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Biomedical subjects

Adam Torbicki

Publications and source records attributed to Adam Torbicki.

At least 19 recordsLinked to original sources

Long-term sinus rhythm maintenance after cardioversion of persistent atrial fibrillation: is the treatment's success predictable?

The aim of our study was to identify the clinical and echocardiographic predictors of long-term success of cardioversion in patients with persistent atrial fibrillation (AF). Our study comprised 104 patients (F/M 33/71; mean age 60.4 +/- 7.9 years) assigned to SR restoration and maintenance with sequentially administered antiarrhythmic drugs. Their clinical and transthoracic echocardiographic (TTE) variables were recorded prior to cardioversion and examined for correlation with sinus rhythm (SR) maintenance at 1 year. The variables under consideration included age, gender, echo parameters such as long and short left atrial (LA) axis, LA and right atrial (RA) area, fractional shortening (FS) and left ventricular end-diastolic diameter, AF duration, New York Heart Association functional class, and concomitant diseases. Generalized additive logistic regression method was used to investigate impact of the selected variables on long-term SR maintenance. At 1 year, SR was present in 63.5% of patients. Left atrium area (LA(ar)) > 28 cm (P < 0.02) and FS value >26% (P < 0.05), both measured at baseline, were significantly associated with SR maintenance after 1 year. Patients with large LA(ar) values (>28 cm(2)) presented a significant decrease (31.45 +/- 3.07 cm(2) vs 28.94 +/- 3.81 cm(2); P < 0.008) during 30 days following SR maintenance. In patients with LA(ar) >28 cm(2) we noted an atrial decrease of 2.57 +/- 3.2 cm(2) (P < 0.004) during 30 days following SR restoration, which turned out to be an independent factor related to SR presence at 1 year of follow-up (relative risk 1.83; 95% confidence interval: 1.03-2.95; P < 0.01). Of all the considered variables only LA area and FS value seem to be relatively reliable predictors of SR sustainability at 1 year after an effective cardioversion of persistent AF.

Aged↗

Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is clinically characterized by a sustained elevation in mean pulmonary artery pressure leading to significant morbidity and mortality. The disorder is typically sporadic, and in such cases the term idiopathic PAH (IPAH) is used. However, cases that occur within families (familial PAH (FPAH)) display similar clinical and histopathological features, suggesting a common etiology. Heterozygous mutations of a type II member of the TGF-beta cell signaling superfamily known as BMPR2 on chromosome 2q33 have been identified in many kindreds with FPAH, yet display both reduced penetrance and sex bias. This report presents the compilation of data for 144 distinct mutations that alter the coding sequence of the BMPR2 gene identified in 210 independent PAH subjects. This large data set characterizes the extent of sequence variation and reveals that the majority (71%) of mutations in FPAH and IPAH comprise nonsense, frameshift, and splice-site defects, and gene rearrangements. These predict premature termination of the transcript with likely loss through the process of nonsense-mediated decay (NMD). A total of 44 missense mutations were identified that substitute amino acid residues at highly conserved sites within recognized functional domains of the mature receptor. We assess this category of mutations in the context of their heterogeneous effects on cell signaling when assayed by in vitro cell-based systems. Disease-causing mutation hot-spots within BMPR2 are summarized. Taken together, these observations are likely to aid in the development of targeted mutation detection strategies relevant for patient management. Finally, we examine the age- and sex-dependent reduced penetrance of BMPR2 mutations by reviewing bmpr2 animal models and the requirement for additional genetic and/or environmental modifiers of disease. In conclusion, these data provide compelling genetic evidence that haploinsufficiency is the predominant molecular mechanism underlying disease predisposition, and support the concept of a critical threshold of signaling activity below which disease may be precipitated.

Bone Morphogenetic Protein Receptors, Type II↗

Serum N-terminal brain natriuretic peptide as a prognostic parameter in patients with pulmonary hypertension.

