Four-year clinical results of transcatheter self-expanding Medtronic CoreValve implantation in high-risk patients with severe aortic stenosis.

BACKGROUND: transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement for patients with severe aortic stenosis considered inoperable or at high operative risk, but the long-term outcome remains unknown. HYPOTHESIS: we assessed the 4-year clinical and echocardiographic outcomes of patients undergoing TAVI with the self-expanding Medtronic CoreValve prosthesis. METHODS: sixty-three patients (mean age 80 ± 6 years) with severe aortic stenosis (AS) at high risk for surgical aortic valve replacement (Logistic EuroSCORE 28.8 ± 10.9%) were included in this study. RESULTS: all-cause cumulative mortality at 1, 2, 3 and 4 years was 14.3, 25.4, 28.6 and 36.5%, respectively. The cumulative incidence of documented major stroke at 4 years was 6.3%. In survivors, there was a significant improvement in functional status at 4 years. Paravalvular leak (trivial/mild to moderate) was observed in the majority of patients post-TAVI with no case of progression to severe regurgitation at 4-year follow-up. In multivariate analysis, independent predictor for increased all-cause mortality was left ventricular ejection fraction <40% (HR: 5.347, 95% CI: 1.126-25.381, P = 0.035). CONCLUSION: our study demonstrated favourable long-term (4 years) outcomes after successful TAVI using the third-generation Medtronic CoreValve device.

Anesthetic management of patients undergoing transcatheter aortic valve implantation.

OBJECTIVE: To compare 2 anesthetic techniques, general anesthesia or monitored anesthesia care, performed by the same cardiac anesthesiologists for transcatheter aortic valve implantation in the authors' institution. DESIGN: A retrospective study. SETTING: A single specialized cardiac surgery center. PARTICIPANTS: Ninety-eight patients with severe aortic valve stenosis and a high logistic EuroSCORE considered not eligible to undergo conventional aortic valve replacement. INTERVENTION: General anesthesia or monitored anesthesia care. MEASUREMENTS AND MAIN RESULTS: General anesthesia was used in 57 and monitored anesthesia care in 41 patients. The authors compared the following parameters: Duration of procedure, transfusion requirements, cardiac indices, superior vena cava saturation (ScVO2) before and after the aortic valve implantation, hospital length of stay and 30-day mortality. The only significant differences between the groups concerned were the duration of anesthesia (p<0.001) and ScVO2 values. Anesthesia duration was prolonged significantly when general anesthesia was administered, and ScVO2 was significantly higher both before and after the valve implantation in the general anesthesia group. Thirty-day mortality was 5.3% in the general anesthesia group and 4.9% in the monitored anesthesia group. CONCLUSIONS: It would appear that both anesthetic techniques may be used for patients with a high logistic EuroSCORE undergoing transcatheter aortic valve implantation.

Transcatheter aortic valve implantation: restoring the qualities of life in old age.

Transcatheter aortic valve implantation (TAVI) is a tremendous therapeutic advance for patients with severe aortic stenosis and high-surgical risk. Since TAVI-treated patients are elderly with multiple co-existing conditions, limited life expectancy and disproportionate health-care expenditures, the aspect of the health-related quality of life (HRQoL) benefits becomes of fundamental importance. Based on recent evidence, TAVI appears to improve significantly HRQoL measures compared with optimal standard care, which are restored to age-adjusted population norms over time.

Sirolimus-Coated Balloon in an All-Comer Population of Coronary Artery Disease Patients: The EASTBOURNE Prospective Registry.

