Frequency, Penetrance, and Variable Expressivity of Dilated Cardiomyopathy-Associated Putative Pathogenic Gene Variants in UK Biobank Participants.

BACKGROUND: There is a paucity of data regarding the phenotype of dilated cardiomyopathy (DCM) gene variants in the general population. We aimed to determine the frequency and penetrance of DCM-associated putative pathogenic gene variants in a general adult population, with a focus on the expression of clinical and subclinical phenotype, including structural, functional, and arrhythmic disease features. METHODS: UK Biobank participants who had undergone whole exome sequencing, ECG, and cardiovascular magnetic resonance imaging were selected for study. Three variant-calling strategies (1 primary and 2 secondary) were used to identify participants with putative pathogenic variants in 44 DCM genes. The observed phenotype was graded DCM (clinical or cardiovascular magnetic resonance diagnosis); early DCM features, including arrhythmia or conduction disease, isolated ventricular dilation, and hypokinetic nondilated cardiomyopathy; or phenotype-negative. RESULTS: Among 18 665 individuals included in the study, 1463 (7.8%) possessed ≥1 putative pathogenic variant in 44 DCM genes by the main variant calling strategy. A clinical diagnosis of DCM was present in 0.34% and early DCM features in 5.7% of individuals with putative pathogenic variants. ECG and cardiovascular magnetic resonance analysis revealed evidence of subclinical DCM in an additional 1.6% and early DCM features in an additional 15.9% of individuals with putative pathogenic variants. Arrhythmias or conduction disease (15.2%) were the most common early DCM features, followed by hypokinetic nondilated cardiomyopathy (4%). The combined clinical/subclinical penetrance was ≤30% with all 3 variant filtering strategies. Clinical DCM was slightly more prevalent among participants with putative pathogenic variants in definitive/strong evidence genes as compared with those with variants in moderate/limited evidence genes. CONCLUSIONS: In the UK Biobank, ≈1 of 6 of adults with putative pathogenic variants in DCM genes exhibited early DCM features potentially associated with DCM genotype, most commonly manifesting with arrhythmias in the absence of substantial ventricular dilation or dysfunction.

Catheter ablation of intramural outflow tract premature ventricular complexes: a multicentre study.

AIMS: Ablation of outflow tract ventricular arrhythmias may be limited by a deep intramural location of the arrhythmogenic source. This study evaluates the acute and long-term outcomes of patients undergoing ablation of intramural outflow tract premature ventricular complexes (PVCs). METHODS AND RESULTS: This multicenter series included patients with structurally normal heart or nonischemic cardiomyopathy and intramural outflow tract PVCs defined by: (a) ≥ 2 of the following criteria: (1) earliest endocardial or epicardial activation < 20ms pre-QRS; (2) Similar activation in different chambers; (3) no/transient PVC suppression with ablation at earliest endocardial/epicardial site; or (b) earliest ventricular activation recorded in a septal coronary vein. Ninety-two patients were included, with a mean PVC burden of 21.5±10.9%. Twenty-six patients had had previous ablations. All PVCs had inferior axis, with LBBB pattern in 68%. In 29 patients (32%) direct mapping of the intramural septum was performed using an insulated wire or multielectrode catheter, and in 13 of these cases the earliest activation was recorded within a septal vein. Most patients required special ablation techniques (one or more), including sequential unipolar ablation in 73%, low-ionic irrigation in 26%, bipolar ablation in 15% and ethanol ablation in 1%. Acute PVC suppression was achieved in 75% of patients. Following the procedure, the PVC burden was reduced to 5.8±8.4%. The mean follow-up was 15±14 months and 16 patients underwent a repeat ablation. CONCLUSION: Ablation of intramural PVCs is challenging; acute arrhythmia elimination is achieved in 3/4 patients, and non-conventional approaches are often necessary for success.

Pacing maneuvers from the aortic cusps: A useful technique during ablation of focal arrhythmias arising from the aortic root.

