Statistics at high-altitudes: Relevance for the interpretation of metrics that reveal cardiac morphology and performance.

Survey of four ratio-based metrics, commonly used to evaluate left ventricular performance. The numerator of each ratio is plotted against the corresponding denominator, implying that the slope of the colored line reflects the value of the ratio.9,11 Similar graphs can be constructed for the other cardiac compartments. Data sets obtained at various altitudes and defined with reference to sea level, based on Rao et al.6 Acronyms: E/A unitless ratio of the early (E) and late (A) diastolic wave peak velocities (cm/s); EDD, end-diastolic diameter (mm); EDV, end-diastolic volume (mL); EF, ejection fraction (%); ESD, end-systolic diameter (mm); ESV, end-systolic volume (mL); FS, fractional shortening (%).

What characterizes device-related thrombosis following LAAC, if ejection fraction fails to shine?

Cardiac compartmental size depends on sex, with smaller values found in (healthy) women compared to a matched group of men. Various types of heart disease may cause dilation of the affected chamber. For example, atrial fibrillation (AF) is associated with enlarged left atrial (LA) size, often also implying increased left ventricular (LV) size. Sex-specific differences appear to persist during disease states. Thus, chamber volumes depend on both sex and the severity of the underlying disorder, and require quantification to evaluate the effect of interventions. Often, we rely on the popular performance metric ejection fraction (EF) which refers to the ratio of the minimum and maximum LV or LA volumetric values observed during the cardiac cycle. Here we discuss a sex stratified analysis of LVEF and LAEF in AF patients as treated by LA appendage closure, while comparing those with or without device-related thrombosis. Also, an alternative analysis based on primary data is presented while emphasizing its attractiveness. In any event, age- and sex-specific reference values as broadly documented for various imaging modalities should be applied to LA and LV.

TMAD enters the toolbox for evaluating selected heart transplant patients.

Adaptation of the heart is often a blessing for the patient, but sometimes a diagnostic challenge for the responsible physician. The clinical difficulty may be enhanced when employing diagnostic tools that are hard to interpret. Ratio-based metrics are notorious in this respect, and particularly risky in the follow-up evaluation of heart transplant patients. However, measures expressed as physical units contribute to a comprehensive clinical evaluation and guide proper patient management.

Multiparametric analysis of coronary flow in psoriasis using a coronary flow reserve companion.

BACKGROUND: Coronary microvascular dysfunction (CMD) is usually evaluated measuring coronary flow velocity reserve (CFVR). A more comprehensive analysis of CFVR including additional consideration of the associated logical companion-CFVR, where hyperemic diastolic coronary flow velocity may act as surrogate, was applied in this study to elucidate the mechanism of CMD in psoriasis. METHODS AND RESULTS: Coronary flow velocity reserve was analysed using transthoracic echocardiographs of 127 psoriasis patients (age 36 ± 8 years; 104 males) and of 52 sex- and age-matched healthy controls. CFVR determination was repeated in the patient subgroup (n = 78) receiving anti-inflammatory therapy. Baseline and hyperemic microvascular resistance (MR) were calculated. CMD was defined as CFVR ≤ 2.5. Four endotypes of CMD were identified referring to concordant or discordant impairments of hyperemic flow or CFVR. We evaluated the companion-CFVR, as derived from the quadratic mean of hyperemic and diastolic flow velocity at rest. Coronary flow parameters, including CFVR (p = 0.01), were different among the two endotypes having CFVR > 2.5. Specifically, all 11 (14%) patients with CFVR deterioration despite therapy, belonged to endotype 1, and had higher baseline and hyperemic MR (p < 0.0001, both). Interestingly, while CFVR was comparable in patients with worsened versus those with improved CFVR, the companion-CFVR could discriminate by being lower in patients with worsened CFVR (p = 0.01). CONCLUSIONS: The reduced CFVR in psoriasis is driven by decreased companion-CFVR, combined with increased hyperemic MR. Adoption of the mandatory companion-CFVR enables a personalized characterization superior to that achieved by exclusive consideration of CFVR.

Ratiology and a Complementary Class of Metrics for Cardiovascular Investigations.

