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\begin{document}

\title{LONGITUDINAL SYSTOLIC DYSFUNCTION IN HYPERTENSIVE CARDIOMYOPATHY WITH
NORMAL EJECTION FRACTION}



\author[1]{Jose Salas}%
\author[2]{Oscar  Sanchez}%
\author[3]{Oscar Baltazar González}%
\author[4]{Maria Elena Soto}%
\affil[1]{Centenario Hospital Miguel Hidalgo}%
\affil[2]{Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde}%
\affil[3]{Hospital Civil de Guadalajara Unidad Hospitalaria Juan I Menchaca}%
\affil[4]{INC IGNACIO CHAVEZ}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background: The left ventricle (LV) journey in their transition from
hypertrophy to heart failure is marked by many subcellular events
partially understood yet. The moment in which the structural
abnormalities reach the umbral to induce myocardial dysfunction remains
elusive. Aims: To evaluate the anatomic-functional relationship between
LV wall thickness and longitudinal systolic dysfunction. Material and
Methods: We prospectively performed clinical history and transthoracic
echocardiogram on healthy individuals and patients with hypertension,
left ventricle ejection fraction (LVEF) [?]50\%, and absence of heart
failure symptoms. Results: A total of 226 patients and 101 healthy
individuals were recruited. The distribution for sex was similar between
groups. The mean age was 67\selectlanguage{ngerman}±13 years old in the patients, and 44\% had
concentric LV hypertrophy. LVEF was identical in both groups (63±6\%);
in contrast, global longitudinal strain (GLS) (-18.8±2.5\% vs.
-20.4±2\%) and mitral annulus plane systolic excursion (MAPSE) (13.8±2.8
vs. 15.5±2mm) were lower. ROC curve classified optimally decreased GLS
with LV septum thickness \selectlanguage{english}[?]13mm and decreased MAPSE with thickness \selectlanguage{english}[?]14mm.
Multivariable logistic regression found that LV septum thickness is the
only variable associated with longitudinal systolic dysfunction (OR=
1.1, CI95\%= 1.05 -- 1.15, p= 0.001, R squared= 0.38). Discussion: A
progressive increase in LV wall thickness due to myocyte hypertrophy and
interstitial expansion is associated with LV systolic longitudinal
dysfunction. Conclusions: Patients with moderate or severe ventricular
hypertrophy (septum \selectlanguage{english}[?]13mm) had longitudinal systolic dysfunction, GLS
decreases with minor structural change than MAPSE, and LVEF is
insensitive in detecting longitudinal myocardial dysfunction in patients
with hypertension.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\par\null

\textbf{LONGITUDINAL SYSTOLIC DYSFUNCTION IN HYPERTENSIVE CARDIOMYOPATHY
WITH NORMAL EJECTION FRACTION}

\textbf{Shortened title:} LONGITUDINAL SYSTOLIC DYSFUNCTION IN
HYPERTENSIVE CARDIOMYOPATHY

\selectlanguage{ngerman}\textbf{Salas-Pacheco José L. MD, MSc}

José Luis Salas Pacheco

Cardiology department, Centenario Hospital Miguel Hidalgo

Ferrocarril avenue, Alameda. Aguascalientes México. Zip code: 20259

\textbf{Lomelí-Sánchez Oscar MD, MSc}

Oscar Lomelí Sánchez

Cardiology department, Antiguo Hospital Civil de Guadalajara Fray
Antonio Alcalde

Coronel Calderón 777, El Retiro, Guadalajara, México. Zip code: 44280

\textbf{Baltazar-González O. MD}

Oscar Baltazar González

Cardiology department, Hospital Civil Juan I. Menchaca

Salvador Quevedo, Independencia, Guadalajara, México. Zip code: 44340

\textbf{Soto ME MD, MSc, PhD}

María Elena Soto López

Immunology department, Instituto Nacional de Cardiología Ignacio Chávez

Juan Badiano 1, Sección XVI, Tlalpan, México City, Zip code: 14080

\textbf{Corresponding author:}

Salas-Pacheco José L. MD, MSc

José Luis Salas Pacheco

Cardiology department, Centenario Hospital Miguel Hidalgo

Ferrocarril avenue, Alameda. Aguascalientes México. Zip code: 20259

mail: \emph{jolsalp@gmail.com}

telephone: 449 994 6720

fax: none

\textbf{ABSTRACT}

\textbf{Background:} The left ventricle (LV) journey in their transition
from hypertrophy to heart failure is marked by many subcellular events
partially understood yet. The moment in which the structural
abnormalities reach the umbral to induce myocardial dysfunction remains
elusive.