BACKGROUND: The ablation of arrhythmias arising near the His-bundle region in the non-coronary aortic cusp (NCAC) is challenging. Among the aortic sinuses of Valsalva, the NCAC is located between the right atrium and the left atrium. For this reason, pacing from the NCAC should result in atrial capture while pacing from the right and left coronary cusps (LCC) may result in ventricular capture. The objective of this study is to prove that atrial capture during pacing from the sinuses of Valsalva may be used to confirm a correct position in the non-coronary cusp. METHODS: A total of 30 patients with structurally normal heart undergoing left sided ablation procedures, underwent electrophysiological study of the aortic cusps. Each of the aortic valve cusps was paced with increasing outputs and analyzed offline to determine their unique electrocardiographic characteristics. RESULTS: In the NCAC, we obtained an atrial capture in 29 out of 30 patients (96.6%). The atrial capture was highly specific for a position in the NCAC (p < .001). The median output required to capture from the cusp was 10 mA (range 5-25 mA) at a pulse width of 2 ms. In the right coronary cusp (RCC) and LCC, we obtained ventricular capture in all patients (100%). The median output required to capture from the cusp was 10 mA (range 10-25 mA) in RCC and 25 mA (range 10-25 mA) in LCC at a pulse width of 2 ms. CONCLUSIONS: Atrial capture during a pacemapping from the aortic cusps can be considered proof of a correct position in NCAC.

Prognostic Value of Nonischemic Ringlike Left Ventricular Scar in Patients With Apparently Idiopathic Nonsustained Ventricular Arrhythmias.

BACKGROUND: Left ventricular (LV) scar on late gadolinium enhancement (LGE) cardiac magnetic resonance has been correlated with life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). We investigated the prognostic significance of a specific LV-LGE phenotype characterized by a ringlike pattern of fibrosis. METHODS: A total of 686 patients with apparently idiopathic nonsustained VA underwent contrast-enhanced cardiac magnetic resonance. A ringlike pattern of LV scar was defined as LV subepicardial/midmyocardial LGE involving at least 3 contiguous segments in the same short-axis slice. The end point of the study was time to the composite outcome of all-cause death, resuscitated cardiac arrest because of ventricular fibrillation or hemodynamically unstable ventricular tachycardia and appropriate implantable cardioverter defibrillator therapy. RESULTS: A total of 28 patients (4%) had a ringlike pattern of scar (group A), 78 (11%) had a non-ringlike pattern (group B), and 580 (85%) had normal cardiac magnetic resonance with no LGE (group C). Group A patients were younger compared with groups B and C (median age, 40 vs 52 vs 45 years; P<0.01), more frequently men (96% vs 82% vs 55%; P<0.01), with a higher prevalence of family history of sudden cardiac death or cardiomyopathy (39% vs 14% vs 6%; P<0.01) and more frequent history of unexplained syncope (18% vs 9% vs 3%; P<0.01). All patients in group A showed VA with a right bundle-branch block morphology versus 69% in group B and 21% in group C (P<0.01). Multifocal VAs were observed in 46% of group A patients compared with 26% of group B and 4% of group C (P<0.01). After a median follow-up of 61 months (range, 34-84 months), the composite outcome occurred in 14 patients (50.0%) in group A versus 15 (19.0%) in group B and 2 (0.3%) in group C (P<0.01). After multivariable adjustment, the presence of LGE with ringlike pattern remained independently associated with increased risk of the composite end point (hazard ratio, 68.98 [95% CI, 14.67-324.39], P<0.01). CONCLUSIONS: In patients with apparently idiopathic nonsustained VA, nonischemic LV scar with a ringlike pattern is associated with malignant arrhythmic events.

Phenotypic Expression, Natural History, and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating Variants.

