The effect of cardiac shock wave therapy on myocardial function and perfusion in the randomized, triple-blind, sham-procedure controlled study.

BACKGROUND: Recent triple-blind sham procedure-controlled study revealed neutral effects of the cardiac shock wave therapy (CSWT) on exercise tolerance and symptoms in patients with stable angina. Current data about the effects of CSWT on global and regional myocardial contractility and perfusion is limited. Hereby we report the results of an imaging sub-study that evaluated the capacity of CSWT to ameliorate myocardial ischemia induced during dobutamine stress echocardiography (DSE) and cardiac single photon emission computed tomography (SPECT). METHODS: Prospective, randomized, triple-blind, sham procedure-controlled study enrolled 72 adult subjects who complied with defined inclusion criteria. The subjects were assigned to the OMT + CSWT and the OMT + sham procedure study groups with 1:1 ratio. Application of the CSWT covered all segments of the left ventricle. Imaging ischemia tests were performed in 59 study patients: DSE and SPECT before the CSWT treatment and after 6 months, with DSE carried out additionally at 3 months after randomization. Co-primary endpoints of the study were: change in wall motion score index (WMSI), representing the stress-induced impairment of regional myocardial function, and change in summed difference score (SDS), representing the amount of perfusion defect. RESULTS: OMT + CSWT and OMT + sham procedure study groups included 30 and 29 patients, respectively. Regional myocardial contractility during DSE significantly improved at 3 months follow-up in OMT + CSWT group compared to baseline as shown by WMSI at stress (1.4 ± 0.4 vs 1.6 ± 0.4, p = 0.001), but not in OMT + sham procedure group (1.5 ± 0.3 vs 1.6 ± 0.4, p = 0.136). The difference in stress DSE results between both study groups disappeared after 6 months. SPECT results demonstrated a significant reduction of inducible ischemia in OMT + CSWT group compared to OMT + sham procedure group at 6 months follow-up (SDS dropped from 5.4 ± 3.7 to 3.6 ± 3.8 vs 6.4 ± 5.9 to 6.2 ± 5 respectively, p = 0.034). CONCLUSIONS: Cardiac shock wave treatment showed the ability to reduce stress-induced myocardial ischemia, as assessed by wall motion abnormalities and perfusion defects, compared to sham procedure. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT02339454 ). The trial was registered retrospectively on 12 January 2015.

Could careful patient selection for renal denervation warrant a positive effect on arterial stiffness and left ventricular mass reduction?

AIMS: After the sequence of Symplicity HTN trials, the impact of the procedure on lowering blood pressure (BP) and cardiovascular risk is still debatable. We present initial results of the multimodal pilot study that aimed at carefully selecting proper patients and investigating the effects of RASD on cardiac morphology and central haemodynamic parameters in 15 patients with resistant arterial hypertension prior and 6 months after RASD. METHODS AND RESULTS: The multimodal (applanation tonometry, echocardiography and cardiac magnetic resonance (CMR)) study findings have shown a significant BP decrease (190/112 ± 23/12 to 153/91 ± 18/11 mm Hg, P < 0.002), a decrease of the arterial markers (carotid-femoral pulse wave velocity decreased from 11.46 ± 2.92 m/s to 9.17 ± 2.28 m/s and the augmentation index decreased from 25.47 ± 10.55 to 21 ± 12.19, P < 0.006), a significant left ventricular mass index decrease by 10% both by echocardiography (140.83 ± 38.46 to 115.26 ± 25.37 g/m2, n = 14, P < 0.001) and CMR (108.32 ± 39.02 to 97.25 ± 30.06 g/m2, n = 15, P = 0.003). A significant decrease of CMR retrograde flow volume in the ascending aorta non-dependent on BP was also found. CONCLUSIONS: Our study is characterised by strict and extensive patient selection criteria for renal artery sympathetic denervation (RASD), which seem to warrant a positive effect of the procedure on BP, arterial stiffness and left ventricular mass 6 months after RASD, although it should be confirmed in larger controlled trials.

The association of biological sex and long-term outcomes in patients with acute dyspnea at the emergency department.