\textbf{Aims:} To evaluate the anatomic-functional relationship between
LV wall thickness and longitudinal systolic dysfunction.

\textbf{Material and Methods:} We prospectively performed clinical
history and transthoracic echocardiogram on healthy individuals and
patients with hypertension, left ventricle ejection fraction (LVEF)
\selectlanguage{english}[?]50\%, and absence of heart failure symptoms.

\textbf{Results:} A total of 226 patients and 101 healthy individuals
were recruited. The distribution for sex was similar between groups. The
mean age was 67+-13 years old in the patients, and 44\% had concentric LV
hypertrophy. LVEF was identical in both groups (63+-6\%); in contrast,
global longitudinal strain (GLS) (-18.8+-2.5\% vs. -20.4+-2\%) and mitral
annulus plane systolic excursion (MAPSE) (13.8+-2.8 vs. 15.5+-2mm) were
lower. ROC curve classified optimally decreased GLS with LV septum
thickness \selectlanguage{english}[?]13mm and decreased MAPSE with thickness \selectlanguage{english}[?]14mm. Multivariable
logistic regression found that LV septum thickness is the only variable
associated with longitudinal systolic dysfunction (OR= 1.1,
CI\textsubscript{95\%}= 1.05 -- 1.15, p= 0.001, R squared= 0.38).

\textbf{Discussion:} A progressive increase in LV wall thickness due to
myocyte hypertrophy and interstitial expansion is associated with LV
systolic longitudinal dysfunction.

\textbf{Conclusions:} Patients with moderate or severe ventricular
hypertrophy (septum \selectlanguage{english}[?]13mm) had longitudinal systolic dysfunction, GLS
decreases with minor structural change than MAPSE, and LVEF is
insensitive in detecting longitudinal myocardial dysfunction in patients
with hypertension.

Keywords

Hypertension, Left ventricular hypertrophy, Left ventricular
dysfunction, Heart failure

\textbf{LONGITUDINAL SYSTOLIC DYSFUNCTION IN HYPERTENSIVE CARDIOMYOPATHY
WITH NORMAL EJECTION FRACTION}

INTRODUCTION

Myocardial alterations originated from hypertension are collectively
known as hypertensive heart disease. Structurally it is characterized by
increased left ventricle (LV) wall thickness, concentric LV hypertrophy,
and left atrium dilatation. There are abnormalities predominantly in
diastolic function in the early stages, while in the late, arise
ventricular dilatation, systolic dysfunction, and decreased ejection
fraction\textsuperscript{1}. Despite preserved left ventricular ejection
fraction (LVEF), some patients have abnormalities in the longitudinal
components of contractile mechanics and systolic dysfunction in the
early stages\textsuperscript{2}. Previous evidence proposed increased
circumferential and radial functions as the compensatory mechanisms that
maintained LVEF in the normal range\textsuperscript{3}. However,
increased LV wall thickness due to hypertrophy and myocardial
incompressibility are the factors that create the artifact that results
in normal LVEF\textsuperscript{4}. Thus, in patients with hypertensive
heart disease, systolic dysfunction can be observed since early stages,
before symptoms of heart failure or decrease in global systolic function
indices appear\textsuperscript{5}. Multiple structural and functional
events characterize the continuum from LV hypertrophy to heart failure;
however, the point in which occurs the transition to ventricular
dysfunction remains elusive. This study aimed to evaluate the
anatomic-functional relationship between LV wall thickness and
longitudinal systolic dysfunction in individuals with hypertension,
normal LVEF, and absence of heart failure symptoms.