BACKGROUND: Filamin C truncating variants (FLNCtv) cause a form of arrhythmogenic cardiomyopathy: the mode of presentation, natural history, and risk stratification of FLNCtv remain incompletely explored. We aimed to develop a risk profile for refractory heart failure and life-threatening arrhythmias in a multicenter cohort of FLNCtv carriers. METHODS: FLNCtv carriers were identified from 10 tertiary care centers for genetic cardiomyopathies. Clinical and outcome data were compiled. Composite outcomes were all-cause mortality/heart transplantation/left ventricle assist device (D/HT/LVAD), nonarrhythmic death/HT/LVAD, and sudden cardiac death/major ventricular arrhythmias. Previously established cohorts of 46 patients with LMNA and 60 with DSP-related arrhythmogenic cardiomyopathies were used for prognostic comparison. RESULTS: Eighty-five patients carrying FLNCtv were included (42±15 years, 53% men, 45% probands). Phenotypes were heterogeneous at presentation: 49% dilated cardiomyopathy, 25% arrhythmogenic left dominant cardiomyopathy, 3% arrhythmogenic right ventricular cardiomyopathy. Left ventricular ejection fraction was <50% in 64% of carriers and 34% had right ventricular fractional area changes (RVFAC=(right ventricular end-diastolic area - right ventricular end-systolic area)/right ventricular end-diastolic area) <35%. During follow-up (median time 61 months), 19 (22%) carriers experienced D/HT/LVAD, 13 (15%) experienced nonarrhythmic death/HT/LVAD, and 23 (27%) experienced sudden cardiac death/major ventricular arrhythmias. The sudden cardiac death/major ventricular arrhythmias incidence of FLNCtv carriers did not significantly differ from LMNA carriers and DSP carriers. In FLNCtv carriers, left ventricular ejection fraction was associated with the risk of D/HT/LVAD and nonarrhythmic death/HT/LVAD. CONCLUSIONS: Among patients referred to tertiary referral centers, FLNCtv arrhythmogenic cardiomyopathy is phenotypically heterogeneous and characterized by a high risk of life-threatening arrhythmias, which does not seem to be associated with the severity of left ventricular dysfunction.

Prevalence and prognostic significance of ischemic late gadolinium enhancement pattern in non-ischemic dilated cardiomyopathy.

BACKGROUND: Typical late gadolinium enhancement (LGE) patterns in dilated cardiomyopathy (DCM) include intramyocardial and subepicardial distribution. However, the ischemic pattern of LGE (subendocardial and transmural) has also been reported in DCM without coronary artery disease (CAD), but its correlates and prognostic significance are still not known. On these bases, this study sought to describe the prevalence and prognostic significance of the ischemic LGE pattern in DCM. METHODS: A total of 611 DCM patients with available cardiac magnetic resonance were retrospectively analyzed. A composite of all-cause-death, major ventricular arrhythmias (MVAs), heart transplantation (HTx) or ventricular assist device (VAD) implantation was the primary outcome of the study. Secondary outcomes were a composite of sudden cardiac death or MVAs and a composite of death for refractory heart failure, HTx or VAD implantation. RESULTS: Ischemic LGE was found in 7% of DCM patients without significant CAD or history of myocardial infarction, most commonly inferior/inferolateral/anterolateral. Compared to patients with non-ischemic LGE, those with ischemic LGE had higher prevalence of hypertension and atrial fibrillation or flutter. Ischemic LGE was associated with worse long-term outcomes compared to non-ischemic LGE (36% vs 23% risk of primary outcome events at 5 years respectively, P = .006), and remained an independent predictor of primary outcome after adjustment for clinically and statistically significant variables (adjusted hazard ratio 2.059 [1.055-4.015], P = .034 with respect to non-ischemic LGE). CONCLUSIONS: The ischemic pattern of LGE is not uncommon among DCM patients without CAD and is independently associated with worse long-term outcomes.

The Use of a Handheld Ultrasound Device to Guide the Axillary Vein Access during Pacemaker and Cardioverter-Defibrillator Implantation. A Feasibility Study.