BACKGROUND: Drug-coated balloons (DCB) represent 1 of the most promising innovations in interventional cardiology and may represent a valid alternative to drug-eluting stents. Currently, some sirolimus-coated balloons (SCB) are being investigated for several coronary artery disease applications. OBJECTIVES: This study sought to understand the role of a novel SCB for the treatment of coronary artery disease. METHODS: EASTBOURNE (All-Comers Sirolimus-Coated Balloon European Registry) is a prospective, multicenter, investigator-driven clinical study that enrolled real-world patients treated with SCB. Primary endpoint was target lesion revascularization (TLR) at 12 months. Secondary endpoints were procedural success, myocardial infarction (MI), all-cause death, and major adverse clinical events (a composite of death, MI, and TLR). All adverse events were censored and adjudicated by an independent clinical events committee. RESULTS: A total population of 2,123 patients (2,440 lesions) was enrolled at 38 study centers in Europe and Asia. The average age was 66.6 ± 11.3 years, and diabetic patients were 41.5%. De novo lesions (small vessels) were 56%, in-stent restenosis (ISR) 44%, and bailout stenting occurred in 7.7% of the patients. After 12 months, TLR occurred in 5.9% of the lesions, major adverse clinical events in 9.9%, and spontaneous MI in 2.4% of the patients. The rates of cardiac/all-cause death were 1.5% and 2.5%, respectively. The primary outcome occurred more frequently in the ISR cohort (10.5% vs 2.0%; risk ratio: 1.90; 95% CI: 1.13-3.19). After multivariate Cox regression model, the main determinant for occurrence of the primary endpoint was ISR (OR: 5.5; 95% CI: 3.382-8.881). CONCLUSIONS: EASTBOURNE, the largest DCB study in the coronary field, shows the safety and efficacy of a novel SCB in a broad population of coronary artery disease including small vessels and ISR patients at mid-term follow-up. (The All-Comers Sirolimus-Coated Balloon European Registry [EASTBOURNE]; NCT03085823).

Long-term quality of life improvement after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a novel therapeutic option for severe aortic stenosis in old patients with high surgical risk. The aim of this study was to assess changes in quality of life (QoL) along with functional status and late survival after this procedure. METHODS: Thirty-six consecutive patients (80.5 ± 5.9 years, 21 men and 15 women) with a logistic Euroscore of 29.7 ± 13.7 underwent TAVI using the 18-Fr CoreValve prosthesis. Aortic valve prosthesis was inserted retrograde using a femoral or a subclavian arterial approach. QoL was evaluated by administering the Short Form 36 (SF-36) tool and the shorter SF-12 version 2 (SF-12v2) questionnaires before and 1-year after TAVI. RESULTS: TAVI was successfully performed in all patients. The estimated 1-year overall survival rate using Kaplan-Meier method was 68%. One-year follow-up also showed a marked improvement in echocardiographic parameters (peak gradient 76.2 ± 26.1 vs 15.4 ± 7.8 mm Hg, P < .001; aortic valve area 0.7 ± 0.1 vs 2.6 ± 2.7 cm(2), P < .001) with a significant change in New York Heart Association class (3 ± 0.7 vs 1.2 ± 0.4, P < .001). Both preprocedural summary SF-36 and SF-12v12 physical and mental scores showed a significant improvement 1 year after TAVI (21.6 vs 46.7, P < .001; 42.9 vs 55.2, P < .001; 22 vs 48.9, P < .001; 43.3 vs 52.2, P < .001, respectively). CONCLUSIONS: Our results show a marked 1-year clinical benefit in functional status and physical and mental health in patients who underwent TAVI.

Cytokine gene polymorphisms are associated with markers of disease severity and prognosis in patients with idiopathic dilated cardiomyopathy.

AIMS: To identify potential genetic associations of five cytokine gene polymorphisms with disease severity and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Eighty patients with DCM were genotyped for transforming growth factor beta1 (TGF-ß1)+869 T/C (codon10 Leu→Pro), TGF-ß1 +915 G/C (codon25 Arg→Pro), interleukin (IL)-6 -174G/C, tumor necrosis factor-alpha (TNF-α) -308A/G, interferon-gamma (IFN-γ) +874T/A, IL-10 -1082A/G, IL-10 -819T/C and IL-10 -592A/C gene polymorphisms. In homozygous TT patients for TGF-ß1 +869 T/C polymorphism mean VO(2) max was significantly higher than in CC homozygous patients (25.67±6.73ml/kg/min vs. 20.29±6.35 ml/kg/min, p = 0.046), which remained significant only for patients younger than 39 years old after adjusting for age and sex (p = 0.009). C carriers of TGF-ß1 +915 G/C polymorphism are 4.2 times more likely to be in a worse NYHA stage (III-IV) than non C carriers [OR: 4.25, 95% CI (1.53-11.80), p = 0.006]. Patients GG homozygous for IL-6 -174G/C polymorphism presented greater left ventricle end-systolic (p = 0.018) and end-diastolic (p = 0.04) diameters in comparison to the CC homozygous. The AA homozygote for IFN-γ +874T/A polymorphism (p = 0.02) and the combination of the TGF-ß1 +869 T/C and TGF-ß1 +915 G/C genotypes were associated with adverse outcome (p = 0.014). CONCLUSION: Specific cytokine gene polymorphisms seem to be associated with worse prognosis as well as with measures of disease severity in DCM.

