Stages Of Cardiac Disease Research Articles

Changes in peak oxygen consumption on excercise and cardiomyopathy disease stage in Fabry disease

Abstract Background Fabry disease (FD) is an X-linked lysosomal storage disorder manifesting as deficiency in the enzyme α-Galactosidase A (1) resulting in multi-organ accumulation of globotriaosylceramide (Gb3) (2) This causes predominantly cardiac, renal and cerebrovascular manifestations. Shortness of breath and exercise intolerance are common and can be related to multiple underlying mechanisms. Cardiopulmonary exercise testing (CPEX) quantifies aerobic fitness, functional capacity, chronotropic and haemodynamic response to exercise, and attributes effort intolerance to different aetiologies, including impaired cardiac and respiratory function. Purpose We hypothesise that there is progressive effort intolerance that reflects continual cardiac Gb3 accumulation, becoming common during myocardial hypertrophy and disabling in the fibrosis and inflammation stage. The aims of this study were to ascertain frequency and severity of exercise intolerance in FD by investigating the relationship between peak maximal oxygen uptake (VO2 max) and cardiac disease stage, quantified based on a four-point scale, as proposed in published literature (3). Methods This was a retrospective review of adults with FD and exercise intolerance attending a specialist clinic who had undergone either CPEX or six-minute walk testing (6MWT) in those less mobile. Biochemical, cardiac magnetic resonance (CMR) imaging and transthoracic echocardiographic (TTE) data were also collected. Results N=54 patients underwent CPEX and N=35 patient underwent 6MWT. Estimated peak VO2 max was calculated using 6MWD in those undergoing 6MWT. Median age was 54 (IQR 40-62) years and 53% were male. Patients were equally distributed across disease stage (1-4). There were significant trends in age (increasing) and gender (male predominance) from stage 1-4. Age/sex-normalised peak VO2 max values were calculated as per published literature due to the confounding effect of age and male gender. Mean normalised VO2 max was 35.5ml/kg/min for the cohort, an underperformance of 12.3 ± 8.0 ml/kg/min. The magnitude of underperformance began from stage 1 (no cardiomyopathy) and increased with each stage (Figure 1). Impairments in renal (creatinine and albumin: creatinine ratio) and cardiac biomarkers (troponin and N-terminal pro brain natriuretic peptide) was associated with reduced VO2 max (Table 1). Increased indexed left ventricular mass on CMR and impairments in atrial volume and function on TTE were also associated with a reduction in VO2 max (Table 1). Conclusion This study is the first of its kind to demonstrate impairments in peak aerobic capacity in adults with FD and no cardiomyopathy (stage 1) which impairs further with cardiac disease stage. Future work should focus on how disease-modifying therapy can target this using VO2 as an endpoint and marker of response.Normalised peak VO2 max + disease stageVO2 max and blood / imaging parameters

Assessment of Right Atrial Function in Patients with First Inferior Myocardial Infarction with & Without Right Ventricular Involvement by 2D Speckle Tracking Echocardiography

Background: The right atrium (RA), has received the least attention by researchers. Many reports demonstrated that, RA function may be impaired in the early stages of cardiac disease. The RA plays an important role in maintaining right ventricular (RV) output. RA functional changes have been evaluated in patients with coronary artery disease, but RA affection is not fully elucidated in patients with myocardial infarction (MI) Objective: To assess RA function by 2-Dimensional speckle tracking echocardiography (2D-STE) imaging in patients with acute first left ventricular (LV) inferior wall MI with and without RV involvement. Patients & methods:-Sixty patients with acute first inferior MI were included in this study; 30 patients had ECG signs of inferior MI without RV infarction (group II) and 30 patients had ECG signs of inferior MI with RV involvement (group III). Twenty five age and sex -matched healthy volunteers were included as a control group (group I). Assessment of RA function was done in all subjects using (2D-STE) for measurements of RA septal and free walls longitudinal strain and strain rate (SR). Results:-RA septal wall & global systolic strain were significantly reduced in group III (22.5±14.8% and 40.4±24.5%) compared to group I (37.5±16.3% and 60.4±22.4%) and group II (35.7±17.4% and 54.9±25.73%), (P<0.001), (P=0.008) respectively. RA septal wall and global early diastolic strain rate were also significantly reduced in group III (- 0.77±0.46 s-1 and – 3.61±0.55 s-1) compared to group I (-1.38±0.74 s-1 and – 4.41±0.67 s-1) and group II (-1.07±0.76 s-1 and -3.73±0.76 s-1), (P=0.005), (P<0.001) respectively. Conclusion:-In patients with first LV inferior wall MI with RV involvement, RA functional parameters (RA septal and global strain and SR) were significantly impaired in comparison to healthy controls and patients with first LV inferior wall MI without RV affection. This result may illustrate the significant relation between RV & RA which is still under research.

