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Background: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is the most widely used measure of quality of life (QoL) in HF patients. This prospective study aimed to assess the relationship between QoL and exercise capacity in HF patients.

Methods: The study subjects were 118 consecutive patients with chronic HF (62 +/- 10 years, 57 females, in NYHA I-III). Patients answered a MLHFQ questionnaire in the same day of complete clinical, biochemical and echocardiographic assessment. They also underwent a 5 min walk test (6-MWT), in the same day, which grouped them into; Group I: <= 300 m and Group II: > 300 m. In addition, left ventricular (LV) ejection fraction (EF), divided them into: Group A, with preserved EF (HFpEF) and Group B with reduced EF (HFrEF).

Results: The mean MLHFQ total scale score was 48 (+/- 17). The total scale, and the physical and emotional functional MLHFQ scores did not differ between HFpEF and HFpEF. Group I patients were older (p = 0.003), had higher NYHA functional class (p = 0.002), faster baseline heart rate (p = 0.006), higher prevalence of smoking (p = 0.015), higher global, physical and emotional MLHFQ scores (p < 0.001, for all), larger left atrial (LA) diameter (p = 0.001), shorter LV filling time (p = 0.027), higher E/e' ratio (0.02), shorter isovolumic relaxation time (p = 0.028), lower septal a' (p = 0.019) and s' (p = 0.023), compared to Group II. Independent predictors of 6-MWT distance for the group as a whole were increased MLHFQ total score (p = 0.005), older age (p = 0.035), and diabetes (p = 0.045), in HFpEF were total MLHFQ (p = 0.007) and diabetes (p = 0.045) but in HFrEF were only LA enlargement (p = 0.005) and age (p = 0.013. A total MLHFQ score of 48.5 had a sensitivity of 67% and specificity of 63% (AUC on ROC analysis of 72%) for limited exercise performance in HF patients.

Conclusions: Quality of life, assessment by MLHFQ, is the best correlate of exercise capacity measured by 6-MWT, particularly in HFpEF patients. Despite worse ejection fraction in HFrEF, signs of raised LA pressure independently determine exercise capacity in these patients.

The objective of this thesis is to evaluate the use of Doppler echocardiography markers ofglobal dyssynchrony [total isovolumic time (t-IVT)] in the following 6 studies: 1) Its prognostic role in predicting cardiac events in patients undergoing CABG surgery,compared with conventional global systolic and diastolic measurements. 2) Its additional value in predicting six minute walk test (6-MWT) in patients with leftventricular (LV) ejection fraction (EF) <45%. 3) Its prognostic value in comparison with other clinical, biochemical and echocardiographicvariables in patients with chronic systolic heart failure (HF). 4) The relationship between 6-MWT and cardiac function measurements in a consecutivegroup of patients, irrespective of EF and to identify predictors of exercise capacity. 5) To investigate the effect of age on LV t-IVT and Tei index compared with conventionalsystolic and diastolic parameters. 6) To assess potential additional value of markers of global LV dyssynchrony in predictingcardiac resynchronization therapy (CRT) response in HF patients.

Study I

Methods: This study included 74 patients before routine CABG who were followed up for18±12 months. Results: At follow-up, 29 patients were hospitalized for a cardiac event or died. LV-ESD wasgreater (P=0.003), fractional shortening (FS) lower (p<0.001), E:A ratio and Tei index higher(all P<0.001), and t-IVT longer (P<0.001) in patients with events. Low FS [0.66 (0.50–0.87),P<0.001], high E:A ratio [l4.13 (1.17–14.60), P=0.028], large LV-ESD [0.19 (0.05–0.84),P=0.029], and long t-IVT [1.37 (1.02–1.84), P=0.035] predicted events and deaths. Conclusion: Despite satisfactory surgical revascularization, long t-IVT and systolicdysfunction suggest persistent ventricular dyssynchrony that contributes to post-CABGcardiac events.

Study II

Methods: We studied 77 patients (60±12 year, and 33.3% females) with stable HF using 6-MWT.iii Results: E’ wave (r=0.61, p<0.001), E/e’ ratio (r=-0.49, p<0.001), t-IVT (r=-0.44, p<0.001),Tei index (r=-0.43, p<0.001) and NYHA class (r=-0.53, p<0.001) had the highest correlationwith the 6-MWT distance. In multivariate analysis, only E/e’ ratio [0.800 (0.665-0.961),p=0.017], and t-IVT [0.769 (0.619-0.955), p=0.018] independently predicted poor 6-MWTperformance (<300m). Conclusions: In HF, the higher the filling pressures and the more dyssynchronous the LV, thepoorer is the patient’s exercise capacity.

Study III

Methods: We studied 107 systolic HF patients; age 68±12 year, 25% females and measuredplasma NT-pro-BNP. Results: Over a follow-up period of 3718 months, t-IVT ≥12.3 sec/min, mean E/Em ratio≥10, log NT-pro-BNP levels ≥2.47 pg/ml and LV EF ≤32.5% predicted clinical events. Theaddition of t-IVT and NT-pro-BNP to conventional clinical and echocardiographic variablessignificantly improved the χ2 for the prediction of outcome from 33.1 to 38.0, (p<0.001). Conclusions: Prolonged t-IVT adds to the prognostic stratification of patients with systolicHF.

Study IV

Methods: We studied 147 HF patients (61±11 year, 50.3% male) with 6-MWT.Results: The 6-MWT correlated with t-IVT (r=-0.49, p<0.001) and Tei index (r=-0.43,p<0.001) but not with any of the other clinical or echocardiographic parameters. Group Ipatients (<300m) had lower Hb (p=0.02), lower EF (p=0.003), larger left atrium (p=0.02),thicker septum (p=0.02), lower A wave (p=0.01) and lateral wall a’ (p=0.047), longerisovolumic relaxation time (r=0.003) and longer t-IVT (p= 0.03), compared with Group II(>300m). Only t-IVT ratio [1.257 (1.071-1.476), p=0.005], LV EF [0.947 (0.903-0.993),p=0.02], and E/A ratio [0.553 (0.315-0.972), p=0.04] independently predicted poor 6-MWTperformance. Conclusion: In HF, the limited 6-MWT is related mostly to severity of global LVdyssynchrony, more than EF or raised filling pressures.

Study V

Methods: We studied 47 healthy individuals (age 62±12 year, 24 female), arbitrarilyclassified into: M (middle age), S (seniors), and E (elderly). Results: Age strongly correlated with t-IVT (r=0.8, p<0.001) and with Tei index (r=0.7,p<0.001), E/A ratio (r=-0.6, p<0.001), but not with global or segmental systolic function measurements or QRS duration. The normal upper limit of the t-IVT (95% CI) for the three groups was 8.3 s/min, 10.5 s/min and 14.5 s/min, respectively, being shorter in the S compared with the E group (p=0.001). T-IVT correlated with A wave (r=0.66, p<0.001), E/Aratio (r=-0.56, p<0.001), septal e’ (r=-0.49, p=0.001) and septal a’ (r=0.4, p=0.006), but notwith QRS. Conclusions: In normals, age is associated with exaggerated LV global dyssynchrony anddiastolic function disturbances, but systolic function remains unaffected.

Study VI

Methods: We studied 103 HF patients (67±12 year, 82.5% male) recruited for CRTtreatment. Results: Prolonged t-IVT [0.878 (0.802-0.962), p=0.005], long QRS duration [0.978 (0.960-0.996), p=0.02] and high tricuspid regurgitation pressure drop (TRPD) [1.047 (1.001-1.096),p=0.046] independently predicted response to CRT. A t-IVT ≥11.6 s/min was 67% sensitiveand 62% specific (AUC 0.69, p=0.001) in predicting CRT response. Respective values for aQRS ≥ 151ms were 66% and 62% (AUC 0.65, p=0.01). Combining the two variables had asensitivity of 67% but higher specificity of 88% in predicting CRT response. In atrialfibrillation (AF) patients, only prolonged t-IVT ≥11 s/min [0.690 (0.509-0.937), p=0.03]independently predicted CRT response with a sensitivity of 69% and specificity of 79% (AUC0.78, p=0.015). Conclusion: Combining prolonged t-IVT and broad QRS had higher specificity in predictingresponse to CRT, with the former the sole predictor of response in AF patients.

Background: The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional capacity assessed by 6 min walk test (6-MWT) in patients with heart failure (HF), irrespective of ejection fraction (EF).

Methods: In 147 HF patients (mean age 61 +/- 11 years, 50.3% male), a 6-MWT and an echo-Doppler study were performed in the same day. Global LV dyssynchrony was indirectly assessed by total isovolumic time - t-IVT [in s/min; calculated as: 60 - (total ejection time + total filling time)], and Tei index (t-IVT/ejection time). Patients were divided into two groups based on the 6-MWT distance (Group I: <= 300 m and Group II: > 300 m), and also in two groups according to EF (Group A: LVEF >= 45% and Group B: LVEF <45%).