Ischaemia-modified albumin in pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) may be associated with subendocardial ischaemia. We investigated whether ischaemia-modified albumin (IMA), an established marker of ischaemia, is elevated in stable patients with PH. METHODS: We studied 32 patients with PH and an equal number of age-matched normal volunteers. We assessed serum IMA levels with the albumin cobalt-binding test. RESULTS: Patients' mean +/- SD (range) pulmonary arterial pressure was 56 +/- 12 (33-73) mmHg and their exercise capacity was 394 +/- 145 (121-688) m in the 6-min walk test. IMA was 92 +/- 14 (69-115) U ml(-1) in the patient group and 93 +/- 9.4 (76-122) U ml(-1) in the control group with no significant difference between the two (p = 0.85), although almost one-third of the patients had detectable troponin-I. CONCLUSIONS: We conclude that IMA, a marker of ischaemia, does not differ in patients with advanced clinically stable PH compared with normal subjects.

Transfemoral percutaneous removal of a knotted Swan-Ganz catheter.

Intracardiac knotting of balloon-tipped flow-directed catheters during a heart catheterization procedure represents a rare but serious complication. In case that such an event occurs, leading to inability to remove the catheter, various different methods have been described to solve the problem, varying from the least invasive to open heart surgery. The formation of large knots requires surgical removal in the vast majority of cases. We describe the successful nonsurgical removal of a Swan-Ganz catheter, after the formation of a large double knot, during a right heart catheterization performed without fluoroscopic guidance in the intensive care unit. This technique could serve as a last resort in cases that surgical removal seems inevitable due to size-related inapplicability of other nonsurgical methods.

Conduction abnormalities after transcatheter aortic valve implantation.

In the last few years, transcatheter aortic valve implantation (TAVI) has become an alternative procedure in patients with severe aortic stenosis and high risk for surgical aortic replacement. Due to the anatomic correlation between aortic valve structure and conduction system of the heart, one of the most common complications after TAVI is conduction system disturbances which including bundle branch block, complete heart block and need for permanent pacemaker implantation. Although these disturbances are usually not lethal, they may have a great influence on patients' state and long term-survival. Several risk factors for conduction disturbances have been identified which including age, anatomy of the heart, periprocedural factors, type of implanted valve, preexisting abnormalities and comorbidities. As this technique becomes more familiar to physicians, patients should be carefully screened for risk factors for the development of conduction abnormalities after TAVI in order to provide effective prevention and proper treatment.

Management of Coronary Artery Disease and Conduction Abnormalities in Transcatheter Aortic Valve Implantation.

OPINION STATEMENT: Transcatheter aortic valve replacement (TAVR) is an expanding, catheter-based technology that allows the implantation of a prosthetic valve without requiring open heart surgery for the treatment of severe aortic stenosis (AS). The frequency of coronary artery disease (CAD) in patients (pts) with severe AS undergoing surgical treatment ranges from 30 to 50 %. This tends to be higher in pts undergoing TAVR with a prevalence of 49-76 % and is more prevalent with older age and the fact that TAVR is commonly performed in high-risk groups with more advanced cardiovascular disease. The overall influence of CAD on TAVR procedural outcomes remains controversial, and the management of concomitant artery disease is still under discussion. There are three major issues that must be addressed: the impact of CAD, optimal timing of percutaneous coronary intervention (PCI) and TAVR, and extent of revascularization. Today, TAVR is commonly performed as a stand-alone procedure with variable degrees of concomitant CAD tolerated without intervention. One of the major potential complications with TAVR is the damage to the conduction system. The requirement of permanent pacemaker (PM) implantation ranges from 9 to 49 % of cases with a mean of ~20 %, whereas surgical aortic valve replacement (sAVR) is associated with a complete heart block that requires permanent PM in 3-12 % of cases. Reports have demonstrated an increased incidence of conduction damage in patients undergoing TAVR with the CoreValve (Medtronic Minneapolis, MN, USA) prosthesis (mean 20.8 %, range 9.3-30.0 %) compared with the Edwards SAPIEN (Edwards Lifesciences LLC; Irvine, CA, USA) prosthesis (mean 5.4 %, range 0-10.1 %). Factors predicting PM implantation include preexisting bundle branch block (BB) or conduction abnormalities. The prognostic significance of new left bundle branch block (LBBB) after TAVR is unclear. In the future, new valve designs may improve the incidence of permanent PM implantation after TAVR.

Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic heart failure.

OBJECTIVES: We sought to investigate the effects of physical training on circulating proinflammatory cytokines and the soluble apoptosis mediators Fas (sFas) and Fas ligand (sFasL) in patients with chronic heart failure (CHF). BACKGROUND: Recent investigations have shown an overexpression of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with CHF, which may be related to their exercise intolerance and clinical deterioration. METHODS: Plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors I and II (sTNF-RI and sTNF-RII, respectively), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sFas and sFasL were measured in 24 patients with stable CHF (New York Heart Association functional class II/III; left ventricular ejection fraction 23.2 +/- 1.3%) and in 20 normal control subjects before and after a 12-week program of physical training in a randomized, crossover design. Functional status of patients with CHF was evaluated by using a cardiorespiratory exercise test to measure peak oxygen consumption (VO2max). RESULTS: Physical training produced a significant reduction in plasma levels of TNF-alpha (7.5 +/- 1.0 pg/ml vs. 4.6 +/- 0.7 pg/ml, p < 0.001), sTNF-RI (3.3 +/- 0.2 ng/ml vs. 2.7 +/- 0.2 ng/ml, p < 0.005), sTNF-RII (2.6 +/- 0.2 ng/ml vs. 2.3 +/- 0.2 ng/ml, p = 0.06), IL-6 (8.3 +/- 1.2 pg/ml vs. 5.9 +/- 0.8 pg/ml, p < 0.005), sIL-6R (34.0 +/- 3.0 ng/ml vs. 29.2 +/- 3.0 ng/ml, p < 0.01), sFas (5.5 +/- 0.7 ng/ml vs. 4.5 +/- 0.8 ng/ml, p = 0.05) and sFasL (34.9 +/- 5.0 pg/ml vs. 25.2 +/- 4.0 pg/ml, p < 0.05), as well as a significant increase in VO2max (16.3 +/- 0.7 ml/kg per min vs. 18.7 +/- 0.8 ml/kg per min, p < 0.001). Good correlations were found between a training-induced increase in VO2max and a training-induced reduction in levels of the proinflammatory cytokine TNF-alpha (r = -0.54, p < 0.01) and the apoptosis inducer sFasL (r = -0.57, p < 0.005) in patients with CHF. In contrast, no significant difference in circulating cytokines and apoptotic markers was found with physical training in normal subjects. CONCLUSIONS: Physical training reduces plasma levels of proinflammatory cytokines and the sFas/sFasL system in patients with CHF. These immunomodulatory effects may be related to the training-induced improvement in functional status of patients with CHF.

Repeated exercise stress testing identifies early and late preconditioning.

BACKGROUND: The warm-up phenomenon has been considered to trigger preconditioning. We investigated whether repeated exercise treadmill tests in humans are capable of inducing adaptation to ischemia by triggering both the early and late phase of preconditioning. METHODS: In 25 consecutive patients with stable coronary artery disease, four repeated treadmill tests were performed. Thirty minutes following the first test (T1) a second one was performed (T2), followed 6 h later by a third test (T3). Twenty-four hours later all patients were subjected to a fourth exercise test (T4). In every fifth patient, simultaneous echocardiographic examination was performed at the time of the exercise tests in an attempt to reveal ischemic abnormalities. RESULTS: At baseline there was no difference between the variables. At ST segment depression >1.5 mm, the rate-pressure product (RPP) was higher in T2 and T4 (231.3+/-17.9 and 232.6+/-15.8 mm Hg s 10(2)) than in T1 and T3 (210+/-17 and 210.2+/-16.7 mm Hg s 10(2)), p<0.001. Additionally, time to the onset of chest pain was longer in T2 and T4 (430.8+/-60.5 and 438+/-47 s) than in T1 and T3 (345.6+/-69 and 345.6+/-58 s), p<0.001. At peak exercise, the RPP was higher in T2 and T4 (278.6+/-21.6 and 278.3+/-19.6 mm Hg s 10(2)) than in T1 and T3 (255.6+/-23.1 and 256.6+/-23 mm Hg s 10(2)), p<0.001. The wall motion score index was higher in T1 and T3 (1.65+/-0.17 and 1.53+/-0.16) than in T2 and T4 (1.3+/-0.07 and 1.37+/-0.1), p<0.001. CONCLUSION: By using repeated exercise treadmill tests both the early and late phase of protection can be obtained.

