Left atrial trajectory impairment in hypertrophic cardiomyopathy disclosed by geometric morphometrics and parallel transport

The analysis of full Left Atrium (LA) deformation and whole LA deformational trajectory in time has been poorly investigated and, to the best of our knowledge, seldom discussed in patients with Hypertrophic Cardiomyopathy. Therefore, we considered 22 patients with Hypertrophic Cardiomyopathy (HCM) and 46 healthy subjects, investigated them by three-dimensional Speckle Tracking Echocardiography, and studied the derived landmark clouds via Geometric Morphometrics with Parallel Transport. Trajectory shape and trajectory size were different in Controls versus HCM and their classification powers had high AUC (Area Under the Receiving Operator Characteristic Curve) and accuracy. The two trajectories were much different at the transition between LA conduit and booster pump functions. Full shape and deformation analyses with trajectory analysis enabled a straightforward perception of pathophysiological consequences of HCM condition on LA functioning. It might be worthwhile to apply these techniques to look for novel pathophysiological approaches that may better define atrio-ventricular interaction

Proof-of-concept trial results of the HeartMan mobile personal health system for self-management in congestive heart failure

This study tested the effectiveness of HeartMan—a mobile personal health system offering decisional support for management of congestive heart failure (CHF)—on health-related quality of life (HRQoL), self-management, exercise capacity, illness perception, mental and sexual health. A randomized controlled proof-of-concept trial (1:2 ratio of control:intervention) was set up with ambulatory CHF patients in stable condition in Belgium and Italy. Data were collected by means of a 6-min walking test and a number of standardized questionnaire instruments. A total of 56 (34 intervention and 22 control group) participants completed the study (77% male; mean age 63 years, sd 10.5). All depression and anxiety dimensions decreased in the intervention group (p < 0.001), while the need for sexual counselling decreased in the control group (p < 0.05). Although the group differences were not significant, self-care increased (p < 0.05), and sexual problems decreased (p < 0.05) in the intervention group only. No significant intervention effects were observed for HRQoL, self-care confidence, illness perception and exercise capacity. Overall, results of this proof-of-concept trial suggest that the HeartMan personal health system significantly improved mental and sexual health and self-care behaviour in CHF patients. These observations were in contrast to the lack of intervention effects on HRQoL, illness perception and exercise capacity

Multivariate prediction of spontaneous repetitive responses in ventricular myocardium exposed in vitro to simulated ischemic conditions.

Guinea-pig ventricular myocardium was partly exposed to normal Tyrode's superfusion and partly to altered conditions (using modified Tyrode's solution) set to simulate acute myocardial ischemia (PO2 80 +/- 10 mmHg; no glucose; pH 7.00 +/- 0.05; K+ 12 mM). Using a double-chamber tissue bath and standard microelectrode technique, the occurrence of spontaneous repetitive responses was investigated during simulated ischemia (occlusion) and after reperfusing the previously ischemic superfused tissue with normal Tyrode's solution (reperfusion). In 62 experiments (42 animals) the effects of: (1) duration of simulated ischemia (1321 +/- 435 s), (2) stimulation rate (1002 +/- 549 ms) and (3) number of successive simulated ischemic periods (occlusions) (1.58 +/- 0.92) on: (1) resting membrane potential, (2) action potential amplitude, (3) duration of 50 and 90\% action potentials and (4) maximal upstroke velocity of action potential were studied. All variables were considered as gradients (delta) between normal and ischemic tissue. Both during occlusion and upon reperfusion, spontaneous repetitive responses were coded as single, couplets, salvos (three to nine and > 10) or total spontaneous repetitive responses (coded present when at least one of the above-mentioned types was seen). The incidence of total spontaneous repetitive responses was 31\% (19/62) on occlusion and 85\% (53/62) upon reperfusion. Cox's models (forced and stepwise) were used to predict multivariately the occurrence of arrhythmic events considered as both total spontaneous repetitive responses and as separate entities. These models were applicable since continuous monitoring of the experiments enabled exact timing of spontaneous repetitive response onset during both occlusion and reperfusion. In predicting reperfusion spontaneous repetitive responses, total spontaneous repetitive responses and blocks observed during the occlusion period were also considered. Total occlusion spontaneous repetitive responses were predicted by: (1) longer delta 50\% action potential duration (t = 2.68), (2) shorter delta 90\% action potential duration (t = -2.17) and (3) fewer occlusive periods (t = -2.46). Total reperfusion spontaneous repetitive responses were predicted by a longer delta action potential amplitude (t = 2.18). Due to few events during occlusion, prediction of individual arrhythmic entities was not possible. Upon reperfusion single spontaneous repetitive responses were predicted by longer delta maximal upstroke velocity of action potential (t = 2.59) and shorter delta 90\% action potential duration (t = -2.55); couplets were predicted by longer delta 50\% action potential duration (t = 3.26); longer delta action potential amplitude predicted salvos (> 10) (t = 3.26).(ABSTRACT TRUNCATED AT 400 WORDS

Age- and Gender-Normalized Coronary Incidence and Mortality Risks in Primary and Secondary Prevention