BACKGROUND AND IMPORTANCE: Marked differences have been described between women and men in disease prevalence, clinical presentation, response to treatment and outcomes. However, such data are scarce in the acutely ill. An awareness of differences related to biological sex is essential for the success of clinical care and outcomes in patients presenting with acute dyspnea, the most frequent cause of emergency department (ED) admission. OBJECTIVES: The aim of the present study was to assess the effect of biological sex on 1-year all-cause mortality in patients presenting with acute dyspnea to the ED. DESIGN, SETTINGS AND PARTICIPANTS: Consecutive adult patients presenting with acute dyspnea in two Lithuanian EDs were included. Clinical characteristics, laboratory data and medication use at discharge were collected. Follow-up at 1 year was performed via national data registries. OUTCOMES MEASURE AND ANALYSIS: The primary outcome of the study was 1-year all-cause mortality. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model, with and without adjustment for the following confounders: age, systolic blood pressure, creatinine, sodium and hemoglobin. MAIN RESULTS: A total of 1455 patients were included. Women represented 43% of the study population. Compared to men, women were older [median (interquartile range [IQR]) age 74 (65-80) vs. 68 (59-77) years, P < 0.0001]. The duration of clinical signs before admission was shorter for women [median (IQR) duration 4 (1-14) vs. 7(2-14) days, P = 0.006]. Unadjusted 1-year all-cause mortality was significantly lower in women (21 vs. 28%, P = 0.001). Adjusted HR of 1-year all-cause mortality was lower in women when compared to men [HR 0.68 (0.53-0.88), P = 0.0028]. Additional sensitivity analyses confirmed the survival benefit for women in subgroups including age greater and lower than 75 years, the presence of comorbidities and causes of dyspnea (cardiac or noncardiac). CONCLUSION: Women have better 1-year survival than men after the initial ED presentation for acute dyspnea. Understanding the biological sex-related differences should lead toward precision medicine, and improve clinical decision-making to promote gender equality in health.

Biologically Active Adrenomedullin (bio-ADM) is of Potential Value in Identifying Congestion and Selecting Patients for Neurohormonal Blockade in Acute Dyspnea.

PURPOSE: This study was designed to evaluate the role of biologically active adrenomedullin (bio-ADM) in congestion assessment and risk stratification in acute dyspnea. METHODS: This is a sub-analysis of the Lithuanian Echocardiography Study of Dyspnea in Acute Settings. Congestion was assessed by means of clinical (peripheral edema, rales) and sonographic (estimated right atrial pressure) parameters. Ninety-day mortality was chosen for outcome analysis. RESULTS: There were 1188 patients included. Bio-ADM concentration was higher in patients with peripheral edema at admission (48.2 [28.2-92.6] vs 35.4 [20.9-59.2] ng/L, P < .001). There was a stepwise increase in bio-ADM concentration with increasing prevalence of rales: 29.8 [18.8-51.1], 38.5 [27.5-67.1], and 51.1 [33.1-103.2] ng/L in patients with no rales, rales covering less than one-half, and greater than or equal to one-half of the pulmonary area, respectively (P < 0.001). Bio-ADM concentration demonstrated gradual elevation in patients with normal, moderately, and severely increased estimated right atrial pressure: 25.1 [17.6-42.4] ng/L, 36.1 [23.1-50.2], and 47.1 [30.7-86.7] ng/L, respectively (P < .05). Patients with bio-ADM concentration >35.5 ng/L were at more than twofold increased risk of dying (P < .001). Survival in those with high bio-ADM was significantly modified by neurohormonal blockade at admission (P < .05), especially if NT-proBNP levels were lower than the median (P = .002 for interaction). CONCLUSION: Bio-ADM reflects the presence and the degree of pulmonary, peripheral, and intravascular volume overload and is strongly related to 90-day mortality in acute dyspnea. Patients with high bio-ADM levels demonstrated survival benefit from neurohormonal blockade.

Readmission following both cardiac and non-cardiac acute dyspnoea is associated with a striking risk of death.

