Profound Left Ventricular Dysfunction Research Articles

Cardioprotective effects of triiodothyronine supplementation against ischemia reperfusion injury by preserving calcium cycling proteins in isolated rat hearts.

Hypothyroidism is associated with profound left ventricular dysfunction. Triiodothyronine (T3) supplementation may improve cardiac function after ischemic reperfusion (I/R) injury. In the present study, the effect of T3 on major calcium cycling proteins and high-energy phosphate content during I/R was evaluated. Isolated perfused rat hearts were divided into 5 groups: Sham Control (Sham, n=10), Control (n=8), T3 10 nM (T3-10, n=10), T3 25 nM (T3-25, n=10) and T3 50 nM (T3-50, n=10). T3 was administrated for 60 min before 30 min of ischemia and 120 min of reperfusion. The protein contents of Ca2+-release channels (RyR2), Ca2+-adenosine triphosphatase (SERCA2a), phospholamban (PLB), sarcolemmal Ca2+-adenosine triphosphatase (PMCA) and sodium-calcium exchanger (NCX), as well as the high-energy phosphate content in heart tissues were measured by western blot analysis. The results revealed that T3 improved the contractile recovery (left ventricular developed pressure; +dP/dt, -dP/dt) after I/R. Western blotting assays demonstrated that I/R depressed the contents of RYR2, SERCA2a and phosphorylated RYR2 and PLB; there were no effects on the contents of PLB, PMCA and NCX. T3 reversed I/R-induced degradation of RyR2 and SERCA2a, restored the phosphorylation of RyR2 and PLB, and preserved the high-energy phosphate contents of ATP and creatine phosphate. T3 supplementation protected the heart against I/R injury via the preservation of Ca2+-cycling proteins and high-energy phosphate content.

Left Ventricle Decompression Strategies in Pediatric Peripheral Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is widely used in patients with potentially reversible acute cardiac and/or pulmonary failure who are unresponsive to conventional treatment. Patients with profound left ventricular (LV) dysfunction under venous-arterial (V-A) ECMO may experience LV distention, pulmonary edema, and thrombus formation. It is critical to unload the left ventricle to prevent such complications. The aim of this study was to identify the risks, timing and methods of LV decompression in pediatric peripheral ECMO. Between August 2006 and November 2017, 51 patients received peripheral ECMO support in our pediatric intensive care unit. All of them were less than 18 years of age and non-cardiotomy surgery-related. We retrospectively reviewed the patients' clinical presentations, decompression methods and outcomes. The overall success rate of ECMO removal was 76.5% (39/51), and the survival rate after discharge was 62.7% (32/51). The myocarditis group had the most favorable outcomes among the ECMO patients (100% survival). LV decompression was needed in 12 patients who had profound LV dysfunction under V-A ECMO. Five patients received medical treatment successfully, and the other 7 patients underwent intra-aortic balloon pump (IABP) procedures. In the IABP group, 1 patient still needed further pigtail-decompression. All of our decompression patients survived with good neurological outcomes (Glasgow Outcome Scale 5). The patients with profound LV dysfunction under peripheral VA ECMO were at risk of thromboembolic events and LV decompress was needed. If medical decompression fails, IABP is a feasible approach for LV decompression in pediatric peripheral ECMO.

Integrated backscatter as a fibrosis marker in the metabolic syndrome: association with biochemical evidence of fibrosis and left ventricular dysfunction

Myocardial fibrosis is an important contributor to heterogeneity of left ventricular (LV) dysfunction in the metabolic syndrome (MS). Comparison of strain with calibrated integrated backscatter (cIB) and serological fibrosis markers could provide a means to understand the association of cardiac function with markers of fibrosis. We studied 172 patients with MS (age 50 ± 13 years) and 61 healthy controls in a prospective, cross-sectional study. Echocardiographic evaluation included myocardial velocities and deformation, and calibrated cIB. Procollagen type III amino-terminal propeptide (PIIINP) and procollagen type I carboxy-terminal propeptide (PICP) were measured from serum. MS patients demonstrated LV systolic and diastolic function, and myocardial echodensity disturbances, as well as elevated serum PIIINP and PICP levels. For most functional variables, calibrated cIB in the basal septum was the strongest determinant of impaired LV performance, independent of higher procollagen levels, LV mass index, age, body mass index, creatinine level, and C-reactive protein. Patients with increased abdominal fat deposit (assessed by the waist-to-hip ratio) presented higher levels of procollagen peptides and septal calibrated cIB, and with more profound LV dysfunction as indicated by lower myocardial deformation and early diastolic velocity, and higher E/e'. Myocardial echodensity is a stronger correlate of LV systolic and diastolic dysfunction in MS, than circulating procollagen peptides. Both fibrosis and LV function abnormalities are increased at a higher waist-to-hip ratio, which might provide a rationale for the implementation of intensified therapy in this subset of patients.

