Prominent Longitudinal Strain Reduction of Basal Left Ventricular Segments in Patients With Coronavirus Disease-19.

BACKGROUND: Coronavirus disease-19 (COVID-19) has been associated with overt and subclinical myocardial dysfunction. We observed a recurring pattern of reduced basal left ventricular (LV) longitudinal strain on speckle-tracking echocardiography in hospitalized patients with COVID-19 and subsequently aimed to identify characteristics of affected patients. We hypothesized that patients with COVID-19 with reduced basal LV strain would demonstrate elevated cardiac biomarkers. METHODS AND RESULT: Eighty-one consecutive patients with COVID-19 underwent speckle-tracking echocardiography. Those with poor quality speckle-tracking echocardiography (n = 2) or a known LV ejection fraction of <50% (n = 4) were excluded. Patients with an absolute value basal longitudinal strain of <13.9% (2 standard deviations below normal) were designated as cases (n = 39); those with a basal longitudinal strain of ≥13.9% were designated as controls (n = 36). Demographics and clinical variables were compared. Of 75 included patients (mean age 62 ± 14 years, 41% women), 52% had reduced basal strain. Cases had higher body mass index (median 34.1; interquartile range 26.5-37.9 kg/m2 vs median 26.9, interquartile range, 24.8-30.0 kg/m2, P = .009), and greater proportions of Black (74% vs 36%, P = .0009), hypertensive (79% vs 56%, P = .026), and diabetic patients (44% vs 19%, P = .025) compared with controls. Troponin and N-terminal pro-brain natriuretic peptide levels trended higher in cases, but were not significantly different. CONCLUSIONS: Reduced basal LV strain is common in patients with COVID-19. Patients with hypertension, diabetes, obesity, and Black race were more likely to have reduced basal strain. Further investigation into the significance of this strain pattern is warranted.

Thrombospondins in the transition from myocardial infarction to heart failure.

The heart's reaction to ischemic injury from a myocardial infarction involves complex cross-talk between the extra-cellular matrix (ECM) and different cell types within the myocardium. The ECM functions not only as a scaffold where myocytes beat synchronously, but an active signaling environment that regulates the important post-MI responses. The thrombospondins are matricellular proteins that modulate cell--ECM interactions, functioning as "sensors" that mediate outside-in and inside-out signaling. Thrombospondins are highly expressed during embryonic stages, and although their levels decrease during adult life, can be re-expressed in high quantities in response to cardiac stress including myocardial infarction and heart failure. Like a Swiss-army knife, the thrombospondins possess many tools: numerous binding domains that allow them to interact with other elements of the ECM, cell surface receptors, and signaling molecules. It is through these that the thrombospondins function. In the present review, we provide basic as well as clinical evidence linking the thrombospondin proteins with the post myocardial infarction response, including inflammation, fibrotic matrix remodeling, angiogenesis, as well as myocyte hypertrophy, apoptosis, and contractile dysfunction in heart failure. We will describe what is known regarding the intracellular signaling pathways that are involved with these responses, paving the road for future studies identifying these proteins as therapeutic targets for cardiac disease.

Hyperactive adverse mechanical stress responses in dystrophic heart are coupled to transient receptor potential canonical 6 and blocked by cGMP-protein kinase G modulation.

RATIONALE: The heart is exquisitely sensitive to mechanical stimuli to adapt rapidly to physiological demands. In muscle lacking dystrophin, such as Duchenne muscular dystrophy, increased load during contraction triggers pathological responses thought to worsen the disease. The relevant mechanotransducers and therapies to target them remain unclear. OBJECTIVES: We tested the role of transient receptor potential canonical (TRPC) channels TRPC3 and TRPC6 and their modulation by protein kinase G (PKG) in controlling cardiac systolic mechanosensing and determined their pathophysiological relevance in an experimental model of Duchenne muscular dystrophy. METHODS AND RESULTS: Contracting isolated papillary muscles and cardiomyocytes from controls and mice genetically lacking either TRPC3 or TRPC6 were subjected to auxotonic load to induce stress-stimulated contractility (SSC, gradual rise in force and intracellular Ca(2+)). Incubation with cGMP (PKG activator) markedly blunted SSC in controls and Trpc3(-/-); whereas in Trpc6(-/-), the resting SSC response was diminished and cGMP had no effect. In Duchenne muscular dystrophy myocytes (mdx/utrophin deficient), the SSC was excessive and arrhythmogenic. Gene deletion or selective drug blockade of TRPC6 or cGMP/PKG activation reversed this phenotype. Chronic phosphodiesterase 5A inhibition also normalized abnormal mechanosensing while blunting progressive chamber hypertrophy in Duchenne muscular dystrophy mice. CONCLUSIONS: PKG is a potent negative modulator of cardiac systolic mechanosignaling that requires TRPC6 as the target effector. In dystrophic hearts, excess SSC and arrhythmia are coupled to TRPC6 and are ameliorated by its targeted suppression or PKG activation. These results highlight novel therapeutic targets for this disease.