Oral Doxycycline Improves Outcomes of Stage III AL Amyloidosis - a Matched Case Control Study

Background: Survival of patients with cardiac AL amyloidosis remains poor due to high mortality in the first 6-12 months. Rapidly effective regimes such as CyBorD are unable to overcome poor prognosis in very advanced AL amyloidosis (Venner et al and Palladini et al Leukemia 2014). The median survival of moderately advanced AL is ~60% at 2 years with CyBorD (Palladini et al Blood 2015). Last year, we reported a small series suggesting that oral doxycycline improves survival in cardiac AL amyloidosis (Wechalekar et al ASH abstract 2014) based on the possible cardio-protective effect of doxycycline on the heart from toxic amyloidogenic light chains. We now report a larger cohort confirming those findings.Methods: All patients with cardiac AL amyloidosis treated at the Royal Free Amyloidosis Treatment Centre, London, received oral doxycycline as adjuvant to standard chemotherapy. Doxycyline was given orally 100 mg twice daily until completion of treatment and continued as long as tolerated without unacceptable toxicity or patient preference. A cohort of matched control patient (approximately two controls for each patient) (matched based on cardiac disease stage, absolute NT-proBNP level, age and presenting dFLC) was randomly selected from the cohort of 1000 patients treated in the prospective ALChemy trial. The primary outcome measure was overall survival, haematological response and cardiac response. Organ involvement, haematological/organ responses were defined as per the 2010 amyloidosis consensus criteria.Patients and results: A total of 30 patients treated with doxycycline and 73 mathced controls were identified. The median age was 65 yrs (range 47-87 yrs), all patients had cardiac involvement with 6 having Mayo stage II (2 doxycycline and 4 controls), remainder with Mayo stage III disease (including 28 with Mayo stage IIIb disease). The median NT-proBNP was 4728 pMol/L (range 559-37889), high sensitivity troponin 0.1 mcg/L (range 0.032-0.95), eGFR 63 ml/min (range 15-100) and dFLC 505 mg/L (range 54-3428). There was no significant difference at baseline between the treated and control groups in terms of length of follow up, supine systolic BP, LV wall thickness, ejection fraction, NT-proBNP, hs-TNT, eGFR, proteinuria or dFLC. 72% had a velcade based regime, 23% had a thalidomide based protocol and 5% melphalan based regime. 23% in the doxycycline and 16% in the control group switched treatment due to lack of deep clonal response. The median duration on doxycycline was 6 months (range 1-24 months). Three patients had to discontinue doxycycline early (2 months each) due to photosensitive rash in 2 and nausea in one patient. Overall 33% achieved a complete haematological response (CR), 9 % VGPR and 29% PR. In the doxycycline group 56% achieved a CR, 10% had a VGPR, 30% PR compared to 35% CR,.8% VGPR, 37% PR in the control group. The median follow up of the whole cohort is 13 months and there were a total of 58 deaths. 72% of the control patients have died compared to 16% of the doxycycline treated group (at 2.3 months). The median overall survival was 13 months in the control group and not reached in the doxycycline group. The 12 and 24 month survival in the doxycycline treated group was 82% and 82%, respectively compared to 53% and 40% in the control group (log rank p<0.0001). The survival advantage was marked in stage IIIa patients but there was no impact of doxycycline in the stage IIIb patients. On an intent to treat basis, 60% of the doxycycline group and 18% of the control group achieved cardiac responses by NT-proBNP criteria (chi square p<0.0001).Conclusions: Treatment with doxycycline in combination with chemotherapy significantly improves the overall survival in patients with advanced cardiac stage IIIa AL amyloidosis but not in those with very advanced stage IIIb disease. There was a significantly a higher CR/VGPR rate compared to controls which translated into significantly greater number of cardiac responses. This larger study confirms the previous preliminary results of using adjuvant doxycycline in AL amyloidosis and strongly support the rationale to proceed with a randomised trial. [Display omitted] DisclosuresWechalekar:Celgene: Honoraria; Takeda: Honoraria; Amgen: Research Funding. Off Label Use: Doxycycline for AL amyloidosis.