STUDY OBJECTIVES: Baseline prognostic assessment in patients with pulmonary hypertension (PH) may help in the selection of treatment. High plasma levels of natriuretic peptide type B have been reported in patients with right ventricular (RV) dysfunction and suggest poor prognosis in patients with idiopathic pulmonary arterial hypertension (IPAH). We prospectively assessed the correlation of N-terminal brain natriuretic peptide (NT-proBNP) with echocardiographic and hemodynamic indexes of RV function as well as with baseline functional status and long-term survival of PH patients. PATIENTS AND DESIGN: Fifty-five consecutive patients with a mean (+/- SD) age of 41 +/- 15 years and severe PH (including 36 patients with IPAH) were followed up for up to 36 months. Serum samples for NT-proBNP were secured, and 6-min walk test (6 MWT), RV catheterization, and echocardiography were all performed on the same day, before the introduction of targeted treatment. RESULTS: The median baseline serum NT-proBNP concentration was 1,674 pg/mL (range, 51 to 10,951 pg/mL). NT-proBNP concentration correlated with 6MWT distance (r = 0.6; p < 0.001), cardiac index, pulmonary vascular resistance, and right atrial pressure (RAP), but not with pulmonary arterial pressure. NT-proBNP levels were also related to the ratio of the diastolic area of the RV and the LV, and to pericardial effusion during echocardiography. Receiver operating characteristic analysis identified > or = 1,400 pg/mL as the best NT-proBNP threshold predicting fatal outcome for the entire study group as well as for IPAH patients (sensitivity, 88% and 100%, respectively; specificity, 53% and 56%, respectively). In multivariate analysis, NT-proBNP, troponin T, and RAP were identified as independent factors for poor prognosis for the entire study group, while only NT-proBNP and RAP were identified as markers for poor prognosis in the IPAH subgroup. CONCLUSIONS: NT-proBNP level is related to the right heart morphology and dysfunction in PH patients. A serum NT-proBNP level of > or = 1,400 pg/mL was found to be useful in identifying patients with poor long-term prognosis both in the whole studied group and in the IPAH subgroup.

Adult↗

Sildenafil citrate therapy for pulmonary arterial hypertension.

BACKGROUND: Sildenafil inhibits phosphodiesterase type 5, an enzyme that metabolizes cyclic guanosine monophosphate, thereby enhancing the cyclic guanosine monophosphate-mediated relaxation and growth inhibition of vascular smooth-muscle cells, including those in the lung. METHODS: In this double-blind, placebo-controlled study, we randomly assigned 278 patients with symptomatic pulmonary arterial hypertension (either idiopathic or associated with connective-tissue disease or with repaired congenital systemic-to-pulmonary shunts) to placebo or sildenafil (20, 40, or 80 mg) orally three times daily for 12 weeks. The primary end point was the change from baseline to week 12 in the distance walked in six minutes. The change in mean pulmonary-artery pressure and World Health Organization (WHO) functional class and the incidence of clinical worsening were also assessed, but the study was not powered to assess mortality. Patients completing the 12-week randomized study could enter a long-term extension study. RESULTS: The distance walked in six minutes increased from baseline in all sildenafil groups; the mean placebo-corrected treatment effects were 45 m (+13.0 percent), 46 m (+13.3 percent), and 50 m (+14.7 percent) for 20, 40, and 80 mg of sildenafil, respectively (P<0.001 for all comparisons). All sildenafil doses reduced the mean pulmonary-artery pressure (P=0.04, P=0.01, and P<0.001, respectively), improved the WHO functional class (P=0.003, P<0.001, and P<0.001, respectively), and were associated with side effects such as flushing, dyspepsia, and diarrhea. The incidence of clinical worsening did not differ significantly between the patients treated with sildenafil and those treated with placebo. Among the 222 patients completing one year of treatment with sildenafil monotherapy, the improvement from baseline at one year in the distance walked in six minutes was 51 m. CONCLUSIONS: Sildenafil improves exercise capacity, WHO functional class, and hemodynamics in patients with symptomatic pulmonary arterial hypertension.

3',5'-Cyclic-GMP Phosphodiesterases↗

Pulmonary arterial hypertension: evaluation of the newly diagnosed patient.

