Left ventricular outflow tract velocity-time integral improves outcome prediction in patients with secondary mitral regurgitation.

AIMS: Left ventricular outflow velocity-time integral (LVOT-VTI) has been shown to improve outcome prediction in different patients' subsets, with or without heart failure (HF). Nevertheless, the prognostic value of LVOT-VTI in patients with HF and secondary mitral regurgitation (MR) has never been investigated so far. Therefore, in the present study, we aimed to assess the prognostic value different metrics of LV forward output, including LVOT-VTI, in HF patients with secondary MR. METHODS AND RESULTS: Consecutive patients with HF and moderate-to-severe/severe secondary MR and systolic dysfunction (i.e., left ventricular ejection fraction [LVEF] <50%) were retrospectively selected and followed-up for the primary endpoint of cardiac death. Out of the 287 patients analyzed (aged 74 ± 11 years, 70% men, 46% ischemic etiology, mean LVEF 30 ± 9%, mean LVOT-VTI 20 ± 5 cm), 71 met the primary endpoint over a 33-month median follow-up (16-47 months). Patients with an LVOT-VTI ≤17 cm (n = 96, 32%) showed the greatest risk of cardiac death (Log Rank 44.3, p < 0.001) and all-cause mortality (Log rank 8.6, p = 0.003). At multivariable regression analysis, all the measures of LV forward volume (namely LVOT-VTI, stroke volume index, cardiac output, and cardiac index) were predictors of poor outcomes. Among these, LVOT-VTI was the most accurate in risk prediction (univariable C-statistics 0.70 [95%CI 0.64-0.77]). CONCLUSION: Left ventricular forward output, noninvasively estimated through LVOT-VTI, improves outcome prediction in HF patients with low LVEF and secondary MR.

Echocardiographic Biventricular Coupling Index to Predict Precapillary Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a frequent and detrimental condition. Right heart catheterization (RHC) is the gold standard to identify PH subtype (precapillary from postcapillary PH) and is key for treatment allocation. In this study, the novel echocardiographic biventricular coupling index (BCI), based on the ratio between right ventricular stroke work index and left ventricular E/E' ratio, was tested for the discrimination of PH subtype using RHC as the comparator. METHODS: BCI was derived in 334 consecutive patients who underwent transthoracic echocardiography and RHC for all indications. BCI was then tested in a validation cohort of 1,349 patients. RESULTS: The accuracy of BCI to identify precapillary PH was high in the derivation cohort (area under the curve, 0.82; 95% CI, 0.78-0.88; P < .001; optimal cut point, 1.9). BCI identified patients with precapillary PH with high accuracy also in the validation cohort (area under the curve, 0.87 [95% CI, 0.85-0.89; P < .001]; subgroup with PH: area under the curve, 0.91 [95% CI, 0.89-0.93; P < .001]; cut point, 1.9; sensitivity, 82%; specificity, 89%; positive predictive value, 77%; negative predictive value, 92%). BCI outperformed both the D'Alto score (Z = 3.56; difference between areas = 0.05; 95% CI, 0.02-0.07; P < .001) and the echocardiographic pulmonary-to-left atrial ratio index (Z = 2.88; difference between areas = 0.02; 95% CI, 0.01-0.04; P = .004). CONCLUSIONS: BCI is a novel, noninvasive index based on routinely available echocardiographic parameters that identifies with high accuracy patients with precapillary PH. BCI may be of value in the screening workup of patients with PH.

CMR predictors of secondary moderate to severe mitral regurgitation and its additive prognostic role in previous myocardial infarction.

