormalities in Hypertrophic Cardiomyopathy Sarcomere Gene Mutation Carriers.

BACKGROUND: Assessing myocardial strain by cardiac magnetic resonance feature tracking (FT) has been found to be useful in patients with overt hypertrophic cardiomyopathy (HCM). Little is known, however, of its role in sarcomere gene mutation carriers without overt left ventricular hypertrophy (subclinical HCM). METHODS: Thirty-eight subclinical HCM subjects and 42 healthy volunteers were enrolled in this multicenter case-control study. They underwent a comprehensive cardiac magnetic resonance study. Two-dimensional global radial, circumferential, and longitudinal strain of the left ventricle (LV) were evaluated by FT analysis. RESULTS: The subclinical HCM sample was 41 (22-51) years old and 32% were men. FT analysis revealed a reduction in global radial strain (29±7.2 versus 47.9±7.4; P<0.0001), global circumferential strain (-17.3±2.6 -versus -20.8±7.4; P<0.0001) and global longitudinal strain (-16.9±2.4 versus -20.5±2.6; P<0.0001) in subclinical HCM compared with control subjects. The significant differences persisted when considering the 23 individuals free of all the structural and functional ECG and cardiac magnetic resonance abnormalities previously described. Receiver operating characteristic curve analyses showed that the differential diagnostic performances of FT in discriminating subclinical HCM from normal subjects were good to excellent (global radial strain with optimal cut-off value of 40.43%: AUC, 0.946 [95% CI, 0.93-1.00]; sensitivity 90.48%, specificity 94.44%; global circumferential strain with cut-off, -18.54%: AUC, 0.849 [95% CI, 0.76-0.94]; sensitivity, 88.10%; specificity, 72.22%; global longitudinal strain with cut-off, -19.06%: AUC, 0.843 [95% CI, 0.76-0.93]; sensitivity, 78.57%; specificity, 78.95%). Similar values were found for discriminating those subclinical HCM subjects without other phenotypic abnormalities from healthy volunteers (global radial strain with optimal cut-off 40.43%: AUC, 0.966 [95% CI, 0.92-1.00]; sensitivity, 90.48%; specificity, 95.45%; global circumferential strain with cut-off, -18.44%: AUC, 0.866 [95% CI, 0.76-0.96]; sensitivity, 92.86%; specificity, 77.27%; global longitudinal strain with cut-off, -17.32%: AUC, 0.838 [95% CI, 0.73-0.94]; sensitivity, 90.48%; specificity, 65.22%). CONCLUSIONS: Cardiac magnetic resonance FT-derived parameters are consistently lower in subclinical patients with HCM, and they could emerge as a good tool for discovering the disease during a preclinical phase.

Clinical characteristics and outcome of end stage hypertrophic cardiomyopathy: Role of age and heart failure phenotypes.

BACKGROUND: A minority of patients with hypertrophic cardiomyopathy (HCM) presents advanced heart failure (HF) during their clinical course, in the context of left ventricular (LV) remodeling with reduced LV ejection fraction (LVEF), or of severe diastolic dysfunction without impaired LVEF. Aim of this study was to describe a multicentric end stage (ES) HCM population and analyze clinical course and outcome among its different phenotypes. METHODS: Data of all HCM patients from 7 Italian referral centres were retrospectively evaluated. ES was diagnosed in presence of: LVEF <50% (ES-rEF) or NYHA functional class ≥II with severe diastolic dysfunction (ES-pEF). Outcomes were: HCM-related and all-cause mortality; combined arrhythmic events; advanced HF treatments. RESULTS: Study population included 331 ES patients; 87% presented ES-rEF and 13% ES-pEF. At ES recognition, patients with ES-pEF were more commonly females, had more frequently NYHA III/IV, atrial fibrillation and greater maximal LV wall thickness. Over a median follow-up of 5.6 years, 83 (25%) patients died, 46 (15%) experienced arrhythmic events and (26%) 85 received advanced HF treatments. Incidence of HCM-related and all-cause mortality, and of combined arrhythmic events did not differ in ES-pEF and ES-rEF patients, but ES-pEF patients were less likely to receive advanced HF treatments. Older age at ES recognition was an independent predictor of increased HCM-related mortality (p = 0.01) and reduced access to advanced HF treatments (p < 0.0001). CONCLUSIONS: Two different HCM-ES phenotypes can be recognized, with ES-pEF showing distinctive features at ES recognition and receiving less frequently advanced HF treatments. Older age at ES recognition has a major impact on outcomes.

Transcatheter Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy: A Multicenter Propensity Score-Based Analysis.