Background: Although ultrasound guidance for axillary vein (AV) access (USGAVA) has been described as a reliable technique for cardiac implantable electronic device (CIED) implantation, no data is available on the use of handheld ultrasound devices (HUD) in such a setting. Objective: We investigated the feasibility of using a HUD for USGAVA in patients referred to our Institution for CIED implantation. Methods: The procedure details of 80 consecutive patients undergoing USGAVA (Group-1) from June 2020 to June 2021 were prospectively collected and compared to those of an age and sex-matched cohort of 91 patients (Group-2) who had undergone AV access with the traditional venipuncture guided by fluoroscopic landmarks. Results: The two groups were comparable for the success rate of venous access (92.5% versus 93.4%, p = 0.82), complication rate (1.3% versus 0.9%, p = 1.0), and procedure time (71 ± 32 min versus 70 ± 29 min, p = 0.9). However, Group-2 had a longer X-ray exposure time (7.6 ± 8.4 min versus 5.7 ± 7.3 min, p = 0.03). In Group-1, the univariate logistic regression analysis demonstrated that the AV diameter was associated with successful USGAVA (odds ratio = 3.34, 95% confidence interval 1.47-7.59, p < 0.01), with a 3-fold increase of probability of success per each 1 mm increase in the AV diameter. Conclusions: USGAVA using a HUD for CIED implantation is a feasible, effective, and safe technique; moreover, it saves X-ray exposure time without lengthening the implant procedure time.

Distal Reoperations after Repair of Acute Type A Aortic Dissection-Incidence, Causes and Outcomes.

Background and Aim of the Study: In patients with acute type A aortic dissection (A-AAD) whether initial repair should include also aortic arch replacement is still debated. We aimed to assess if extensive aortic repair prevents from reoperations patients with A-AAD. Methods: Outcomes after distal reoperation following repair of A-AAD (n = 285; 1977 to 2018) were analysed in 22 of 226 who underwent ascending aorta/hemiarch replacement (Group 1 R ) and 7 of 59 who had ascending aorta/arch replacement (Group 2 R ). Results: Distal reoperation was more common in Group 1 R (n = 22) than in Group 2 R (n = 0) (p < 0.001) while thoracic endovascular stenting was more frequent in Group 2 R (7 vs 3, p < 0.001). Indications for reoperation were pseudoaneurysm at distal anastomosis (n = 4, 18%) and progression of aortic dissection (n = 18, 82%) in Group 1 R . Indication for thoracic endovascular stenting was progressive aortic dissection in 3 patients of Group 1 R and in 6 of Group 2 R . Second reoperation was required in 2 patients from Group 1 R (2%) during a mean follow-up of 5 years. Median follow-up was 4 years in Group 1 R and 7 years in Group 2 R (p = 0.36). Hospital mortality was 14% in Group 1 R and 0% in Group 2 R (p = 0.3). Actuarial survival is 68 ± 10%, and 62 ± 11% for Group 1 R and 100% for Group 2 R at 5 and 10 years (p = 0.076). Conclusions: Distal reoperations after A-AAD repair have an acceptable mortality. An extensive initial repair has lower rate of reoperation and better mid-term survival and should be indicated especially for young patients in experienced centers.

Left Atrial Appendage Closure: A Current Overview Focused on Technical Aspects and Different Approaches.

Several studies in literature have shown that 90% of emboli related to non-valvular atrial fibrillation originate from left atrial appendage. Percutaneous closure or surgical exclusion of left atrial appendage in patients with high bleeding and high cardioembolic risk is currently a well established procedure in literature, clinical practice and guidelines. Knowledge of different techniques of left atrial appendage closure is necessary to individualize the procedure according to the patient anatomy and pre-procedural imaging evaluations. In this review the authors will evaluate different left atrial appendage closure systems and the different pre and intra procedural imaging methods.

Carotid artery molecular calcification assessed by [18F]fluoride PET/CT: correlation with cardiovascular and thromboembolic risk factors.