Incidence of cardiac arrest increases with the indiscriminate use of dexmedetomidine: A case series and review of published case reports

Dexmedetomidine has predictable, complex, and negative cardiovascular effects that lead to additional adverse effects such as bradycardia and hypotension in up to 42% of patients and might cause profound left ventricular dysfunction and refractory shock. Usually, these temporary effects can be successfully counteracted with atropine, ephedrine, and volume supplementation. Clinicians need to be well informed about the potential of dexmedetomidine to cause bradycardia, which may progress to pulseless electrical activity, particularly in patients older than 50 years and patients with cardiac abnormalities. Here, we report the clinical characteristics of six patients who were scheduled for various neurosurgical procedures within a period of three months and suffered from cardiac arrest following dexmedetomidine administration. We urge clinicians to take caution against the negative effects of dexmedetomidine, especially when it is used in patients older than 50 years with underlying cardiac disease and in combination with cardiodepressant drugs.

On the Nature of Ventricular Tachycardia in Coronary Heart Disease

The prerequisites for the development of uniform ventricular tachycardia (VT) late after myocardial infarction (MI) have been fairly well understood for many years. Compared with survivors of cardiac arrest or patients evaluated for nonsustained VT, patients with uniform VT have more extensive infarction, more profound left ventricular dysfunction, and more abnormal endocardial activation during sinus rhythm.1,2 The slow conduction required for formation of VT circuits is caused by tissue disruption secondary to myocyte death and secondary fibrosis, as well as electric remodeling (eg, altered connexin expression) of the surviving cells.3,4 Although infarct-related damage may be transmural, the importance of the endocardial substrate for the formation of VT circuits has been established by histological-electrophysiological correlation3,5,6 and by the effects of catheter and surgical ablation. Given the importance of the topic, it is puzzling that there have been few data collected on the influence of modern cardiovascular care on the development of VT. There is a general sense that current pharmacological therapy and appropriate revascularization have reduced the incidence of VT after MI, but it is not clear how these therapies might affect the underlying pathophysiology. Article see p 1887 In this light, the study by Wijnmaalen and coworkers in this issue of Circulation offers considerable promise.7 In this study, 36 consecutive patients with VT late after MI (mean 13±9 years) were carefully evaluated to compare the influence of acute reperfusion of the infarct-related artery on the characteristics of the spontaneous/induced VT and the underlying VT substrate. There were 14 patients in the reperfused group and 22 who were not reperfused. The baseline characteristics of the 2 groups were similar, although the reperfused group presented with VT earlier after MI and were slightly younger. The majority …

Mechanisms of disease/hypothesis: Neurogenic left ventricular dysfunction and neurogenic pulmonary oedema

Acute onset of cardiovascular dysfunction may be the result of insults to the central nervous and autonomic system. Several cerebral regions (insular cortex, lateral, hypothalamus, and brain stem) have been identified as part of the "central autonomic network". The brain stem plays an integral role in controlling and mediating autonomic tone. Case reports. These two case reports demonstrate the intimate connectivity between the cardiovascular/pulmonary system and the central nervous system in a 13-year-old girl with occipital angiomatosis, but no history of heart disease who developed profound left ventricular dysfunction and pulmonary oedema following pontine haemorrhage, and in a 5-year-old girl who developed severe pulmonary oedema after suffering from status epilepticus. The two case reports suggest that cardiovascular dysfunction secondary to central nervous insults and neurogenic pulmonary oedema are not two separate clinical entities, but may very well encompass two different presentations of central autonomic disturbances.

