Pulmonary venous flow velocity patterns in 404 individuals without cardiovascular disease

OBJECTIVE To determine the pulmonary venous flow velocity (PVFV) values in a large normal population. DESIGN Prospective study in consecutive individuals. SETTING University hospital. METHODS Among 404 normal individuals, the flow velocity pattern in the right upper pulmonary vein was recorded in 315 subjects using transthoracic echocardiography, and in both upper pulmonary veins in 100 subjects using transoesophageal echocardiography. Subjects were divided into five age groups. The PVFV values were compared between transthoracic and transoesophageal echocardiography within the age groups, and intraindividually between the right and left upper pulmonary veins in transoesophageal echocardiography. RESULTS Normal PVFV values for the right upper pulmonary vein in transthoracic and transoesophageal echocardiography are presented. The duration of flow reversal at atrial contraction was overestimated using transthoracic echocardiography (mean (SD): 96 (21) ms in transoesophageal echocardiography, 120 (28) ms in transthoracic echocardiography, p < 0.0001). Systolic to diastolic peak flow velocity ratio (S:D) increased earlier with advancing age with transoesophageal echocardiography than with transthoracic echocardiography. Similar results were found for the corresponding time-velocity integrals. Data from the left and right upper pulmonary veins differed with respect to onset and deceleration of flow velocities, but not for flow durations or peak velocities. CONCLUSIONS Normal PVFV values generally show a wide range. The data presented will be of value in assessing left ventricular diastolic function and mitral regurgitation using the PVFV pattern.

Fatal aortic endocarditis associated with community-acquired Serratia marcescens infection in a dog

A 12 yr old Dalmatian was referred for evaluation of acute lethargy, fever, neurologic signs, and a recently ausculted heart murmur. Echocardiography in combination with blood cultures resulted in a diagnosis of nonhospital-acquired Serratia marcescens bacteremia and aortic valve endocarditis. Despite early diagnosis and aggressive therapy, the dog failed to respond to antimicrobials and died within 6 hr after admission. Necropsy findings included aortic valve endocarditis, septicemia, and diffuse thromboembolic disease. There was no history of pre-existing underlying disease or immunosuppressive therapy, and the dog had not been hospitalized before referral.

Successful treatment of Bartonella henselae endocarditis in a cat

This report describes the clinical presentation, diagnosis and treatment of a cat with vegetative valvular endocarditis temporally associated with natural infection with Bartonella henselae. Lethargy, abnormal gait and weakness were the main clinical signs that resulted in referral for diagnostic evaluation. Using a novel and sensitive culture approach, B henselae was isolated from the blood. Following antibiotic therapy there was total resolution of clinical signs, the heart murmur, the valvular lesion by echocardiography, and no Bartonella species was isolated or amplified from a post-treatment blood culture. In conjunction with previous case reports, infective endocarditis can be associated with natural B henselae infection in cats; however, early diagnosis and treatment may result in a better prognosis than previously reported.

Impact of B-type natriuretic peptide on short-term clinical outcomes following transcatheter aortic valve implantation

Aims: We aimed to assess the impact of B-type natriuretic peptide (BNP) on short-term outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). Methods and results: Of 500 consecutive patients with severe aortic stenosis undergoing TAVI at our institution, we studied 340 patients who had a BNP assessment prior to TAVI. Patients were divided into tertiles - low: BNP ≤201 pg/mL (n=114), mid: BNP 202-595 pg/mL (n=113) and high: BNP ≥596 pg/mL (n=113). The primary endpoint was all-cause mortality, cardiac death and major adverse cardiac and cerebrovascular events (MACCE; death, major stroke and myocardial infarction) at 30 days. Compared with low tertile, high tertile patients were at higher baseline surgical risk (STS score 5.5±3.0 vs. 7.4±4.1, p=0.002). On echocardiography, high tertile patients had smaller valve areas (0.74±0.21 vs. 0.66±0.23 cm2, p=0.008), higher left ventricular (LV) mass indices (123.40±33.66 vs. 168.22±47.96 g/m2, p<0.001) and lower LV ejection fractions (61.59±7.18 vs. 42.65±15.41%, p<0.001) as compared with low tertile patients. At 30 days, a significantly higher incidence of death (hazard ratio [HR] 7.41, p=0.001) cardiac death (HR 5.82, p=0.006) and MACCE (HR 9.04, p<0.001) was observed among high as compared to low tertile patients. Conclusions: In TAVI patients, higher BNP values at baseline are associated with an increased risk for an adverse event periprocedurally and after 30 days, respectively.