With a quickly growing range of therapeutic options precise prognostic stratification became particularly important for clinical decision making in patients with pulmonary arterial hypertension (PAH). Assessment of disease-specific functional class remains the simplest method and is a fairly reliable way of assessing severity of PAH, and current guidelines recommend a therapeutic algorithm based on functional class evaluation. Six-minute walk is the most widely used test assessing exercise tolerance both in clinical practice and in clinical trials testing new therapies in PAH. Right heart catheterization with a vasoreactivity test is mandatory to identify a subgroup that has good long-term prognosis when treated with calcium channel blockers alone. Echocardiographic variables of documented prognostic value in PAH are not those directly correlated with pulmonary arterial pressure (PAP). Instead, the presence of pericardial effusion, enlarged right atrium, and elevated Doppler index of right ventricular performance have been the most consistently reported signs of poor prognosis. Low or decreasing brain natriuretic peptide (BNP) suggests a good outcome whereas troponin T leak persisting despite therapy is a poor prognostic sign. Biomarkers seem particularly useful for noninvasive follow-up of patients with PAH, and due to simplicity and low costs may successfully compete with echocardiography.

Biomarkers↗

A decrease of enlarged left atrium following cardioversion of atrial fibrillation predicts the long-term maintenance of sinus rhythm.

BACKGROUND: Although increased left atrial size (LA) has been long regarded as one of the factors negatively influencing the long-term maintenance of sinus rhythm (SR) following cardioversion (CV) of atrial fibrillation (AF), some reports suggested that CV might be effective also in patients with large LA.Aim. We sought to determine the role of LA enlargement in long-term SR maintenance after CV of persistent AF. METHODS: 104 consecutive patients (33 females, 71 males, mean age 60.4+/-7.4 years) were assigned to SR restoration and maintenance with serial antiarrhythmic drugs. Transthoracic echocardiographic (TTE) variables were recorded prior to CV. Generalised additive logistic regression was used to investigate the impact of LA enlargement on the long-term SR maintenance. RESULTS: SR was present in 63.5% of patients after one year of follow-up. Increased LA area >28 cm (RR 1.72; 1.09-2.71; p<0.02) and increased fractional shortening values in ranges between 26-40% (1.2; 1.01-1.44; p<0.05) were significantly associated with SR maintenance after one year. In order to determine the influence of the LA diameter on the probability of SR maintenance, we analysed mean LA(ar) values prior to and after CV. Patients with large LA(ar) (28 cm(2)) presented a significant decrease of LA size (31.45+/-3.07 cm(2) vs 28.94+/-3.81 cm(2); p<0.008) during the first 30 days after SR restoration. In the group of patients with LA(ar) 28 cm(2) we noted decrease in LA size by 2.57+/-3.2 cm(2), whereas in patients with a smaller LA volume this decrease was significantly lower, being 0.47+/-2.9 cm(2) (p<0.004). CONCLUSIONS: LA enlargement does not preclude a favourable outcome after CV of AF. The decrease in LA area occurring during 30 days following CV favours long term SR maintenance.

Aged↗

Pulmonary embolism: role of echocardiography and of biological markers.

Echocardiography and biomarkers: what should be their place in the algorithms designed for pulmonary embolism (PE)? Our opinions on that continue to evolve. This manuscript attempts a snapshot reflecting the position of cardiac imaging and cardiac biomarkers in suspected and confirmed PE. Comparing the prognostic performance of brain natriuretic peptide (BNP) and troponins, it seems that with thresholds set appropriately high, troponins could be more helpful in the identification of patients with adverse prognosis while low BNP levels are reliable markers of good prognosis. Because of the relatively short plasma half-life, BNP as well as NT-proBNP could be repeated to monitor evolution of the hemodynamic status of the patient and the results of implemented treatment. The role of echocardiography outside massive PE seems to be decreasing, although if considered together with information provided on potential alternative or additional cardiovascular diseases as well as intracardiac or intravascular thrombi, its place in a tentative management algorithm in PE seems still secured.

Biomarkers↗

[Infective endocarditis in a patient with multiple myeloma. A case report].

A case of a 59 year old male with infective endocarditis is presented. Antibiotic therapy seemed effective, however, inflammation laboratory parameters increased two weeks after clinical improvement and body temperature normalisation. Subsequent extensive laboratory investigations revealed multiple myeloma. The patient underwent successful aortic valve replacement and received pharmacological therapy for multiple myeloma. Difficulties in diagnosing and treatment of patients with infective endocarditis who have other concomitant diseases, are discussed.