OBJECTIVES: There is growing evidence that sodium fluoride ([18F]fluoride) PET/CT can detect active arterial calcifications at the molecular stage. We investigated the relationship between arterial mineralization in the left common carotid artery (LCC) assessed by [18F]fluoride PET/CT and cardiovascular/thromboembolic risk. METHODS: In total, 128 subjects (mean age 48 ± 14 years, 51% males) were included. [18F]fluoride uptake in the LCC was quantitatively assessed by measuring the blood-pool-corrected maximum standardized uptake value (SUVmax) on each axial slice. Average SUVmax (aSUVmax) was calculated over all slices and correlated with 10-year risk of cardiovascular events estimated by the Framingham model, CHA2DS2-VASc score, and level of physical activity (LPA). RESULTS: The aSUVmax was significantly higher in patients with increased risk of cardiovascular (one-way ANOVA, p < 0.01) and thromboembolic (one-way ANOVA, p < 0.01) events, and it was significantly lower in patients with greater LPA (one-way ANOVA, p = 0.02). On multivariable linear regression analysis, age ( = 0.07, 95% CI 0.05 - 0.10, p < 0.01), body mass index ( = 0.02, 95% CI 0.01 - 0.03, p < 0.01), arterial hypertension ( = 0.15, 95% CI 0.08 - 0.23, p < 0.01), and LPA ( = -0.10, 95% CI -0.19 to -0.02, p=0.02) were independent associations of aSUVmax. CONCLUSIONS: Carotid [18F]fluoride uptake is significantly increased in patients with unfavorable cardiovascular and thromboembolic risk profiles. [18F]fluoride PET/CT could become a valuable tool to estimate subjects' risk of future cardiovascular events although still major trials are needed to further evaluate the associations found in this study and their potential clinical usefulness. KEY POINTS: • Sodium fluoride ([18F]fluoride) PET/CT imaging identifies patients with early-stage atherosclerosis. • Carotid [18F]fluoride uptake is significantly higher in patients with increased risk of cardiovascular and thromboembolic events and inversely correlated with the level of physical activity. • Early detection of arterial mineralization at a molecular level could help guide clinical decisions in the context of cardiovascular risk assessment.

Mobile health applications for the detection of atrial fibrillation: a systematic review.

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia and an important risk factor for stroke and heart failure. We aimed to conduct a systematic review of the literature and summarize the performance of mobile health (mHealth) devices in diagnosing and screening for AF. METHODS AND RESULTS: We conducted a systematic search of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Forty-three studies met the inclusion criteria and were divided into two groups: 28 studies aimed at validating smart devices for AF diagnosis, and 15 studies used smart devices to screen for AF. Evaluated technologies included smartphones, with photoplethysmographic (PPG) pulse waveform measurement or accelerometer sensors, smartbands, external electrodes that can provide a smartphone single-lead electrocardiogram (iECG), such as AliveCor, Zenicor and MyDiagnostick, and earlobe monitor. The accuracy of these devices depended on the technology and the population, AliveCor and smartphone PPG sensors being the most frequent systems analysed. The iECG provided by AliveCor demonstrated a sensitivity and specificity between 66.7% and 98.5% and 99.4% and 99.0%, respectively. The PPG sensors detected AF with a sensitivity of 85.0-100% and a specificity of 93.5-99.0%. The incidence of newly diagnosed arrhythmia ranged from 0.12% in a healthy population to 8% among hospitalized patients. CONCLUSION: Although the evidence for clinical effectiveness is limited, these devices may be useful in detecting AF. While mHealth is growing in popularity, its clinical, economic, and policy implications merit further investigation. More head-to-head comparisons between mHealth and medical devices are needed to establish their comparative effectiveness.

Impact of the COVID-19 lockdown on the arrhythmic burden of patients with implantable cardioverter-defibrillators.