Cardiovascular investigations often involve ratio-based metrics or differences: ejection fraction, arterial pressure augmentation index, coronary fractional flow reserve, pulse pressure. Focusing on a single number (ratio or difference) implies that information is lost. The lost companions constitute a well-defined but thus far unrecognized class, having additive value, a physical dimension, and often a physiological meaning. Physiologists should play a prominent role in exploring these complementary avenues and also define alternatives.

Temporal changes in left ventricular longitudinal strain in general population: Clinical correlates and impact on cardiac remodeling.

BACKGROUND: Recent studies in patients and general population have reported the role of left ventricular (LV) longitudinal strain (LS) as an independent predictor of outcome. However, there are few data on changes in LS over time. We therefore investigated in a general population clinical correlates of temporal changes in LS. We also explored the potential correlation between temporal changes in LV volumes and LS. METHODS AND RESULTS: We measured LV end-systolic (ESV) and end-diastolic (EDV) volumes by conventional echocardiography and LS by 2D speckle tracking in 627 participants (mean age 50.6 years, 51.4% women; 41.3% hypertensives) at baseline and after 4.7 years. For statistical analysis, we used the absolute values of LS. In stepwise regression, the magnitude of the decrease in all LV LS indexes over time was greater in men than in women (P < 0.0001). Higher baseline mean arterial pressure (MAP), a larger longitudinal increase in MAP, and stopping diuretic treatment during follow-up were related to larger decreases in LS indexes. In multivariable-adjusted analysis, we observed an inverse correlation between baseline ESV and LV LS (P ≤ 0.0017). Similarly, lower baseline LS and a larger decrease in LS over time were correlated with a lesser longitudinal decrease in ESV (P ≤ 0.0004). CONCLUSIONS: A significant decrease in LS over time was associated with male sex, higher baseline MAP, ∆MAP, and alteration in antihypertensive treatment. We suggested an interaction between a longitudinal decrease in LV deformation and adverse cardiac remodeling, while underscoring the importance of deformation analysis based on LS assessment in patients at risk.

Women and Men in the History of Western Cardiology: Some Notes on Their Position as Patients, Role as Investigational Study Subjects, and Impact as Professionals.

Nowadays, it is generally appreciated that studies in the medical field should not only include sex-related aspects but also consider age. In the past, taking the era of Hippocrates as a starting point for the Western medical sciences, such aspects were less urgent and barely relevant. However, considering such details during daily life became increasingly important as the traditional roles of men and women in society and household converged. In the Western world, this fundamental transition process started recently and is advancing at an accelerated pace. Research about the role of women has also evolved, starting from plain history about the lives of women to a description of the relation between men and women, resulting in the gender concept. The present survey highlights a historical selection of observations referring to the impact of men and women on the medical sciences, as patient, study object, and professional. Whenever relevant, focus will be on the field of cardiovascular investigations as documented in the Western world. Rather than being exhaustive, we focus on a few remarkable icons, including Trota of Salerno, Hildegard von Bingen, and Miguel Serveto.

Sex-Specific Cardiovascular Comorbidities with Associations in Dermatologic and Rheumatic Disorders.

Cardiology, dermatology, and rheumatology form a fascinating triad. Many skin and joint disorders are associated with cardiovascular comorbidities because they share etiologic elements. Female predominance is often remarkable and likely related to autoimmune pathology. Although studies have shown that X-encoded genes may be involved in the differences in immunity between males and females, other studies have also shown that sex chromosomes are irrelevant and that estrogens and androgens are responsible for the differences. The elevated immune activity in females provides a beneficial position in coping with a pathogenic stimulus but may also enhance their susceptibility to autoimmunity. The complexity of the immune system and its role as a defensive force against infection requires an armamentarium to precisely identify and selectively control inflammatory processes or cells which promote atherosclerosis. On the other hand, the inflammation in skin diseases seems to be an active source of diverse proinflammatory cytokines and chemokines which can predispose to cardiovascular comorbidities. Also, it has been shown that comorbidity disproportionately accelerates risk in women.The skin offers a readily available window to facilitate detection of risk factors or even to assist the diagnostic process regarding a variety of disorders, including those with cardiovascular involvement. Current imaging techniques provide exquisite capabilities for diagnosing and possibly even counteracting atherosclerotic plaque formation, before serious cardiovascular events occur. Combining imaging approaches (such as videocapillaroscopy, intravascular ultrasound, and FDG positron emission tomography) with insights based on immunology will likely accelerate advances in this area.We review major dermatologic manifestations and rheumatologic disorders which are associated with cardiac and vascular abnormalities. In particular we discuss sex-specific aspects concerning incidence and severity of cardiovascular disease associated with systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, atopic dermatitis, and hidradenitis suppurativa.