Diagnosis, Differential↗

[Feasibility of home self-administration of low molecular weight heparin by patients with atrial fibrillation recurrence. A new approach to thromboembolic prophyllaxis].

We checked the feasibility of self-screening for atrial fibrillation (AF) by instructed patients pts and prompt home self-administration of an initial dose of low-molecular weight heparin (LMWH) prior to seeking medical attention. INVESTIGATED GROUP AND METHODS: Pts with persistent AF and low risk of systemic embolisation qualified to elective cardioversion (CV) were the subjects of our interest. All pts were trained to identify AF by palpation of the radial pulse and to self-inject LMWH in case of arrhythmia recurrence. 232 pts (mean age 59.8 +/- 8.6 years) who maintained sinus rhythm (SR) during 4 weeks following successful cardioversion (CV) and correctly recognized AF recurrence and those without episodes of AF were equipped with nadroparine after acenocoumarol discontinuation. Thromboembolic prophylaxis was continued with antiplatelets agents or those no additional risk factors of systemic embolisation were left without medical therapy. RESULTS: 191 pts had AF recurrence during the mean 2.6 +/- 1.7 years observation period, 172 of them correctly identified AF episode, including 162 who performed LMWH injections at home. 7 pts, who had performed LMWH injections, presented with SR on arrival to hospital, 6 pts had AF1.2 out of 21 pts who failed to identify their AF episodes and 1 pt of those who correctly detected the AF recurrence but failed to perform LMWH self-injection suffered from ischemic stroke (sensitivity 96.1%, specificity 60.4%). No side effects of domiciliary LMWH self-injection were found. CONCLUSION: When properly trained, the majority of pts can accurately diagnose AF recurrence and self-inject initial dose of LMWH, what is feasible and may represent an attractive anti-thromboembolic strategy.

Acenocoumarol↗

End points and clinical trial designs in pulmonary arterial hypertension: clinical and regulatory perspectives.

To date, randomized controlled clinical trials performed in pulmonary arterial hypertension (PAH) have been relatively short-term studies involving mainly patients with advanced disease. The primary end points in these trials have addressed exercise capacity, usually by using the 6-min walk test. Although this approach is still warranted in future trials assessing new treatments, it is likely that the focus will shift toward trials of longer duration, involving patients with less advanced disease, and that different drugs and drug-combination regimens will be compared. In such trials, it is possible that a composite of markers indicating clinical deterioration (e.g., hospitalization for right heart failure, the requirement for the introduction of an alternative treatment, and predefined indicators of worsening exercise tolerance) may be more useful as primary end points. Quality of life will become a very important issue; however, appropriate quality-of-life questionnaires for PAH have yet to be developed. In addition, hemodynamics will likely remain valuable as secondary end points, but future clinical trials should include hemodynamics obtained both during exercise and at rest. Finally, cardiopulmonary exercise testing, echocardiographic studies, and biochemical parameters, such as brain natriuretic peptide or troponin T, may also prove useful as secondary end points in the future.

Clinical Trials as Topic↗

Diagnosis and differential assessment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is diagnosed by various investigations that are essential for making the diagnosis, and by additional tests to clarify the category of pulmonary hypertension (PH). A diagnostic algorithm can guide the evaluation of PH, but like all guidelines the algorithm can be modified according to specific clinical circumstances. Most patients are diagnosed as the result of an evaluation of symptoms, whereas others are diagnosed during screening of asymptomatic populations at risk. Right heart catheterization (RHC) must be performed in patients with suspected PH to establish the diagnosis and document pulmonary hemodynamics. Before initiation of medical therapy, assessment of acute vasoreactivity (during catheterization) is necessary to determine the appropriate therapy for an individual patient. An acute response is generally defined as a decrease in mean pulmonary arterial pressure of at least 10 mm Hg with the mean pulmonary arterial pressure decreasing to 40 mm Hg or below, accompanied by a normal or high cardiac output. After PAH is diagnosed, disease severity should be assessed in order to accurately determine risk:benefit profiles for various therapeutic options. Useful tools to predict outcome include functional class, exercise capacity, pulmonary hemodynamics, acute vasoreactivity, right ventricular function, as well as brain natriuretic peptide, endothelin-1, uric acid, and troponin levels. Repeating these tests serially on treatment is useful for monitoring the response to a given therapy. Close follow-up at a center specializing in management of PH is recommended, with careful periodic reassessment and adjustment of therapy.