Background: The prognostic impact of catheter ablation (CA) of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients has not yet been satisfactorily elucidated. Objectives: The aim of the study was to assess the impact of CA of AF on clinical outcomes in a large cohort of HCM patients. Methods: In this retrospective multicenter study, 555 HCM patients with AF were enrolled, 140 undergoing CA and 415 receiving medical therapy. 1:1 propensity score matching led to the inclusion of 226 patients (113 medical group, 113 intervention group) in the final analysis. The primary outcome was a composite of all-cause mortality, heart transplant and acute heart failure exacerbations. Secondary outcomes included AF recurrence and transition to permanent AF. Additionally, an inverse probability weighted (IPW) model was examined. Results: At propensity score matching analysis, after a median follow-up of 58.1 months, the primary endpoint occurred in 29 (25.7%) patients in intervention group vs 42 (37.2%) in medical group (P = 0.9). Thromboembolic strokes and major arrhythmic events in intervention vs medical group were 9.7% vs 7.1% (P = 0.144) and 4.4 vs 8.0% (P = 0.779), respectively. Fewer patients in intervention vs medical group experienced AF recurrences (63.7% vs 84.1%, P = 0.001) and transition to permanent AF pattern (20.4% vs 33.6%, P = 0.026). IPW analysis showed consistent results. Severe complications related to CA were uncommon (0.7%). Conclusions: After 5 years of follow-up, CA did not improve major adverse cardiac outcomes in a large cohort of patients with HCM and AF. Nevertheless, CA seems to facilitate the maintenance of sinus rhythm and slow the progression to permanent AF, without significant safety concerns.

A matter of sex-persistent predictive value of MECKI score prognostic power in men and women with heart failure and reduced ejection fraction: a multicenter study.

Background: A sex-based evaluation of prognosis in heart failure (HF) is lacking. Methods and results: We analyzed the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score registry, which includes HF with reduced ejection fraction (HFrEF) patients. A cross-validation procedure was performed to estimate weights separately for men and women of all MECKI score parameters: left ventricular ejection fraction (LVEF), hemoglobin, kidney function assessed by Modification of Diet in Renal Disease, blood sodium level, ventilation vs. carbon dioxide production slope, and peak oxygen consumption (peakVO2). The primary outcomes were the composite of all-cause mortality, urgent heart transplant, and implant of a left ventricle assist device. The difference in predictive ability between the native and sex recalibrated MECKI (S-MECKI) was calculated using a receiver operating characteristic (ROC) curve at 2 years and a calibration plot. We retrospectively analyzed 7,900 HFrEF patients included in the MECKI score registry (mean age 61 ± 13 years, 6,456 men/1,444 women, mean LVEF 33% ± 10%, mean peakVO2 56.2% ± 17.6% of predicted) with a median follow-up of 4.05 years (range 1.72-7.47). Our results revealed an unadjusted risk of events that was doubled in men compared to women (9.7 vs. 4.1) and a significant difference in weight between the sexes of most of the parameters included in the MECKI score. S-MECKI showed improved risk classification and accuracy (area under the ROC curve: 0.7893 vs. 0.7799, p = 0.02) due to prognostication improvement in the high-risk settings in both sexes (MECKI score >10 in men and >5 in women). Conclusions: S-MECKI, i.e., the recalibrated MECKI according to sex-specific differences, constitutes a further step in the prognostic assessment of patients with severe HFrEF.

A case of primary cardiac sarcoma with an acute presentation: The role of multimodality imaging.

The case highlights the value of contrast echocardiography in raising clinical suspicion of malignancy, allowing a diagnostic work-up and the treatment of the primitive heart tumors.

Oral procainamide as pharmacological treatment of recurrent and refractory ventricular tachyarrhythmias: A single-center experience.

BACKGROUND: Antiarrhythmic therapy for recurrent ventricular arrhythmias in patients who have undergone catheter ablation, and in whom amiodarone and/or beta-blockers were ineffective or contraindicated, is a controversial issue. OBJECTIVE: The present study sought to evaluate the efficacy and tolerability of oral procainamide in patients with recurrent ventricular arrhythmias when the standard therapy strategy had failed. METHODS: All patients treated with procainamide for recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) in our institution between January 2010 and May 2019 were enrolled. The primary endpoint was the total number of implantable cardioverter-defibrillator (ICD) interventions after the beginning of procainamide therapy. Secondary endpoints were the total number of VTs and VFs recorded on the ICDs' controls and discontinuation of therapy. The events occurring during procainamide treatment were compared with a matched-duration period before the initiation of therapy with procainamide. Patients therefore served as self-controls. RESULTS: A total of 34 consecutive patients (32 male, 94.1%; mean age 74.4 ± 9.7 years) were included in the retrospective analysis. The mean time of procainamide treatment was 12.9 ± 13.7 months (median 9 [2-20] months). The mean dose of procainamide was 1207 ± 487 mg/day. Procainamide therapy significantly decreased ICD interventions (median 5 [0-22.5] vs 15.5 [3-32.25], P < .05). Procainamide also decreased the total number of VT/VF episodes (median 5.5 [0.75-30] vs 19 [7.5-30], P < .05). Only 3 patients (8.8%) presented severe side effects (dyspnea or hypotension), requiring discontinuation of therapy. CONCLUSION: Oral procainamide was associated with a significant decrease in ICD therapies and ventricular arrhythmias, showing an acceptable profile of tolerability.

Chromosomal alterations detected by comparative genomic hybridization in nonfunctioning endocrine pancreatic tumors.

We have used comparative genomic hybridization to investigate changes in DNA copy number in 20 nonfunctioning endocrine pancreatic tumors. The total number of regional DNA imbalances per tumor showed variation from case to case and high genetic heterogeneity was observed. From 1 to 22 chromosomal anomalies were detected in 13 of the 20 cases evaluated. Overall gains predominated over losses with a ratio of about 3.9:1 (58 gains/15 losses). The mean total number of regions displaying imbalances increased from 1.25 per tumor for benign tumors to 5.25 for malignant tumors, although statistical significance was not reached (P=0.074).