Brief report: antisynthetase syndrome-associated myocarditis.

BACKGROUND: The antisynthetase (AS) syndrome is characterized by autoimmune myopathy, interstitial lung disease, cutaneous involvement, arthritis, fever, and antibody specificity. We describe 2 patients with AS syndrome who also developed myocarditis, depressed biventricular function, and congestive heart failure. METHODS AND RESULTS: Both patients were diagnosed with AS syndrome based on clinical manifestations, detection of serum AS antibodies, and myositis confirmation with the use of skeletal muscle magnetic resonance imaging and skeletal muscle biopsy. In addition, myocarditis resulting in heart failure was confirmed with the use of cardiac magnetic resonance imaging and from endomyocardial biopsy findings. After treatment for presumed AS syndrome-associated myocarditis, one patient recovered and the other patient died. CONCLUSIONS: AS syndrome is a rare entity with morbidity and mortality typically attributed to myositis and lung involvement. This is the first report of AS syndrome-associated myocarditis leading to congestive heart failure in 2 patients. Given the potentially fatal consequences, myocarditis should be considered in patients with AS syndrome presenting with heart failure.

Anti-hypertrophic and anti-oxidant effect of beta3-adrenergic stimulation in myocytes requires differential neuronal NOS phosphorylation.

RATIONALE: Stimulation of ß3-adrenoreceptors (ß3-AR) blunts contractility and improves chronic left ventricular function in hypertrophied and failing hearts in a neuronal nitric oxide synthase (nNOS) dependent manner. nNOS can be regulated by post-translational modification of stimulatory phosphorylation residue Ser1412 and inhibitory residue Ser847. However, the role of phosphorylation of these residues in cardiomyocytes and ß3-AR protective signaling has yet to be explored. OBJECTIVE: We tested the hypothesis that ß3-AR regulation of myocyte stress requires changes in nNOS activation mediated by differential nNOS phosphorylation. METHODS AND RESULTS: Endothelin (ET-1) or norepinephrine induced hypertrophy in rat neonatal ventricular cardiomyocytes (NRVMs) was accompanied by increased ß3-AR gene expression. Co-administration of the ß3-AR agonist BRL-37433 (BRL) reduced cell size and reactive oxygen species (ROS) generation, while augmenting NOS activity. BRL-dependent augmentation of NOS activity and ROS suppression due to NE were blocked by inhibiting nNOS (L-VNIO). BRL augmented nNOS phosphorylation at Ser1412 and dephosphorylation at Ser847. Cells expressing constitutively dephosphorylated Ser1412A or phosphorylated Ser847D nNOS mutants displayed reduced nNOS activity and a lack of BRL modulation. BRL also failed to depress ROS from NE in cells with nNOS-Ser847D. Inhibiting Akt decreased BRL-induced nNOS-Ser1412 phosphorylation and NOS activation, whereas Gi/o blockade blocked BRL-regulation of both post-translational modifications, preventing enhancement of NOS activity and ROS reduction. BRL resulted in near complete dephosphorylation of Ser847 and a moderate rise in Ser1412 phosphorylation in mouse myocardium exposed to chronic pressure-overload. CONCLUSION: ß3-AR regulates myocardial NOS activity and ROS via activation of nNOS involving reciprocal changes in phosphorylation at two regulatory sites. These data identify a novel and potent anti-oxidant and anti-hypertrophic pathway due to nNOS post-translational modification that is coupled to ß3-AR receptor stimulation.

Pulmonary capillary wedge pressure augments right ventricular pulsatile loading.