METHODS

We prospectively recruited from our hypertension clinics between June
2020 to March 2021 patients 18 years and older, of both sexes, with a
diagnosis of hypertension defined as systolic blood pressure greater
than 140mmHg or diastolic greater than 90mmHg or under antihypertensive
treatment. We excluded patients with LVEF less than 50\%, moderate or
severe mitral annulus calcification, moderate or severe valvular
disease, presence of a pacemaker or defibrillator, advanced chronic
kidney disease, and a history of cardiac surgery or ischemic heart
disease. In addition, healthy individuals 18 years older were included
and matched for age and sex with the patients.

A detailed clinical history, physical examination, and echocardiogram
were performed on both groups. The transthoracic echocardiogram was made
with a contemporary ultrasound machine (Epiq 7, Philips, Andover MA) and
a sectorial transducer (2-5 MHz) following the American Society of
Echocardiography (ASE) recommendations\textsuperscript{6}. Images and
video clips acquired in B-mode were used to quantify the diameters and
volume of the different cavities. LV mass was calculated using the
modified Devereux formula\textsuperscript{7}. The left atrium and LV
volumes were calculated using the Simpson method. LV geometry was
obtained based on LV mass index (MI) and relative wall thickness (RWT).
Normal geometry was defined as RWT \textless{} 0.43 and LVMI \textless{}
95 g/m\textsuperscript{2} in women or \textless{} 115
g/m\textsuperscript{2} in men. Concentric remodeling as RWT \selectlanguage{english}[?] 0.43 and
LVMI \textless{} 95 g/m\textsuperscript{2} in women or \textless{} 115
g/m\textsuperscript{2} in men. And concentric hypertrophy as RWT \selectlanguage{english}[?] 0.43
and LVMI \selectlanguage{english}[?] 95 g/m\textsuperscript{2} in women or \selectlanguage{english}[?] 115
g/m\textsuperscript{2} in men\textsuperscript{6}.

LVEF was obtained with the biplanar method in apical four and
two-chamber views. Mitral annulus plane systolic excursion (MAPSE) was
quantified as the average of the values obtained from the displacement
of the medial and lateral mitral annulus towards the apex during
systole, measured in apical four-chamber view with M mode. Left
ventricular diastolic function was evaluated according to the ASE
recommendations, using transmitral flow pulsed Doppler, mitral annulus
tissue Doppler velocities, left atrium volume, and the tricuspid
regurgitation jet maximum velocity \textsuperscript{8}. The pulmonary
artery systolic pressure was obtained by adding to this last value the
right atrium pressure (estimated by the diameter and collapsibility of
the inferior vena cava).

B-mode images were acquired for deformation analysis between 40 and 80
Hz in apical four-chamber, two-chamber, and long-axis projections. They
were processed offline with QLab Software, version 13 (Philips, Andover
MA). Once adequate tracking of the region of interest was corroborated
by visual inspection, the images were approved for analysis. Global LV
longitudinal strain (GLS) was calculated as the average value of
longitudinal deformation of 17 LV segments.

We defined LV longitudinal dysfunction as GLS greater than -17\% or
decreased MAPSE. Limits for MAPSE were established based on sex and
age\textsuperscript{9}. In women younger than 60 years, low MAPSE was
\selectlanguage{english}[?]10mm, in those older than 60 years \selectlanguage{english}[?]8mm. In men younger than 60 years,
\selectlanguage{english}[?]11mm and more aged than 60 years \selectlanguage{english}[?]9mm. The Institutional ethics
committee approved the study, and each patient consented to participate
in the study.

STATISTICAL ANALYSIS

According to their distribution, the variables are described with mean +-
standard deviation or median with interquartile range 25-75. The
Kolmogorov-Smirnov test evaluated the distribution normality. The
comparisons between clinical and echocardiographic variables were
performed with the Chi-square test, student t-test, or Mann Whitney
U-test according to variable type and distribution. Correlations were
assessed with Pearson's or Spearman's correlation coefficients.
Differences between subgroups of patients with hypertension (subdivided
according to LV geometry) were calculated with one-way ANOVA with
Tukey's posthoc test. Multivariate analysis was performed with binomial
logistic regression, considering longitudinal systolic dysfunction as
the dependent variable. The receiver operating characteristic (ROC)
curve identified the optimal Youden point for classifying longitudinal
systolic dysfunction based on LV septum diameter. Differences were
considered significant when the p-value was less than 0.05 bilaterally.
The analysis was performed with R software, version 4.03, interface with
R studio.