Cardiovascular magnetic resonance and computed tomography in the evaluation of aneurysmal coronary-cameral fistula.

Coronary artery fistulas represent abnormal communications between a coronary artery and a major vessel like venae cavae, pulmonary arteries or veins, the coronary sinus, or a cardiac chamber. The latter is called coronary cameral fistula is a rare condition and is most of the times congenital but can be also post traumatic or post surgical, especially after cardiovascular interventional procedures. Most patients are asymptomatic and coronary-cameral fistulae are discovered incidentally during angiographic evaluation for coronary vascular disorders, while other patients have a clinical presentation ranging from angina pectoris to heart failure. In this article, we report a rare case of an aneurysmal right coronary cameral fistula draining into the left ventricle. Echocardiography usually represents the first diagnostic imaging approach, but often due to a poor acoustic window may not show the entire course of the fistula which is crucial for the final diagnosis. ECG-gated cardiovascular CT may play an important role in the evaluation of the origin, course, termination and morphology of the fistula, its relation to the adjacent anatomical structures as well as the morphology and contractility of the heart. Cardiac MRI instead plays an additional crucial role regarding not only the above mentioned factors but also in estimating the blood flow within the fistula, providing more detailed information about the cardiac function but also about myocardial wall viability.

The role of TNF-α, Fas/Fas ligand system and NT-proBNP in the early detection of asymptomatic left ventricular dysfunction in cancer patients treated with anthracyclines.

BACKGROUND: Anthracycline-induced cardiotoxicity typically presents as congestive heart failure (CHF). As immuno-inflammatory activation and apoptosis are important mechanisms in the process of heart failure, the use of biomarkers that could detect cardiovascular toxicity before the clinical presentation is of great importance. We studied whether sTNF-a, sTNF-RI, sTNF-RII, Fas/FasLigand system and NT-proBNP associate with early cardiac dysfunction in patients receiving cardiotoxic drugs. METHODS: Two groups of breast cancer patients-group A with metastatic disease under chemotherapy with epirubicin and group B with no residual disease under a less cardiotoxic regimen-as well as healthy women were included in this prosprective study. NT-proBNP, sTNF-a, sTNF-RI, sTNF-RII, sFas, sFas-Ligand and left ventricular ejection fraction (LVEF) were determined in all patients before and after the completion of chemotherapy. RESULTS: In Group A, an increase in sFas levels (p < 0.001), a decrease in the sFasL levels (p = 0.010), an NT-proBNP increase (p < 0.001) and a significant reduction of LVEF (p < 0.001) was recorded post-chemotherapy. The decrease in LVEF correlated significantly with the increase in sFas, the decrease in sFasL and the rise in NT-proBNP levels. In Group B, TNF-RI levels were higher (p = 0.024) and mean sFas-L levels lower (p = 0.021) post chemotherapy with no LVEF drop. Two of group A (7.6%) patients developed symptomatic CHF 12 and 14 months respectively after the end of chemotherapy. CONCLUSION: SFas, sFas-L and NT-proBNP correlate with reductions in LVEF and could be used as sensitive biochemical indices for the detection of asymptomatic left ventricular dysfunction in cancer patients under cardiotoxic chemotherapy.

Growth hormone administration reduces circulating proinflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy.