A 32‐year‐old woman with arthralgias and severe hypotension

A 32‐year‐old woman with arthralgias and severe hypotension

Diagnosis of Myocarditis

Determining the etiology of cardiac dysfunction in patients with heart failure influences management and prognosis.1 Myocarditis, diagnosed by the current histopathological Dallas criteria, accounts for &10% of patients with new-onset cardiac dysfunction submitted to endomyocardial biopsy.1,2 Despite complete evaluation including history, physical examination, blood work, echocardiography, coronary angiography, and endomyocardial biopsy, &50% of patients with dilated cardiomyopathy have no etiology identified.1 Recent data suggest that patients in the “idiopathic” category may be suffering from myocardial inflammation due to persistent viral replication or autoimmune activation after a viral infection. These studies raise the question of whether the current histopathological criteria for myocardial inflammation (the Dallas criteria) are sensitive enough to identify the population with viral or autoimmune-related heart compromise. The Dallas criteria were proposed in 1986 and provided a histopathological categorization by which the diagnosis of myocarditis could be established. Dallas criteria myocarditis requires an inflammatory infiltrate and associated myocyte necrosis or damage not characteristic of an ischemic event. Borderline myocarditis requires a less intense inflammatory infiltrate and no light microscopic evidence of myocyte destruction.3 These criteria have been used exclusively by American investigators over the last 2 decades. Sampling error, variation in expert interpretation, variance with other markers of viral infection and immune activation in the heart, and variance with treatment outcomes all suggest that the Dallas criteria are no longer adequate. Chow et al and Hauck et al4,5 demonstrated by biopsying postmortem hearts of patients who had died with myocarditis that, from a single endomyocardial biopsy, histological myocarditis could be demonstrated in only 25% of samples. With >5 biopsies, Dallas criteria myocarditis could be diagnosed in approximately two thirds of subjects. A recent MRI study used focal imaging abnormalities to guide heart biopsy investigation of possible myocarditis. The authors showed that the earliest myocardial …

Assessment of myocardial viability using F-18 fluorodeoxyglucose/Tc-99m sestamibi dual-isotope simultaneous acquisition SPECT: Comparison with Tl-201 stress-reinjection SPECT

This study compared technetium 99m sestamibi/fluorine 18 fluorodeoxyglucose dual-isotope simultaneous acquisition (DISA) with stress-reinjection thallium 201 single photon emission computed tomography (SPECT) with regard to their ability to detect myocardial viability. The study cohort consisted of 42 angiographically significant coronary artery disease patients with symptomatic congestive heart failure or regional wall motion abnormalities. In total, 398 dysfunctional segments in 40 patients were analyzed (2 patients were excluded because of poor-quality F-18 fluorodeoxyglucose images). Of the segments, 217 were diagnosed as viable and 144 as nonviable by both DISA and Tl-201, 33 were viable by DISA but nonviable by Tl-201, and 4 were viable by Tl-201 but nonviable by DISA. Most discrepancies were in the inferior wall. Of the 40 patients, 16 underwent revascularization. From the follow-up results for the 105 dysfunctional segments in these 16 patients, DISA viability appears to be a significant predicting factor (P = .014) for functional recovery after revascularization statistically whereas Tl-201 viability does not (P = .09). Our study suggests that DISA viability provides more accurate prediction of postrevascularization functional recovery than Tl-201 viability. Given the small number of patients who underwent revascularization, the superiority of DISA over Tl-201 in detecting myocardial viability may be firmly established by further study on a large scale for patients with profound left ventricular dysfunction.

Triiodothyronine-enhanced left ventricular function after ischemic injury

Hypothyroidism is associated with profound left ventricular dysfunction. Brain-dead organ donors and patients undergoing cardiopulmonary bypass are chemically hypothyroid with significantly reduced circulating free triiodothyronine (T 3). To test the hypothesis that T 3 enhances left ventricular function in a hormonally deficient environment a total of 36 healthy New Zealand White rabbit hearts were studied using a modified Langendorff preparation with Krebs-Henseleit perfusate and intraventricular balloon. In 9 normal rabbit hearts a cumulative dose-response curve with logarithmically increasing doses of T 3 was obtained. The vehicle solution for T 3 dissolution served as control (n = 9). Left ventricular function was assessed from peak developed pressure at baseline and after T 3 administration. Triiodothyronine had no effect in normal hearts on peak developed pressure or end-diastolic pressure. In 18 rabbits, the acute effect of T 3 administration after ischemia was investigated. Preischemic left ventricular function was measured to serve as baseline, and hearts were subjected to 37 °C global ischemia. Triiodothyronine (n = 9) or vehicle (n = 9) was infused during reperfusion, and left ventricular peak developed pressure was measured at 30 and 60 minutes of reperfusion. Recovery of function (expressed as percent return of left ventricular peak developed pressure) was significantly improved within 15 minutes of reperfusion (65.0% ± 2.1% versus 80.2% ± 4.1%) and remained significantly improved throughout the reperfusion period ( p < 0.05 by analysis of variance). These data suggest that although T 3 possesses no inotropic properties, it significantly improves postischemic left ventricular function. The rapidity of the functional improvement suggests that these effects may be due to plasma membrane-mediated mechanisms.