Myocardial Ablation of G Protein-Coupled Receptor Kinase 2 (GRK2) Decreases Ischemia/Reperfusion Injury through an Anti-Intrinsic Apoptotic Pathway

Studies from our lab have shown that decreasing myocardial G protein-coupled receptor kinase 2 (GRK2) activity and expression can prevent heart failure progression after myocardial infarction. Since GRK2 appears to also act as a pro-death kinase in myocytes, we investigated the effect of cardiomyocyte-specific GRK2 ablation on the acute response to cardiac ischemia/reperfusion (I/R) injury. To do this we utilized two independent lines of GRK2 knockout (KO) mice where the GRK2 gene was deleted in only cardiomyocytes either constitutively at birth or in an inducible manner that occurred in adult mice prior to I/R. These GRK2 KO mice and appropriate control mice were subjected to a sham procedure or 30 min of myocardial ischemia via coronary artery ligation followed by 24 hrs reperfusion. Echocardiography and hemodynamic measurements showed significantly improved post-I/R cardiac function in both GRK2 KO lines, which correlated with smaller infarct sizes in GRK2 KO mice compared to controls. Moreover, there was significantly less TUNEL positive myocytes, less caspase-3, and -9 but not caspase-8 activities in GRK2 KO mice compared to control mice after I/R injury. Of note, we found that lowering cardiac GRK2 expression was associated with significantly lower cytosolic cytochrome C levels in both lines of GRK2 KO mice after I/R compared to corresponding control animals. Mechanistically, the anti-apoptotic effects of lowering GRK2 expression were accompanied by increased levels of Bcl-2, Bcl-xl, and increased activation of Akt after I/R injury. These findings were reproduced in vitro in cultured cardiomyocytes and GRK2 mRNA silencing. Therefore, lowering GRK2 expression in cardiomyocytes limits I/R-induced injury and improves post-ischemia recovery by decreasing myocyte apoptosis at least partially via Akt/Bcl-2 mediated mitochondrial protection and implicates mitochondrial-dependent actions, solidifying GRK2 as a pro-death kinase in the heart.

Inhibition of Fas-associated death domain-containing protein (FADD) protects against myocardial ischemia/reperfusion injury in a heart failure mouse model

AIM As technological interventions treating acute myocardial infarction (MI) improve, post-ischemic heart failure increasingly threatens patient health. The aim of the current study was to test whether FADD could be a potential target of gene therapy in the treatment of heart failure. METHODS Cardiomyocyte-specific FADD knockout mice along with non-transgenic littermates (NLC) were subjected to 30 minutes myocardial ischemia followed by 7 days of reperfusion or 6 weeks of permanent myocardial ischemia via the ligation of left main descending coronary artery. Cardiac function were evaluated by echocardiography and left ventricular (LV) catheterization and cardiomyocyte death was measured by Evans blue-TTC staining, TUNEL staining, and caspase-3, -8, and -9 activities. In vitro, H9C2 cells transfected with ether scramble siRNA or FADD siRNA were stressed with chelerythrin for 30 min and cleaved caspase-3 was assessed. RESULTS FADD expression was significantly decreased in FADD knockout mice compared to NLC. Ischemia/reperfusion (I/R) upregulated FADD expression in NLC mice, but not in FADD knockout mice at the early time. FADD deletion significantly attenuated I/R-induced cardiac dysfunction, decreased myocardial necrosis, and inhibited cardiomyocyte apoptosis. Furthermore, in 6 weeks long term permanent ischemia model, FADD deletion significantly reduced the infarct size (from 41.20 ± 3.90% in NLC to 26.83 ± 4.17% in FADD deletion), attenuated myocardial remodeling, improved cardiac function and improved survival. In vitro, FADD knockdown significantly reduced chelerythrin-induced the level of cleaved caspase-3. CONCLUSION Taken together, our results suggest FADD plays a critical role in post-ischemic heart failure. Inhibition of FADD retards heart failure progression. Our data supports the further investigation of FADD as a potential target for genetic manipulation in the treatment of heart failure.

