Advanced Heart Failure: Therapeutic Options and Challenges in the Evolving Field of Left Ventricular Assist Devices.

Heart Failure is a chronic and progressively deteriorating syndrome that has reached epidemic proportions worldwide. Improved outcomes have been achieved with novel drugs and devices. However, the number of patients refractory to conventional medical therapy is growing. These advanced heart failure patients suffer from severe symptoms and frequent hospitalizations and have a dismal prognosis, with a significant socioeconomic burden in health care systems. Patients in this group may be eligible for advanced heart failure therapies, including heart transplantation and chronic mechanical circulatory support with left ventricular assist devices (LVADs). Heart transplantation remains the treatment of choice for eligible candidates, but the number of transplants worldwide has reached a plateau and is limited by the shortage of donor organs and prolonged wait times. Therefore, LVADs have emerged as an effective and durable form of therapy, and they are currently being used as a bridge to heart transplant, destination lifetime therapy, and cardiac recovery in selected patients. Although this field is evolving rapidly, LVADs are not free of complications, making appropriate patient selection and management by experienced centers imperative for successful therapy. Here, we review current LVAD technology, indications for durable MCS therapy, and strategies for timely referral to advanced heart failure centers before irreversible end-organ abnormalities.

Cardiotrophin-1 in Asymptomatic Hypertensive Patients With Mild Diastolic Dysfunction: Potential Prognostic Value in Early Stages of Hypertensive Heart Disease.

BACKGROUND: Regardless of the advancements in modern technology and treatment options, heart failure (HF) exhibits impervious mortality and morbidity rates. Arterial hypertension poses one of the greatest risks for developing HF, yet the exact pathophysiological path and changes that lead from isolated hypertension to HF are still unclear. Cardiotrophin-1 (CT-1) serves as a promising prognostic biomarker for the onset of HF in hypertensive patients. The aim of this study was to investigate whether CT-1 levels are elevated in a selected group of asymptomatic hypertensive patients. METHODS: In a selected cohort of 40 asymptomatic patients with early diastolic dysfunction (grade I), without any signs of increased filling pressures in the left ventricle, as well as 20 healthy individuals, the levels of CT-1 brain natriuretic peptide (BNP) along with various echocardiographic parameters were evaluated. RESULTS: The mean age of the hypertensive patients was 56 ± 5 years and 52± 3.5 years for the normotensive controls. The hypertensive group exhibited higher levels of CT-1, which was not affected by left ventricular hypertrophy. Notably, in patients with normal E/E' < 8 (n = 30), CT-1 levels were 1165 ± 471 pg/ml compared to 2069 ± 576 pg/ml in patients with marginal E/E' > 8 and <14 (n = 10), p = 0.001. CONCLUSIONS: Our study demonstrated elevated CT-1 levels in a cohort of asymptomatic hypertensive patients, exhibiting mild diastolic dysfunction. These findings are suggestive of the potentially prognostic value of this particular biomarker in the early stages of hypertensive heart disease.

SGLT-2 Inhibitors and the Inflammasome: What's Next in the 21st Century?

The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in the kidney and the heart is increasingly being suggested to play a key role in mediating inflammation. In the kidney, NLRP3 activation was associated with the progression of diabetic kidney disease. In the heart, activation of the NLRP3 inflammasome was related to the enhanced release of interleukin-1ß (IL-1ß) and the subsequent induction of atherosclerosis and heart failure. Apart from their glucose-lowering effects, SGLT-2 inhibitors were documented to attenuate activation of the NLRP3, thus resulting in the constellation of an anti-inflammatory milieu. In this review, we focus on the interplay between SGLT-2 inhibitors and the inflammasome in the kidney, the heart and the neurons in the context of diabetes mellitus and its complications.

Relationship between autonomic nervous system function and continuous interstitial glucose measurement in patients with type 2 diabetes.

AIMS: The Aim of the present study was to examine whether there is a relationship between autonomic nervous system function and glycemic variability (GV) in patients with type 2 diabetes (T2D). METHODS: A total of 50 (29 males) patients with T2D (mean age 58.4 ± 9.9 years, median diabetes duration 5.5 [IQR 2.0-9.25] years), on oral antidiabetic agents, underwent ECG recording and subcutaneous glucose monitoring, simultaneously and continuously, for 24 hours. RESULTS: After adjustment for HbA1c and diabetes duration, total power of heart rate variability (HRV) was inversely associated with the standard deviation of the mean interstitial tissue glucose (MITG) and with the M-value during the entire recording (r: -0.29, P = 0.052; r: -0.30, P = 0.047, resp.) and during the night (r: -0.29, P = 0.047; r: -0.31, P = 0.03, resp.). Most of the HRV time-domain indices were significantly correlated with standard deviation of the MITG and the M-value. These correlations were stronger for the HRV recordings during the night. No significant association was found between HRV parameters and MAGE. CONCLUSIONS: HRV is inversely associated with GV in patients with T2D, which might be a sign of causation between GV and autonomic dysfunction. Prospective studies are needed to further investigate the importance of GV in the pathogenesis of long-term complications of diabetes.

