BACKGROUND—Mitral valve prolapse (MVP) may present with ventricular arrhythmias and sudden cardiac death (SCD) even in the absence of hemodynamic impairment. The structural basis of ventricular ...electric instability remains elusive.
METHODS AND RESULTS—The cardiac pathology registry of 650 young adults (≤40 years of age) with SCD was reviewed, and cases with MVP as the only cause of SCD were re-examined. Forty-three patients with MVP (26 females; age range, 19–40 years; median, 32 years) were identified (7% of all SCD, 13% of women). Among 12 cases with available ECG, 10 (83%) had inverted T waves on inferior leads, and all had right bundle-branch block ventricular arrhythmias. A bileaflet involvement was found in 70%. Left ventricular fibrosis was detected at histology at the level of papillary muscles in all patients, and inferobasal wall in 88%. Living patients with MVP with (n=30) and without (control subjects; n=14) complex ventricular arrhythmias underwent a study protocol including contrast-enhanced cardiac magnetic resonance. Patients with either right bundle-branch block type or polymorphic complex ventricular arrhythmias (22 females; age range, 28–43 years; median, 41 years), showed a bileaflet involvement in 70% of cases. Left ventricular late enhancement was identified by contrast-enhanced cardiac magnetic resonance in 93% of patients versus 14% of control subjects (P<0.001), with a regional distribution overlapping the histopathology findings in SCD cases.
CONCLUSIONS—MVP is an underestimated cause of arrhythmic SCD, mostly in young adult women. Fibrosis of the papillary muscles and inferobasal left ventricular wall, suggesting a myocardial stretch by the prolapsing leaflet, is the structural hallmark and correlates with ventricular arrhythmias origin. Contrast-enhanced cardiac magnetic resonance may help to identify in vivo this concealed substrate for risk stratification.
Persistent antiphospholipid (aPL) antibodies are occasionally found in subjects without prior history of thromboembolic events (TEs), raising the dilemma of whether to initiate or not a primary ...thromboprophylaxis. A first TE is considered rare in aPL carriers, but previous studies did not consider the aPL profile nor was the test positivity confirmed in a reference laboratory. In this study, 104 subjects with high-risk aPL profile (positive lupus anticoagulant, anticardiolipin, and anti-β2–glycoprotein I antibodies, triple positivity) confirmed in a reference laboratory, were followed up for a mean of 4.5 years. There were 25 first TEs (5.3% per year): the cumulative incidence after 10 years was 37.1% (95% confidence interval CI, 19.9%-54.3%). On multivariate analysis, male sex (hazard ratio = 4.4; 95% CI, 1.5-13.1, P = .007) and risk factors for venous thromboembolism (hazard ratio = 3.3; 95% CI, 1.3-8.5, P = .01) were independent predictors for TEs. Aspirin did not significantly affect the incidence of TE. In conclusion, the occurrence of a first TE in carriers of high-risk aPL profile is considerable; it is more frequent among male subjects and in the presence of additional risk factors for venous TE. These data can help in the decision to initiate primary thromboprophylaxis in these subjects.
Despite the fact that assessment of right ventricular longitudinal strain (RVLS) carries important implications for patient diagnosis, prognosis, and treatment, its implementation in clinical ...settings has been hampered by the limited reference values and the lack of uniformity in software, method, and definition used for measuring RVLS. Accordingly, this study was designed to establish (1) the reference values for RVLS by 2-dimensional speckle-tracking echocardiography; and (2) their relationship with demographic, hemodynamic, and cardiac factors.
In 276 healthy volunteers (55% women; age, 18-76 years), free wall and septum RVLS (6 segments) and free wall RVLS (3 segments) using both 6- and 3-segment regions of interest were obtained. Feasibility of 6-segment RVLS was 92%. Free wall RVLS from 3- versus 6-segment regions of interest had similar values, yet 6-segment region of interest was more feasible (86% versus 73%; P<0.001) and reproducible. Reference values (lower limits of normality) were as follows: 6-segment RVLS, -24.7±2.6% (-20.0%) for men and -26.7±3.1% (-20.3%) for women; 3-segment RVLS, -29.3±3.4% (-22.5%) for men and -31.6±4.0% (-23.3%) for women (P<0.001). Free wall RVLS was 5±2 strain units (%) larger in magnitude than 6-segment RVLS, 10±4% larger than septal RVLS, and 2±4% larger in women than in men (P<0.001). At multivariable analysis, age, sex, pulmonary systolic pressure, right atrial minimal volume, as well as right atrial and left ventricular longitudinal strain resulted as correlates of RVLS values.
This is the largest study providing sex- and method-specific reference values for RVLS. Our data may foster the implementation of 2-dimensional speckle-tracking echocardiography-derived RV analysis in clinical practice.
Recent European Association of Echocardiography and American Society of Echocardiography guidelines on three-dimensional echocardiography state that normal values of left ventricular (LV) parameters ...for age and body size remain to be established.
In 226 consecutive healthy subjects (125 women; age range, 18-76 years), comprehensive three-dimensional echocardiographic analyses of LV parameters were performed, and values were compared with those obtained by conventional echocardiography.