Amplatzer left atrial appendage occlusion: single center 10-year experience

OBJECTIVES To report a 10-year single center experience with Amplatzer devices for left atrial appendage (LAA) occlusion. BACKGROUND Intermediate-term outcome data following LAA occlusion are scarce. METHODS Short- and intermediate-term outcomes of patients who underwent LAA occlusion were assessed. All procedures were performed under local aesthesia without transesophageal echocardiography. Patients were discharged on acetylsalicylic acid and clopidogrel for 1-6 months. RESULTS LAA occlusion was attempted in 152 patients (105 males, age 72 ± 10 years, CHA2 DS2 -Vasc-score 3.4 ± 1.7, HAS-BLED-score 2.4 ± 1.2). Nondedicated devices were used in 32 patients (21%, ND group) and dedicated Amplatzer Cardiac Plugs were used in 120 patients (79%, ACP group). A patent foramen ovale or atrial septal defect was used for left atrial access and closed at the end of LAA occlusion in 40 patients. The short-term safety endpoints (procedural complications, bleeds) occurred in 15 (9.8%) and the efficacy endpoints (death, stroke, systemic embolization) in 0 patients. Device embolization occurred more frequently in the ND as compared to the ACP group (5 patients or 12% vs. 2 patients or 2%). Mean intermediate-term follow up of the study population was 32 months (range 1-120). Late deaths occurred in 15 patients (5 cardiovascular, 7 noncardiac, 3 unexplained). Neurologic events occurred in 2, peripheral embolism in 1, and major bleeding in 4 patients. The composite efficacy and safety endpoint occurred in 7% and 12% of patients. CONCLUSION LAA closure may be a good alternative to oral anticoagulation. This hypothesis needs to be tested in a randomized clinical trial to ensure that all potential biases of this observational study are accounted for.

Controversies of fetal cardiac intervention

Remarkable advances in ultrasound imaging technology have made it possible to diagnose fetal cardiovascular lesions as early as 12-14 weeks of gestation and to assess their physiological relevance by echocardiography. Moreover, invasive techniques have been developed and refined to relieve significant congenital heart disease (CHD), such as critical aortic and pulmonary stenoses in the pediatric population including neonates. Recognition of the fact that certain CHDs can evolve in utero, and early intervention may improve the outcome by altering the natural history of such conditions has led to the evolution of a new fetal therapy, i.e. fetal cardiac intervention. Two entities, pulmonary valvar atresia and intact ventricular septum (PA/IVS) and hypoplastic left heart syndrome (HLHS), are associated with significant morbidity and mortality even with postnatal surgical therapy. These cases are believed to occur due to restricted blood flow, leading to impaired growth and function of the right or left ventricle. Therefore, several centers started the approach of antenatal intervention with the primary goal of improving the blood flow through the stenotic/atretic valve orifices to allow growth of cardiac structures. Even though centers with a reasonable number of cases seem to have improved the technique and the immediate outcome of fetal interventions, the field is challenged by ethical issues as the intervention puts both the mother and the fetus at risk. Moreover, the perceived benefits of prenatal treatment have to be weighed against steadily improving postnatal surgical and hybrid procedures, which have been shown to reduce morbidity and mortality for these complex heart defects. This review is an attempt to provide a balanced opinion and an update on fetal cardiac intervention.