Cigarette Smoking Is Associated with Prolongation of the QTc Interval Duration in Patients with Type 2 Diabetes Mellitus.

Aims. Aim of the study was to evaluate the effect of smoking on autonomic nervous system (ANS) activity and QTc interval duration in patients with Type 2 diabetes mellitus (T2DM). Methods. A total of 70 patients with T2DM (35 chronic smokers, 35 nonsmokers) treated with oral antidiabetic medications underwent continuous ECG Holter monitoring for 24 hours and analysis of time- and frequency-domain measures of heart rate variability (HRV). HRV over short time was also assessed using the deep breathing test. In addition, baroreflex sensitivity (BRS) was evaluated using the spontaneous sequence method. The mean QTc interval was measured from the 24-hour ECG recordings. Results. Smokers had lower body mass index (BMI) and exhibited higher 24-hour mean heart rate. There was no difference regarding all measures of ANS activity between the two groups. Smokers showed increased mean QTc duration during the 24 hours (439.25 ± 26.95 versus 425.05 ± 23.03 ms, P = 0.021) as well as in both day (439.14 ± 24.31 ms, P = 0.042) and night periods (440.91 ± 32.30 versus 425.51 ± 24.98 ms, P = 0.033). The association between smoking status and mean QTc interval persisted after adjusting for BMI. Conclusions. Cigarette smoking is associated with prolongation of the QTc interval in patients with T2DM by a mechanism independent of ANS dysfunction.

Behavior of coagulation factors and normal inhibitors of coagulation during the acute phase of myocardial infarction.

Acute coronary syndromes are characterized by increased endothelial activation. The aim of this study was to investigate the behavior of coagulation factors V, VII, VIII and normal inhibitors antithrombin III and protein C during the acute phase of myocardial infarction. Thirty-six patients (27 men, nine women) and 35 normal individuals were studied during the acute phase of myocardial infarction, in the first 24 h. A group of 35 normal individuals was used as a control group. Blood samples were taken within the first 24 h of the hospital admission. The plasma levels of the coagulation factors were measured by the clot formation method, whereas the normal inhibitors were measured by ELISA. In the acute phase of myocardial infarction significant changes occur in coagulant and fibrinolytic factors. A decrease in plasma levels of factor V, antithrombin III and protein C was found in patients with acute myocardial infarction, compared to control group, whereas an increase in plasma levels of factor VII were observed. This study concludes that acute myocardial infarction causes consumption of fibrinolytic factors, whereas the coagulant factors seem to increase when being activated.

Transient left ventricular dysfunction in Churg Strauss syndrome: a case report.

A 42 year old woman was admitted to our hospital for investigation of eosinophilia. There were no findings from the physical examination of the lungs and heart. The echocardiography showed a segmental hypokinesia of the interventricular septum and the apex causing left ventricular dysfunction with an ejection fraction 45% and mild pericardial effusion. Cardiac magnetic resonance was performed, for detection of lesions associated with the underline disease, using electrocardiogram-triggered T2-weighted and T1-weighted multislice spin-echo images (before and after an intravenous bolus of gadolinium).The analysis of T2-weighted images revealed increased signal on the mid part of interventricular septum, suggesting myocardial oedema. In the delayed-enhanced images, areas of late phase gadolinium enhancement (indicative of fibrosis) were identified in the mid part of interventricular septum. Methylprednisolone therapy was started. The patient had follow-up echocardiographic examination every month and on sixth month improvement of left ventricular dysfunction was shown with an ejection fraction 55%.In conclusion our case is a typical Churg Strauss Syndrome with characteristic myocardial involvement which improved after corticosteroid treatment. The cardiac magnetic resonance has significant role for early and accurate detection and differentiation of myocardial damage even in preserved cardiac wall motion and cavity size.

Late recurrence of pulmonic valve endocarditis in an adult patient with ventricular septal defect: a case report.

A 54-year-old female patient with a congenital ventricular septal defect (VSD) was admitted to the authors' hospital for an investigation of mild fever of four months' duration. Her history revealed pulmonary valve endocarditis contracted 18 years previously. Echocardiography revealed an echogenic mobile mass on the pulmonic valve that caused mild regurgitation, while blood cultures were positive for Streptococcus viridans. The patient was administered ceftriaxone and gentamycin, and had an uneventful clinical course. She was advised to undergo surgical closure of the VSD in order to avoid any recurrence of endocarditis.

Complete heart block and severe aortic stenosis in a patient with rheumatoid arthtritis: a case report.

BACKGROUND: A 77-year-old male patient with a history of rheumatoid arthritis was admitted to our hospital for investigation of syncope and dyspnea on exertion class II according to NYHA class association. CASE PRESENTATION: The electrocardiogram revealed complete heart block whereas the echocardiogram showed severe aortic valve stenosis with a peak gradient = 80 mmHg. A permanent pacemaker was implanted in addition to aortic valve replacement. The coexistence of complete heart block and severe aortic stenosis with rheumatoid arthritis are presented. CONCLUSION: Further studies are necessary to assess whether a true association of the above conditions exist.