Diagnosis, Differential↗

Rate control vs rhythm control in patients with nonvalvular persistent atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study.

STUDY OBJECTIVES: The relative risks and benefits of strategies of rate control vs rhythm control in patients with atrial fibrillation (AF) remain to be fully explored. DESIGN: The How to Treat Chronic Atrial Fibrillation (HOT CAFE) Polish trial was designed to evaluate in a randomized, multicenter, and prospective manner the feasibility and long-term outcomes of rate control vs rhythm control strategies in patients with persistent AF. PATIENTS: Our study population comprised 205 patients (134 men and 71 women; mean [+/- SD] age, 60.8 +/- 11.2 years) with a mean AF duration of 273.7 +/- 112.4 days. The mean observation period was 1.7 +/- 0.4 years. One hundred one patients were randomly assigned to the rate control group and received rate-slowing therapy guided by repeated 24-h Holter monitoring. Direct current cardioversion and atrioventricular junctional ablation with pacemaker placement were alternative nonpharmacologic strategies for patients with tachycardia that was resistant to medical therapy. One hundred four patients were randomized to sinus rhythm restoration and maintenance using serial cardioversion supported by a predefined stepwise antiarrhythmic drug regimen (ie, disopyramide, propafenone, sotalol, and amiodarone). In both groups, thromboembolic prophylaxis followed current guidelines. MEASUREMENTS AND RESULTS: At the end of follow-up, 63.5% of patients in the rhythm control arm remained in sinus rhythm. No significant differences in the composite end point (ie, all-cause mortality, number of thromboembolic events, or major bleeding) were found between the rate control group and the rhythm control group (odds ratio, 1.98; 95% confidence interval, 0.28 to 22.3; p > 0.71). The incidence of hospital admissions was much lower in the rate control arm (12% vs 74%, respectively; p < 0.001). New York Heart Association functional class improved in both study groups, while mean exercise tolerance, as measured by the maximal treadmill workload, improved only in the rhythm control group (5.2 +/- 5.1 vs 7.6 +/- 3.3 metabolic equivalents, respectively; p < 0.001). The rhythm control strategy led to an increased mean left ventricular fractional shortening (29 +/- 7% vs 31 +/- 7%, respectively; p < 0.01). One episode of pulmonary embolism occurred in the rate control group despite oral anticoagulation therapy, while three patients in the rhythm control arm of the study experienced ischemic strokes (not significant). CONCLUSIONS: The Polish HOT CAFE study revealed no significant differences in major end points between the rate control group and the rhythm control group.

Anti-Arrhythmia Agents↗

[Pulmonary hypertension--some problems resolved. More remain to be solved].

Pulmonary hypertension especially arterial and idiopathic is still a poorly understood disease often affecting young adults and leading to right ventricular overload, failure and death due to low cardiac output. Justification for new, aggressive, costly but effective methods of pharmacological and interventional treatment of pulmonary hypertension require precise, repeatedly performed prognostic assessment. This is currently provided not only by repeated right heart catheterization but mostly by exercise testing as well as non-invasive techniques such as echo-Doppler and biochemical myocyte markers including B-type natriuretic peptide and cardiac troponin. Such methods should allow better timing of atrial septostomy and listing for lung transplantation.

Biomarkers↗

[Value of spiral computed tomography in pulmonary hypertension].