RESULTS

A total of 226 patients with hypertension and 101 healthy individuals
were included. The group with hypertension was older, more obese, and
blood pressure was higher. The mean duration of hypertension was 4.3+-
1.6 years. The distribution for sex was similar between groups. Table 1
shows demographic characteristics.

In all healthy individuals, the echocardiogram was normal. LVEF was 63 +-
6\%. MAPSE was 15.5+- 2 mm and correlated inversely with age. Lateral
mitral tissue Doppler S' wave velocity was 10+-2.2 cm/sec and GLS
-20.4+-2\%. LV diastolic function was normal in 57 (56.4\%); the
remainder showed slow relaxation. Those with normal diastolic function
were younger (47+-12 vs. 65.8+-13 years, p= 0.001); however, E/e' ratio
was normal in all and without difference according to age (6.4+-1.9 vs.
6.7+-2.2, p= 0.09).

The patients had multiple structural and functional cardiac
abnormalities. Table 2 shows echocardiographic data. Only 28 (13\%)
patients had normal LV geometry; the rest, concentric remodeling or
concentric hypertrophy. LVEF was similar to that of the control group.
In contrast, GLS was lower (-18.8+-2.5\% vs -20.4+-2\%), as were S' mitral
velocity (8+-2.2 vs 10+-2.2cm/sec) and MAPSE (13.8+-2.8 vs 15.5+-2mm). We
found decreased GLS in 27\% of patients and decreased MAPSE in 12\%.
Most patients had grade 1 diastolic dysfunction, and only 14\% had grade
2 diastolic dysfunction. None showed a restrictive filling pattern.

Table 3 shows the characteristics of the patients when analyzed
according to the type of ventricular geometry. The geometric pattern
predominantly associated with longitudinal dysfunction was concentric
hypertrophy. GLS was abnormal in 62 patients, of whom 50 (80\%) had
concentric hypertrophy. Similarly, of 27 patients with low MAPSE, 26
(96\%) had concentric hypertrophy. A progressive increase in LV septum
thickness was related to the deterioration of longitudinal systolic
function (Figure 1).

In patients of both sexes with low GLS, we observed that the mean septal
thickness was 13.4mm, while low MAPSE occurred with 13.8mm in women and
14.1mm in men. All patients with low MAPSE had concomitantly low GLS.

By ROC curve (Figures 2 and 3) it was recognized that LV septum diameter
greater than 13mm classifies adequately patients with low GLS (AUC=
0.85, sensitivity 71\%, specificity 82\%, p= 0.001), and septal diameter
of 14mm low MAPSE (AUC= 0.9, sensitivity 74\%, specificity 90\%, p=
0.001).

In contrast to patients with normal longitudinal function, those with
dysfunction had severe left atrium dilatation, worse diastolic function,
and higher pulmonary artery systolic pressure. Despite the plethora of
structural and functional disturbances, LVEF was similar among the
different geometric patterns, and did not show correlation with LV
septum thickness (r= 0.04, p= 0.5), GLS (r= - 0.2, p= 0.01) or MAPSE (r=
0.13, p= 0.05). On the other hand, MAPSE and GLS showed hight
correlation (r= -0.7, p= 0.001).

LV longitudinal systolic dysfunction was related to body weight, greater
ventricular wall thickness, worst ventricular geometry, and greater LV
mass in the hypertensive group. However, in multivariate analysis, only
LV septum thickness was independently associated. Each millimeter of
increase in LV septum diameter increased the Odds Ratio of longitudinal
dysfunction by 10 (OR= 1.1, CI\textsubscript{95\%}= 1.05 -- 1.15, p=
0.001, R squared= 0.38). High collinearity was observed between
ventricular wall thickness with ventricular geometry and mass, an
expected result since the latter two variables derive from the former.

DISCUSSION

The main findings of this study showed that only patients with moderate
or severe ventricular hypertrophy (septum \selectlanguage{english}[?]13mm) had longitudinal
systolic dysfunction, that GLS decrease with minor structural change
than MAPSE, and that LVEF is insensitive in detecting longitudinal
myocardial dysfunction in patients with hypertension.