BACKGROUND: Right ventricular failure from increased pulmonary vascular loading is a major cause of morbidity and mortality, yet its modulation by disease remains poorly understood. We tested the hypotheses that, unlike the systemic circulation, pulmonary vascular resistance (R(PA)) and compliance (C(PA)) are consistently and inversely related regardless of age, pulmonary hypertension, or interstitial fibrosis and that this relation may be changed by elevated pulmonary capillary wedge pressure, augmenting right ventricular pulsatile load. METHODS AND RESULTS: Several large clinical databases with right heart/pulmonary catheterization data were analyzed to determine the R(PA)-C(PA) relationship with pulmonary hypertension, pulmonary fibrosis, patient age, and varying pulmonary capillary wedge pressure. Patients with suspected or documented pulmonary hypertension (n=1009) and normal pulmonary capillary wedge pressure displayed a consistent R(PA)-C(PA) hyperbolic (inverse) dependence, C(PA)=0.564/(0.047+R(PA)), with a near-constant resistance-compliance product (0.48±0.17 seconds). In the same patients, the systemic resistance-compliance product was highly variable. Severe pulmonary fibrosis (n=89) did not change the R(PA)-C(PA) relation. Increasing patient age led to a very small but statistically significant change in the relation. However, elevation of the pulmonary capillary wedge pressure (n=8142) had a larger impact, significantly lowering C(PA) for any R(PA) and negatively correlating with the resistance-compliance product (P<0.0001). CONCLUSIONS: Pulmonary hypertension and pulmonary fibrosis do not significantly change the hyperbolic dependence between R(PA) and C(PA), and patient age has only minimal effects. This fixed relationship helps explain the difficulty of reducing total right ventricular afterload by therapies that have a modest impact on mean R(PA). Higher pulmonary capillary wedge pressure appears to enhance net right ventricular afterload by elevating pulsatile, relative to resistive, load and may contribute to right ventricular dysfunction.

The Anrep effect: 100 years later.

Myocardial stretch elicits a rapid increase in developed force, which is mainly caused by an increase in myofilament calcium sensitivity (Frank-Starling mechanism). Over the ensuing 10-15 min, a second gradual increase in force takes place. This slow force response to stretch is known to be the result of an increase in the calcium transient amplitude and constitutes the in vitro equivalent of the Anrep effect described 100 years ago in the intact heart. In the present review, we will update and discuss what is known about the Anrep effect as the mechanical counterpart of autocrine/paracrine mechanisms involved in its genesis. The chain of events triggered by myocardial stretch comprises 1) release of angiotensin II, 2) release of endothelin, 3) activation of the mineralocorticoid receptor, 4) transactivation of the epidermal growth factor receptor, 5) increased formation of mitochondria reactive oxygen species, 6) activation of redox-sensitive kinases upstream myocardial Na(+)/H(+) exchanger (NHE1), 7) NHE1 activation, 8) increase in intracellular Na(+) concentration, and 9) increase in Ca(2+) transient amplitude through the Na(+)/Ca(2+) exchanger. We will present the experimental evidence supporting each of the signaling steps leading to the Anrep effect and its blunting by silencing NHE1 expression with a specific small hairpin interference RNA injected into the ventricular wall.

Thrombospondin-4 is required for stretch-mediated contractility augmentation in cardiac muscle.

RATIONALE: One of the physiological mechanisms by which the heart adapts to a rise in blood pressure is by augmenting myocyte stretch-mediated intracellular calcium, with a subsequent increase in contractility. This slow force response was first described over a century ago and has long been considered compensatory, but its underlying mechanisms and link to chronic adaptations remain uncertain. Because levels of the matricellular protein thrombospondin-4 (TSP4) rapidly rise in hypertension and are elevated in cardiac stress overload and heart failure, we hypothesized that TSP4 is involved in this adaptive mechanism. OBJECTIVE: To determine the mechano-transductive role that TSP4 plays in cardiac regulation to stress. METHODS AND RESULTS: In mice lacking TSP4 (Tsp4⁻/⁻), hearts failed to acutely augment contractility or activate stretch-response pathways (ERK1/2 and Akt) on exposure to acute pressure overload. Sustained pressure overload rapidly led to greater chamber dilation, reduced function, and increased heart mass. Unlike controls, Tsp4⁻/⁻ cardiac trabeculae failed to enhance contractility and cellular calcium after a stretch. However, the contractility response was restored in Tsp4⁻/⁻ muscle incubated with recombinant TSP4. Isolated Tsp4⁻/⁻ myocytes responded normally to stretch, identifying a key role of matrix-myocyte interaction for TSP4 contractile modulation. CONCLUSION: These results identify TSP4 as myocyte-interstitial mechano-signaling molecule central to adaptive cardiac contractile responses to acute stress, which appears to play a crucial role in the transition to chronic cardiac dilatation and failure.