UNLABELLED: Pulmonary hypertension (PH) represents an important diagnostic problem, because of its non-specific clinical presentation. AIMS OF THE STUDY: Estimation of sensitivity and specificity of spiral computed tomography (SCT) in diagnosis of PH. Estimation of the influence of the cause and character of PH on morphology of pulmonary arteries and right ventricle-pulmonary artery coupling. MATERIAL AND METHODS: 102 patients with clinical suspicion of acute pulmonary embolism (APE) or chronic PH (54F, av. age 51.3 +/- 17.3). Diameters of pulmonary arteries obtained in SCT, systolic pulmonary pressure calculated from the tricuspid gradient pressure, and indices of the right ventricle-pulmonary artery dynamical coupling (AcT) obtained from the echo-Doppler method were compared. RESULTS: Increased diameter (> 18 mm) of interlobar arteries was the most specific sign of PH (specificity 92%, sensitivity 45%). Diameter of proximal pulmonary arteries and pulmonary pressure was correlated in patients with APE (r = 0.487, p < 0.003), but not in those with chronic PH (r = 0.223). In a group of patients with pulmonary arterial hypertension (PAH), enlargement of proximal pulmonary arteries seemed to result in less disturbed right ventricle-pulmonary artery dynamic coupling. CONCLUSIONS: 1. SCT measurements of diameters of pulmonary arteries have relatively low sensitivity for PH, precluding its reliable exclusion. 2. The relationship between the pulmonary pressure and the diameters of pulmonary arteries was found in acute but not in chronic PH, in which right ventricle-pulmonary artery dynamical coupling seemed less disturbed when pulmonary arteries were markedly dilated.

Adolescent↗

[Inhaled nitric oxide (NO) for vasoreactivity testing in pulmonary hypertension].

UNLABELLED: Thirty patients (24F, 6M, aged 40.5 +/- 15.4 years) with chronic precapillary pulmonary hypertension (primary pulmonary hypertension--PPH)--20 pts, associated with connective tissue disease--6 pts, due to thromboembolism--2 pts and Eisenmenger syndrome--2 pts) were submitted to 5 min inhalation of 10 and 20 ppm of nitric oxide (NO) during right heart catheterization. For the whole group this test resulted in minimal changes in directly assessed hemodynamics. However, individual reactions differed markedly between patients. Assuming three levels of criteria of preserved reactivity (liberal, standard, demanding) 11/30 (37%) patients had fall in PAP and PVR > or = 20% from baseline, 4/30 (13%) decreased PAP and PVR by > or = 20% and 30% respectively and 2 (7%) patients normalized PAP and decreased PVR > or = 50% from baseline, respectively. Interestingly, even liberal criteria were fulfilled positive test was observed exclusively in patients with primary PH. In one patient with connective tissue disease and systemic hypertension acute pulmonary congestion appeared during NO testing, with concomitant increase in systemic arterial pressure and pulmonary wedge pressure. No other complications were noted and no rebound PH after discontinuation of NO was observed in any of the patients. CONCLUSION: 1. Acute inhaled nitric oxide test appears to be safe in patients with PH and no coexisting left heart dysfunction. 2. It allows for stratification of patients according to the degree of preserved pulmonary vascular reactivity. However, criteria which would permit to select optimal treatment based on the results of NO test require further studies.

Administration, Inhalation↗

[Right ventricle structure and function in patients with obstructive sleep apnea (OSA)].

UNLABELLED: The structure and function of right ventricle was echocardiographically assessed in patients (pts) with OSA and analyzed taking into account the presence of obesity and/or systemic hypertension (SH). Therefore, 118 pts (98 M, 20 F, aged 48,5 8,4 yr) were divided into OH = obese with z OSA and SH (n = 22), ON = obese with OSA, and no SH (n = 20), OC = OSA without either obesity and SH (n = 21), GH = obese without OSA but with SH (n = 18), GN = obese without either OSA or SH (n =17). Control group (ZZ) comprised 20 healthy subjects (14M,6F). Right ventricular diameter (RVD), diastolic (DRVW), and systolic right ventricle free wall thickness (SRVW) were measured and its systolic thickening (ST-RVW) was calculated. Acceleration time of ejection into pulmonary artery (AcT) was measured with Doppler echocardiography. RESULTS: St. sign. p < 0.05 between: 1: all groups except OH and ON, GH and GN, GH and OC, GN and OC; 2--like 1 except ZZ and OC; 3--OH and all subgroup except ON, ON and GH, ON and ZZ, OC and GN; 4-- ON and all subgroups except OH, OH and OC, OH and GH, OH and GN. CONCLUSIONS: Enlargement and functionally compromised RV is found in OBS mostly with concomitant obesity. Pulmonary hypertension at rest in patients with isolated OSA is rare and also requires additional contributing factors.

Adult↗