Amplatzer left atrial appendage occlusion through a patent foramen ovale

OBJECTIVES: To assess feasibility and outcomes of left atrial appendage (LAA) closure when using a patent foramen ovale (PFO) for left atrial access. Background: Because of the fear of entering the left atrium too high, using a PFO for left atrial access during LAA occlusion (LAAO) is generally discouraged. We report our single-center experience using a concomitant PFO for LAAO, thereby avoiding transseptal puncture. METHODS: LAAO was performed with local anesthesia and fluoroscopic guidance only (no echocardiography). The Amplatzer Cardiac Plug (ACP) was used in all patients. After LAAO, the PFO was closed at the same sitting, using an Amplatzer occluder through the ACP delivery sheath. Patients were discharged the same or the following day on dual antiplatelet therapy for 1-6 months, at which time a follow-up transesophageal echocardiogram (TEE) was performed. RESULTS: In 49 (96%) of 51 patients (35 males, age 70.9 ± 11.9 years), LAAO was successful using the PFO for left atrial access. In one patient, a long tunnel PFO precluded LAAO, which was performed via a more caudal transseptal puncture. In a second patient, a previously inserted ASD occluder precluded LAAO, which was abandoned because of pericardial bleeding. PFO closure was successful in all patients. Follow-up TEE was performed in 43 patients 138 ± 34 days after the procedure. It showed proper sitting of both devices in all patients. CONCLUSIONS: Using a PFO for LAAO had a high success rate and could be the default access in all patients with a PFO, potentially reducing procedural complications arising from transseptal puncture.

Accuracy and reproducibility of aortic annulus sizing using a dedicated three-dimensional computed tomography reconstruction tool in patients evaluated for transcatheter aortic valve replacement

Aims: To evaluate the accuracy and reproducibility of aortic annulus sizing using a multislice computed tomography (MSCT) based aortic root reconstruction tool compared with conventional imaging among patients evaluated for transcatheter aortic valve replacement (TAVR). Methods and results: Patients referred for TAVR underwent standard preprocedural assessment of aortic annulus parameters using MSCT, angiography and transoesophageal echocardiography (TEE). Three-dimensional (3-D) reconstruction of MSCT images of the aortic root was performed using 3mensio (3mensio Medical Imaging BV, Bilthoven, The Netherlands), allowing for semi-automated delineation of the annular plane and assessment of annulus perimeter, area, maximum, minimum and virtual diameters derived from area and perimeter (aVD and pVD). A total of 177 patients were enrolled. We observed a good inter-observer variability of 3-D reconstruction assessments with concordance coefficients for agreement of 0.91 (95% CI: 0.87-0.93) and 0.91 (0.88-0.94) for annulus perimeter and area assessments, respectively. 3-D derived pVD and aVD correlated very closely with a concordance coefficient of 0.97 (0.96-0.98) with a mean difference of 0.5±0.3 mm (pVD-aVD). 3-D derived pVD showed the best, but moderate concordance with diameters obtained from coronal MSCT (0.67, 0.56-0.75; 0.3±1.8 mm), and the lowest concordance with diameters obtained from TEE (0.42, 0.31-0.52; 1.9±1.9 mm). Conclusions: MSCT-based 3-D reconstruction of the aortic annulus using the 3mensio software enables accurate and reproducible assessment of aortic annulus dimensions.

Association of congenital, diffuse electrical disease in children with normal heart: sick sinus syndrome, intraventricular conduction block, and monomorphic ventricular tachycardia.

INTRODUCTION Rhythm disturbances in children with structurally normal hearts are usually associated with abnormalities in cardiac ion channels. The phenotypic expression of these abnormalities ("channelopathies") includes: long and short QT syndromes, Brugada syndrome, congenital sick sinus syndrome, catecholaminergic polymorphic ventricular tachycardia, Lènegre-Lev disease, and/or different degrees of cardiac conduction disease. METHODS The study group consisted of three male patients with sick sinus syndrome, intraventricular conduction disease, and monomorphic sustained ventricular tachycardia. Clinical data and results of electrocardiography, Holter monitoring, electrophysiology, and echocardiography are described. RESULTS In all patients, the ECG during sinus rhythm showed right bundle branch block and long QT intervals. First-degree AV block was documented in two subjects, and J point elevation in one. A pacemaker was implanted in all cases due to symptomatic bradycardia (sick sinus syndrome). Atrial tachyarryhthmias were observed in two patients. The common characteristic ventricular arrhythmia was a monomorphic sustained ventricular tachycardia, inducible with ventricular stimulation and sensitive to lidocaine. In one patient, radiofrequency catheter ablation was successfully performed. No structural abnormalities were found in echocardiography in the study group. CONCLUSION Common clinical and ECG features suggest a common pathophysiology in this group of patients with congenital severe electrical disease.

