Single-Procedure Outcomes and Quality-of-Life Improvement 12 Months Post-Cryoballoon Ablation in Persistent Atrial Fibrillation: Results From the Multicenter CRYO4PERSISTENT AF Trial.

OBJECTIVES: The CRYO4PERSISTENT AF (Cryoballoon Ablation for Early Persistent Atrial Fibrillation) trial aims to report long-term outcomes after a single pulmonary vein isolation (PVI)-only ablation procedure using the second-generation cryoballoon in persistent atrial fibrillation (PerAF) patients. BACKGROUND: Pulmonary vein isolation is recognized as the cornerstone of atrial fibrillation (AF) ablation, including ablation of PerAF. METHODS: The CRYO4PERSISTENT AF trial (NCT02213731) is a prospective, multicenter, single-arm trial designed to assess single-procedure outcomes of PVI using the cryoballoon. The primary endpoint was freedom from AF, atrial flutter, or atrial tachycardia ≥30 s after a 90-day blanking period. After enrollment, but before ablation, patients without 100% AF burden (18-h Holter monitoring or 3 consecutive electrocardiograms in a time frame ≥14 days) were excluded. Patients were followed at 3, 6, and 12 months, with 48-h Holter monitoring at 6 and 12 months. Quality of life and symptoms were evaluated at baseline and 12 months. Arrhythmia recurrence and adverse events were adjudicated by an independent committee. RESULTS: A total of 101 patients (62 ± 11 years of age, 74% men, left ventricular ejection fraction 56 ± 8%, left atrial diameter 43 ± 5 mm) meeting criteria, undergoing cryoballoon-based PVI, with follow-up data, were included. Kaplan-Meier estimate of freedom from AF, atrial flutter, or atrial tachycardia recurrence was 60.7% at 12 months. Compared with baseline, there were significantly fewer patients with arrhythmia-related symptoms at 12 months (16% vs. 92%; p < 0.0001). The symptom reduction was supported by significant improvement in 36-Item Short Form Health Survey composite scores and European Heart Rhythm Association score at 12 months. The only device related event was transient phrenic nerve injury in 2 (2%) patients, with resolution pre-discharge. CONCLUSIONS: Cryoballoon ablation for treatment of PerAF demonstrated 61% single-procedure success at 12 months post-ablation in addition to significant reduction in arrhythmia-related symptoms and improved quality of life. (Cryoballoon Ablation for Early Persistent Atrial Fibrillation [Cryo4 Persistent AF]; NCT02213731).

Economic evaluation of trimetazidine in the management of chronic stable angina in Greece.

BACKGROUND: To evaluate the cost-effectiveness of trimetazidine (TMZ) as add-on therapy to standard-of-care (SoC) compared to SoC alone in patients with chronic stable angina who did not respond adequately to first line therapy with b-blockers, nitrates or calcium channel antagonists in Greece. METHODS: A Markov model with 3-month cycles and 1-year time horizon was developed to assess the comparators. The analysis was conducted from a third-party payer perspective. The clinical inputs and utility values were extracted from the published literature. Resource consumption data were obtained from local experts, using a questionnaire developed for the purpose of the study and were combined with unit cost data (in €2016) obtained from official sources. Cost effectiveness was assessed by calculating the incremental cost effectiveness ratio (ICER). Probabilistic sensitivity analysis (PSA) was performed to account for uncertainty and variation in the input parameters of the model. RESULTS: The analysis showed that the cost of TMZ plus SoC was €1755.57 versus €1751.76 of SoC alone. In terms of health outcomes, TMZ plus SoC was associated with 0.6650 QALYs versus 0.6562 QALYs for SoC alone. The incremental analysis resulted in an ICER of €430.67 per QALY gained. PSA revealed that the probability of TMZ plus SoC being cost-effective over SoC was 89 %, at a threshold of €34,000 per QALY gained. CONCLUSION: The results indicate that TMZ as add -on treatment may be a highly cost-effective option for the symptomatic treatment of patients with chronic stable angina in Greece relative to SoC alone.

Duration of treadmill exercise testing combined with QRS score predicts adverse cardiac outcome at long-term follow-up.