Results: In the cohort of patients as a whole, the 6-MWT correlated with t-IVT (r = -0.49, p < 0.001) and Tei index (r = -0.43, p < 0.001) but not with any of the other clinical or echocardiographic parameters. Group I had lower hemoglobin level (p = 0.02), lower EF (p = 0.003), larger left atrium (p = 0.02), thicker interventricular septum (p = 0.02), lower A wave (p = 0.01) and lateral wall late diastolic myocardial velocity a' (p = 0.047), longer isovolumic relaxation time (r = 0.003) and longer t-IVT (p = 0.03), compared with Group II. In the patients cohort as a whole, only t-IVT ratio [1.257 (1.071-1.476), p = 0.005], LV EF [0.947 (0.903-0.993), p = 0.02], and E/A ratio [0.553 (0.315-0.972), p = 0.04] independently predicted poor 6-MWT performance (< 300 m) in multivariate analysis. None of the echocardiographic measurements predicted exercise tolerance in HFpEF.

Conclusion: In patients with HF, the limited exercise capacity, assessed by 6-MWT, is related mostly to severity of global LV dyssynchrony, more than EF or raised filling pressures. The lack of exercise predictors in HFpEF reflects its multifactorial pathophysiology.

Dual antiplatelet therapy (DAPT) remains the gold standard in patients who underwent percutaneous coronary intervention (PCI). This meta-analysis aims to evaluate the clinical safety of 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor after PCI with drug-eluting stents (DES). We searched PubMed, MEDLINE, Embase, Scopus, Google Scholar, Cochrane Central Registry, and ClinicalTrials.gov databases and identified 5 randomized controlled trials with 29,831 patients who underwent PCI with DES and compared 1-month versus >1-month DAPT. The primary end point was major bleeding, and the co-primary end point was stent thrombosis. The secondary end point included all-cause mortality, cardiovascular death, myocardial infarction, stroke, and major adverse cardiovascular or cerebrovascular events. Compared with >1-month DAPT, the 1-month DAPT was associated with a lower rate of major bleeding (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.45 to 0.97, p = 0.03, I2 = 71%), whereas stent thrombosis had a similar rate in both study groups (OR 1.08, 95% CI 0.81 to 1.44, p = 0.60, I2 = 0.0%). The study groups had similar risks for all-cause mortality (OR 0.89, 95% CI 0.77 to 1.04, p = 0.14, I2 = 0.0%), cardiovascular death (OR 0.84, 95% CI 0.59 to 1.19, p = 0.32, I2 = 0.0%), myocardial infarction (OR 1.04, 95% CI 0.89 to 1.21, p = 0.62, I2 = 0.0%), and stroke (OR 0.82, 95% CI 0.64 to 1.05, p = 0.11, I2 = 6%). The risk of major adverse cardiovascular or cerebrovascular events was lower (OR 0.86, 95% CI 0.76 to 0.97, p = 0.02, I2 = 25%) in the 1-month DAPT compared with >1-month DAPT. In conclusion, in patients who underwent PCI with DES, 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor reduced major bleeding with no risk of increased thrombotic risk compared with longer-term DAPT.

Aim: The aim of this meta-analysis was to evaluate the safety of 1-month dual antiplatelet therapy (DAPT) followed by aspirin or a P2Y12 receptor inhibitor, after percutaneous coronary intervention (PCI) with drug-eluting stents (DES), based on the available evidence.

Methods: PubMed, MEDLINE, Embase, Scopus, Google Scholar, CENTRAL, and ClinicalTrials.gov database search identified four RCTs of 26,431 patients who underwent PCI with DES and compared 1-month versus >1-month DAPT. The primary endpoint was major bleeding and co-primary endpoint stent thrombosis, and secondary endpoints included all-cause mortality, cardiovascular death, myocardial infarction (MI), stroke, and major adverse clinical events (MACE).

Results: Compared with >1-month DAPT, the 1-month DAPT was associated with a similar rate of major bleeding (OR = 0.74, 95%CI: 0.51–1.07, p = 0.11, I² = 67%), stent thrombosis (OR = 1.10, 95%CI: 0.82–1.47, p = 0.53, I² = 0.0%), similar risk for all-cause mortality (OR = 0.89, 95%CI: 0.77–1.04, p = 0.14, I² = 0%), CV death (OR = 0.80, 95% CI: 0.55–1.60, p = 0.24, I² = 0.0%), MI (OR = 1.02, 95% CI: 0.88–1.19, p = 0.78, I² = 0.0%), and stroke (OR = 0.76, 95% CI: 0.54–1.08, p = 0.13, I² = 29%). The risk of MACE was lower (OR = 0.84, 95% CI: 0.73–0.98, p = 0.02, I² = 39%) in the 1-month DAPT compared with the >1-month DAPT. Only patients with stable CAD had lower risk of MACE with 1-month DAPT (OR = 0.81, 95% CI: 0.67–0.98, p = 0.03, I² = 21%) compared with >1-month DAPT.

Conclusion: This meta-analysis proved the non-inferiority of 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor compared with long-term DAPT in patients undergoing PCI with DES.

Background: Catheter ablation (CA) has become a conventional treatment for atrial fibrillation (AF), but remains with high recurrence rate. The aim of this meta-analysis was to determine left atrial (LA) structure and function indices that predict recurrence of AF.

Methods: We systematically searched PubMed-Medline, EMBASE, Scopus, Google Scholar and the Cochrane Central Registry, up to September 2017 in order to select clinical trials and observational studies which reported echocardiographic predictors of AF recurrence after CA. Eighty-five articles with a total of 16 126 patients were finally included.

Results: The pooled analysis showed that after a follow-up period of 21 +/- 12 months, patients with AF recurrence had larger LA diameter with weighted mean difference (WMD: 2 center dot 99 ([95% CI 2 center dot 50-3 center dot 47], P<0 center dot 001), larger LA volume index (LAVI) maximal and LAVI minimal (P<0 center dot 0001 for both), larger LA area (P<0 center dot 0001), lower LA strain (P<0 center dot 0001) and lower LA total emptying fraction (LA EF) (P<0 center dot 0001) compared with those without AF recurrence. The most powerful LA predictors (in accuracy order) of AF recurrence were as follows: LA strain <19% (OR: 3 center dot 1[95% CI, -1.3-10 center dot 4], P<0 center dot 0001), followed by LA diameter >= 50 mm (OR: 2 center dot 75, [95% CI 1 center dot 66-4 center dot 56,] P<0 center dot 0001), and LAVmax >150 ml (OR: 2 center dot 25, [95% CI, 1.1-5 center dot 6], P = 0 center dot 0002).

Conclusions: Based on this meta-analysis results, a dilated left atrium with diameter more than 50 mm and volume above 150 ml or myocardial strain below 19% reflect an unstable LA that is unlikely to hold sinus rhythm after catheter ablation for atrial fibrillation.

Background: The recently published COMPLETE trial has demonstrated that patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD), who underwent successful percutaneous coronary intervention (PCI) of both culprit and non-culprit (vs. culprit-only) lesions had a reduced risk of major adverse cardiac events (MACE), but not of cardiovascular or total mortality. The aim of this meta-analysis was to assess the efficacy of complete revascularization on cardiovascular or total mortality reduction using available randomized controlled trials (RCTs) including the COMPLETE trial, in hemodynamically stable STEMI patients with MVD. Methods: PubMed, MEDLINE, Embase, Scopus, Google Scholar, CENTRAL and ClinicalTrials.gov databases search identified 10 RCTs of 7033 patients with STEMI and MVD which compared complete (n = 3420) vs. only culprit lesion (n = 3613) PCI for a median 27.7 months follow-up. Random effect risk ratios were used to estimate for efficacy and safety outcomes. Results: Complete revascularization reduced the risk of MACE (10.4% vs.16.6%; RR = 0.59, 95% CI: 0.47 to 0.74, p < 0.0001), CV mortality (2.87% vs. 3.72%; RR = 0.73, 95% CI: 0.56 to 0.95, p = 0.02), reinfarction (5.1% vs. 7.1%; RR = 0.67, 95% CI: 0.52 to 0.86, p = 0.002), urgent revascularization (7.92% vs.17.4%; RR = 0.47, 95% CI: 0.30 to 0.73, p < 0.001), and CV hospitalization (8.68% vs.11.4%; RR = 0.65, 95% CI: 0.44to 0.96, p = 0.03) compared with culprit only revascularization. All-cause mortality, stroke, major bleeding events, or contrast induced nephropathy were not affected by the revascularization strategy. Conclusion: The findings of this meta-analysis suggest that in patients with STEMI and MVD, complete revascularization is superior to culprit-only PCI in reducing the risk of MACE outcomes, including cardiovascular mortality, without increasing the risk of adverse safety outcomes.