Disseminated Lyme disease and dilated cardiomyopathy: A systematic review.

Lyme carditis is a well-established manifestation of early disseminated Lyme infection, yet the relationship between late disseminated Lyme disease and the development of dilated cardiomyopathy (DCM) remains unclear. The present systematic review aims to summarize existing literature on the association between late disseminated Lyme disease and DCM. A systematic review was conducted in PubMed, Embase, CENTRAL, and MEDLINE databases, after which a total of 11 observational studies (n = 771) were ultimately included for final data extraction. Although most studies (7/11) identified evidence associating Borrelia-infection with DCM, further research is required to isolate late disseminated Borrelia infection as a causative agent of DCM.

Case Report: Steroid-Responsive Takotsubo Cardiomyopathy Associated With Cytokine Storm and Obstructive Shock.

A growing body of evidence suggests that inflammation may play a key role in the development of Takotsubo stress cardiomyopathy. Here, we report the case of a 63-year-old woman who presented with chest pain and was diagnosed with this cardiomyopathy. After an initial improvement, the patient experienced a systemic inflammatory response of unclear origin and deteriorated rapidly into obstructive shock. Her presentation was considered consistent with cytokine storm. She was, therefore, treated with steroids with rapid improvement in her clinical picture. She relapsed after the taper. Endomyocardial biopsy soon after initiation of pulse dose steroids showed macrophage and lymphocytic infiltration. This case highlights the potential intimate connection between systemic inflammatory response and Takotsubo stress cardiomyopathy and contributes to the evolving understanding of inflammation in the pathogenesis of this disease.

In vivo key role of reactive oxygen species and NHE-1 activation in determining excessive cardiac hypertrophy.

Growing in vitro evidence suggests NHE-1, a known target for reactive oxygen species (ROS), as a key mediator in cardiac hypertrophy (CH). Moreover, NHE-1 inhibition was shown effective in preventing CH and failure; so has been the case for AT1 receptor (AT1R) blockers. Previous experiments indicate that myocardial stretch promotes angiotensin II release and post-translational NHE-1 activation; however, in vivo data supporting this mechanism and its long-term consequences are scanty. In this work, we thought of providing in vivo evidence linking AT1R with ROS and NHE-1 activation in mediating CH. CH was induced in mice by TAC. A group of animals was treated with the AT1R blocker losartan. Cardiac contractility was assessed by echocardiography and pressure-volume loop hemodynamics. After 7 weeks, TAC increased left ventricular (LV) mass by ~45% vs. sham and deteriorated LV systolic function. CH was accompanied by activation of the redox-sensitive kinase p90(RSK) with the consequent increase in NHE-1 phosphorylation. Losartan prevented p90(RSK) and NHE-1 phosphorylation, ameliorated CH and restored cardiac function despite decreased LV wall thickness and similar LV systolic pressures and diastolic dimensions (increased LV wall stress). In conclusion, AT1R blockade prevented excessive oxidative stress, p90(RSK) and NHE-1 phosphorylation, and decreased CH independently of hemodynamic changes. In addition, cardiac performance improved despite a higher work load.

Pressure-volume relation analysis of mouse ventricular function.

Nearly 40 years ago, the Sagawa laboratory spawned a renaissance in the use of instantaneous ventricular pressure-volume (P-V) relations to assess cardiac function. Since then, this analysis has taken hold as the most comprehensive way to quantify ventricular chamber function and energetics and cardiovascular interactions. First studied in large mammalian hearts and later in humans employing a catheter-based method, P-V analysis was translated to small rodents in the late 1990s by the Kass laboratory. Over the past decade, this approach has become a gold standard for comprehensive examination of in vivo cardiac function in mice, facilitating a new era of molecular cardiac physiology. The catheter-based method remains the most widely used approach in mice. In this brief review, we discuss this instrumentation, the theory behind its use, and how volume signals are calibrated and discuss elements of P-V analysis. The goal is to provide a convenient summary of earlier investigations and insights for users whose primary interests lie in genetic/molecular studies rather than in biomedical engineering.

Biochemical and mechanical dysfunction in a mouse model of desmin-related myopathy.