In the different geometric patterns, LVEF was similar. However,
longitudinal systolic function worsened as LV septum thickness
increased. MacIver et al. described this finding using a mathematical
model; it corrected LVEF based on wall thickness and myocardial
strain\textsuperscript{10}. The MacIver hypothesis was confirmed in
patients with hypertensive heart disease with concentric LV hypertrophy
and patients with heart failure with preserved
LVEF\textsuperscript{11-14}. Similarly, Shimizu et al. observed in
individuals with hypertensive cardiomyopathy a subnormal systolic
function (lower midmyocardium fractional shortening) despite preserved
ejection fraction (normal endocardial fractional
shortening)\textsuperscript{15}. Therefore, LV geometric modifications
and the principle of myocardial incompressibility account for normal
LVEF in hearts whit longitudinal dysfunction. Myocardial
incompressibility states that myocardial shortening in longitudinal
direction causes thickening in the orthogonal plane; thus, myocardial
volume remains relatively constant throughout the cardiac
cycle\textsuperscript{16}. The only variation in myocardial volume was
described by Yin et al., as approximately 2-4ml per 100g of tissue and
is the result of compression of intramyocardial blood
vessels\textsuperscript{17}.

Based on wall thickness, left ventricular hypertrophy is classified
arbitrarily as mild (10-12mm in women or 11-13mm in men), moderate
(13-15mm in women or 14-16mm in men), or severe (\textgreater{}15mm in
women or \textgreater{}16mm)\textsuperscript{18}. The Increased myocyte
diameter and expansion of the interstitium due to pathological fibrosis
cause ventricular wall thickening\textsuperscript{19}. The increase in
connective tissue initially impairs diastolic function and then the
systolic. In this work, we observed that only patients with moderate or
severe hypertrophy presented longitudinal dysfunction. Previous
histological studies showed a direct relationship between LV pressure
overload and myocardial fibrous tissue content. In his seminal study,
Rossi observed in postmortem hearts that the normal connective tissue
matrix volume is 6.7\%; however, there was connective tissue volume
expansion up to 31\% in patients with hypertension\textsuperscript{20}.
The fibrotic process affects the entire ventricular wall diffusely.
However, the subendocardium suffers earlier dysfunction due to its
distal location from epicardial coronary flow, extreme changes in
pressure and compression, and intrinsic susceptibility to microvascular
fibrosis\textsuperscript{21}. Increased damage to the subendocardium
results in longitudinal LV dysfunction that is echocardiographically
evident only as diastolic dysfunction, despite normal LVEF. The use of
more sensitive techniques than LVEF may reveal LV longitudinal systolic
dysfunction.

Hypertension and ventricular hypertrophy are risk factors for heart
failure. It was observed that at least two-thirds of patients with heart
failure with preserved LVEF have systolic dysfunction (decreased
GLS)\textsuperscript{22}. In this study, although we included only
patients without heart failure, longitudinal systolic dysfunction was
present in 27.4\% measured by GLS and 11.9\% by MAPSE. This finding
suggests that functional alterations are present long before the onset
of heart failure. As demonstrated in multiple studies, LV strain
quantification by speckle tracking is a more sensitive technique in the
earlier detection of functional abnormalities\textsuperscript{23}. On
the other hand, MAPSE is easy to quantify, highly reproducible, and does
not require adequate sonographic windows nor advanced echocardiographic
modalities.

According to the results of this study, LVEF does not provide specific
information on the myocardium's contractile mechanics or contractile
state in hypertensive patients. Given that hypertension and ventricular
hypertrophy are precursors of heart failure, we should reconsider how we
quantify ventricular function in this population. If moderate or severe
LV wall thickness or systolic dysfunction are identified, patients could
benefit from the appropriate therapeutic intervention for preventing the
evolution to heart failure.

CONCLUSIONS

The results of this work allow us to make the anatomical-functional
association between increased LV wall thickness and longitudinal
systolic dysfunction in patients with hypertension. Only moderate or
severe LV septal thickening (\textgreater{}13mm) has an association with
longitudinal dysfunction. LV abnormal geometry and myocardial
incompressibility are the mechanisms that create the artifact of normal
LVEF in the presence of systolic dysfunction. Quantification of MAPSE
and GLS overcomes LVEF limitations and provides essential information on
the myocardial contractile state in hypertensive patients without heart
failure symptoms.