BACKGROUND: A prolonged total isovolumic time (T-IVT) has been shown to be associated with worsening survival in patients submitted to coronary artery surgery. However, it is not known whether it has prognostic significance in patients with chronic systolic heart failure (HF).

AIM: To determine the prognostic value of T-IVT in comparison with other clinical, biochemical and echocardiographic variables in patients with chronic systolic HF.

METHODS: Patients (n=107; age 68+/-12years, 25% women) with chronic systolic HF, left ventricular ejection fraction (EF) <45%, and sinus rhythm, underwent a complete Doppler echocardiographic study, that included tissue Doppler long axis velocities and total isovolumic time (T-IVT), determined as [60-(total ejection time+total filling time)]. Plasma N-terminal pro-B natriuretic peptide (NT-pro-BNP) was also measured. The associations of dichotomous variables selected according to the Receiver Operator Characteristic analysis were assessed using the Cox proportional hazard model.

RESULTS: Follow-up period was 37+/-18months. Multivariate predictors of events were T-IVT >/=12.3% s/min, mean E/E(m) ratio >/=10, log NT-pro-BNP levels >/=2.47pg/ml and LV EF</=32.5%. On Kaplan-Meier analysis, patients with prolonged T-IVT, high mean E/E(m) ratio, increased NT-pro-BNP levels and decreased LV EF had a worse outcome compared with those without. The addition of T-IVT and NT-pro-BNP to conventional clinical and echocardiographic variables significantly improved the chi-square for the prediction of the outcome from 33.1 to 38.0, (P<0.001).

CONCLUSIONS: Prolonged T-IVT added to the prognostic stratification of patients with systolic HF.

AIMS: Left ventricular (LV) systolic dysfunction may be associated with compromised stroke volume, which may be caused by asynchrony, reflected on the prolongation of isovolumic time (t-IVT). To assess the prognostic role of Doppler echocardiographic measurements in predicting cardiac events after coronary artery bypass grafting (CABG).

METHODS AND RESULTS: The study included 74 patients undergoing routine CABG. A pre-CABG Doppler echocardiographic assessment of LV dimensions, filling and ejection was performed and t-IVT was determined as [60 - (total ejection time + total filling time)]. Follow-up period was 18 +/- 12 months. Of the 74 patients (age 65 +/- 16 years, 59 males), 29 underwent hospital admission for a cardiac event or died. There were no differences in age, gender, incidence of previous infarct or mitral regurgitation, LV-EDD (left ventricular end-diastolic dimension), left atrial or right ventricular size in patients with cardiac events compared with those without events. Left ventricular end-systolic dimension (LV-ESD) was greater (4.5 +/- 0.9 vs. 3.9 +/- 0.9 cm, P = 0.003), fractional shortening (FS) was lower (21 +/- 4 vs. 32 +/- 8%), E:A ratio and Tei index were higher (2.1 +/- 0.8 vs. 1.0 +/- 0.6 and 0.9 +/- 0.3 vs. 0.6 +/- 0.3, all P < 0.001), and t-IVT was longer (16 +/- 5 vs.10 +/- 4 s/min, P < 0.001) in patients with events. Multivariate predictors of post-CABG events (odds ratio 95% confidence interval) were low FS [0.66 (0.50-0.87), P < 0.001], high E:A ratio [l4.13 (1.17-14.60), P = 0.028], large LV-ESD [0.19 (0.05-0.84), P = 0.029], and long t-IVT [1.37 (1.02-1.84), P = 0.035].

CONCLUSION: Despite satisfactory surgical revascularization, long t-IVT and systolic dysfunction suggest persistent ventricular dyssynchrony that contributes to post-CABG cardiac events. Early assessment of such patients for potential benefit from electrical resynchronization may optimize their cardiac performance and hence clinical outcome.

Aim: The aim of this study was to identify echocardiographic LV systolic and diastolic measurements that predict clinical events post-coronary artery bypass graft (CABG) surgery. Methods: We collected data from 27 patients (age 70 +/- 7 years) who underwent elective CABG, before and within 6 weeks after surgery. LV systolic function was assessed by conventional echocardiographic parameters. A number of LV filling measurements were also made, which included total isovolumic time (t-IVT), Tei index, and restrictive filling pattern. Postoperative cardiac events were death or hospitalization for chest pain, breathlessness, or arrhythmia. Results: Patient's follow-up period was 17 +/- 10 months. Of the 27 patients (age 70 +/- 7 years, 22 male), 10 had postoperative cardiac events. LV ejection fraction (EF) and fractional shortening (FS) were lower (P = 0.01, and P = 0.007, respectively), t-IVT longer (P < 0.001), and Tei index was higher (P < 0.001) preoperatively in patients with events compared to those without. The same differences between groups remained after surgery; EF (P = 0.002), FS (P = 0.002), t-IVT (P < 0.001), and Tei index (P < 0.001). T-IVT was the only preoperative predictor of events (P = 0.038) but its postoperative value as well as that of FS predicted events (P = 0.034, and P = 0.042, respectively). T-IVT of 12.2 s/min and FS of 26% were 80% sensitive and 88% specific for predicting postoperative events. Conclusion: Despite successful surgical revascularization residual impairment of LV systolic function and persistent asynchrony in the form of prolonged t-IVT are associated with postoperative events. Since these abnormalities remained despite full medical therapy, they may thus suggest a need for electrical resynchronization therapy.

BACKGROUND: Six minute walking test (6-MWT) may serve as a reproducible test for assessing exercise capacity in heart failure (HF) patients and can be clinically predicted. We aimed in this study to ascertain if global markers of ventricular asynchrony can predict 6MWT distance in a group of patients with HF and left ventricular (LV) ejection fraction (EF) <45%.

METHODS AND RESULTS: This study included 77 consecutive patients (60+/-12 years) with stable HF. LV end-diastolic and end-systolic dimensions, shortening fraction (SF), EF, myocardial velocities, t-IVT, and Tei index were measured, as well as 6-MWT distance. Patients with limited exercise performance (</=300 m) had lower SF (p=0.02) and EF (p=0.017), longer t-IVT (p=0.001), higher Tei index (p=0.002) and higher E/E' ratio (p<0.001) compared with good performance patients. In multivariate analysis, only E/E' ratio [0.800 (0.665-0.961), p=0.017], and t-IVT [0.769 (0.619-0.955), p=0.018] independently predicted poor exercise performance.

CONCLUSIONS: In heart failure patients, the higher the filling pressures and the more asynchronous the left ventricle, the poorer is the patient's exercise capacity. These findings highlight specific LV functional disturbances that should be targeted for better optimization of medical and/or electrical therapy.

The KOSovan Acute Coronary Syndrome (KOS-ACS) Registry is established as a prospective, continuous, nationwide, web-based registry that is operated online. The KOS-ACS registry is designed with the following objectives: (1) to obtain data on the demographic, clinical, and laboratory characteristics of ACS patients treated in Kosovo; (2) to create a national database with information on health care in ACS patients treated in Kosovo; (3) to identify the national features of associations between ACS characteristics and clinical outcomes, including mortality, complications, the length of hospital stay, and the quality of clinical care; and (4) to propose a practical guide for improving the quality and efficiency of ACS treatment in Kosovo. The Kosovo Society of Cardiology and University of Prishtina will be responsible for the development of the KOS-ACS registry and centralized data analysis at the national level. The KOS-ACS Registry will enroll all patients admitted, at any of the registered clinical centers, with the diagnosis of ACS and who will be clinically managed at any of the Kosovo hospitals. Data on patient demographics, clinical characteristics, previous and hospital drug treatment, and reperfusion therapy will be collected. The type of ACS (unstable angina, NSTEMI, or STEMI) will also be clearly defined. The time from first medical contact to balloon inflation (FMC-to-balloon) and door-to-ballon time will be registered. In-hospital death and complications will be registered. Data on the post-hospital primary outcome (MACE: cardiac death, all-cause mortality, hospitalization, stroke, need for coronary revascularization) of patients, at 30 days and 1 year, will be included in the registry.

Heart failure (HF) represents a serious clinical and public cause of mortality, morbidity, as well as healthcare expenditures. Guidelines for treatment of HF join in recommending multimedical regimen at targeted doses as the best medical strategy, despite that a significant percentage of patients remain symptomatic. Studies have shown that these patients might benefit from cardiac resynchronization therapy (CRT), particularly those presenting with broad QRS duration, >135 msec. Trials have already shown that CRT results in improved morbidity and survival of these patients particularly those in New York Heart Association class III-IV HF, but almost 30% do not show any symptomatic or survival benefit, hence are classified as nonresponders. Exhaustive efforts have been made in using noninvasive methods of assessing left ventricle (LV) dyssynchrony in predicting nonresponders to CRT, including Doppler echocardiography, magnetic resonance imaging, and even single photon emission computed tomography analysis, but only with modest success. In this report, we aimed to review the available evidence for assessing markers of mechanical LV dyssynchrony by various echocardiographic modalities and their respective strength in predicting favorable response to CRT treatment, comparing global with segmental ones. While the accuracy of segmental markers of dyssynchrony in predicting satisfactory response to CRT remains controversial because of various technical limitations, global markers seem easier to measure, reproducible, and potentially accurate in reflecting overall cavity response and its clinical implications. More studies are needed to qualify this proposal.