Upper reference values (mean+ 2 SDs) for three-dimensional LV end-diastolic and end-systolic volumes were 85 and 34 mL/m(2) in men and 72 and 28 mL/m(2) in women, respectively. Indexing LV volumes to body surface area did not eliminate gender differences. Lower reference values (mean - 2 SDs) for ejection fraction were 54% in men and 57% in women and for stroke volume were 25 and 24 mL/m(2), respectively. Upper reference values for LV mass were 97 g/m(2) in men and 90 g/m(2) in women and for end-diastolic sphericity index were 0.49 and 0.48, respectively. Significant age dependency of LV parameters was identified and reported across age groups. Three-dimensional echocardiographic LV volumes were larger, ejection fraction was similar, and LV stroke volume and mass were significantly smaller in comparison with the corresponding values obtained by conventional echocardiography.
The investigators report a comprehensive analysis of LV geometry and function using three-dimensional echocardiography in a relatively large cohort of healthy Caucasian subjects with a wide age range. These may serve to establish age-specific and gender-specific reference ranges, which are crucial for the routine implementation of three-dimensional echocardiography to detect LV remodeling and dysfunction in clinical practice.
Left atrial (LA) longitudinal strain (LS) using two-dimensional speckle-tracking echocardiography has emerged as an important diagnostic and prognostic parameter in various cardiovascular conditions. ...However, its reference values, their correlations with demographics characteristics, and its physiologic determinants remain to be established.
Accordingly, 171 healthy volunteers (mean age, 45 ± 12 years; 61% women) in whom LS was obtained from both apical four- and two-chamber dedicated views of the left atrium, considering the P-P interval on the electrocardiogram as the reference cardiac cycle, were prospectively studied. From the LA LS curve we measured the extent of the negative deflection (LSneg), representing LA active contraction, the positive deflection (LSpos) during LA filling, and total LS (LStot), as the sum of LSneg and LSpos values.
Average values for biplane LA LSpos, LSneg, and LStot were 19.7%, -14.5%, and 33.3%, respectively. On multivariate analysis, age, left ventricular (LV) global LS and volume, and LV diastolic function were the main physiologic determinants of LA LSpos (R
= 0.57) and LStot (R
= 0.40), whereas systolic blood pressure, E/A ratio, global LS, and LV stroke volume were the main determinants of LA LSneg (R
= 0.20). Women had higher LSpos and LStot than men, particularly before 50 years of age. LA LSpos and LStot decreased with aging, with different trends in men and women.
LA LS values are different in men and women and should be interpreted taking into account patient age and LV function as well. These reference values may help identify subclinical LA dysfunction in several cardiovascular or systemic conditions.
BACKGROUND—The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast-enhanced cardiac magnetic resonance remain ...to be elucidated.
METHODS AND RESULTS—We compared 35 athletes (80% men, age14–48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38±25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls.
CONCLUSIONS—Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography.
Background This study assessed the prevalence of left ventricular (LV) involvement and characterized the clinical, electrocardiographic, and imaging features of LV phenotype in patients with ...arrhythmogenic right ventricular cardiomyopathy (ARVC). Differential diagnosis between ARVC-LV phenotype and dilated cardiomyopathy (DCM) was evaluated. Methods and Results The study population included 87 ARVC patients (median age 34 years) and 153 DCM patients (median age 51 years). All underwent cardiac magnetic resonance with quantitative tissue characterization. Fifty-eight ARVC patients (67%) had LV involvement, with both LV systolic dysfunction and LV late gadolinium enhancement (LGE) in 41/58 (71%) and LV-LGE in isolation in 17 (29%). Compared with DCM, the ARVC-LV phenotype was statistically significantly more often characterized by low QRS voltages in limb leads, T-wave inversion in the inferolateral leads and major ventricular arrhythmias. LV-LGE was found in all ARVC patients with LV systolic dysfunction and in 69/153 (45%) of DCM patients. Patients with ARVC and LV systolic dysfunction had a greater amount of LV-LGE (25% versus 13% of LV mass;
<0.01), mostly localized in the subepicardial LV wall layers. An LV-LGE ≥20% had a 100% specificity for diagnosis of ARVC-LV phenotype. An inverse correlation between LV ejection fraction and LV-LGE extent was found in the ARVC-LV phenotype (
=-0.63;
<0.01), but not in DCM (
=-0.01;
=0.94). Conclusions LV involvement in ARVC is common and characterized by clinical and cardiac magnetic resonance features which differ from those seen in DCM. The most distinctive feature of ARVC-LV phenotype is the large amount of LV-LGE/fibrosis, which impacts directly and negatively on the LV systolic function.