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\textbf{Table 1. Demographic characteristics}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{Variable}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{Global} n= 327\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{Hypertension} n= 226\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{Control} n= 101\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{p}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Age}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
60 (17.8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
67 (13)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
55 (15)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{Gender} female male\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
214 (60) 141 (40)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
143 (63) 83 (37)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
71 (70) 30 (30)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.13\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Weight}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
74.4 (16)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
76 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
71 (13)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.008\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Height}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
163 (9.7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
161 (9.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
165 (8.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.004\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{BMI}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
28 (5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
29 (5.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
26 (4.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{BSA}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.8 (0.22)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.84 (2.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.8 (0.19)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.9\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Obesity}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
104 (29)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
82 (36)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
22 (21)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.006\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Overweight}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
153 (43)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
98 (43)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
55(54)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.04\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Arterial pressure} Systolic Diastolic Mean AP Pulse
pressure\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
126 (15) 78 (9) 94 (10) 48 (11)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
134 (11.3) 81 (8) 99 (8) 52 (10)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
111 (8.4) 71 (5.7) 85 (5.7) 40 (7.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001 0.001 0.001 0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Diabetes}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
28 (7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
28 (12.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
AP: arterial pressure, BMI: body mass index, BSA: body surface
area.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
AP: arterial pressure, BMI: body mass index, BSA: body surface
area.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
AP: arterial pressure, BMI: body mass index, BSA: body surface
area.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
AP: arterial pressure, BMI: body mass index, BSA: body surface
area.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
AP: arterial pressure, BMI: body mass index, BSA: body surface
area.\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 2. Echocardiographic characteristics}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textbf{Variable}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textbf{Hypertension} n= 226\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textbf{Control} n= 101\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textbf{p}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LV MI (g/m\textsuperscript{2})}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
96 (27)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
73 (15)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{RWT}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.55 (0.11)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.41 (0.06)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LV geometry} Normal Conc remodeling Conc hypertrophy\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
28 (13) 98 (43) 100 (44)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
68 (67) 33 (33) 0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.001 0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LV volumes} end-diastolic (mL) end-systolic (mL) SV index
(mL/m\textsuperscript{2})\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
47 (12) 17 (6) 30 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
48 (9.6) 18 (5) 30 (6)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.2 0.8 0.9\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LA VI (ml/m\textsuperscript{2})}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
38.7 (12)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
29 (7)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.02\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LVEF (\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
63 (6)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
63 (6)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.76\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\selectlanguage{ngerman}\textbf{S´ mitral (cm/s)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
8.1 (2.2)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9.9 (2.2)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.03\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{GLS (\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
-18.8 (2.5)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
-20.4 (2)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{MAPSE (mm)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
13.8 (2.8)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
15.5 (2)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Diastolic function} Normal Grade 1 DD Grade 2 DD\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
21 173 32\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
57 44 0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.001 0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\selectlanguage{ngerman}\textbf{E/e´ ratio}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9.5 (3.7)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6.6 (2)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{PASP (mmHg)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
31 (8.4)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
21 (4)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Conc: concentric, DD: diastolic dysfunction, GLS: global longitudinal
strain, LA: left atrium, LV: left ventricle, LVEF: left ventricle