BACKGROUND: In-stent restenosis (ISR) remains an important concern despite the recent advances in the drug-eluting stent (DES) technology. The introduction of drug-eluting balloons (DEB) offers a good solution to such problem.

OBJECTIVES: We performed a meta-analysis to assess the clinical efficiency and safety of DEB compared with DES in patients with DES-ISR.

METHODS: A systematic search was conducted and all randomized and observational studies which compared DEB with DES in patients with DES-ISR were included. The primary outcome measure-major adverse cardiovascular events (MACE)-as well as individual events as target lesion revascularization (TLR), stent thrombosis (ST), myocardial infarction (MI), cardiac death (CD) and all-cause mortality, were analyzed.

RESULTS: Three randomized and 4 observational studies were included with a total of 2052 patients. MACE (relative risk [RR]=1.00, 95% confidence interval (CI) 0.68 to 1.46, P=0.99), TLR (RR=1.15 [CI 0.79 to 1.68], P=0.44), ST (RR=0.37[0.10 to 1.34], P=0.13), MI (RR=0.97 [0.49 to 1.91], P=0.93) and CD (RR=0.73 [0.22 to 2.45], P=0.61) were not different between patients treated with DEB and with DES. However, all-cause mortality was lower in patients treated with DEB (RR=0.45 [0.23 to 0.87, P=0.019) and in particular when compared to only first generation DES (RR 0.33 [0.15-0.74], P=0.007). There was no statistical evidence for publication bias.

CONCLUSIONS: The results of this meta-analysis showed that DEB and DES have similar efficacy and safety for the treatment of DES-ISR.

Introduction: Despite the recent findings in randomized clinical trials (RCTs) with limited sample sizes and the updates in clinical guidelines, the current available data for the complete revascularization (CR) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) at the time of primary percutaneous coronary intervention (PCI) are still contradictory.

Aim: The aim of this meta-analysis of the existing RCTs was to assess the efficacy of the CR versus revascularization of infarct-related artery (IRA) only during primary PCI in patients with STEMI and multivessel disease (MVD).

Patients and methods: We searched PubMed, MEDLINE, Embase, Scopus, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases aiming to find RCTs for patients with STEMI and MVD which compared CR with IRA-only. Random effect risk ratios (RRs) were calculated for efficacy and safety outcomes.

Results: Ten RCTs with 3291 patients were included. The median follow-up duration was 17.5 months. Major adverse cardiac events (RR=0.57; 0.43-0.76; P<0.0001), cardiac mortality (RR=0.52; 0.31-0.87; P=0.014), and repeat revascularization (RR=0.50; 0.30-0.84; P=0.009) were lower in CR compared with IRA-only strategies. However, there was no significant difference in the risk of all-cause mortality, recurrent nonfatal myocardial infarction, stroke, major bleeding events, and contrast-induced nephropathy.

Conclusion: For patients with STEMI and MVD undergoing primary PCI, the current evidence suggests that the risk of major adverse cardiac events, repeat revascularization, and cardiac death is reduced by CR. However, the risk for all-cause mortality and PCI-related complications is not different from the isolated culprit lesion-only treatment. Although these findings support the cardiac mortality and safety benefit of CR in stable STEMI, further large trials are required to provide better guidance for optimum management of such patients.

Aim The aim of this study was to investigate the impact of gender on the prediction of limited exercise capacity in heart failure (HF) patients assessed by 6 minute walk test (6-MWT).

Methods In 147 HF patients (mean age 61 ± 11 years, 50.3% male), a 6-MWT and a Doppler echocardiographic study were performed in the same day. Conventional cardiac measurements were obtained and global LV dyssynchrony was indirectly assessed using total isovolumic time − t-IVT [in s/min; calculated as: 60 − (total ejection time − total filling time)] and Tei index (t-IVT/ejection time). Patients were divided into two groups according to gender, which were again divided into two subgroups based on the 6-MWT distance (Group I: ≤ 300 m, and Group II: > 300 m).

Results Female patients were younger (p = 0.02), and had higher left ventricular (LV) ejection fraction — EF (p = 0.007) but with similar 6-MWT distance to male patients (p = 68). Group I male patients had lower hemoglobin level (p = 0.02) and lower EF (p = 0.03), compared with Group II, but none of the clinical or echocardiographic variables differed between groups in female patients. In multivariate analysis, only t-IVT [0.699 (0.552–0.886), p = 0.003], and LV EF [0.908 (0.835–0.987), p = 0.02] in males, and NYHA functional class [4.439 (2.213–16.24), p = 0.02] in females independently predicted poor 6-MWT distance (< 300 m).

Conclusion Despite similar limited exercise capacity, gender determines the pattern of underlying cardiac disturbances; ventricular dysfunction in males and subjective NYHA class in female heart failure patients.

Background and Aim. Total isovolumic time (t-IVT) and Tei index both reflect global left ventricular (LV) dyssynchrony. They have been shown to be sensitive in responding to myocardial revascularization and in predicting clinical outcome in heart failure patients. Since most these patients are senior, determining the exact effect of age on such parameters remains mandatory. The aim of this study was to investigate the effect of age on LV t-IVT and Tei index compared with conventional systolic and diastolic parameters in normal individuals.

Methods. We studied 47 healthy individuals, mean age 62±12 years (24 female), who were arbitrarily classified into three groups: M (middle age), S (seniors), and E (elderly), using spectral Doppler echocardiography and tissue-Doppler imaging. We studied the interrelation between age, LV systolic and diastolic function parameters as well as t-IVT [60 – (total ejection time + total filling time) in s/min], and Tei index (T-IVT/ejection time).

Results. LV ejection fraction was 68±6%, E/A ratio 1±0.4, filling time 538±136ms, ejection time 313±26ms, t-IVT 7.7±2.6 s/min and Tei index 0.41±0.14. Age strongly correlated with t-IVT (r=0.8, p<0.001) and with Tei index (r=0.7, p<0.001) but not with QRS duration. Age also correlated with E/A ratio (r=-0.6, p<0.001), but not with global or segmental systolic function measurements. Mean values for t-IVT were 5.5 (95% CI, 4.6-6.3 s/min) for M, 6.9 (95% CI, 6.0-7.8 s/min) for S and 9.5 (95% CI, 8.4-10.6 s/min) for E groups. The corresponding upper limit of the t-IVT 95% normal CI (calculated as mean ±2SD) for the three groups was 8.3 s/min, 10.5 s/min and 14.5 s/min, respectively. The upper limit of normal t-IVT 95% CI was significantly shorter in the S compared with the E group (p=0.001). T-IVT correlated with A wave (r=0.66, p<0.001), E/A ratio (r=-0.56, p<0.001), septal e’ (r=-0.49, p=0.001) and septal a’ (r=0.4, p=0.006), but not with QRS.

Conclusions. In normals, age is associated with exaggerated LV global dyssynchrony and diastolic function disturbances, but systolic function remains unaffected. The strong relationship between age and t-IVT supports its potential use as a marker of global LV dyssynchrony. In addition, variations in the upper limit of normal values, particularly in the elderly may have significant clinical applications in patients recommended for CRT treatment.

Recent European Society of Cardiology and American Heart Association/American College of Cardiology Guidelines did not recommend biomarker-guided therapy in the management of heart failure (HF) patients. Combination of echo- and B-type natriuretic peptide (BNP) may be an alternative approach in guiding ambulatory HF management. Our aim was to determine whether a therapy guided by echo markers of left ventricular filling pressure (LVFP), lung ultrasound (LUS) assessment of B-lines, and BNP improves outcomes of HF patients. Consecutive outpatients with LV ejection fraction (EF) <= 50% have been prospectively enrolled. In Group I (n=224), follow-up was guided by echo and BNP with the goal of achieving E-wave deceleration time (EDT) >= 150 ms, tissue Doppler index E/e' < 13, B-line numbers < 15, and BNP <= 125 pg/ml or decrease > 30%; in Group II (n=293), follow-up was clinically guided, while the remaining 277 patients (Group III) did not receive any dedicated follow-up. At 60 months, survival was 88% in Group I compared to 75% in Group II and 54% in Group III (chi(2) 53.5; p<0.0001). Survival curves exhibited statistically significant differences using Mantel-Cox analysis. The number needed to treat to spare one death was 7.9 (Group I versus Group II) and 3.8 (Group I versus Group III). At multivariate Cox regression analyses, major predictors of all-cause mortality were follow-up E/e' (HR: 1.05; p=0.0038) and BNP > 125 pg/ml or decrease <= 30% (HR: 4.90; p=0.0054), while BNP > 125 pg/ml or decrease <= 30% and B-line numbers >= 15 were associated with the combined end point of death and HF hospitalization. Evidence-based HF treatment guided by serum biomarkers and ultrasound with the goal of reducing elevated BNP and LVFP, and resolving pulmonary congestion was associated with better clinical outcomes and can be valuable in guiding ambulatory HF management.