The aims of the present study were to investigate the incidence and characteristics of conduction disorders (CDs) after transcatheter aortic valve implantation (TAVI), to analyze the predictors of ...permanent pacemaker (PPM) implantation, and to evaluate the outcomes of CDs over time. In particular, we sought to investigate whether the depth of deployment and other technical aspects of valve implantation might predict the need for PPM implantation after TAVI. TAVI has been reported to favor the onset or worsening of CDs often requiring PPM implantation. A total of 70 patients with aortic stenosis due to dystrophic calcification underwent TAVI with third-generation CoreValve Revalving System from May 2007 to April 2009. We collected electrocardiograms at baseline, during TAVI, during hospitalization and at the 1-, 3-, 6-, and 12-month follow-up visits thereafter. The clinical, anatomic, and procedural variables were tested to identify the predictors of PPM implantation. The PPM dependency at follow-up was analyzed. Six patients were excluded from the analysis because of a pre-existing PPM. Of the 64 patients, 32 (50%) had one or more atrioventricular-intraventricular CDs at baseline. TAVI induced a worsening in the CDs in 49 (77%) of the 64 patients, with 25 (39%) requiring in-hospital PPM implantation. On multivariate analysis, the independent predictors of PPM implantation were the depth of the prosthesis implantation (p = 0.039) and the pre-existing right bundle branch block (p = 0.046). A trend in the recovery of the CDs over time was recorded, although 2 patients required PPM implantation 1 month after discharge for late complete atrioventricular block. In conclusion, TAVI often induces or worsens CDs, requiring PPM in more than one third of patients, although a trend in the recovery of CDs during the midterm was recorded. The independent predictors of PPM implantation were the depth of prosthesis implantation and pre-existing right bundle branch block.
Current risk stratification for sudden cardiac death (SCD) in nonischemic dilated cardiomyopathy (NIDC) relies on left ventricular (LV) dysfunction, a poor marker of ventricular electrical ...instability. Contrast-enhanced cardiac magnetic resonance has the ability to accurately identify and quantify ventricular myocardial fibrosis (late gadolinium enhancement LGE).
To evaluate the impact of the presence and amount of myocardial fibrosis on arrhythmogenic risk prediction in NIDC.
One hundred thirty-seven consecutive patients with angiographically proven NIDC were enrolled for this study. All patients were followed up for a combined arrhythmic end point including sustained ventricular tachycardia (VT), appropriate implantable cardioverter-defibrillator (ICD) intervention, ventricular fibrillation (VF), and SCD.
LV-LGE was identified in 76 (55.5%) patients. During a median follow-up of 3 years, the combined arrhythmic end point occurred in 22 (16.1%) patients: 8 (5.8%) sustained VT, 9 (6.6%) appropriate ICD intervention, either against VF (n = 5; 3.6%) or VT (n = 4; 2.9%), 3 (2.2%) aborted SCD, and 2 (1.5%) died suddenly. Kaplan-Meier analysis revealed a significant correlation between the LV-LGE presence (not the amount and distribution) and malignant arrhythmic events (P < .001). In univariate Cox regression analysis, LV-LGE (hazard ratio HR 4.17; 95% confidence interval CI 1.56-11.2; P = .005) and left bundle branch block (HR 2.43; 95% CI 1.01-5.41; P = .048) were found to be associated with arrhythmias. In multivariable analysis, the presence of LGE was the only independent predictor of arrhythmias (HR 3.8; 95% CI 1.3-10.4; P = .01).
LV-LGE is a powerful and independent predictor of malignant arrhythmic prognosis, while its amount and distribution do not provide additional prognostic value. Contrast-enhanced cardiac magnetic resonance may contribute to identify candidates for ICD therapy not fulfilling the current criteria based on left ventricular ejection fraction.
Abstract
A neurogenic pathway, involving airway TRPV-1, has been implicated in acute cardiovascular events occurring after peaks of air pollution. We tested whether inhaled prostaglandin-E
2
(PGE
2
) ...and bradykinin (BK) regulate TRPV-1 activity in vivo by changing cough response to capsaicin (CPS) and affecting heart rate variability (HRV), while also taking into account the influence of TRPV-1 polymorphisms (SNPs). Moreover, we assessed the molecular mechanism of TRPV-1 modulation in vitro. Seventeen healthy volunteers inhaled 100 μg PGE
2
, 200 μg BK or diluent in a randomized double-blind fashion. Subsequently, the response to CPS was assessed by cough challenge and the sympathetic activity by HRV, expressed by low (nLF) and high (nHF) normalized frequency components, as well as nLF/nHF ratio. Intracellular Ca
2+
was measured in HeLa cells, transfected with wild-type TRPV-1, pre-treated with increasing doses of PGE
2
, BK or diesel exhaust particulate (DEP), after CPS stimulation. Six functional TRPV-1 SNPs were characterized in DNA from each subject. Inhalation of PGE
2
and BK was associated with significant increases in cough response induced by 30 μM of CPS (cough number after PGE
2
= 4.20 ± 0.42;
p
< 0.001, and after BK = 3.64 ± 0.37;
p
< 0.01), compared to diluent (2.77 ± 0.29) and in sympathetic activity (nLF/nHF ratio after PGE
2
= 6.1;
p
< 0.01, and after BK = 4.2;
p
< 0.05), compared to diluent (2.5–3.3). No influence of SNPs was observed on autonomic regulation and cough sensitivity. Unlike PGE
2
and BK, DEP directly activated TRPV-1. Inhalation of PGE
2
and BK sensitizes TRPV-1 and is associated with autonomic dysregulation of cardiac rhythm in healthy subjects.
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