OBJECTIVE: Total exercise duration and abnormal QRS score values are treadmill exercise testing (TET) prognostic parameters that have been shown to be significantly and independently associated with cardiac mortality. We evaluated the prognostic value of a new index (M score, Michaelides score) incorporating TET duration and QRS score values in a simple index. METHODS: In this study, we included 626 patients, who underwent TET and coronary arteriography. Cardiac catheterization showed the presence of coronary artery disease in 64.3% of these patients. The M score was calculated by adding the value of the Athens QRS score to the duration of TET (in minutes). The outcome measure was a composite of myocardial infarction or death. Patients were prospectively followed for 38+/-21 months (median 36 months). RESULTS: The composite endpoint was more frequent among the patients of the 1st quartile (M-score values <-5.8). In univariate analysis, mortality of the first-quartile patients was significantly higher (14 vs. 1.1%, P<0.001). In multivariate Cox's regression analysis for age, sex, diabetes, smoking status, hypertension, hypercholesterolemia, maximum ST depression at TET, angina during TET, coronary artery disease on angiography, and echocardiographic left ventricular ejection fraction, the first quartile of M-score values was found to be independently associated with the composite endpoint (relative risk = 3.26, 95% confidence interval = 2.01-5.29, P<0.001). CONCLUSION: This study shows that a new index termed the M score, which incorporates QRS score and exercise duration, predicts mortality and occurrence of myocardial infarction at long-term follow-up of high-risk individuals, independently of TET-induced ST-segment changes.

Multiple cardiac metastases from a malignant melanoma.

Metastatic tumors in the pericardium or the heart are more common than primary tumors and their incidence has increased during the last decades due to the prolonged survival of patients with cancer and the increased prevalence of the disease in the general population. We present the case of a 36-year-old patient admitted to our hospital due to fatigue, dyspnea, and episodes of dizziness and fainting during the last month. He had a history of a malignant skin melanoma surgically removed 4 years ago. The echo study identified multiple metastases in the heart involving the pericardium, the myocardium and the right atrium, where the tumor was mobile creating mechanical tricuspid valve stenosis. Malignant metastasis was confirmed by pericardiocentesis and, although treatment with chemotherapy was promptly initiated, the patient died 4 months later. Despite the difficulty in clinical diagnosis of cardiac melanoma, early detection has important therapeutic and prognostic implications. Echocardiography is the most common diagnostic modality and transesophageal approach may be the technique of choice to image intracardiac metastatic tumors.

Aspirin and clopidogrel: a sweeping combination in cardiology.

Platelets play a pivotal role in the pathogenesis of atherothrombosis, believed to be integrally involved in both the development and progression of atherosclerotic heart disease, as well as in its acute thrombotic complications. Antiplatelet therapy constitutes the cornerstone in the management of patients with acute coronary syndromes and generally high-risk patients with atherothrombosis. Until recently, long-term antiplatelet therapy for the treatment and prevention of the complications of atherothrombotic disease was traditionally limited to aspirin. The availability of the thienopyridines, in particular clopidogrel, represents an important addition to the physician's armamentarium. Clopidogrel is currently one of the most widely prescribed drugs for the treatment of symptomatic coronary artery disease. Aspirin and clopidogrel interfere with platelet activation in complementary, but separate pathways. Aspirin irreversibly inhibits cyclooxygenase, thus preventing the production of thromboxane A(2), which is a prothrombotic and vasoconstrictive substance. Clopidogrel, a newer thienopyridine which has largely supplanted ticlopidine due to a more favorable safety profile, irreversibly prevents platelet activation by blocking one of the three known adenosine 5'-diphosphate (ADP) receptors (the P2Y(12) receptor) on the platelet surface, thus interfering with platelet activation, degranulation and aggregation. Both these antiplatelet agents have a potent protective effect against adverse vascular events, but the combination of these two agents has an even stronger antiplatelet effect translating into superior antithrombotic protection in coronary, cerebral or peripheral arterial disease, without an inordinate increase in bleeding complications. A number of seminal clinical trials have demonstrated and confirmed the incremental benefit and efficacy of the combination of clopidogrel and aspirin therapy above and beyond that of aspirin alone, with multiple other important large-scale clinical trials currently ongoing. Newer data are being accumulated from studies where indications for the use of clopidogrel and aspirin continue to expand into other patient groups, rendering this dual antiplatelet drug therapy a sweeping combination in Cardiology. However, important issues remain to be further and more thoroughly explored about the benefit of this antiplatelet drug combination in these other patient groups, such as in patients with heart failure, where preliminary data indicate a favorable effect on thrombotic vascular events, in patients with atrial fibrillation, where there is hope that this combination may replace or be an alternative treatment modality to coumadin in certain subpopulations, in patients undergoing demanding catheter ablation procedures, where data point to a protective effect from thromboembolic events. Another pertaining issue to be further investigated is the occurrence of drug-resistance observed in some patients for both these antithrombotic agents. This article is a comprehensive review of all these data and the landmark trials on the two antiplatelet agents, the issues involved and the current recommendations for their use in patients with atherosclerotic heart disease and other cardiovascular disorders and procedures.