Background and Aim: In patients undergoing diagnostic coronary angiography (CA) and percutaneous coronary interventions (PCI), the benefits associated with radial access compared with the femoral access approach remain controversial. The aim of this meta-analysis was to compare the short-term evidence-based clinical outcome of the two approaches. Methods: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) comparing radial versus femoral access for CA and PCI. We identified 34 RCTs with 29,352 patients who underwent CA and/or PCI and compared 14,819 patients randomized for radial access with 14,533 who underwent procedures using femoral access. The follow-up period for clinical outcome was 30 days in all studies. Data were pooled by meta-analysis using a fixed-effect or a random-effect model, as appropriate. Risk ratios (RRs) were used for efficacy and safety outcomes.Results: Compared with femoral access, the radial access was associated with significantly lower risk for all-cause mortality (RR: 0.74; 95% confidence interval (CI): 0.61 to 0.88; p = 0.001), major bleeding (RR: 0.53; 95% CI:0.43 to 0.65; p ˂ 0.00001), major adverse cardiovascular events (MACE)(RR: 0.82; 95% CI: 0.74 to 0.91; p = 0.0002), and major vascular complications (RR: 0.37; 95% CI: 0.29 to 0.48; p ˂ 0.00001). These results were consistent irrespective of the clinical presentation of ACS or STEMI. Conclusions: Radial access in patients undergoing CA with or without PCI is associated with lower mortality, MACE, major bleeding and vascular complications, irrespective of clinical presentation, ACS or STEMI, compared with femoral access.

AIM: To assess potential additional value of global left ventricular (LV) dyssynchrony markers in predicting cardiac resynchronization therapy (CRT) response in heart failure (HF) patients. METHODS: We included 103 HF patients (mean age 67 +/- 12 years, 83% male) who fulfilled the guidelines criteria for CRT treatment. All patients had undergone full clinical assessment, NT-proBNP and echocardiographic examination. Global LV dyssynchrony was assessed using total isovolumic time (t-IVT) and Tei index. On the basis of reduction in the NYHA class after CRT, patients were divided into responders and non-responders. RESULTS: Prolonged t-IVT [0.878 (range, 0.802-0.962), p = 0.005], long QRS duration [0.978 (range, 0.960-0.996), p = 0.02] and high tricuspid regurgitation pressure drop [1.047 (range, 1.001-1.096), p = 0.046] independently predicted response to CRT. A t-IVT >= 11.6 s/min was 67% sensitive and 62% specifi c (AUC 0.69, p = 0.001) in predicting CRT response. Respective values for a QRS >= 151 ms were 66% and 62% (AUC 0.65, p = 0.01). Combining the two variables had higher specifi city (88%) in predicting CRT response. In atrial fibrillation (AF) patients, only prolonged t-IVT [0.690 (range, 0.509 -0.937), p = 0.03] independently predicted CRT response. CONCLUSION: Combining prolonged t-IVT and the conventionally used broad QRS duration has a significantly higher specifi city in identifying patients likely to respond to CRT. Moreover, in AF patients, only prolonged t-IVT independently predicted CRT response.

Background and Aim: Treatment of patients with left main coronary artery disease (LMCA) with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) remains controversial. The aim of this meta-analysis was to compare the long-term clinical outcomes of patients with unprotected LMCA treated randomly by PCI or CABG. Methods: PubMed, MEDLINE, Embase, Scopus, Google Scholar, CENTRAL and ClinicalTrials.gov database searches identified five randomized trials (RCTs) including 4499 patients with unprotected LMCA comparing PCI (n= 2249) vs. CABG (n= 2250), with a minimum clinical follow-up of five years. Random effect risk ratios were used for efficacy and safety outcomes. The study was registered in PROSPERO. The primary outcome was major adverse cardiac events (MACE), defined as a composite of death from any cause, myocardial infarction or stroke. Results: Compared to CABG, patients assigned to PCI had a similar rate of MACE (risk ratio (RR): 1.13; 95% CI: 0.94 to 1.36;p= 0.19), myocardial infarction (RR: 1.48; 95% CI: 0.97 to 2.25;p= 0.07) and stroke (RR: 0.87; 95% CI: 0.62 to 1.23;p= 0.42). Additionally, all-cause mortality (RR: 1.07; 95% CI: 0.89 to 1.28;p= 0.48) and cardiovascular (CV) mortality (RR: 1.13; 95% CI: 0.89 to 1.43;p= 0.31) were not different. However, the risk of any repeat revascularization (RR: 1.70; 95% CI: 1.34 to 2.15;p< 0.00001) was higher in patients assigned to PCI. Conclusions: The findings of this meta-analysis suggest that the long-term survival and MACE of patients who underwent PCI for unprotected LMCA stenosis were comparable to those receiving CABG, despite a higher rate of repeat revascularization.

Background and Aims: Myocardial infarction (MI) is a major cause of mortality worldwide, irrespective of its presentation as non-ST-segment elevation MI (NSTEMI) or ST-segment elevation MI (STEMI). The objective of this study was to assess national results of management and clinical outcome of acute MI patients in Kosovo.

Methods: This cross-sectional descriptive study, conducted at the Clinic of Cardiology of the University Clinical Center of Kosovo, in Prishtina, included all patients hospitalized with acute MI over a period of 7 years (2014-2020). The primary outcome of the study was in-hospital mortality.

Results: Among 7353 admitted patients with acute MI (mean age 63 ± 12 years, 29% female) and according to the final diagnosis, 4436 (59.4%) patients had STEMI, and 2987 (40.6%) NSTEMI. More patients with STEMI received primary percutaneous intervention (PPCI) than those with NSTEMI (50% vs. 41%, p < 0.001). In-hospital mortality was higher in no PPCI patients compared to PPCI both in NSTEMI (10.7% vs. 2.6%, p < 0.001) and STEMI (20.9% vs. 6.8%, p < 0.001). Age ≥65 years [0.399 (0.267–0.597), p ˂ 0.001], hemoglobin level [0.889 (0.815–0.970), p = 0.008], STEMI [0.491 (0.343–0.704), p ˂ 0.001], lack of PPCI [2.636 (1.798–3.866), p ˂ 0.001], cardiogenic shock [0.002 (0.001–0.006), p < 0.001], reduced left ventricular ejection fraction (LV EF) [0.966 (0.951–0.980), p < 0.001], and heart rate at admission [1.009 (1.000–1.017), p = 0.047], independently predicted mortality. In STEMI, cardiogenic shock (p ˂ 0.001), lack of PPCI (p = 0.006), female gender (p = 0.01), and low LV EF (p = 0.04) predicted mortality but age ≥65 years (p = 0.02), female gender (p = 0.02), low LV EF (p = 0.007), and low hemoglobin (p = 0.04) predicted mortality in NSTEMI.

Conclusion: Between 2014 and 2020, half of patients with acute MI were not treated with PPCI, who had high mortality, particularly when presenting with STEMI. Age, cardiogenic shock, anemia, low LV EF, STEMI and no PPCI independently predicted mortality. Cardiogenic shock and lack of PPCI independently predicted mortality, only in STEMI.

BACKGROUND: Quality of life is as important as survival in heart failure (HF) patients. Controversies exist with regards to echocardiographic determinants of exercise capacity in HF, particularly in patients with preserved ejection fraction (HFpEF). The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional exercise capacity assessed by 6 min walk test (6-MWT) in patients with HFpEF.

METHODS: In 111 HF patients (mean age 63 ± 10 years, 47% female), an echo-Doppler study and a 6-MWT were performed in the same day. Patients were divided into two groups based on the 6-MWT distance (Group I: ≤ 300 m and Group II: >300 m).

RESULTS: Group I were older (p = 0.008), had higher prevalence of diabetes (p = 0.027), higher baseline heart rate (p = 0.004), larger left atrium - LA (p = 0.001), longer LV filling time - FT (p = 0.019), shorter isovolumic relaxation time (p = 0.037), shorter pulmonary artery acceleration time - PA acceleration time (p = 0.006), lower left atrial lateral wall myocardial velocity (a') (p = 0.018) and lower septal systolic myocardial velocity (s') (p = 0.023), compared with Group II. Patients with HF and reduced EF (HFrEF) had lower hemoglobin (p = 0.007), higher baseline heart rate (p = 0.005), higher NT-ProBNP (p = 0.001), larger LA (p = 0.004), lower septal s', e', a' waves, and septal mitral annular plane systolic excursion (MAPSE), shorter PA acceleration time (p < 0.001 for all), lower lateral MAPSE, higher E/A & E/e', and shorter LVFT (p = 0.001 for all), lower lateral e' (p = 0.009), s' (p = 0.006), right ventricular e' and LA emptying fraction (p = 0.012 for both), compared with HFpEF patients. In multivariate analysis, only LA diameter [2.676 (1.242-5.766), p = 0.012], and diabetes [0.274 (0.084-0.898), p = 0.033] independently predicted poor 6-MWT performance in the group as a whole. In HFrEF, age [1.073 (1.012-1.137), p = 0.018] and LA diameter [3.685 (1.348-10.071), p = 0.011], but in HFpEF, lateral s' [0.295 (0.099-0.882), p = 0.029], and hemoglobin level [0.497 (0.248-0.998), p = 0.049] independently predicted poor 6-MWT performance.