Paraseptal accessory pathway in Wolff-Parkinson- White-Syndrom: ablation from the right, from the left or within the coronary sinus/middle cardiac vein?

AIMS In 1999 the consensus statement "living anatomy of the atrioventricular junctions" was published. With that new nomenclature the former posteroseptal accessory pathway (APs) are termed paraseptal APs. The aim of this study was to identify ECG features of manifest APs located in this complex paraseptal space. METHODS AND RESULTS ECG characteristics of all patients who underwent radiofrequency ablation of an AP during a 3 year period were analyzed. Of the 239 patients with one or more APs, 30 patients had a paraseptal AP with preexcitation. Compared to APs within the coronary sinus (CS) or the middle cardiac vein (MCV) the right sided paraseptal APs significantly more often showed an isoelectric delta wave in lead II and/or a negative delta wave in aVR. The left sided paraseptal APs presented a negative delta wave in II significantly more often compared to the right sided APs. CONCLUSIONS According to the site of radiofrequency ablation, paraseptal APs are classified into 4 subgroups: paraseptal right, paraseptal left, inside the CS or inside the MCV. Subtle differences in preexcitation patterns of the delta wave as well as of the QRS complex exist. However, the definitive localization of APs remains reserved to the periinterventional intracardiac electrogram analysis.

B-type natriuretic peptide for diagnosis and treatment of congestive heart failure

BACKGROUND Prognostic classification of congestive heart failure (CHF) is difficult and only possible with the help of additional diagnostic tools. B-type natriuretic peptide (BNP) has been used as a diagnostic and prognostic marker for patients (pts) with CHF. In this study, the clinical value of BNP for stratification and treatment of pts with CHF was evaluated. PATIENTS AND METHODS 33 out-pts with CHF (age 57 +/- 12 years) were included. Left-ventricular (LV) ejection fraction (EF) was 27 +/- 8% (mean +/- SD) and NYHA-class 2.4 +/- 0.7. Following parameters were measured: BNP and sodium from blood samples, exercise performance from 6-minute walking test (6MWT, meters) (n = 18), LV end-diastolic diameter (LVEDD) and LV mass (LVM) from 2D-echocardiography (n = 33), as well as LV end-diastolic pressure (LVEDP, n = 23) and systemic vascular resistance (SVR, n = 20) from heart-catheterisation. Ten pts were hospitalised in the preceding 6 months because of worsening CHF or for optimisation of medical therapy. BNP was measured at the beginning and end of the hospital-stay. Follow-up was for 1 year. RESULTS Pts with a high NYHA-class had a higher BNP (pg/ml) than those with a low NYHA- class: NYHA I 51 +/- 20, II 281 +/- 223, III 562+/-346 and IV 1061 +/- 126 pg/ml (p = 0.002). BNP correlated with LVEDP (r = 0.50, p <0.02), SVR (r =0.49, p <0.03) and inversely with 6MWT (r =-0.60, p <0.009), LVEF (r = -0.49, p <0.004) and sodium (r = -0.36, p = 0.04). In the hospitalised pts, mean BNP (pg/ml) was 881 +/- 695 at admission,and 532 +/- 435 at discharge (n.s.). Decrease in BNPduring hospitalisation paralleled weight-loss and was significantly greater in patients with >1000 pg/ml BNP at admission (n = 5) as compared to the 5 patients with BNP <1000 (p <0.03). Patients with an adverse event during 1-year follow-up had significantly higher BNP both at steady-state (603 +/-359 pg/ml) and at time of decompensation than patients with a favourable outcome (227 +/- 218 pg/ml,p <0.001). CONCLUSIONS BNP correlates well with the clinical severity of CHF (NYHA-class) and is directly related to filling pressure (LVEDP), LV function(LVEF) and exercise performance (6 MWT). Furthermore, BNP has prognostic impact with regard to adverse clinical events.