ejection fraction, MAPSE: mitral annulus plane systolic excursion, MI:
mass index, PASP: pulmonary artery systolic pressure, RWT: relative wall
thickness, VI: volume index\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Conc: concentric, DD: diastolic dysfunction, GLS: global longitudinal
strain, LA: left atrium, LV: left ventricle, LVEF: left ventricle
ejection fraction, MAPSE: mitral annulus plane systolic excursion, MI:
mass index, PASP: pulmonary artery systolic pressure, RWT: relative wall
thickness, VI: volume index\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Conc: concentric, DD: diastolic dysfunction, GLS: global longitudinal
strain, LA: left atrium, LV: left ventricle, LVEF: left ventricle
ejection fraction, MAPSE: mitral annulus plane systolic excursion, MI:
mass index, PASP: pulmonary artery systolic pressure, RWT: relative wall
thickness, VI: volume index\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Conc: concentric, DD: diastolic dysfunction, GLS: global longitudinal
strain, LA: left atrium, LV: left ventricle, LVEF: left ventricle
ejection fraction, MAPSE: mitral annulus plane systolic excursion, MI:
mass index, PASP: pulmonary artery systolic pressure, RWT: relative wall
thickness, VI: volume index\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 3. Echocardiographic characteristics in patients with
hypertension according to ventricular geometry. n= 226}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{Variable}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{Normal} n= 28\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{Concentric remodeling} n= 98\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{Concentric hypertrophy} n= 100\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{p}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{LV septum (mm)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
9 (0.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
11 (1.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
13 (1.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{RWT}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.39 (0.03)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.56 (0.1)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.59 (0.1)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{LV MI (ml/m\textsuperscript{2})}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
77 (19)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
78 (12)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
119 (21)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{LV SVI (ml/m\textsuperscript{2})}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
30 (6.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
28 (6.7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
31 (9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{LA VI (ml/m\textsuperscript{2})}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
34 (19)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
35 (9.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
43 (14)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Diastolic function} Normal Grade 1 DD Grade 2 DD\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
11 17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6 84 8\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4 73 23\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001 0.001 0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{PASP (mmHg)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
26.5 (7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
29 (7.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
34 (8.5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{LVEF (\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
62 (4.8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
63.6 (6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
63 (6.7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.13\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\selectlanguage{ngerman}\textbf{S´ mitral (cm/s)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8.5 (2.8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8.8 (2.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7.4 (1.8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{GLS (\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
-20. 2 (2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
-19.6 (2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
-17.5 (2.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{MAPSE (mm)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
15.8 (2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
14.9 (2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
12 (2.7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
DD: diastolic dysfunction, GLS: global longitudinal strain, LA: left
atrium, LV: left ventricle, LVEF: left ventricle ejection fraction,
MAPSE: mitral annulus plane systolic excursion, MI: mass index, PASP:
pulmonary artery systolic pressure, RWT: relative wall thickness, SV:
stroke volume, SVI: stroke volume index, VI: volume index.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
DD: diastolic dysfunction, GLS: global longitudinal strain, LA: left
atrium, LV: left ventricle, LVEF: left ventricle ejection fraction,
MAPSE: mitral annulus plane systolic excursion, MI: mass index, PASP:
pulmonary artery systolic pressure, RWT: relative wall thickness, SV:
stroke volume, SVI: stroke volume index, VI: volume index.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
DD: diastolic dysfunction, GLS: global longitudinal strain, LA: left
atrium, LV: left ventricle, LVEF: left ventricle ejection fraction,
MAPSE: mitral annulus plane systolic excursion, MI: mass index, PASP:
pulmonary artery systolic pressure, RWT: relative wall thickness, SV:
stroke volume, SVI: stroke volume index, VI: volume index.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
DD: diastolic dysfunction, GLS: global longitudinal strain, LA: left
atrium, LV: left ventricle, LVEF: left ventricle ejection fraction,
MAPSE: mitral annulus plane systolic excursion, MI: mass index, PASP:
pulmonary artery systolic pressure, RWT: relative wall thickness, SV:
stroke volume, SVI: stroke volume index, VI: volume index.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
DD: diastolic dysfunction, GLS: global longitudinal strain, LA: left
atrium, LV: left ventricle, LVEF: left ventricle ejection fraction,
MAPSE: mitral annulus plane systolic excursion, MI: mass index, PASP:
pulmonary artery systolic pressure, RWT: relative wall thickness, SV:
stroke volume, SVI: stroke volume index, VI: volume index.\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Figure 1. Boxplot showing the distribution of LVEF (left), MAPSE
(center), and GLS (right) in patients with hypertension according to LV
geometry. MAPSE and GLS panels show the decrease in longitudinal
systolic function as the LV geometry worsens. Moreover, LVEF remains
equal between groups.

Figure 2. ROC curve depicting low global longitudinal strain
classification according to LV septum thickness. Low GLS was defined as
\textgreater{} -17\%.

Figure 3. ROC curve depicting low MAPSE classification according to LV
septum thickness. Low MAPSE was defined according to sex and age.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}

\selectlanguage{english}
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