CONCLUSIONS: In HF patients determinants of exercise capacity differ according to severity of overall LV systolic function, with left atrial enlargement in HFrEF and longitudinal systolic shortening in HFpEF as the the main determinants.

Structural and functional cardiac changes are known in obese adults. We aimed to assess the relationship between body mass index (BMI) and cardiac function in overweight and obese asymptomatic adolescents. Ninety three healthy adolescents, aged 12.6±1.2years, received weight, height, BMI, waist, hips, waist/hips ratio assessment, hematology and biochemistry tests and an echocardiogram. Based on BMI, subjects were divided into: lean (L, n=32), overweight (Ov, n=33) and obese (Ob, n=32). Interventricular septal and LV posterior wall thickness were increased parallel to the BMI (L: 0.84±0.1cm, Ov: 0.88±0.1cm, Ob: 0.96±0.1cm, p<0.001, and L: 0.78±0.1cm, Ov: 0.8±0.1cm, Ob: 0.94±0.1cm, p<0.001, respectively) as were relative wall thickness (RWT) and mass index (LVMI) (L: 0.34±0.05, Ov: 0.34±0.05, Ob: 0.40±0.04, p<0.001, and L: 47.7±8.4g/m(2), Ov: 51.9±8.3g/m(2), Ob: 65.2±13.3g/m(2), p=0<001, respectively). LV early diastolic (E') lateral and septal velocities (L: 15.3±3.9cm/s, Ov: 13.6±4cm/s, Ob: 10.5±3.4cm/s, p<0.001, and L: 12.2±2.3cm/s, Ov: 11.1±2.4cm/s, Ob: 9.8±3.1cm/s, p=0.003, respectively), and systolic (S') velocities (L: 9.2±1.4cm/s, Ov: 9.3±2.3cm/s, Ob: 8.04±1.5cm/s, p=0.018, and L: 9.05±2.3cm/s, Ov: 9±2.4cm/s, Ob: 7.6±1.1cm/s, p=0.014, respectively) were all reduced, only in obese adolescents. LV lateral E' (r=-0.44, p<0.001) and S' (r=-0.29, p=0.005) correlated with BMI. In asymptomatic adolescents, LV wall is thicker and diastolic function impaired and correlate with BMI. These findings demonstrate early cardiac functional disturbances which might explain the known obesity risk for cardiac disease.

Background and Aim. The Metabolic Syndrome (MetS) has been shown to be independently associated with increased risk for incident heart failure (HF) and coronary artery disease. The aim of this study was to investigate the additional effect of MetS on LA dysfunction in a group of patients with HF and preserved ejection fraction (HFpEF) and its relationship with symptoms.

Methods. This study included 194 consecutive patients (age 62 ± 9 years) with stable HFpEF. LV dimensions, ejection fraction (EF), mitral annulus peak systolic excursion (MAPSE), myocardial velocities (s’, e’ and a’), LA dimensions and volumes were measured. Total LA emptying fraction (LA EF) was measured by Simpson rule volumes. Based on the NCEP-ATP III criteria, patients were divided into two groups; MetS (n=95) and non-MetS (n=108) and were compared with 34 age and gender matched controls.

Results. Age and gender were not different between patients and control neither between MetS and non-Met. LV dimensions, EF and longitudinal function indices were also not different. The MetS patients had higher LV mass index (p=0.038), lower septal and lateral e’ (p=0.003 and p=0.001, respectively) velocities, larger LA minimal volume (p=0.007) and lower LA EF (p<0.001) compared with the non-MetS patients. Age, LA EF and MetS independently predicted the NYHA class.

Conclusions. Despite no difference in LV systolic function, patients with HFpEF and MetS have worse LA emptying fraction, compared with HFpEF and non-MetS patients. In addition, LA reservoir function impairment and MetS independently predict patients limiting symptoms, thus add to a better understanding of HFpEF.

Background and Aim: Type 2 diabetes mellitus (T2DM) is a known risk factor in patients with heart failure (HF), but its impact on phenotypic presentations remains unclear. This study aimed to prospectively examine the relationship between T2DM and functional exercise capacity, assessed by the 6-min walk test (6-MWT) in chronic HF.

Methods: We studied 344 chronic patients with HF (mean age 61 ± 10 years, 54% female) in whom clinical, biochemical, and anthropometric data were available and all patients underwent an echo-Doppler study and a 6-MWT on the same day. The 6-MWT distance divided the cohort into; Group I: those who managed ≤ 300 m and Group II: those who managed >300 m. Additionally, left ventricular (LV) ejection fraction (EF), estimated using the modified Simpson's method, classified patients into HF with preserved EF (HFpEF) and HF with reduced EF (HFrEF).

Results: The results showed that 111/344 (32%) patients had T2DM, who had a higher prevalence of arterial hypertension (p = 0.004), higher waist/hips ratio (p = 0.041), higher creatinine (p = 0.008) and urea (p = 0.003), lower hemoglobin (p = 0.001), and they achieved shorter 6-MWT distance (p < 0.001) compared with those with no T2DM. Patients with limited exercise (<300 m) had higher prevalence of T2DM (p < 0.001), arterial hypertension (p = 0.004), and atrial fibrillation (p = 0.001), higher waist/hips ratio (p = 0.041), higher glucose level (p < 0.001), lower hemoglobin (p < 0.001), larger left atrium (LA) (p = 0.002), lower lateral mitral annular plane systolic excursion (MAPSE) (p = 0.032), septal MAPSE (p < 0.001), and tricuspid annular plane systolic excursion (TAPSE) (p < 0.001), compared with those performing >300 m. In the cohort as a whole, multivariate analysis, T2DM (p < 0.001), low hemoglobin (p = 0.008), atrial fibrillation (p = 0.014), and reduced septal MAPSE (p = 0.021) independently predicted the limited 6-MWT distance. In patients with HFpEF, diabetes [6.083 (2.613–14.160), p < 0.001], atrial fibrillation [6.092 (1.769–20.979), p = 0.002], and septal MAPSE [0.063 (0.027–0.184), p = 0.002], independently predicted the reduced 6-MWT, whereas hemoglobin [0.786 (0.624–0.998), p = 0.049] and TAPSE [0.462 (0.214–0.988), p = 0.041] predicted it in patients with HFrEF.

Conclusion: Predictors of exercise intolerance in patients with chronic HF differ according to LV systolic function, demonstrated as EF. T2DM seems the most powerful predictor of limited exercise capacity in patients with HFpEF.

Background: The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins’ prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF.

Methods: We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization.

Results: Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72–0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76–0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69–0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68–0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69–0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79–0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77–0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64–0.99, P = 0.04 and HR 0.76 95% CI: 0.61–0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies’ analyses; the effect was also larger and significant for lipophilic than hydrophilic statins.

Conclusions: In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure.

Background and Aim: Dobutamine stress echocardiography (DSE) is a well-established noninvasive investigation for significant coronary artery disease (CAD). The aim of this study was to evaluate the accuracy of cardiac Doppler parameters in predicting CAD.

Methods: We prospectively studied 103 consecutive patients with suspected CAD based on typical symptoms; 59 proved to have CAD, and 44 patients proved to have no-CAD (n = 44). All patients underwent a complete stress Doppler echocardiographic examination. Total isovolumic time (T-IVT) as a marker of cavity dyssynchrony and wall motion score index (WMSI) were also calculated.

Results: At peak dobutamine stress, the compromised LV longitudinal excursion (MAPSE), systolic septal and lateral velocities (s’), and diastolic indices were more pronounced in the CAD patients compared with those without CAD, but LV dimension did not differ between groups (p > 0.05). The WMSI was higher and t-IVT more prolonged in patients with CAD (p < 0.01 for both). Similarly, the changes were more pronounced in patients with significant CAD compared with insignificant CAD. On multivariate model, Δ mean s’, OR 2.016 (1.610 to 3.190; p < 0.001), Δ E velocity OR 2.502 (1.179 to 1.108; p < 0.001), Δ t-IVT 2.206 (1.180 to 2.780; p < 0.001) and Δ WMSI OR 1.911 (1.401 to 3.001; p = 0.001) were the most powerful independent predictors of the presence of CAD, particularly when significant (>75%). Δ mean s’ < 5.0 was 85% sensitive, 89% specific with AUC 0.92. Respective values for Δ E velocity <6.0 cm/s were 82%, 90% and 0.91; for Δ t-IVT > 4.5, 78%, 77% and 0.81 and for Δ FT ≥ 150 ms, 76%, 78% and 0.84 in predicating significant CAD. WMSI ≥ 0.7 was 75% sensitive, 77% specific with AUC of 0.81 in predicting significant CAD. The accuracy of DSE was higher in significant CAD compared to insignificant CAD (80% vs. 74%; p = 0.03).