BACKGROUND: Recent studies have shown that an abnormal proinflammatory cytokine expression and apoptotic process contribute to adverse left ventricular remodeling and progress of chronic heart failure. This study investigates the effects of growth hormone (GH) administration on serum levels of representative proinflammatory cytokines and soluble apoptosis mediators in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy (IDC). METHODS: Serum levels of tumor necrosis factor-alpha (TNF-alpha), its soluble receptors (sTNF-RI, sTNF-RII), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), soluble Fas (sFas) and soluble Fas Ligand (sFasL) were determined (enzyme-linked immunosorbent assay method) in 10 patients with IDC (New York Heart Association class III, ejection fraction 24% +/- 2%) before and after a 3-month subcutaneous administration of 4 IU GH every other day (randomized crossover design). Peak oxygen consumption (Vo(2)max) was also used to evaluate the functional status of patients with IDC. RESULTS: Treatment with GH produced a significant reduction in serum levels of TNF-alpha (8.2 +/- 1.2 vs 5.7 +/- 1.1 pg/mL, P <.05), sTNF-RI (3.9 +/- 0.4 vs 3.2 +/- 0.3 ng/mL, P <.05), sTNF-RII (2.6 +/- 0.3 vs 2.2 +/- 0.2 ng/mL, P <.05), IL-6 (5.5 +/- 0.6 vs 4.4 +/- 0.4 pg/mL, P =.05), sIL-6R (32.7 +/- 3.0 vs 28.2 +/- 3.0 ng/mL, P <.05), sFas (4.4 +/- 0.8 vs 3.1 +/- 0.6 ng/mL, P <.05), and sFasL (34.2 +/- 11.7 vs 18.8 +/- 7.3 pg/mL, P <.01). A significant improvement was also observed in VO2max after the completion of 3 months' treatment with GH (15.0 +/- 0.8 vs 17.2 +/- 1.0 mL/kg/min, P <.05). Good correlations were found between GH-induced reduction in TNF-alpha levels and increase in VO2max (r = -0.64, P <.05) as well as between GH-induced reduction in sFasL and increase in VO2max (r = -0.56, P =.08). CONCLUSIONS: GH administration reduces serum levels of proinflammatory cytokines and soluble Fas/FasL system in patients with IDC. These immunomodulatory effects may be associated with improvement in clinical performance and exercise capacity of patients with IDC.

Doppler-derived left ventricular end-diastolic pressure prediction model using the combined analysis of mitral and pulmonary A waves in patients with coronary artery disease and preserved left ventricular systolic function.

The aim of this study was to analyze the components of mitral and pulmonary A waves and to construct a Doppler-derived left ventricular (LV) end-diastolic pressure (EDP) prediction model based on the combined analysis of transmitral and pulmonary venous flow velocity curves. Combined analysis of transmitral and pulmonary venous flow velocity curves at atrial contraction is a reliable predictor of increased LV filling pressure. The duration of pulmonary and mitral A waves is determined by the sum of respective acceleration and deceleration time. Mitral flow and left upper pulmonary vein flow velocity curves were recorded simultaneously with LVEDP in 40 consecutive patients (aged 59 +/- 8 years) with coronary artery disease and preserved LV systolic function. Differences in all parameters represent values of pulmonary minus those of mitral A wave curve. The difference in deceleration time was the strongest candidate, being included in all models. After redundancy evaluation, we reached the following model: LVEDP = 20.61 + 0.229 x difference in deceleration time (r(2) = 0.80, p <0.001). In the entire study group, the difference in duration and in deceleration time of the A wave was highly correlated with LVEDP (r = 0.79, p <0.001, and r = 0.88, p <0.001, respectively). The entire study group was further divided according to whether LVEDP was above (group I, 20 patients) or below (group II, 20 patients) the median value (15.5 mm Hg). In group I, the difference in duration and in deceleration time correlated well (r = 0.62, p = 0.01, and r = 0.75, p = 0.001, respectively) with LVEDP, whereas in group II only the difference in deceleration time correlated well (r = 0.68, p = 0.005). In patients with coronary artery disease and preserved LV systolic function, the combined analysis of mitral and pulmonary A waves can predict LVEDP. The difference in deceleration time between pulmonary and mitral A waves can reliably evaluate high and normal LVEDP.