AIMS: Readmission and mortality are the most common and often combined endpoints in acute heart failure (AHF) trials, but an association between these two outcomes is poorly investigated. The aim of this study was to determine whether unplanned readmission is associated with a greater subsequent risk of death in patients with acute dyspnoea due to cardiac and non-cardiac causes. METHODS AND RESULTS: Derivation cohort (1371 patients from the LEDA study) and validation cohort (1986 patients from the BASEL V study) included acute dyspnoea patients admitted to the emergency department. Cox regression analysis was used to determine the association of 6 month readmission and the risk of 1 year all-cause mortality in AHF and non-AHF patients and those readmitted due to cardiovascular and non-cardiovascular causes. In the derivation cohort, 666 (49%) of patients were readmitted at 6 months and 282 (21%) died within 1 year. Six month readmission was associated with an increased 1 year mortality risk in both the derivation cohort [adjusted hazard ratio (aHR) 3.0 (95% confidence interval, CI 2.2-4.0), P < 0.001] and the validation cohort (aHR 1.8, 95% CI 1.4-2.2, P < 0.001). The significant association was similarly observed in AHF (aHR 3.2, 95% CI 2.1-4.9, P < 0.001) and other causes of acute dyspnoea (aHR 2.9, 95% CI 1.9-4.5, P < 0.001), and it did not depend on the aetiology [aHR 2.2, 95% CI 1.6-3.1 for cardiovascular readmissions; aHR 4.1, 95% CI 2.9-5.7 for non-cardiovascular readmissions (P < 0.001 for both)] or timing of readmission. CONCLUSION​S: Our study demonstrated a long-lasting detrimental association between readmission and death in AHF and non-AHF patients with acute dyspnoea. These patients should be considered 'vulnerable patients' that require personalized follow-up for an extended period.

Safety of diuretic administration during the early management of dyspnea patients who are not finally diagnosed with acute heart failure.

OBJECTIVES: Investigating whether it is safe or not to administrate diuretics to patients arriving at emergency departments in a stage of acute dyspnea but without a final diagnosis of acute heart failure. METHODS: We analyzed an unselected multinational sample of patients with dyspnea without a final diagnosis of acute heart failure from Global Research on Acute Conditions Team (France, Lithuania, Tunisia) and Basics in Acute Shortness of Breath Evaluation (Switzerland) registries. Thirty-day all-cause mortality and 30-day postdischarge all-cause readmission rate of treated patients with diuretics at emergency departments were compared with untreated patients by unadjusted and adjusted hazard and odds ratios. Interaction and stratified analyses were performed. RESULTS: We included 2505 patients. Among them, 365 (14.6%) received diuretics in emergency departments. Thirty-day mortality was 4.5% (treated/untreated = 5.2%/4.3%, hazard ratio: 1.22; 95% confidence interval, 0.75-2.00) and 30-day readmission rate was 11.3% (14.7%/10.8%, odds ratio: 1.41; 95% confidence interval, 0.95-2.11). After adjustment, no differences were found between two groups in mortality (hazard ratio: 0.86; 95% confidence interval, 0.51-1.44) and readmission (odds ratio: 1.15; 95% confidence interval, 0.72-1.82). Age significantly interacted with the use of diuretics and readmission (P = 0.03), with better prognosis when used in patients >80 years (odds ratio: 0.27; 95% confidence interval, 0.07-1.03) than in patients ≤80 years (odds ratio: 1.56; 95% confidence interval, 0.94-2.63). CONCLUSIONS: Diuretic administration to patients presenting to emergency departments with dyspnea while they were undiagnosed and in whom acute heart failure was finally excluded was not associated with 30-day all-cause mortality and 30-day postdischarge all-cause readmission rate.

Improved cardiac and venous pressures during hospital stay in patients with acute heart failure: an echocardiography and biomarkers study.