An R120G mutation in alphaB-crystallin (CryAB(R120G)) causes desmin-related myopathy (DRM). In mice with cardiomyocyte-specific expression of the mutation, CryAB(R120G)-mediated DRM is characterized by CryAB and desmin accumulations within cardiac muscle, mitochondrial deficiencies, activation of apoptosis, and heart failure (HF). Excessive production of reactive oxygen species (ROS) is often a hallmark of HF and treatment with antioxidants can sometimes prevent the progression of HF in terms of contractile dysfunction and cardiomyocyte survival. It is unknown whether blockade of ROS is beneficial for protein misfolding diseases such as DRM. We addressed this question by blocking the activity of xanthine oxidase (XO), a superoxide-generating enzyme that is upregulated in our model of DRM. The XO inhibitor oxypurinol was administered to CryAB(R120G) mice for a period of 1 or 3 months. Mitochondrial function was dramatically improved in treated animals in terms of complex I activity and conservation of mitochondrial membrane potential. Oxypurinol also largely restored normal mitochondrial morphology. Surprisingly, however, cardiac contractile function and cardiac compliance were unimproved, indicating that the contractile deficit might be independent of mitochondrial dysfunction and the initiation of apoptosis. Using magnetic bead microrheology at the single cardiomyocyte level, we demonstrated that sarcomeric disarray and accumulation of the physical aggregates resulted in significant changes in the cytoskeletal mechanical properties in the CryAB(R120G) cardiomyocytes. Our findings indicate that oxypurinol treatment largely prevented mitochondrial deficiency in DRM but that contractility was not improved because of mechanical deficits in passive cytoskeletal stiffness.

Prevalence and Clinical Correlates of Echo-Estimated Right and Left Heart Filling Pressures in Hospitalized Patients With Coronavirus Disease 2019.

OBJECTIVES: The prevalence of elevated right and left heart filling pressures in coronavirus disease 2019 is not well characterized. We aimed to characterize the prevalence of pulmonary hypertension and concurrent elevated left heart filling pressure in hospitalized patients with coronavirus disease 2019. We hypothesized that a significant proportion of coronavirus disease 2019 patients has evidence of pulmonary hypertension associated with elevated left heart filling pressure on transthoracic echocardiography. DESIGN: Retrospective cohort study. SETTING: Academic tertiary-care center. PATIENTS: Hospitalized coronavirus disease 2019 patients who underwent clinical transthoracic echocardiography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure variable of interest was right ventricular systolic pressure, calculated using the American Society of Echocardiography guidelines. Pulmonary hypertension was defined as right ventricular systolic pressure greater than 40 mm Hg. Left heart filling pressure was estimated with Nagueh's method for pulmonary artery occlusion pressure using E/e' ratio, and normal was considered pulmonary artery occlusion pressure less than 16 mm Hg. Clinical characteristics and outcomes were compared between the patients with and without pulmonary hypertension. A total of 73 patients (median age 66 yr [57-75 yr]; 46% women) were included. Median right ventricular systolic pressure was 39 mm Hg (interquartile range, 32-50 mm Hg), and 36 patients (49.3%) had evidence of pulmonary hypertension. Patients with pulmonary hypertension were more likely to require ICU admission (86% vs 65%; p = 0.035) and have acute respiratory distress syndrome (72% vs 49%; p = 0.0053) than those without. In-hospital mortality was 26% for those with pulmonary hypertension compared with 14% for those without (p = 0.19). Patients with pulmonary hypertension had higher median-estimated pulmonary artery occlusion pressure (17.4 mm Hg [12.7-21.3 mm Hg] vs 12.1 mm Hg [10.0-14.1 mm Hg]; p = 0.0008), and elevated left heart filling pressure was present in 59% of those with pulmonary hypertension. CONCLUSIONS: Pulmonary hypertension is common in hospitalized patients with coronavirus disease 2019 and is associated with poor clinical outcomes. Left ventricular filling pressure is elevated in over half of those with pulmonary hypertension and may represent a target to reduce right ventricular afterload and potentially improve outcomes in coronavirus disease 2019.

Adverse ventricular remodeling and exacerbated NOS uncoupling from pressure-overload in mice lacking the beta3-adrenoreceptor.