BACKGROUND: We aimed to determine predictors and the additive prognostic role of moderate to severe (MS) ischemic mitral regurgitation (MR) in myocardial infarction (MI). METHODS: Four hundred twenty-two patients with previous MI underwent cardiac magnetic resonance (CMR) imaging for the assessment of left ventricular (LV) ejection fraction (EF), end-diastolic (EDV) and end-systolic volume (ESV), sphericity index, wall motion score index (WMSI), and late gadolinium enhancement (LGE). Echocardiography was performed to assess MR. RESULTS: Thirty-eight had from moderate to severe MR (MS-MR group) and 384 did not (No MS-MR group). The S-MR group had higher LV volumes, sphericity index, WMSI, and LGE extent, and lower LVEF. At univariate logistic regression analysis, dilated volumes, SI >0.43, dyskinesia of inferolateral wall, papillary muscle (PM)-LGE, and LGE extent >16% were associated with MS-MR. At multivariate analysis, only SI (OR=5.7) and PM-LGE (OR=3) were independently associated with MS-MR. Considering only patients without LV dilatation, only dyskinesia in the inferolateral wall was a predictor of MS-MR (OR 34.8). Thirty cardiac events (cardiac death, appropriate implantable cardioverter-defibrillator firing, and resuscitated cardiac arrest) occurred during a median follow-up of 1,276 days. After adjusting the prognostic variables at univariate analysis by age (>65 years) and selecting those that were significant (EDV > 95 ml/m2, ESV >53 ml/m2, EF <30%, WMSI >1.65, LGE >12%, S-MR), only WMSI >1.65 and MS-MR remained an independent predictor of cardiac events. CONCLUSIONS: Increased WMSI and PM-LGE in the overall population and inferolateral dyskinesia in patients without ESV dilatation are predictors of MS-MR; MS-MR and elevated WMSI have independent negative prognostic value.

Deep venous thromboembolism after a trauma in a football player double heterozygous for factor V Leiden and prothrombin G20210A mutation: The role of genetic testing in sport.

Traumatic vascular injuries to the lower limb are frequent in athletes, particularly in sports characterized by high-speed collisions. However, the diagnosis is not always straightforward, for the lack of clearly visible abnormalities without provocative testing or appropriate imaging. The failure of an early diagnosis can lead to devastating consequences. In these subjects, it may be useful to investigate the personal susceptibility to thrombotic events such as the presence of a hereditary hypercoagulable state. We experienced a case of a soccer player with progressive swelling and severe pain of the calf after a trauma during a football match 3 days previously, who came to our hospital for suspected deep vein thrombosis, confirmed by echo-Doppler ultrasound. A thrombophilia screening detected a double heterozygosity for factor V Leiden and prothrombin G20210A mutation in the presence of a strong family history for thromboembolism. Immediate treatment with elastic stocking compression and enoxaparin was started. The patient was discharged on warfarin therapy maintained for six months, with the warning to avoid trauma activities during anticoagulation. Thrombotic genetic testing in athletes who experience episodes of deep vein thrombosis might offer important opportunities for patient management, such as prolonged anticoagulant therapy or avoidance of risk factors such as trauma-related sports.

Maternal and sex dependency of insulin resistance: longitudinal PET and echocardiography study from the healthy fetus to the adult minipig.

UNLABELLED: Cardiovascular and metabolic vulnerability have an early developmental origin. We evaluated the potential influence of innate life factors, including the metabolism of the mother and the sex of the offspring, on cardiometabolic risk, including organ-specific insulin resistance, subclinical cardiac dysfunction, and DNA oxidative damage throughout the lifespan. METHODS: Two female minipigs were studied during late pregnancy, and their offspring were restudied at the ages of 1 mo (n = 11), 6 mo (n = 9), and 9 mo (n = 10, 6 offspring and 4 age-matched animals). We measured insulin-mediated glucose disposal in skeletal muscle, adipose tissue, liver, and myocardium using (18)F-FDG PET; cardiac function using 2-dimensional strain echocardiography; and DNA damage using the comet assay. RESULTS: Glucose metabolism showed the 2 sows to have differences similar to those in their respective 1-mo-old offspring. Over time, compared with female animals, male animals developed myocardial insulin resistance (male animals vs. female animals: 34 ± 5 vs. 58 ± 8 µmol/min/kg at 6 mo, P = 0.03; 29 ± 8 vs. 60 ± 7 µmol/min/kg at 9 mo, P = 0.02). Cardiac function progressively deteriorated in male animals from 1 mo (radial strain, -60% ± 7%; strain rate, -5.4 ± 0.9 s(-1)) to 6 mo (radial strain, -41% ± 5%; strain rate, -2.5 ± 0.2 s(-1), P < 0.05 vs. 1 mo) and 9 mo (radial strain, -32% ± 5%; strain rate, -1.6 ± 0.2 s(-1), P < 0.01 vs. 1 mo) and was significantly different from that in female animals (radial strain, -48% ± 4%; strain rate, -3.1 ± 0.2 s(-1), P < 0.05 and P < 0.01, respectively). Oxidative damage was reduced in female animals and increased in male animals across age categories (P < 0.05). CONCLUSION: The metabolism of minipig offspring is influenced by maternal insulin sensitivity during early life stages. Sex-related effects prevail thereafter in healthy minipigs, documenting a precocious onset of cardiometabolic vulnerability in male offspring.