Conclusions: Compromised LV longitudinal systolic function, lower delta E wave, prolonged t-IVT, and increased WMSI were the most powerful independent predictors of the presence and significance of CAD. These finding strengthen the role of comprehensive DSE analysis in diagnosing ischemic disturbances secondary to significant CAD.

Background and Aim: Predictors of exercise capacity in heart failure (HF) with preserved ejection fraction (HFpEF) remain of difficult determination. The aim of this study was to identify predictors of exercise capacity in a group of patients with HFpEF and right ventricle (RV) dysfunction

Methods: In 143 consecutive patients with HFpEF (age 62 ± 9 years, LV EF ≥45) and 41 controls, a complete echocardiographic study was performed. In addition to conventional measurements, LA compliance was calculated using the formula: [LAV max − LAV min/LAV min × 100]. Exercise capacity was assessed using the six‐minute walking test (6‐MWT). Tricuspid annular plane systolic excursion (TAPSE) < 1.7 cm was utilized to categorize patients with RV dysfunction (n = 40) from those with maintained RV function (n = 103).

Results: Patients with RV dysfunction were older (P = 0.002), had higher NYHA class (P = 0.001), higher LV mass index (P = 0.01), reduced septal and lateral MAPSE (all P < 0.001), enlarged LA (P = 0.001) impaired LA compliance index (P < 0.001) and exhibited a more compromised 6‐MWT (P = 0.001). LA compliance index correlated more closely with 6‐MWT (r = 0.51, P < 0.001) compared with the other LA indices (AP diameter, transverse diameter and volume indexed; r = −0.30, r = −0.35 and r = −0.38, respectively). In multivariate analysis, LA compliance index <60% was 88% sensitive and 61% specific (AUC 0.80, CI = 0.67–0.92 P = 0.001) in predicting exercise capacity.

Conclusion: An impairment in LA compliance was profound in patients with HFpEF and RV dysfunction and seems to be most powerful independent predictor of limited exercise capacity.

Cardiac resynchronization therapy (CRT) is associated with reverse left atrial (LA) remodeling. The aim of this meta-analysis was to assess the relationship between clinical response to CRT and LA function changes. We conducted a systematic search of all electronic databases up to September 2019 which identified 488 patients from seven studies. At (mean) 6 months follow-up, LA systolic strain and emptying fraction (EF) were increased in CRT responders, with a -5.70% weighted mean difference (WMD) [95% confidence interval (CI) -8.37 to -3.04, p < 0.001 and a WMD of -8.98% [CI -15.1 to -2.84, p = 0.004], compared to non-responders. The increase in LA strain was associated with a fall in left ventricle (LV) end-systolic volume (LVESV) r = -0.56 (CI -0.68 to -0.40, p < 0.001) and an increase in the LV ejection fraction (LVEF) r = 0.58 (CI 0.42 to 0.69, p < 0.001). The increase in LA EF correlated with the fall in LVESV r = -0.51 (CI -0.63 to -0.36, p < 0.001) and the increase in the LVEF r = 0.48 (CI 0.33 to 0.61, p = 0.002). The increase in LA strain correlated with the increase in the LA EF, r = 0.57 (CI 0.43 to 0.70, p < 0.001). Thus, the improvement of LA function in CRT responders reflects LA reverse remodeling and is related to its ventricular counterpart.

Aims: Inflammation plays a central role in the pathogenesis and clinical manifestations of atherosclerosis. Randomized controlled trials have investigated the potential benefit of colchicine in reducing cardiovascular (CV) events in patients with coronary artery disease (CAD) but produced conflicting results. The aim of this meta-analysis was to evaluate the efficacy and safety of colchicine in patients with CAD.

Methods: We systematically searched selected electronic databases from inception until 10 December 2020. Primary clinical endpoints were: major adverse cardiac events; all-cause mortality; CV mortality; recurrent myocardial infarction; stroke; hospitalization; and adverse medication effects. Secondary endpoints were short-term effect of colchicine on inflammatory markers.

Results: Twelve randomized controlled trials with a total of 13 073 patients with CAD (colchicine n = 6351 and placebo n = 6722) were included in the meta-analysis. At mean follow-up of 22.5 months, the colchicine group had lower risk of major adverse cardiac events (6.20 vs. 8.87%; P <.001), recurrent myocardial infarction (3.41 vs. 4.41%; P =.005), stroke (0.40 vs. 0.90%; P =.002) and hospitalization due to CV events (0.90 vs. 2.87%; P =.02) compared to the control group. The 2 patient groups had similar risk for all-cause mortality (2.08 vs. 1.88%; P =.82) and CV mortality (0.71 vs. 1.01%; P =.38). Colchicine significantly reduced high-sensitivity C-reactive protein (−4.25, P =.001) compared to controls but did not significantly affect interleukin (IL)-β1 and IL-18 levels.

Conclusion: Colchicine reduced CV events and inflammatory markers, high-sensitivity C-reactive protein and IL-6, in patients with coronary disease compared to controls. Its impact on cardiovascular and all-cause mortality requires further investigation.

Aim: We aimed in this study to assess the role of left atrial (LA), in addition to left ventricular (LV) indices, in predicting exercise capacity in patients with heart failure (HF). Methods: This study included 88 consecutive patients (60 ± 10 years) with stable HF. LV end-diastolic and end-systolic dimensions, ejection fraction (EF), mitral and tricuspid annulus peak systolic excursion (MAPSE and TAPSE), myocardial velocities (s′, e′ and a′), LA dimensions, LA volume and LA emptying fraction were measured. A 6-min walking test (6-MWT) distance was performed on the same day of the echocardiographic examination. Results: Patients with limited exercise performance (≤ 300 m) were older (p = 0.01), had higher NYHA functional class (p = 0.004), higher LV mass index (p = 0.003), larger LA (p = 0.002), lower LV EF (p = 0.009), larger LV end-systolic dimension (p = 0.007), higher E/A ratio (p = 0.03), reduced septal MAPSE (p < 0.001), larger LA end-systolic volume (p = 0.03), larger LA end-diastolic volume (p = 0.005) and lower LA emptying fraction (p < 0.001) compared with good performance patients. In multivariate analysis, only the LA emptying fraction [0.944 (0.898–0.993), p = 0.025] independently predicted poor exercise performance. An LA emptying fraction < 60% was 68% sensitive and 73% specific (AUC 0.73, p < 0.001) in predicting poor exercise performance. Conclusion: In heart failure patients, the impaired LA emptying function is the best predictor of poor exercise capacity. This finding highlights the need for routine LA size and function monitoring for better optimization of medical therapy in HF.

Background: The aim of this study was to investigate the relationship between diabetes mellitus (DM) and left atrial (LA) remodelling in a group of patients with heart failure and reduced ejection fraction (HFrEF), and their combined impact on cardiac events (CE).

Methods: This study included 136 consecutive HFrEF patients (65 +/- 11 years), 36 had DM, and 86 had increased LA stiffness (LASt). All patients underwent complete conventional and tissue Doppler echocardiographic measurements were made including LA volumes and function. LASt was calculated using the formula: LASt = E/e' ratio / PALS.

Results: At 55 +/- 37 months follow-up, free survival from CE was 69% in patients without DM and 44.4% in those with DM (p < .0001). The CE free survival was lower in patients with increased LASt compared to normal LASt, (50 versus. 80%, p < .001), irrespective of the presence of DM (27 versus. 71%, p < .001).The best cut-off value of LASt for predicting CE in the group as a whole was >= 0.82% [81% sensitivity, 72% specificity and AUC 0.82 (p < .001)]. LASt >= 0.82% also predicted CE in no DM patients [78% sensitivity, 71% specificity and AUC 0.80 (p < .001)] and was a stronger predictor in DM patients [85% sensitivity, 71% specificity and AUC = 0.847 (p < .001)].

Conclusion: High LA stiffness is associated with poor clinical outcome in patients with HFrEF. Diabetes has an additional incremental value in determining clinical outcome in those patients.

Background and Aim: Left atrial stiffness (LASt) is an important marker of cardiac function, especially in patients with heart failure (HF); it explains symptoms on the basis of pressure transfer to the pulmonary circulation. The aim of this study was to evaluate the relationship between LASt and cardiac events (CE) in HF patients with reduced to mid-range ejection fraction.