BACKGROUND: In Italy, a nationwide full lockdown was declared between March and May 2020 to hinder the novel coronavirus disease 2019 (COVID-19) pandemic. The potential individual health effects of long-term isolation are largely unknown. The current study investigated the arrhythmic consequences of the COVID-19 lockdown in patients with defibrillators (ICDs) living in the province of Ferrara, Italy. METHODS: Both the arrhythmias and the delivered ICD therapies as notified by the devices were prospectively collected during the lockdown period (P1) and compared to those occurred during the 10 weeks before the lockdown began (P2) and during the same period in 2019 (P3). Changes in outcome over the three study periods were evaluated for significance using McNemar's test. RESULTS: A total of 413 patients were included in the analysis. No differences were found concerning either arrhythmias or shocks or anti-tachycardia pacing. Only the number of patients experiencing non-sustained ventricular tachycardias (NSVTs) during P1 significantly decreased as compared to P2 (p = 0.026) and P3 (p = 0.009). The subgroup analysis showed a significant decrease in NSVTs during P1 for men (vs. P2, p = 0.014; vs. P3, p = 0.040) and younger patients (vs. P2, p = 0.002; vs. P3, p = 0.040) and for ischemic etiology (vs. P2, p = 0.003). No arrhythmic deaths occurred during P1. CONCLUSIONS: The complete nationwide lockdown, as declared by the Italian government during the first COVID-19 pandemic peak, did not impact on the incidence of arrhythmias in an urban cohort of patients with ICDs.

An Integrated Approach for Treatment of Acute Type A Aortic Dissection.

Background and objective: We reviewed a single-institution experience to verify the impact of surgery during different time intervals on early and late results in the treatment of patients with type A acute aortic dissection (A-AAD). Materials and Methods: From 2004 to 2021, a total of 258 patients underwent repair of A-AAD; patients were equally distributed among three periods: 2004-2010 (Era 1, n = 90), 2011-2016 (Era 2, n = 87), and 2017-2021 (Era 3, n = 81). The primary end-point was to assess whether through the years changes in indications, surgical strategies and techniques and increasing experience have influenced early and late outcomes of A-AAD repair. Results: Axillary artery cannulation was almost routinely used in Eras 2 (86%) and 3 (91%) while one femoral artery was mainly cannulated in Era 1 (91%) (p < 0.01). Retrograde cerebral perfusion was predominantly used in Era 1 (60%) while antegrade cerebral perfusion was preferred in Eras 2 (94%,) and 3 (100%); (p < 0.01). There was a significant increase of arch replacement procedures from Era 1 (11%) to Eras 2 (33%) and 3 (48%) (p < 0.01). A frozen elephant trunk was mainly performed in Era 3. Hospital mortality was 13% in Era 1, 11% in Era 2, and 4% in Era 3 (p = 0.07). Actuarial survival at 3 years is 74%, in Era 1, 78% in Era 2, and 89% in Era 3 (p = 0.05). Conclusions: With increasing experience and a more aggressive approach, including total arch replacement, repair of A-AAD can be performed with low operative mortality in many patients. Patient care and treatment by a specific team organization allows a faster diagnosis and referral for surgery allowing to further improve early and late outcomes.

Collateral injury of the conduction system during catheter ablation of septal substrate in nonischemic cardiomyopathy.

INTRODUCTION: In patients with nonischemic cardiomyopathy (NICM) little is known about the clinical impact of catheter ablation (CA) of septal ventricular tachycardia (VT) resulting in the collateral injury of the conduction system (CICS). METHODS AND RESULTS: Ninety-five consecutive patients with NICM underwent CA of septal VT. Outcomes in patients with no baseline conduction abnormalities who developed CICS (group 1, n = 28 [29%]) were compared to patients with no CICS (group 2, n = 17 [18%]) and to patients with preexisting conduction abnormalities or biventricular pacing (group 3, n = 50 [53%]). Group-1 patients were younger, had a higher left ventricular ejection fraction and a lower prevalence of New York Heart Association III/IV class compared to group 3 while no significant differences were observed with group 2. After a median follow-up of 15 months, VT recurred in 14% of patients in group 1, 12% in group 2 (P = .94) and 32% in group 3 (P = .08) while death/transplant occurred in 14% of patients in group 1, 18% in group 2 (P = .69) and 28% in group 3 (P = .15). A worsening of left ventricular ejection fraction (LVEF) (median LVEF variation, -5%) was observed in group 1 compared to group 2 (median LVEF variation, 0%; P < .01) but not group-3 patients (median LVEF variation, -4%; P = .08) with a consequent higher need for new biventricular pacing in group 1 (43%) compared to group 2 (12%; P = .03) and group 3 (16%; P < .01). CONCLUSIONS: In patients with NICM and septal substrate, sparing the abnormal substrate harboring the conduction system provides acceptable VT control while preventing a worsening of the systolic function.