Cardiophysiology Illustrated by Comparing Ventricular Volumes in Healthy Adult Males and Females.

Recent advances in cardiac imaging techniques have substantially contributed to a growing interest in the analysis of global cardiac chamber dimensions and regional myocardial deformation. During the cardiac cycle, ventricular luminal volume varies due to the contraction process, which also confers a shape change including substantial alteration of long axis length, as well as rotation of the base compared to the apex. Local deformation can be assessed by strain (rate) analysis. Reviewing the present literature, it must be concluded that there is no single metric available to comprehensively characterize ventricular function. Every candidate advanced thus far has been found to incompletely reflect ventricular performance. This observation is not surprising in view of the complexity of the cardiac pump system. Additionally, sex-specific modifiers may play a role. More than three decades ago, it was shown that on average the ventricular volume is smaller in healthy women compared to matched males. Therefore, the present contribution concerns the interpretation of data derived from the healthy heart in both men and women. Starting from the classical Starling concept, we apply a simple mathematical transformation which permits an insightful representation of ventricular mechanics. Relating end-systolic volume (ESV) to end-diastolic volume creates the ventricular volume regulation graph which features the pertinent working point of an individual heart. This fundamental approach illustrates why certain proposed performance indexes cannot individually reveal the essence of ventricular systolic function. We demonstrate that particular metrics are highly interconnected and just tell us the same story in a different disguise. It is imperative to understand which associations exist and if they expectedly are (nearly) linear or frankly nonlinear. Notably, ejection fraction (EF) is primarily determined by ESV, while in turn EF is not much different from ventriculo-arterial coupling (VAC). Insight into cardiac function is promoted by identification of the paramount/essential components involved. The smaller ESV (p < 0.0001) implies that EF is higher in women and may also have consequences for VAC.

Cardiovascular Implications of Diabetes, Metabolic Syndrome, Thyroid Disease, and Cardio-Oncology in Women.

Cardiovascular disease may be associated with several comorbidities, including diabetes mellitus, thyroid disorders, and the metabolic syndrome, which are predominantly observed in women and often starting at particular ages. In addition, common treatment options for carcinomas frequently seen in women may induce serious cardiotoxic effects. We review the scope of the problem, the pathophysiologic mechanisms involved, as well as the resulting abnormalities regarding cardiac structure and function as observed by using imaging techniques.

Sex- and Age-Related Reference Values in Cardiology, with Annotations and Guidelines for Interpretation.

The definition of "abnormal" in clinical sciences is often based on so-called reference values which point to a range that experts by some sort of consensus consider as normal when looking at biological variables. Such a level is commonly calculated by taking (twice) the standard deviation from the mean, or considering certain percentiles. The suspicion or even confirmation of a disease is then established by demonstrating that the value measured exceeds the upper or lower reference value. As is often the case, the measurement accuracy may depend on the conditions and specific method employed to collect and analyze data. This implies that, for example, data assessed by 2D echocardiography possibly differ from those obtained by MRI and therefore require modality-specific reference values. In this review we summarize reference values for the electrocardiogram, cardiac compartmental volumes, and arterial vessel size in males and females for various age groups. These values may further depend on other variables such as body size, physical training status, and ethnicity. Additional variables relevant for cardiology such as those referring to the microcirculation and biomarkers are only mentioned with reference to the pertinent literature. In general, the sex- and age-specific differences observed are often remarkable and warrant consideration in clinical practice and basic biomedical sciences.

Heart Transplantation Survival and Sex-Related Differences.