Primary angiosarcoma of the heart causing cardiac rupture

5-FU was discontinued. Previous reports have identified angina1 symptoms as a rare symptom of 5-FU cardiac toxicity.1-5 Some of these patients had also undergone irradiation4 of the left ventricle or had coronary artery disease.‘s3 Underwood et a1.6 suggested coronary artery spasm as a possible mechanism of toxicity. Other proposed mechanisms have included an autoimmune response and inflammatory reaction.lm3 Unlike patients in previous reports our patient had profound left ventricular dysfunction associated with ischemic ECG changes. This episode of 5-FU toxicity is remarkable not only for the acuteness and severity of the myocardial depression but also for the rapid and complete recovery after the drug was discontinued. Furthermore, normal coronary anatomy was documented simultaneously with the severe myocardial failure. An endomyocardial biopsy in the recovery phase did not identify a specific pathologic process. Diffuse coronary artery spasm with subsequent myocardial “stunning” cannot be excluded. Although sluggish flow of dye could reflect low cardiac output and reduced perfusion pressure, arteriolar spasm must also be considered. Cardiac toxicity related to 5-FU therapy is rare but can be life threatening. Myocardial ischemia and profound hemodynamic compromise can occur. The diagnosis should be considered in patients with chest pain, profound hypotension, or congestive heart failure during 5-FU therapy. If suspected, the transient and reversible nature of this toxicity warrants aggressive cardiovascular support until recovery is achieved.

Cardiac Rehabilitation in Patients With Severe Ischemic Left Ventricular Dysfunction

Twenty patients who had had a myocardial infarction and who had a resting left ventricular ejection fraction of 25% or less participated in an 8-week outpatient supervised exercise and education program. No morbidity or mortality occurred during the program, and most patients achieved a substantial improvement in exercise capacity. During a follow-up interval of a mean of 29.7 +/- 13.0 months, four patients died, an annualized mortality of 8 +/- 4%. The outcome of cardiac rehabilitation was assessed 19.1 +/- 4.4 months after completion of the supervised program. Of the 16 survivors, all of whom had been fully employed before their most recent myocardial infarction, 9 (56%) had returned to full-time work, 6 (38%) were medically disabled, and 1 was retired (age 73 years) but fully active. Of the 16 survivors, 13 (81%) completed a questionnaire about their perceptions of their current quality of life. Of the 13 patients, 12 (92%) had continued to exercise regularly. Four patients (31%) reported the ability to perform all desired activities without symptoms, whereas nine patients (69%) noted some impairment in their functional capacity. Thus, in this group of patients with profound left ventricular dysfunction, the rehabilitation potential, as evidenced by return to productive employment and the ability to perform desired activities-including exercise training-was generally favorable.

Delayed recovery of severely “stunned” myocardium with the support of a left ventricular assist device after coronary artery bypass graft surgery

A 53 year old man underwent repeat coronary artery bypass graft surgery after presenting with unstable angina. Because of intraoperative ischemia, the patient developed profound left ventricular dysfunction requiring placement of a left ventricular assist device and intraaortic balloon pump and catecholamine infusion. Serial radionuclide ventriculograms documented delayed recovery of the severely stunned myocardium with mechanical and pharmacologic support.

Experimental and clinical results with a simplified left heart assist device for treatment of profound left ventricular dysfunction.

AbstractDuring the last few years patients with profound heart failure following cardiac surgery have been managed with increasing success with the use of a variety of left heart assist devices. Although some previous experimental studies suggested that cannulation of the left ventricle was superior to that of the left atrium, present studies demonstrate that left atrial cannulation can effectively unload the left ventricle, and significantly decrease left ventricular work. Since 1978, a roller pump type of left heart assist device with cannulation of the left atrium and ascending aorta has been employed in 46 patients with severe postoperative cardiac failure. Twenty‐one patients were successfully weaned from the device; 5 patients died within 90 days of removal of the device, and there were 2 other late deaths 4 months and 4 years postoperatively. There were 14 long‐term survivors (6 months to 54 months). Thirteen of these patients are New York Heart Association class I or II, and 1 patient is New York Heart Association class III. Thus, satisfactory early and late results can be attained with this system. However, it has been postulated that if more complete left heart bypass were utilized, more patients would ultimately survive.

Late functional and hemodynamic status of surviving patients following insertion of the left heart assist device

Since July, 1978, we have inserted a roller pump type of left heart assist device between the left atrium and ascending aorta in 35 patients. There were no significant complications related to use of the device. Seventeen patients recovered sufficiently to have the device removed. There were four early deaths, 60 to 120 days following removal of the device. Three of these patients died of septic complications and one patient died as a result of a cardiac arrest. Of the 13 long-term survivors, seven are working and six are retired. Five patients have mild to moderate cardiac symptoms, whereas eight others are completely asymptomatic. In three patients the ejection fraction was significantly lower than preoperatively; however, in all other patients the ejection fraction either stayed the same or improved postoperatively. We conclude that this type of left heart assist device can provide adequate cardiac support in patients with profound left ventricular dysfunction following cardiac operations. Furthermore, surviving patients generally have satisfactory long-term cardiac function and are leading productive lives.