Exercise testing in asymptomatic patients with heterozygous familial hypercholesterolaemia.

OBJECTIVE: Familial hypercholesterolaemia (FH) is a frequent genetic disorder in Europe, affecting one in 500 people in its heterozygous form. Both homozygous and heterozygous forms are correlated with increased incidence of cardiovascular events. METHODS: We investigated clinical and biochemical parameters possibly associated with the results of exercise testing (ET) in asymptomatic patients with heterozygous FH. The study population was derived from outpatients of the Lipid Center in our department and consisted of 194 patients with heterozygous FH who had no medical history of coronary artery disease (CAD) or angina-like symptoms and who had agreed to undergo ET. RESULTS: Sex, body mass index, smoking status, diabetes mellitus, family history of CAD, presence of xanthomas and total cholesterol, triglyceride, low-density and high-density lipoprotein cholesterol, apolipoproteins A and B and lipoprotein (a) levels did not differ significantly between patients with positive and negative ET. Higher fibrinogen levels, arterial hypertension and family history of CAD were more frequent among patients with positive ET. However, in multivariate analysis adjusted for all the aforementioned variables, only high fibrinogen levels were significantly and independently associated with a positive result of ET. CONCLUSIONS: Lipid and coronary risk factor profiles do not seem to predict exercise-induced myocardial ischaemia in asymptomatic patients with heterozygous FH. However, in this high-risk population for cardiovascular events, fibrinogen levels are an independent predictor of positive ET. The adverse effects of FH on the cardiovascular system may be partly mediated by coagulability factors, whose role in the management of FH patients remains to be fully clarified.

The paradoxical association of common polymorphisms of the renin-angiotensin system genes with risk of myocardial infarction.

BACKGROUND: The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) and the A1166C polymorphism of the angiotensin-II AT1 receptor (AT1R) have been extensively investigated as possible risk factors for myocardial infarction (MI). DESIGN AND METHODS: Genetic association, case-control study, specifically designed to investigate the association of the above-mentioned polymorphisms with risk of MI in a homogeneous, low coronary risk, Caucasian population. The study population consisted of 1603 consecutive patients with acute MI who were recruited from nine clinics, located in three cities, and 699 unrelated adults who were randomly selected from the city catalogues. RESULTS: In univariate analysis, the DD genotype was found to be more prevalent among controls (40.8 vs. 35.2%, P=0.011). In multivariate analysis adjusted for age, gender, smoking status, diabetes mellitus, hypercholesterolaemia, hypertension and family history of coronary artery disease, the presence of the DD genotype was independently and negatively associated with risk of AMI (RR=0.743, 95% CI=0.595-0.927, P=0.008). The CC genotype was not found to be significantly associated with risk of MI, either in univariate (6.2 vs. 6.4%, P=0.856), or in multivariate analysis adjusted for the same confounders (RR=0.743, 95% CI=0.473-1.167, P=0.197). CONCLUSIONS: Contrary to previous reports, in this study the DD genotype of the ACE gene, but not the CC genotype of the AT1R gene, was associated with a lower risk of MI. Our results emphasize the complexity of genotype-phenotype interactions in the pathogenesis of ischaemic heart disease and question the previously hypothesized role of the DD genotype on risk of acute myocardial infarction.

Right ventricle bipolar pacing may prevent appropriate biventricular pacing from two pacemakers. Case report.