The mismatch between patient life expectancy and the service life of implantable devices in current cardioverter-defibrillator therapy: a call for larger device batteries.

In 2005, Bob Hauser published a paper in the Journal of the American College of Cardiology entitled "The growing mismatch between patient longevity and the service life of Implantable Cardioverter-Defibrillators". Now, nearly a decade later, I would like to perform a second look on the problem of a mismatching between ICD device service life and the survival of ICD recipients. Since 2005, the demographics of the ICD population has changed significantly. Primary prevention has become the dominant indication in defibrillator therapy and device implantation is indicated more and more in earlier stages of cardiac diseases. In former larger scale ICD trials, the patient average 5-year survival probability was in a range of 68-71%; in newer CRT-D trials in a range of 72-88%. Due to a progressively widened ICD indication and implantation preferentially performed in patients with better life expectancy, the problem of inadequate device service life is of growing importance. The early days of defibrillator therapy started with a generator volume of 145 ccm and a device service life <18 months. In this early period, the device miniaturization and extension of service life were similar challenges for the technicians. Today, we have reached a formerly unexpected extent of device miniaturization. However, technologic improvements were often preferentially translated in further device miniaturization and not in prolonging device service life. In his analysis, Bob Hauser reported a prolonged device service life of 2.3 years in ICD models with a larger battery capacity of 0.54 up to 0.69 Ah. Between 2008 and 2014, several studies had been published on the problem of ICD longevity in clinical scenarios. These analyses included "older" and currently used single chamber, dual chamber and CRT devices. The reported average 5-year device service life ranged from 0 to 75%. Assuming today technology, larger battery capacities will only result in minimal increase in device volume. Selected ICD patients may further benefit from device miniaturization-but the vast majority may much more benefit from a significant prolongation in device service life. All published cost-effectiveness analyses in ICD therapy show that device costs and device service life are the dominant determinants of the results. The performed "second look-nearly a decade later" revealed that there are still relevant limitations regarding the device service life in current defibrillator therapy. Technical improvements were preferentially transformed into device miniaturization but not into prolonging device service life. But this optimization is strongly enforced. The most feasible solution might be the use of device batteries with larger capacities. The economic burden, mainly caused by non-adequate device service life, may limit the future realization of ICD therapy in a progressively growing patient population. In the former years, physicians and device manufacturers have ignored the patient perspective in defibrillator therapy. However, it is the patient viewpoint that prolonged device service life is much more important than smaller generator size.

Circulating serum markers and QRS scar score in Chagas cardiomyopathy.

Approximately 8 million people have Trypanosoma cruzi infection, and nearly 30% will manifest Chagas cardiomyopathy (CC). Identification of reliable early indicators of CC risk would enable prioritization of treatment to those with the highest probability of future disease. Serum markers and electrocardiogram (EKG) changes were measured in 68 T. cruzi-infected individuals in various stages of cardiac disease and 17 individuals without T. cruzi infection or cardiac disease. T. cruzi-infected individuals were assigned to stage A (normal EKG/chest x-ray [CXR]), B (abnormal EKG/normal CXR), or C (abnormal EKG/cardiac structural changes). Ten serum markers were measured using enzyme-linked immunosorbent assay (ELISA)/Luminex, and QRS scores were calculated. Higher concentrations of transforming growth factor-β1 (TGFβ1), and TGFβ2 were associated with stage B compared with stage A. Matrix Metalloproteinase 2 (MMP2), Tissue Inhibitors of MMP 1, QRS score, and Brain Natriuretic Protein rose progressively with increasing CC severity. Elevated levels of several markers of cardiac damage and inflammation are seen in early CC and warrant additional evaluation in longitudinal studies.