Methods: The study included 215 consecutive ambulatory HF patients with ejection fraction (EF) < 50% (162 HF reduced EF and 53 HF mid-range EF) of mean age 66 +/- 11 years and 24.4% females. Peak LA strain (PALS) was measured by speckle tracking echocardiography and E/e' recorded from the apical four-chamber view. Non-invasive LASt was calculated using the equation: LASt = E/e' ratio/PALS. Documented cardiac events (CE) were HF hospitalization and cardiac death.

Results: During a median follow up of 41 +/- 34 months, 65 patients (30%) had CE. In multivariate analysis model, only raised LV filling pressure (E/e') (OR = 0.292, (95% CI 0.099 to 0.859), p = 0.02), peak pulmonary artery pressure (PAP) (OR = 1.050 (1.009 to 1.094), p = 0.01), PALS (OR = 0.932 (0.873 to 0.994), p = 0.02) and LASt (OR = 3.781 (1.144 to 5.122), p = 0.001) independently predicted CE. LASt >= 0.76% was the most powerful predictor of CE, with 80% sensitivity and 73% specificity (AUC 0.82, CI = 0.73 to 0.87, p < 0.001) followed by PALS <= 16%, with 74% sensitivity and 72% specificity (AUC 0.77, CI = 0.71 to 0.84, p < 0.001). These results were consistent irrespective of EF (p < 0.05).

Conclusion: In this cohort of ambulatory HFrEF and HFmrEF patients, LASt proved the most powerful predictor of clinical outcome.

Aim: This meta-analysis assesses left atrial (LA) cavity and myocardial function measurements that predict pulmonary capillary wedge pressure (PCWP).

Methods: PubMed-MEDLINE, EMBASE, Scopus, Google Scholar and the Cochrane Central Registry were searched up to December 2018 for studies on the relationship of LA diameter, LA indexed volume (LAVI max, LAVI min), peak atrial longitudinal (PALS), peak atrial contraction (PACS) strain and total emptying fraction (LAEF) with PCWP. Eighteen studies with 1343 patients were included. sensitivity and specificity (with 95% CI) for evaluation of diagnostic accuracy and the best cut-off values for different LA indices in predicting raised PCWP were estimated using summary receiver operating characteristic analysis.

Results: The pooled analysis showed association between PCWP and LA diameter: Cohen's d = 0 center dot 87, LAVI max: d = 0 center dot 92 and LAVI min: d = 1 center dot 0 (P<0 center dot 001 for all). A stronger correlation was found between PCWP and PALS: d = 1 center dot 26, and PACS: d = 1 center dot 62, total EF d = 1 center dot 22 (P<0 center dot 0001 for all). PALS <= 19% had a summary sensitivity of 80% (65-90) and summary specificity of 77% (52-92), positive likelihood ratio (LR+) 3 center dot 74, negative likelihood ratio (LR-) DOR > 15 center dot 1 whereas LAVI >= 34 ml m(-2) had summary sensitivity of 75% (55-89) and summary specificity 77% (57-90), with LR+ >3, LR- 0 center dot 32 and DOR >10 center dot 1.

Conclusions: Compromised LA myocardial function and increased size predict raised cavity pressure. These results should assist in optimum follow-up of patients with fluctuating LA pressure.

(1) Background and Aim: Conflicting evidence exists regarding the benefits of percutaneous coronary intervention (PCI) on survival and symptomatic relief of patients with chronic coronary syndrome (CCS) compared with optimal medical therapy (OMT). This meta-analysis is to evaluate the short- and long-term clinical benefit of PCI over and above OMT in CCS. (2) Methods: Main endpoints were major adverse cardiac events (MACEs), all-cause mortality, cardiovascular (CV) mortality, myocardial infarction (MI), urgent revascularization, stroke hospitalization, and quality of life (QoL). Clinical endpoints at very short (≤3 months), short- (<12 months), and long-term (≥ 12 months) follow-up were evaluated. (3) Results: Fifteen RCTs with a total of 16,443 patients with CCS (PCI n = 8307 and OMT n = 8136) were included in the meta-analysis. At mean follow-up of 27.7 months, the PCI group had similar risk of MACE (18.2 vs. 19.2 %; p < 0.32), all-cause mortality (7.09 vs. 7.88%; p = 0.56), CV mortality (8.74 vs. 9.87%; p = 0.30), MI (7.69 vs. 8.29%; p = 0.32), revascularization (11.2 vs. 18.3%; p = 0.08), stroke (2.18 vs. 1.41%; p = 0.10), and hospitalization for anginal symptoms (13.5 vs. 13.9%; p = 0.69) compared with OMT. These results were similar at short- and long-term follow-up. At the very short-term follow-up, PCI patients had greater improvement in the QoL including physical limitation, angina frequency, stability, and treatment satisfaction (p < 0.05 for all) but such benefits disappeared at the long-term follow-up. (4) Conclusions: PCI treatment of CCS does not provide any long-term clinical benefit compared with OMT. These results should have significant clinical implications in optimizing patient's selection for PCI treatment.

Chronic heart failure (HF) is an important public health problem and is associated with high morbidity, high mortality, and considerable healthcare costs. More than 90% of hospitalizations due to worsening HF result from elevations of left ventricular (LV) filling pressures and fluid overload, which are often accompanied by the increased synthesis and secretion of natriuretic peptides (NPs). Furthermore, persistently abnormal LV filling pressures and a rise in NP circulating levels are well known indicators of poor prognosis. Frequent office visits with the resulting evaluation and management are most often needed. The growing pressure from hospital readmissions in HF patients is shifting the focus of interest from traditionally symptom-guided care to a more specific patient-centered follow-up care based on clinical findings, BNP and echo. Recent studies supported the value of serial NP measurements and Doppler echocardiographic biomarkers of elevated LV filling pressures as tools to scrutinize patients with impending clinically overt HF. Therefore, combination of echo and pulsed-wave blood-flow and tissue Doppler with NPs appears valuable in guiding ambulatory HF management, since they are potentially useful to distinguish stable patients from those at high risk of decompensation.

Background: The long COVID-19 syndrome has been recently described and some reports have suggested that acute pericarditis represents important manifestation of long COVID-19 syndrome. The aim of this study was to identify the prevalence and clinical characteristics of patients with long COVID-19, presenting with acute pericarditis.

Methods: We retrospectively included 180 patients (median age 47 years, 62% female) previously diagnosed with COVID-19, exhibiting persistence or new-onset symptoms ≥12 weeks from a negative naso-pharyngeal SARS CoV2 swamp test. The original diagnosis of COVID-19 infection was determined by a positive swab. All patients had undergone a thorough physical examination. Patients with suspected heart involvement were referred to a complete cardiovascular evaluation. Echocardiography was performed based on clinical need and diagnosis of acute pericarditis was achieved according to current guidelines.

Results: Among the study population, shortness of breath/fatigue was reported in 52%, chest pain/discomfort in 34% and heart palpitations/arrhythmias in 37%. Diagnosis of acute pericarditis was made in 39 patients (22%). Mild-to-moderate pericardial effusion was reported in 12, while thickened and bright pericardial layers with small effusions (< 5 mm) with or without comet tails arising from the pericardium (pericardial B-lines) in 27. Heart palpitations/arrhythmias (OR:3.748, p = 0.0030), and autoimmune disease and allergic disorders (OR:4.147, p = 0.0073) were independently related to the diagnosis of acute pericarditis, with a borderline contribution of less likelihood of hospitalization during COVID-19 (OR: 0.100, p = 0.0512).

Conclusion: Our findings suggest a high prevalence of acute pericarditis in patients with long COVID-19 syndrome. Autoimmune and allergic disorders, and palpitations/arrhythmias were frequently associated with pericardial disease.

Introduction: Ventricular septal defect (VSD) is one of the most common congenital cardiac anomalies. Patients with perimembranous VSD may have aortic regurgitation (AR) secondary to prolapse of the aortic cusp.

Case presentation: We present a case of 23-year-old White man with VSD, AR and ascending aortic aneurysm. The patient presented to outpatient clinic with weakness and gradual worsening shortness of breath for the past 5 years. Clinical examination revealed regular heart rhythm and loud continuous systolic-diastolic murmur (Lewin’s grade 6/6), heard all over the precordium, associated with a palpable thrill. The ECG showed right axis deviation, fractionated QRS in V1 and signs of biventricular hypertrophy. The chest X-ray showed cardiomegaly. Transthoracic and transesophageal echocardiograms showed a perimembranous VSD with moderate restrictive shunt (Qp/Qs = 1.6), aortic regurgitation (AR), and ascending aortic aneurysm. Other clinical and laboratory findings were within normal limits.

Conclusions: Perimembranous VSD, may be associated with aortic regurgitation and ascending aortic aneurysm as secondary phenomenon if it is not early diagnosed and successfully treated.