Stimulation of the beta-adrenergic system is important in the pathological response to sustained cardiac stress, forming the rationale for the use of beta-blockers in heart failure. The beta3-adrenoreceptor (AR) is thought to couple to the inhibitory G-protein, G(i), with downstream signaling through nitric oxide, although its role in the heart remains controversial. In this study, we tested whether lack of beta3-AR influences the myocardial response to pressure-overload. Baseline echocardiography in mice lacking beta3-AR (beta3(-/-)) compared to wild type (WT) showed mild LV hypertrophy at 8 weeks that worsened as they aged. beta3(-/-) mice had much greater mortality after transverse aortic constriction (TAC) than WT controls. By 3 weeks of TAC, systolic function was worse. After 9 weeks of TAC, beta3(-/-) mice also had greater LV dilation, myocyte hypertrophy and enhanced fibrosis. NOS activity declined in beta3(-/-)TAC hearts after 9 weeks, and total and NOS-dependent superoxide rose, indicating heightened oxidative stress and NOS uncoupling. The level of eNOS phosphorylation in beta3(-/-)TAC hearts was diminished, and nNOS and iNOS expression levels were increased. GTP cyclohydrolase-1 expression was reduced, although total BH4 levels were not depleted. 3 weeks of BH4 treatment rescued beta3(-/-) mice from worsened remodeling after TAC, and lowered NOS-dependent superoxide. Thus, lack of beta3-AR signaling exacerbates cardiac pressure-overload induced remodeling and enhances NOS uncoupling and consequent oxidant stress, all of which can be rescued with exogenous BH4. These data suggest a cardioprotective role for the beta3-AR in modulating oxidative stress and adverse remodeling in the failing heart.

Cardiovascular Risks and Organ Damage in Secondary Hypertension.

Secondary hypertension is associated with increased cardiovascular risk and exaggerated target organ damage, not only due to the higher and more sustained blood pressure values often observed in these patients but also because certain forms of hypertension can increase cardiovascular risk and organ damage by the neurohormonal and/or molecular pathways activation they exert. Early identification of secondary forms of hypertension can help mitigate organ damage and prevent cardiovascular complications. Signs and symptoms distinction among types of secondary hypertension is essential in order to prevent complications.

Evolution of ventricular hypertrophy and myocardial mechanics in physiological and pathological hypertrophy.

Left ventricular hypertrophy (LVH) is an adaptive response to physiological or pathological stimuli, and distinguishing between the two has obvious clinical implications. However, asymmetric septal hypertrophy and preserved cardiac function are noted in early stages in both cases. We characterized the early anatomic and functional changes in a mouse model of physiological and pathological stress using serial echocardiography-based morphometry and tissue velocity imaging. Weight-matched CF-1 male mice were separated into Controls ( n = 10), treadmill Exercise 1 h daily for 5 days/wk ( n = 7), and transverse aortic constriction (TAC, n = 7). Hypertrophy was noted first in the left ventricle basal septum compared with other segments in Exercise (0.84 ± 0.02 vs. 0.79 ± 0.03 mm, P = 0.03) and TAC (0.86 ± 0.05 vs. 0.77 ± 0.04 mm, P = 0.02) at 4 and 3 wk, respectively. At 8 wk, eccentric LVH was noted in Exercise and concentric LVH in TAC. Septal E/E' ratio increased in TAC (32.6 ± 3.7 vs. 37 ± 6.2, P = 0.002) compared with the Controls and Exercise (32.3 ± 5.2 vs. 32.8 ± 3.8 and 31.2 ± 4.9 vs. 28.2 ± 5.0, respectively, nonsignificant for both). Septal s' decreased in TAC (21 ± 3.6 vs. 17 ± 4.2 mm/s, P = 0.04) but increased in Exercise (19.6 ± 4.1 vs. 29.2 ± 2.3 mm/s, P = 0.001) and was unchanged in Controls (20.1 ± 4.2 vs. 20.9 ± 5.1 mm/s, nonsignificant). With similar asymmetric septal hypertrophy and normal global function during the first 4-8 wk of pathological and physiological stress, there is an early marginal increase with subsequent decrease in systolic tissue velocity in pathological but early and progressive increase in physiological hypertrophy. Tissue velocities may help adjudicate between these two states when there are no overt anatomic or functional differences. NEW & NOTEWORTHY Pathological and physiological stress-induced ventricular hypertrophy have different clinical connotations but present with asymmetric septal hypertrophy and normal global function in their early stages. We observed a marginal but statistically significant decrease in systolic tissue velocity in pathological but progressive increase in velocity in physiological hypertrophy. Tissue velocity imaging could be an important tool in the management of asymmetric septal hypertrophy by adjudicating between these two etiologies when there are no overt anatomic or functional differences.