Acute haemodynamic effects of oestrogen administration in male patients with chronic heart failure.

BACKGROUND: Although there are many studies concerning the effects of long-term oestrogen administration on systemic haemodynamics in postmenopausal women, the effects of oestrogen in patients with chronic heart failure are not defined. AIM: The goal of this study was to evaluate the acute haemodynamic effects of oestrogen in male patients with chronic heart failure. METHODS AND RESULTS: We studied 15 men with advanced heart failure (NYHA II-IV, EF < 35%). A Swan-Ganz thermodilution catheter was advanced in their pulmonary artery and central haemodynamics were assessed at baseline, after placebo administration, and following 0.625 and 1.25 mg of oestrogen infusion. Simultaneously, all patients underwent limb plethysmography. Analysis of variance with repeated measures was used to compare the sequential measurements. Following oestrogen administration, right atrial, pulmonary artery and pulmonary capillary wedge pressures, as well as systemic, pulmonary and forearm vascular resistance were decreased; cardiac output, cardiac index, stroke volume, stroke volume index, stroke work index and forearm blood flow were increased. CONCLUSIONS: In male patients with chronic heart failure, acute oestrogen administration improves the indices of cardiac systolic performance and decreases pulmonary and systemic vascular resistance. These findings imply a beneficial effect of oestrogen in selected patients with chronic heart failure.

Angiotensin II fails to induce preconditioning in vivo--the protective role of myocardial stretch due to pressure overload.

BACKGROUND: Angiotensin II (Ang) has been successfully used as a preconditioning analogue in isolated rabbit hearts. It is also known that local concentrations of Ang accelerate ischemic injury in vivo, while activation of stretch receptors protects ischemic hearts. OBJECTIVES: First, to investigate further whether Ang can mimic preconditioning in vivo. Second, to test the hypothesis that there is an activation of stretch receptors, and that the larger infarct from the left atrium Ang compared with that from the intravenous Ang may be associated with the ischemic injury caused by local administration. METHODS: Male rabbits were divided into four groups - a control group, an ischemic preconditioning group with 5 min ischemia, a left atrial group and an intravenous group with 5 min Ang infusion. All animals were subjected to prolonged ischemia and reperfusion. A second series of experiments was also performed with five groups that had a 5 min mechanical obstruction of the aorta (Ao clamp), also used as a preconditioning analogue with or without the stretch receptor blocker gadolinium (Gd). RESULTS: Contrary to what was expected from the ex vivo experiments, Ang failed to mimic preconditioning (infarct size 39.6 6.1%, 13.7 4.1%, 52.2% 6.9% and 31.2 4.8%, respectively for the above groups). Interestingly, however, when Ang was infused intravenously, it produced a significantly smaller infarct compared with that observed after the same dose was infused into the left atrium (P<0.05). The infarct size was 17.0 3.7% in the Ao clamp group, which was an effect completely prevented by Gd (45.8 4.2%, P<0.01). Although Gd did not alter infarct size in the control and ischemic preconditioning groups, it increased infarct size when added to the intravenous Ang group (Gd-intravenous Ang 48.6 3.3%, P<0.05 compared with intravenous Ang). CONCLUSIONS: Ang fails to mimic preconditioning in vivo, but salvage of ischemic myocardium can be emanated from pressure overload.

Idiopathic pulmonary arterial hypertension in a young patient with the Cohen syndrome.

We admitted a 16-year-old boy with the Cohen syndrome to our institution for increasing dyspnoea. Investigations revealed idiopathic pulmonary hypertension. He was commenced on bosentan and oral anticoagulation and was followed up for nearly 7 years, during which he was readmitted for dynamic measurements of pulmonary artery pressure. Despite initial improvement, the right heart pressures increased again and sildenafil was added. His final hospitalisation was due to increasing breathlessness and episodes of syncope. The addition of prostacyclin conferred no reduction in pulmonary artery pressure. The patient suffered a cardiac arrest and remained intubated for 2 weeks, during which Klebsiella pneumonia and superinfection with the H1N1 swine flu virus occurred. The patient died due to multi-organ failure, nearly 7 years after his initial diagnosis. The Cohen syndrome, its phenotype and clinical findings, and the incidence and treatment of pulmonary hypertension are discussed.