The prevalence of anemia in chronic heart failure.

OBJECTIVES To assess prevalence of anemia and its correlation with NYHA-class in patients with congestive heart failure. BACKGROUND Recently, it was reported that anemia in congestive heart failure patients is common and correlated with the severity of disease. In these patients with anemia, treatment with erythropoietin and intravenous iron improved cardiac function significantly. METHODS 193 patients from a tertiary heart failure outpatient clinic (mean age 54 years) were included in a retrospective analysis. Fourteen patients were in NYHA-class I, 69 class II, 79 class III, and 31 class IV. All patients had clinical and laboratory evaluation, echocardiography and coronary angiography. Patients with secondary anemia or on hemodialysis were excluded. Etiology of heart failure was ischemic in 41%. RESULTS Anemia (hemoglobin<120 g/l) was present in 28 of 193 patients (15%). There was an inverse relationship between NYHA-class and left ventricular ejection fraction (NYHA-class I 45%, class II 32%, class III 25%, class IV 25%). Serum creatinine increased with NYHA-class. Hemoglobin levels were similar in all four NYHA-classes but there were significantly more patients with anemia in NYHA-class III and IV (19%) compared with class I and II (8%, P<0.05). Hemoglobin was similar in surviving patients (mean 140 g/l) and those who died or were transplanted (mean 136 g/l, ns). CONCLUSIONS The prevalence of anemia in our heart failure service is 15% (compared with 56% in the literature) and is correlated to NYHA-class.

RV contractility and exercise-induced pulmonary hypertension in chronic mountain sickness: a stress echocardiographic and tissue Doppler imaging study

OBJECTIVES The aim of this study was to evaluate right ventricular (RV) and left ventricular function and pulmonary circulation in chronic mountain sickness (CMS) patients with rest and stress echocardiography compared with healthy high-altitude (HA) dwellers. BACKGROUND CMS or Monge's disease is defined by excessive erythrocytosis (hemoglobin >21 g/dl in males, 19 g/dl in females) and severe hypoxemia. In some cases, a moderate or severe increase in pulmonary pressure is present, suggesting a similar pathogenesis of pulmonary hypertension. METHODS In La Paz (Bolivia, 3,600 m sea level), 46 CMS patients and 40 HA dwellers of similar age were evaluated at rest and during semisupine bicycle exercise. Pulmonary artery pressure (PAP), pulmonary vascular resistance, and cardiac function were estimated by Doppler echocardiography. RESULTS Compared with HA dwellers, CMS patients showed RV dilation at rest (RV mid diameter: 36 ± 5 mm vs. 32 ± 4 mm, CMS vs. HA, p = 0.001) and reduced RV fractional area change both at rest (35 ± 9% vs. 43 ± 9%, p = 0.002) and during exercise (36 ± 9% vs. 43 ± 8%, CMS vs. HA, p = 0.005). The RV systolic longitudinal function (RV-S') decreased in CMS patients, whereas it increased in the control patients (p < 0.0001) at peak stress. The RV end-systolic pressure-area relationship, a load independent surrogate of RV contractility, was similar in CMS patients and HA dwellers with a significant increase in systolic PAP and pulmonary vascular resistance in CMS patients (systolic PAP: 50 ± 12 mm Hg vs. 38 ± 8 mm Hg, CMS vs. HA, p < 0.0001; pulmonary vascular resistance: 2.9 ± 1 mm Hg/min/l vs. 2.2 ± 1 mm Hg/min/l, p = 0.03). Both groups showed comparable systolic and diastolic left ventricular function both at rest and during stress. CONCLUSIONS Comparable RV contractile reserve in CMS and HA suggests that the lower resting values of RV function in CMS may represent a physiological adaptation to chronic hypoxic conditions rather than impaired RV function. (Chronic Mountain Sickness, Systemic Vascular Function [CMS]; NCT01182792).