Orthotopic heart transplantation (OHT) is the "gold standard" treatment for patients with end-stage heart failure, with approximately 5000 transplants performed each year worldwide. Heart transplantation survival rates have progressively improved at all time points, despite an increase in donor and recipient age and comorbidity and greater recipient urgency; according to the registry of the International Society of Heart and Lung Transplantation (ISHLT), the median survival of patients posttransplantation is currently 12.2 years.Long-term survival is sub-optimal, and outcomes after OHT remain constrained by the development of acute rejection and cardiac allograft vasculopathy (CAV). Moreover, donor organs are in short supply, making optimal organ utilization an ongoing priority. For these reasons, substantial interest continues to exist in identifying factors portending increased survival and improved organ utilization.

Arterial Flow, Pulse Pressure and Pulse Wave Velocity in Men and Women at Various Ages.

The increase in pulse pressure (PP) that occurs with advancing age is predominantly due to reduced arterial distensibility leading to decreased aortic compliance, particularly in the elderly, in whom high blood pressure mainly manifests as isolated systolic hypertension. Since age-related changes in stroke volume are minimal compared with changes in PP, PP is often considered a surrogate measure of arterial stiffness. However, since PP is determined by both cardiac and arterial function, a more precise and reliable means of assessment of arterial stiffness is arterial pulse wave velocity (PWV), a parameter that is only dependent on arterial properties. Arterial stiffness as measured by PWV has been found to be a powerful pressure-related indicator for cardiovascular morbidity and mortality. We analyzed PP and PWV in men and women of various age groups in healthy volunteers as well as cardiac patients with different types of diseases. The findings identified several striking sex-specific differences which demand consideration in guidelines for diagnostic procedures, for epidemiological analysis, and in evaluation of therapeutic interventions.

Heart Function Analysis in Cardiac Patients with Focus on Sex-Specific Aspects.

Cardiac function is best described by investigating the pressure-volume relationships. This information permits description in terms of the ventricular volume regulation graph (VRG), estimation of systolic elastance, evaluation of lusitropic properties, and assessment of ventriculo-arterial coupling. Current techniques yield noninvasive determination of cardiac compartmental volumes, along with systolic/diastolic arterial pressure, while ventricular end-diastolic pressure can be inferred from an echocardiography-based surrogate measure. Ventricular volume is known to vary with age, as well as to be affected by intrinsic cardiac disease and abnormalities of the vascular system. Moreover, 35 years ago it has been shown in healthy adults that left ventricular volume is significantly smaller in women compared to men. This important observation has serious implications for several metrics which are routinely used in clinical practice, e.g., ejection fraction. The remarkable difference between ventricular size in men and women is also a powerful starting point for the study of aging and the investigation of interventions such as exercise. In this review we evaluate sex-specific characteristics of the VRG and the implications for various cardiac patient populations, during basal conditions and intervention such as exercise.

Left ventricular volume analysis as a basic tool to describe cardiac function.

The heart is often regarded as a compression pump. Therefore, determination of pressure and volume is essential for cardiac function analysis. Traditionally, ventricular performance was described in terms of the Starling curve, i.e., output related to input. This view is based on two variables (namely, stroke volume and end-diastolic volume), often studied in the isolated (i.e., denervated) heart, and has dominated the interpretation of cardiac mechanics over the last century. The ratio of the prevailing coordinates within that paradigm is termed ejection fraction (EF), which is the popular metric routinely used in the clinic. Here we present an insightful alternative approach while describing volume regulation by relating end-systolic volume (ESV) to end-diastolic volume. This route obviates the undesired use of metrics derived from differences or ratios, as employed in previous models. We illustrate basic principles concerning ventricular volume regulation by data obtained from intact animal experiments and collected in healthy humans. Special attention is given to sex-specific differences. The method can be applied to the dynamics of a single heart and to an ensemble of individuals. Group analysis allows for stratification regarding sex, age, medication, and additional clinically relevant covariates. A straightforward procedure derives the relationship between EF and ESV and describes myocardial oxygen consumption in terms of ESV. This representation enhances insight and reduces the impact of the metric EF, in favor of the end-systolic elastance concept advanced 4 decades ago.