AIMS: Changes in echocardiographic parameters and biomarkers of cardiac and venous pressures or estimated plasma volume during hospitalization associated with decongestive treatments in acute heart failure (AHF) patients with either preserved left ventricular ejection fraction (LVEF) (HFPEF) or reduced LVEF (HFREF) are poorly assessed. METHODS AND RESULTS: From the metabolic road to diastolic heart failure: diastolic heart failure (MEDIA-DHF) study, 111 patients were included in this substudy: 77 AHF (43 HFPEF and 34 HFREF) and 34 non-cardiac dyspnea patients. Echocardiographic measurements and blood samples were obtained within 4 h of presentation at the emergency department and before hospital discharge. In AHF patients, echocardiographic indices of cardiac and venous pressures, including inferior vena cava diameter [from 22 (16-24) mm to 13 (11-18) mm, P = 0.009], its respiratory variability [from 32 (8-44) % to 43 (29-70) %, P = 0.04], medial E/e' [from 21.1 (15.8-29.6) to 16.6 (11.7-24.3), P = 0.004], and E wave deceleration time [from 129 (105-156) ms to 166 (128-203) ms, P = 0.003], improved during hospitalization, similarly in HFPEF and HFREF patients. By contrast, no changes were seen in non-cardiac dyspnea patients. In AHF patients, all plasma biomarkers of cardiac and venous pressures, namely B-type natriuretic peptide [from 935 (514-2037) pg/mL to 308 (183-609) pg/mL, P < 0.001], mid-regional pro-atrial natriuretic peptide [from 449 (274-653) pmol/L to 366 (242-549) pmol/L, P < 0.001], and soluble CD-146 levels [from 528 (406-654) ng/mL to 450 (374-529) ng/mL, P = 0.003], significantly decreased during hospitalization, similarly in HFPEF and HFREF patients. Echocardiographic parameters of cardiac chamber dimensions [left ventricular end-diastolic volume: from 120 (76-140) mL to 118 (95-176) mL, P = 0.23] and cardiac index [from 2.1 (1.6-2.6) mL/min/m2 to 1.9 (1.4-2.4) mL/min/m2 , P = 0.55] were unchanged in AHF patients, except tricuspid annular plane systolic excursion (TAPSE) that improved during hospitalization [from 16 (15-19) mm to 19 (17-21) mm, P = 0.04]. Estimated plasma volume increased in both AHF [from 4.8 (4.2-5.6) to 5.1 (4.4-5.8), P = 0.03] and non-cardiac dyspnea patients (P = 0.01). Serum creatinine [from 1.18 (0.90-1.53) to 1.19 (0.86-1.70) mg/dL, P = 0.89] and creatinine-based estimated glomerular filtration rate [from 59 (40-75) mL/min/1.73m2 to 56 (38-73) mL/min/1.73m2 , P = 0.09] were similar, while plasma cystatin C [from 1.50 (1.20-2.27) mg/L to 1.78 (1.33-2.59) mg/L, P < 0.001] and neutrophil gelatinase associated lipocalin (NGAL) [from 127 (95-260) ng/mL to 167 (104-263) ng/mL, P = 0.004] increased during hospitalization in AHF. CONCLUSIONS: Echocardiographic parameters and plasma biomarkers of cardiac and venous pressures improved during AHF hospitalization in both acute HFPEF and HFREF patients, while cardiac chamber dimensions, cardiac output, and estimated plasma volume showed minimal changes.

Acute Heart Failure Management.

Acute heart failure (AHF) is a life-threatening medical condition, where urgent diagnostic and treatment methods are of key importance. However, there are few evidence-based treatment methods. Interestingly, despite relatively similar ways of management of AHF throughout the globe, mid-term outcome in East Asia, including South Korea is more favorable than in Europe. Yet, most of the treatment methods are symptomatic. The cornerstone of AHF management is identifying precipitating factors and specific phenotype. Multidisciplinary approach is important in AHF, which can be caused or aggravated by both cardiac and non-cardiac causes. The main pathophysiological mechanism in AHF is congestion, both systemic and inside the organs (lung, kidney, or liver). Cardiac output is often preserved in AHF except in a few cases of advanced heart failure. This paper provides guidance on AHF management in a time-based approach. Treatment strategies, criteria for triage, admission to hospital and discharge are described.