Incremental value of FDG-PET/CT to monitor treatment response in infectious spondylodiscitis.

OBJECTIVE: To assess the added value of serial 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake analysis in predicting clinical response to treatment in infectious spondylodiscitis (IS). We sought to analyze changes in quantitative FDG-PET/CT parameters among patients with clinical response or treatment failure and to compare the sensitivity and specificity of serial FDG-PET/CT and MRI in predicting treatment response in IS. MATERIALS AND METHODS: This retrospective study consisted of 68 FDG-PET/CT examinations in 34 patients performed before and after at least 2 weeks of antibiotic treatment. Serial MRI scans were available in 32 (94%) patients before and after treatment. FDG-avid lesions were quantified as maximum standardized uptake value (SUVmax), partial-volume corrected lesion metabolic volume (LMV), and partial-volume corrected lesion metabolic activity (LMA). RESULTS: All FDG-PET/CT parameters significantly decreased in patients with clinical improvement (31/34, 91%, P < 0.001), while patients with disease progression did not show FDG-PET/CT improvement. FDG uptake decrease was similar between patients undergoing early assessment (< 6 weeks) compared with those performing FDG-PET/CT after 6 weeks of treatment. SUVmax, LMV, and LMA decrease over time was 39.0%, 97.4%, and 97.1%, respectively. In predicting clinical responses, SUVmax reduction > 15% and > 25% showed 94% and 89% sensitivity and 67% and 100% specificity compared with 37% and 50% of MRI, respectively. Low degree of agreement with clinical response was shown for MRI compared with FDG-PET/CT parameters using the Cohen kappa coefficient. CONCLUSIONS: FDG-PET/CT monitoring is a valuable tool to predict clinical response to treatment in IS and has greater sensitivity and specificity compared with MRI.

State of the Art Review on Genetics and Precision Medicine in Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterised by ventricular arrhythmia and an increased risk of sudden cardiac death (SCD). Numerous genetic determinants and phenotypic manifestations have been discovered in ACM, posing a significant clinical challenge. Further to this, wider evaluation of family members has revealed incomplete penetrance and variable expressivity in ACM, suggesting a complex genotype-phenotype relationship. This review details the genetic basis of ACM with specific genotype-phenotype associations, providing the reader with a nuanced perspective of this condition; whilst also proposing a future roadmap to delivering precision medicine-based management in ACM.

Ventricular tachycardia in nonischemic cardiomyopathy: Anteroseptal vs inferolateral origin based on ICD ventricular electrogram timing.

INTRODUCTION: The majority of patients with nonischemic cardiomyopathy (NICM) present a perivalvular substrate that is either predominantly antero-septal (AS) or infero-lateral (IL), corresponding to specific ventricular tachycardia (VT) morphologies. The relative timing of far-field and near-field ventricular electrograms (EGMs) from stored implantable cardioverter-defibrillator (ICD) events of VT may be used to distinguish AS from IL VT in NICM. METHODS AND RESULTS: We analyzed 48 patients with NICM with either a primarily AS (54%) or IL (56%) VT source undergoing catheter ablation between 2003 and 2018. Only patients with retrievable ICD-EGMs of spontaneous VT events which could be matched with VTs induced during the ablation procedure were included. A total of 56 VT events (52% AS origin and 48% IL origin) were analyzed, yielding a mean far-field to near-field interval of 31 ± 13 milliseconds for AS VTs and 47 ± 19 milliseconds for IL VTs (P = .001). At receiver operating characteristic analysis (AUC = 0.734), a far-field to near-field interval of ≥ 60 milliseconds ruled out AS VTs in 29 (100%) cases and diagnosed IL VTs with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 63%. An interval of ≤ 20 milliseconds ruled out IL VTs in 25 (93%) cases and diagnosed AS VTs with a PPV of 83% and NPV of 57%. Significant overlap between the two groups was observed among far-field to near-field intervals in between 20 milliseconds and 60 milliseconds. CONCLUSIONS: The relative timing of far-field and near-field EGMs from stored clinical ICD events of VT can be helpful to differentiate AS vs IL origin of VT in NICM.