Aortic valve sclerosis is associated with systemic endothelial dysfunction.

OBJECTIVES: We sought to examine the association between aortic valve sclerosis (AVS) and systemic endothelial manifestations of the atherosclerotic process. BACKGROUND: Clinical and experimental studies suggest that AVS is a manifestation of the atherosclerotic process. Systemic endothelial dysfunction is an early sign of the atherosclerotic process and can be assessed by ultrasonography of the brachial artery. METHODS: A total of 102 in-hospital patients (76 men; mean age 63.5 +/- 9.7 years) referred to the stress echocardiography laboratory underwent: 1) transthoracic echocardiography, with specific assessment of AVS (thickened valve leaflets with a transaortic flow velocity <2.5 m/s); 2) stress echocardiography; 3) coronary angiography, with evaluation of the Duke score (from 0 [normal] to 100 [most severe disease]); and 4) an endothelial function study, with assessment of endothelium-dependent, post-ischemic, flow-mediated dilation (FMD). RESULTS: Aortic valve sclerosis was present in 35 patients (group I) and absent in 67 (group II). Groups I and II were similar in terms of the frequency of stress-induced wall motion abnormalities (35.3% vs. 19.4%, p = NS) and the angiographic Duke score (33.8 +/- 28.6 vs. 35.2 +/- 29.1, p = NS). Patients with AVS showed a markedly lower FMD than those without AVS (2.2 +/- 3.5% vs. 5.3 +/- 5.3%, p < 0.01). On multivariate analysis, only FMD was highly predictive of AVS, with an odds ratio of 1.18 for each percent decrease in FMD (95% confidence interval 1.05 to 1.32; p = 0.01). CONCLUSIONS: Aortic valve stenosis is associated with systemic endothelial dysfunction. This observation may provide a mechanistic insight into the emerging association between AVS and cardiovascular events.

Noninvasive pacemaker stress echocardiography for diagnosis of coronary artery disease: a multicenter study.

OBJECTIVE: We evaluated the feasibility, safety, and diagnostic accuracy of noninvasive pacemaker stress echocardiography (PASE) test as a potential alternative to exercise or pharmacologic stress in patients with suspected or known coronary artery disease (CAD). BACKGROUND: Transesophageal atrial pacing echocardiography is an accurate test for detection of CAD, but its practical impact has been blunted by semi-invasiveness. In the expanding population of patients with permanent pacemakers (PMs), a pacing stress test can be administered noninvasively by external programming of the PM. METHODS: In a prospective, multicenter, international study design, transthoracic stress-pacing echocardiography was performed in 46 consecutive patients with a permanent PM (33 men, 13 women; age 66.6 +/- 11.1 years) with suspected or known CAD. All patients underwent noninvasive PM-stress test by external programming (10 beats/min increments up to ischemia or target heart rate). Coronary angiography was performed in all patients independently of test results. Significant CAD was defined as >/=50% visually assessed diameter reduction in at least one major epicardial coronary artery. All coronary angiograms were scored by Duke prognostic weight values. RESULTS: Fifteen patients were stimulated in atrial, and the remaining 31 in ventricular mode during stress. No significant side effects were observed. Echocardiographic images were interpretable in all patients. The average duration of stress was 8.9 +/- 3.5 min. Significant CAD was found in 27 patients. Sensitivity of PASE for identifying patients with significant CAD was 70%, specificity was 90%, and accuracy was 78%. When any abnormal wall motion at rest that remained unchanged at peak stress was regarded as a positive result of PASE, then the sensitivity, specificity, and accuracy levels for identifying patients with significant CAD were 85%, 84%, and 85%, respectively. Four of the eight patients with a false negative did not reach the target heart rate. The Duke values had significant correlation with values of wall motion score index at peak stress (r = 0.67) and with peak heart rate (r = -0.3). CONCLUSIONS: Noninvasive PASE is a simple, rapid, safe, and diagnostically efficient option for patients with permanent PM and suspected or known CAD.