Predictors of adverse neurological outcome following cardiac surgery.

Stroke is a debilitating complication of cardiac surgery. Many intraoperative and postoperative factors predict the likelihood of post-cardiac surgery stroke. We evaluated preoperative parameters, seeking correlations with adverse neurological outcome following cardiac surgery. We investigated the possibility of preoperative carotid ultrasonography to select patients for carotid endarterectomy pre- or intraoperatively. We conducted a retrospective analysis of 61 patients who suffered stroke post-cardiac surgery from 2003 to 2006. Data was collected for patient and disease characteristics, preoperative status, intraoperative events and postoperative course. Postoperative neurological complications were subdivided into three groups: mild/temporary events, moderate events such as seizures, and severe events such as stroke. A mild/temporary event was defined as a focal neurological deficit of less than 24 hours in duration. A total of 2,226 cardiac cases were retrospectively evaluated. The frequency of stroke was 61 patients (2.7 percent). The mean age of these patients was 63.7 +/- 7.4 years, and 40 (65.6 percent) were males. Logistic EuroSCORE, left ventricular ejection fraction (as determined by two-dimensional echocardiogram) and aortic cross-clamp time were significantly correlated with postoperative neurological complications, with a p-value of less than 0.05 for all subgroups. There was a significant correlation between the presence of preoperative carotid disease (as proven by pre- and postoperative carotid ultrasonography) and postoperative neurological events (p-value equals 0.033). However, atrial fibrillation did not correlate with postoperative stroke. The stage of cardiac disease (risk factor level, ejection fraction and presence of carotid stenosis) correlates with stroke and may predict an adverse neurological outcome.

Examine Thy Heart With All Diligence

Cardiovascular disease is a major cause of mortality in Western society but at its early phase may manifest as subtle alterations in coronary epicardial or microvascular function, including endothelial dysfunction, abnormal perfusion or permeability, and remodeling, which may precede clinical manifestation of vascular disease. These modifications might be associated with subclinical decline in diastolic and/or systolic function and left ventricular (LV) remodeling. Evaluation of myocardial perfusion and microvascular function to identify areas of persistent ischemia or hibernating myocardium, endothelial, or LV dysfunction is, therefore, important for clinical decision-making and fuels the search for noninvasive techniques assessing different stages of cardiac disease. Several noninvasive or minimally invasive techniques currently used to explore cardiac function, such as echocardiography, scintigraphy, and single-photon emission computed tomography, show diagnostic reliability but low spatial resolution and poor anatomic details. Therefore, higher-resolution techniques, like positron emission tomography, MRI, and computed tomography (CT), have been steadily gaining popularity.1 MRI can assess cardiac function, mass, volume, and myocardial viability, with limited application in patients with metal fragments, and positron emission tomography provides reliable estimates of myocardial perfusion and metabolism, albeit at low spatial resolution. Furthermore, since its inception in the 1970s, CT quickly incorporated into clinical practice, and recent technical advances have placed it in the forefront for comprehensive evaluation of cardiac function at several levels, from the function of the heart as a pump, to the behavior of the microvessels that feed its walls (Figure 1). For example, CT overcomes some of the limitations of MRI, because it can study patients with defibrillators or pacemakers, has a shorter acquisition time, and is more available and affordable than positron emission tomography, thus allowing access to cardiac imaging to a greater number of patients. Figure 1. A, schematic of the different levels for cardiac functional evaluation, including global heart, …

Nitric Oxide in the Pathogenesis of Cardiac Disease

Endothelial dysfunction is characterized by a vasoconstrictive and prothrombotic state in the vasculature; it plays a role in all stages of cardiac disease and is a significant independent predictor of cardiovascular outcomes. Nitric oxide (NO) performs multiple biologic activities in the endothelium, including vasodilation and antithrombotic actions. Reduced NO bioactivity is a major component of endothelial dysfunction. Impaired NO bioactivity is an important factor in the pathogenesis of atherosclerosis and in the metabolic syndrome. The functions of NO bioactivity in the heart go well beyond those in the endothelium, as all 3 NO synthase (NOS) isoforms-endothelial NOS, neuronal NOS, and inducible NOS-are expressed in cardiac myocytes and mediate systolic, diastolic, and chronotropic cardiac functions. Impairment of NO bioactivity is a pathogenic factor in various forms of cardiac disease. Although these findings support the potential use of NO-targeted therapies for treatment of cardiac disease, the complexities of the biologic actions of NO in the vasculature and heart are such that development of therapies is still largely in the preliminary stages.