This article reports on practical problems and possible solutions that may occur in case of upgrading a dual-chamber pacemaker by implanting a second left ventricular ventricular pacing, ventricular sensing, ventricular triggering (VVT) pacemaker. This therapeutic strategy was considered appropriate in the case of a 73-year-old patient with severe heart failure, who was scheduled to undergo coronary artery bypass surgery. A right-sided, dual-chamber pacemaker had been already implanted to the patient. The duration of the paced QRS complex was 220 ms and inter- and intraventricular dyssynchrony was documented in the echocardiographic study. We describe the methodological problems and possible solutions related to biventricular pacing following the abovementioned strategy.

A QRS score versus ST-segment changes during exercise testing: which is the most reliable ischaemic marker after myocardial revascularisation?

BACKGROUND: The diagnostic ability of exercise testing based on ST-segment changes is low for the detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA) or ischaemia after bypass surgery (CABG). The aim of this study was to improve the diagnostic accuracy of exercise testing in patients with a history of PTCA or CABG, with the implementation of a QRS score. METHODS: We studied 128 post-PTCA patients (aged 49 +/- 8 years) and 104 post-CABG patients (aged 54 +/- 8 years), who had either positive exercise tests with or without angina, or negative exercise tests with continuing angina-like symptoms, and underwent cardiac catheterisation. RESULTS: The univariate risk ratio of exercise-induced ST-segment deviation to detect restenosis was 3.05 (p = 0.005) and 0.83 (p = 0.690) in group A and group B patients, respectively. The univariate risk ratios of abnormal QRS score values to detect restenosis were 32.1 (p < 0.001) and 18.8 (p < 0.001) for group A and group B patients, respectively. The univariate risk ratios of the combination of exercise-induced ST-segment changes and of abnormal QRS score values to detect restenosis was 9.43 (p < 0.001) and 3.77 (p < 0.044) for group A and group B patients, respectively. The value of the area under the ROC curves is higher for the QRS score in group A patients, group B patients and for the whole study population. CONCLUSIONS: QRS score values significantly improve the diagnostic ability of ST-segment change-based exercise testing, for the assessment of restenosis after PTCA or ischaemia after CABG.

Significance of exercise-induced ST changes in leads aVR, V5, and V1. Discrimination of patients with single- or multivessel coronary artery disease.

BACKGROUND: It is known that exercise-induced ST-segment elevation in lead V1 (V1-E) detects left anterior descending (LAD) stenosis. It was also postulated that ST elevation in aVR and simultaneous ST depression in V5 (aVR-E + V5-D) is a marker of ischemia due to significant stenosis of the LAD in patients with single-vessel disease. HYPOTHESIS: This study was undertaken to investigate the significance of the concomitant appearance of both electrocardiographic (ECG) ischemic markers, and of each of them alone during exercise, to detect either LAD stenosis as single-vessel coronary artery disease (CAD), or multivessel CAD involving LAD stenosis. METHODS: A total of 196 consecutive patients (152 men and 44 women, mean age 54 +/- 7 years) with at least one of these ECG markers, who underwent treadmill exercise testing with the Bruce protocol and coronary arteriography, were studied. RESULTS: Patients were divided into three groups. In Group A (83 patients with V1-E + aVR-E & V5-D), 93% of patients with single-vessel disease had significant LAD stenosis (p<0.001), whereas 75% of patients with double-vessel disease had significant stenoses of the LAD and the left circumflex (LCx) coronary arteries (p<0.01). In Group B (97 patients with aVR-E & V5-D but without V1-E), 43% of patients with single-vessel disease had significant LAD stenosis (p<0.08), whereas 85% of patients with double-vessel disease had significant stenoses of the LAD and the right coronary artery (RCA) (p<0.01). In Group C (16 patients with only V1-E), 60% of patients with single-vessel disease had significant LAD stenosis (p<0.05), whereas 75% of patients with double-vessel disease had significant LAD and LCx stenoses (p<0.05). CONCLUSIONS: The concomitant appearance of exercise-induced ST elevation in lead V1, ST elevation in lead aVR, and ST depression in lead V5, as well as the isolated appearance of ST elevation in lead V1 detect significant LAD stenosis as single-vessel disease, or significant stenoses of LAD and LCx arteries in patients with double-vessel disease, whereas the appearance of ST elevation in aVR & ST depression in V5 but without ST elevation in V1 correlates strongly with significant LAD and RCA stenoses and usually indicates double-vessel disease.