Papillary muscle ventricular arrhythmias in patients with arrhythmic mitral valve prolapse: Electrophysiologic substrate and catheter ablation outcomes.

BACKGROUND: Mitral valve prolapse (MVP) is a common valve condition and has been associated with sudden cardiac death. Premature ventricular contractions (PVCs) from the papillary muscles (PMs) may play a role as triggers for ventricular fibrillation (VF) in these patients. OBJECTIVES: To characterize the electrophysiological substrate and outcomes of catheter ablation in patients with MVP and PM PVCs. METHODS: Of 597 patients undergoing ablation of ventricular arrhythmias during the period 2012-2015, we identified 25 patients with MVP and PVCs mapped to the PMs (64% female). PVC-triggered VF was the presentation in 4 patients and a fifth patient died suddenly during follow-up. The left ventricle ejection fraction (LVEF) was 50.5% ± 11.8% and PVC burden was 24.4% ± 13.1%. A cardiac magnetic resonance imaging was performed in nine cases and areas of late gadolinium enhancement were found in four of them. A detailed LV voltage map was performed in 11 patients, three of which exhibited bipolar voltage abnormalities. Complete PVC elimination was achieved in 19 (76%) patients and a significant reduction in PVC burden was observed in two (8%). In patients in which the ablation was successful, the PVC burden decreased from 20.4% ± 10.8% to 6.3% ± 9.5% (P = 0.001). In 5/6 patients with depressed LVEF and successful ablation, the LV function improved postablation. No significant differences were identified between patients with and without VF. CONCLUSIONS: PM PVCs are a source of VF in patients with MVP and can induce PVC-mediated cardiomyopathy that reverses after PVC suppression. Catheter ablation is highly successful with more than 80% PVC elimination or burden reduction.

Unipolar voltage mapping criteria for right ventricular septum: Influence of the aortic root.

INTRODUCTION: Unipolar voltage mapping through its wider "field of view" can identify substrate deeper to the endocardium on the right ventricular (RV) free wall and left ventricle. The reference value(s) for normal endocardial (ENDO) unipolar voltage (UNI) for the septal aspect of the right ventricle (RV) and the effect of the aortic root that is directly opposed to the posterior septal plane of the RV outflow tract (RVOT) have not been established. METHODS AND RESULTS: We performed detailed (185 ± 70, range 127-342 points) RV ENDO UNI maps in 9 patients without structural heart disease; 6 had magnetic resonance (MR) imaging; 5 were males; the mean age was 49 ± 11 years. For MR analysis, the location of the aortic root was defined and its effect on unipolar voltage determined. The UNI voltage on posterior RVOT was lower (mean 6.56 ± 2.33 mV, 95% CI 6.08-7.05), compared to the rest of the septal aspect of RV (mean 8.33 ± 2.34 mV, P < 0.001, 95% CI 7.84-8.84). MR analysis confirmed that the lowest voltage region was opposite to MR-defined aortic root. Using a cutoff for UNI abnormality of 6.0 mV for the posterior aspect of the RVOT opposite to the aortic root and 7.5 mV for the rest of the septal aspect of the RV, there was no confluent area of unipolar abnormality in any patient. CONCLUSION: We defined normal ENDO UNI cutoffs as 7.5 mV for the septal aspect of the RV with adjustment to 6.0 mV over the posterior RVOT opposite to the aortic root.