Blutzuckereinstellung bei kardialen Erkrankungen

The early and differentiated optimization of glucose level is essential for the improvement of the cardiovascular outcome. In all stages of cardiac disease, the primary goal is to reach near-normoglycemia. The DIGAMI-1 and 2 studies as well as the Munich Myocardial Infarction Registry successfully demonstrate, that the intensification of treatment with insulin therapy reduces the mortality of myocardial infarction. Glucose-insulin-infusion is advantageous with regard to the use of a well-controllable therapeutic approach. In non-acute cardiac disease, oral treatment strategies and insulin therapy are successful alone or in combination. Acarbose and metformin have been shown to be able to successfully prevent cardiovascular disease. New evidence of positive effects of glitazones with regard to reduction of the rate of restenosis and optimization of endothelial function is currently emerging. Prognosis of cardiovascular disease is significantly influenced by glucose control. There is evidence that the relationship between glycemia and cardiovascular events extends far beyond the diabetic threshold. This can be detected even in impaired glucose tolerance and the non-diabetic range. There is evidence that postprandial glycemia is crucial for the extent of cardiovascular risk. This has also been emphasized by the DECODE-study.

Pulse arrhythmia diagnosis by oscillometric blood pressure measurement

Cardiac arrhythmia is a common clinical symptom and occurs in patients due to underlying cardiac disorders (e.g. CHD, Valvular Heart Diseases) or due to extra - cardiac causes (e.g. hyperthyroidism, arterial hypertension, drugs). In (young) healthy persons occasional idiopathic arrhythmia is common. Most kinds of cardiac arrhythmia lead to a pulse arrhythmia (e.g. atrial fibrillation, PVC), which may be detected in peripheral arteries. Since arrhythmic disorders may be related to (early) stages of cardiac diseases, any arrhythmia needs to be examined. In the course of a measurement oscillometric blood pressure devices record a series of pressure pulses. These pulses provide the so-called “pulse - oscillogram”, which is the basis of the systolic / diastolic pressure and the pulse frequency determination. By investigating all pulse periods within a pulse oscillogram, pulse arrhythmia may be disclosed. Artefacts must be recognized and may not interfere with the analysis. A new oscillometric NIBP device (BP-3BTO Microlife, Taipei, ROC) with an in-built pulse arrhythmia detection (PAD) has been applied to cardiologic patients. Prior to exercise ECG examinations, 52 cardiologic patients (Cardiologic Dep. Merz, Bietigheim, D) have been included into a clinical evaluation trial. An ECG recording (AT-1, Schiller, CH) was provided during all PAD (BP-3BTO, Microlife, FDA pend.) measurements. The cardiac arrhythmia sensitivity and specificity have been determined in specific clinical arrhythmia types. Both values refer to the ECG reference signal. The specificity was 96.42 [%], the sensitivity for atrial fibrillation 66.6 [%], the sensitivity for premature ventricular contraction 85.7 [%]. Sinus bradycardia was detected with a sensitivity of 66.6 [%], and no tachycardia has been missed. The presented NIBP Pulse Arrhythmia Diagnosis safely detects specific kinds of pulse arrhythmia, if they are present during the measurement period. Artefact signals virtually do not lead to erroneous indications. The technology does not replace a diagnostic ECG recording but may be applied as a screening method, preferably in risk - patients (e.g. post - myocardial infarction patients). Due to the limited measurement period, the detection probability of pulse arrhythmia rises with the occurrence frequency of the disorder. The PAD device displays not the type of the detected arrhythmia, but any frequent indication should lead to a subsequent cardiologic examination.