Epidemiologic differences in ischemic heart disease incidence between women and men remain largely unexplained. The reasons of womens protection against coronary artery disease (CAD) are not still clear. However, there are subsets more likely to die of a first myocardial infarction. The purpose of this review is to underline different treatment strategies between genders and describe the role of classical and novel factors defined to evaluate CAD risk and mortality, aimed at assessing applicability and relevance for primary and secondary prevention. Women and men present different age-related risk patterns: it should be important to understand whether standard factors may index CAD risk, including mortality, in different ways and/or whether specific factors might be targeted gender-wise. Take home messages include: HDL-cholesterol levels, higher in pre-menopausal women than in men, are more strictly related to CAD. The same is true for high triglycerides and Lp(a). HDL-cholesterol levels are inversely related to incidence and mortality. In primary prevention the role of statins is not completely ascertained in women although in secondary prevention these agents are equally effective in both genders. Weight and glycemic control are effective to reduce cardiovascular disease (CVD) mortality in women from middle to older age. Blood pressure is strongly and directly related to CVD mortality, from middle to older age, particularly in diabetic and over weighted women. Kidney dysfunction, defined using UAE and eGFR predicts primary CVD incidence and risk in both genders. In secondary prediction, kidney dysfunction predicts sudden death in women in conjunction with left ventricular ejection fraction evaluation. Serum uric acid does not differentiate gender-related CVD incidences, although it increases with age. Age-related differences between genders have been related to loss of ovarian function traditionally and to lower iron stores more recently. QT interval, physiologically longer in women than men, may be an index of arrhythmic risk in patients with mitral valve prolapse and increased circulating levels of catecholamines. However, there are no large population-based studies to assess this. In conjunction with novel parameters, such as inflammatory markers and reproductive hormones, classical risk score in women may be implemented in the future

Rabbit ventricular myocardium undergoing simulated ischemia and reperfusion in a double compartment tissue bath: a model to investigate both antiarrhythmic and arrhythmogenic likelihood.

An ischemia/reperfusion-simulating model in rabbit tissue should be right oriented and clinically relevant to provide a non expensive approach for manipulations of currents involved in the repolarization process. Standard right ventricular guinea-pig (N=18) and newly investigated rabbit (N=12) myocardial strips were placed in a special perfusion chamber allowing partition into two segments independently superfused with oxygenated Tyrode's solution or a modified Tyrode's solution mimicking ischemia by: 1) increased extracellular potassium concentration (12 mmol/L), 2) decreased HCO3 (-) concentration (9 mmol/L), leading to a decrease in pH (6.90 ± 0.05), 3) decreased pO2 by replacement of 95\% O2 and 5\% CO2 by 95\% N2 and 5\% CO2 gas mixture, and 4) complete withdrawal of glucose. There were significant differences in rabbit as compared to guinea-pig preparations in baseline (p<0.02) and post-ischemic-like (p<0.01) APA and RMP with lower values in the formers, and lower post-ischemic Vmax in rabbit preparations (25±15 versus 97±83 V/s, p<0.01) but neither baseline nor post-ischemic-like or absolute changes in APD50, APD90 were different. In ischemia- and reperfusion-like phases, there were high proportions of single spontaneous repetitive responses, both in guinea-pig (respectively 50 and 89\%) and rabbit preparations (respectively 67 and 92\%). Guinea-pig preparations showed higher incidence of severe spontaneous repetitive responses (61 versus 17\%, p<0.02). This rabbit model is proposed to investigate both anti- and pro-arrhythmic effects of drugs acting at various levels electrophysiologically, which may be obtained with great power and relatively few (around 10 per group) preparations. This model should now be tested pharmacologically

Dobutamine effects on spontaneuous variability of ventricular arrhythmias in patients with severe chronic heart failure: the Italian Multicenter Study.

Background. Dobutamina Studio Italiano Multicentrico (Do.S.I.M.) is a prospective, randomized, multicenter interuniversity Italian study aimed at assessing the effects of dobutamine on spontaneous variability of ventricular arrhythmias in sinus rhythm NYHA class III-IV patients with congestive heart failure (CHF). Methods. Out of 74 pre-hoc estimated CHF patients, 68 (92%) were randomized electively to either being washed out of all active drugs except diuretics (group A) or to continue with the standard regimen including digitalis, diuretics and ACE-inhibitors (group B, standard therapy). In 63 patients, complete Holter data were obtained and are reported here. After 72 hours, in both groups, 48-hour Holter monitoring (Holter 1) was performed. The spontaneous variability of ventricular arrhythmias was assessed by calculating the natural logarithm of the sum of hourly incidences (during 48 consecutive hours) of index events such as the mean heart rate or the various forms of total and either sustained or non-sustained ventricular arrhythmias. The results were then grouped for the first and second 24-hour Holter periods. All patients were submitted to 10 μg/kg/min infusion of dobutamine for 72 hours and 48-hour Holter monitoring (Holter 2) was repeated 24 hours before the end of dobutamine infusion. The incidence of arrhythmia and the distribution of laboratory and echocardiographic variables was also studied in group A and B patients. The data of the two groups along with the intrapatient ± 95% confidence intervals were pooled, both on and off dobutamine. Results. There was no significant difference between Holter 1 and Holter 2 in the rates of index events in 63 patients with regard to pro-arrhythmic effects. Pro-arrhythmic effects were seen during dobutamine infusion in 21% of cases, an effect which subsided (to 5%) when dobutamine was discontinued. Interestingly, the positive inotropic effects of dobutamine (based on ejection fraction changes) were parallel (22%) to the pro-arrhythmic changes, although they persisted long after dobutamine discontinuation (18%). The pro-arrhythmic effects of dobutamine, both during (5%) as well as after (1%) drug infusion, were unrelated to heart rate changes. The prevalence and incidence of non-sustained ventricular tachycardia due to dobutamine were 47 and 29% respectively. Conclusions. In sinus rhythm patients with severe CHF, dobutamine had chronotropic effects and increased a depressed ejection fraction without significantly increasing arrhythmogenicity